NMR structural and dynamical investigation of the isolated voltage-sensing domain of the potassium channel KvAP: implications for voltage gating.

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Shenkarev, Zakhar O; Paramonov, Alexander S; Lyukmanova, Ekaterina N; Shingarova, Lyudmila N; Yakimov, Sergei A; Dubinnyi, Maxim A; Chupin, Vladimir V; Kirpichnikov, Mikhail P; Blommers, Marcel J J; Arseniev, Alexander S

2010-04-28

The structure and dynamics of the isolated voltage-sensing domain (VSD) of the archaeal potassium channel KvAP was studied by high-resolution NMR. The almost complete backbone resonance assignment and partial side-chain assignment of the (2)H,(13)C,(15)N-labeled VSD were obtained for the protein domain solubilized in DPC/LDAO (2:1) mixed micelles. Secondary and tertiary structures of the VSD were characterized using secondary chemical shifts and NOE contacts. These data indicate that the spatial structure of the VSD solubilized in micelles corresponds to the structure of the domain in an open state of the channel. NOE contacts and secondary chemical shifts of amide protons indicate the presence of tightly bound water molecule as well as hydrogen bond formation involving an interhelical salt bridge (Asp62-R133) that stabilizes the overall structure of the domain. The backbone dynamics of the VSD was studied using (15)N relaxation measurements. The loop regions S1-S2 and S2-S3 were found mobile, while the S3-S4 loop (voltage-sensor paddle) was found stable at the ps-ns time scale. The moieties of S1, S2, S3, and S4 helices sharing interhelical contacts (at the level of the Asp62-R133 salt bridge) were observed in conformational exchange on the micros-ms time scale. Similar exchange-induced broadening of characteristic resonances was observed for the VSD solubilized in the membrane of lipid-protein nanodiscs composed of DMPC, DMPG, and POPC/DOPG lipids. Apparently, the observed interhelical motions represent an inherent property of the VSD of the KvAP channel and can play an important role in the voltage gating.

Allosteric substrate switching in a voltage-sensing lipid phosphatase.

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Grimm, Sasha S; Isacoff, Ehud Y

2016-04-01

Allostery provides a critical control over enzyme activity, biasing the catalytic site between inactive and active states. We found that the Ciona intestinalis voltage-sensing phosphatase (Ci-VSP), which modifies phosphoinositide signaling lipids (PIPs), has not one but two sequential active states with distinct substrate specificities, whose occupancy is allosterically controlled by sequential conformations of the voltage-sensing domain (VSD). Using fast fluorescence resonance energy transfer (FRET) reporters of PIPs to monitor enzyme activity and voltage-clamp fluorometry to monitor conformational changes in the VSD, we found that Ci-VSP switches from inactive to a PIP3-preferring active state when the VSD undergoes an initial voltage-sensing motion and then into a second PIP2-preferring active state when the VSD activates fully. This two-step allosteric control over a dual-specificity enzyme enables voltage to shape PIP concentrations in time, and provides a mechanism for the complex modulation of PIP-regulated ion channels, transporters, cell motility, endocytosis and exocytosis.

Allosteric substrate switching in a voltage sensing lipid phosphatase

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Grimm, Sasha S.; Isacoff, Ehud Y.

2016-01-01

Allostery provides a critical control over enzyme activity, biasing the catalytic site between inactive and active states. We find the Ciona intestinalis voltage-sensing phosphatase (Ci-VSP), which modifies phosphoinositide signaling lipids (PIPs), to have not one but two sequential active states with distinct substrate specificities, whose occupancy is allosterically controlled by sequential conformations of the voltage sensing domain (VSD). Using fast FRET reporters of PIPs to monitor enzyme activity and voltage clamp fluorometry to monitor conformational changes in the VSD, we find that Ci-VSP switches from inactive to a PIP3-preferring active state when the VSD undergoes an initial voltage sensing motion and then into a second PIP2-preferring active state when the VSD activates fully. This novel 2-step allosteric control over a dual specificity enzyme enables voltage to shape PIP concentrations in time, and provides a mechanism for the complex modulation of PIP-regulated ion channels, transporters, cell motility and endo/exocytosis. PMID:26878552

Disulfide mapping the voltage-sensing mechanism of a voltage-dependent potassium channel.

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Nozaki, Tomohiro; Ozawa, Shin-Ichiro; Harada, Hitomi; Kimura, Tomomi; Osawa, Masanori; Shimada, Ichio

2016-11-17

Voltage-dependent potassium (Kv) channels allow for the selective permeability of potassium ions in a membrane potential dependent manner, playing crucial roles in neurotransmission and muscle contraction. Kv channel is a tetramer, in which each subunit possesses a voltage-sensing domain (VSD) and a pore domain (PD). Although several lines of evidence indicated that membrane depolarization is sensed as the movement of helix S4 of the VSD, the detailed voltage-sensing mechanism remained elusive, due to the difficulty of structural analyses at resting potential. In this study, we conducted a comprehensive disulfide locking analysis of the VSD using 36 double Cys mutants, in order to identify the proximal residue pairs of the VSD in the presence or absence of a membrane potential. An intramolecular SS-bond was formed between 6 Cys pairs under both polarized and depolarized environment, and one pair only under depolarized environment. The multiple conformations captured by the SS-bond can be divided by two states, up and down, where S4 lies on the extracellular and intracellular sides of the membrane, respectively, with axial rotation of 180°. The transition between these two states is caused by the S4 translocation of 12 Å, enabling allosteric regulation of the gating at the PD.

In search of a consensus model of the resting state of a voltage-sensing domain.

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Vargas, Ernesto; Bezanilla, Francisco; Roux, Benoît

2011-12-08

Voltage-sensing domains (VSDs) undergo conformational changes in response to the membrane potential and are the critical structural modules responsible for the activation of voltage-gated channels. Structural information about the key conformational states underlying voltage activation is currently incomplete. Through the use of experimentally determined residue-residue interactions as structural constraints, we determine and refine a model of the Kv channel VSD in the resting conformation. The resulting structural model is in broad agreement with results that originate from various labs using different techniques, indicating the emergence of a consensus for the structural basis of voltage sensing. Copyright © 2011 Elsevier Inc. All rights reserved.

Sensing charges of the Ciona intestinalis voltage-sensing phosphatase.

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Villalba-Galea, Carlos A; Frezza, Ludivine; Sandtner, Walter; Bezanilla, Francisco

2013-11-01

Voltage control over enzymatic activity in voltage-sensitive phosphatases (VSPs) is conferred by a voltage-sensing domain (VSD) located in the N terminus. These VSDs are constituted by four putative transmembrane segments (S1 to S4) resembling those found in voltage-gated ion channels. The putative fourth segment (S4) of the VSD contains positive residues that likely function as voltage-sensing elements. To study in detail how these residues sense the plasma membrane potential, we have focused on five arginines in the S4 segment of the Ciona intestinalis VSP (Ci-VSP). After implementing a histidine scan, here we show that four arginine-to-histidine mutants, namely R223H to R232H, mediate voltage-dependent proton translocation across the membrane, indicating that these residues transit through the hydrophobic core of Ci-VSP as a function of the membrane potential. These observations indicate that the charges carried by these residues are sensing charges. Furthermore, our results also show that the electrical field in VSPs is focused in a narrow hydrophobic region that separates the extracellular and intracellular space and constitutes the energy barrier for charge crossing.

Dimerization of the voltage-sensing phosphatase controls its voltage-sensing and catalytic activity.

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Rayaprolu, Vamseedhar; Royal, Perrine; Stengel, Karen; Sandoz, Guillaume; Kohout, Susy C

2018-05-07

Multimerization is a key characteristic of most voltage-sensing proteins. The main exception was thought to be the Ciona intestinalis voltage-sensing phosphatase (Ci-VSP). In this study, we show that multimerization is also critical for Ci-VSP function. Using coimmunoprecipitation and single-molecule pull-down, we find that Ci-VSP stoichiometry is flexible. It exists as both monomers and dimers, with dimers favored at higher concentrations. We show strong dimerization via the voltage-sensing domain (VSD) and weak dimerization via the phosphatase domain. Using voltage-clamp fluorometry, we also find that VSDs cooperate to lower the voltage dependence of activation, thus favoring the activation of Ci-VSP. Finally, using activity assays, we find that dimerization alters Ci-VSP substrate specificity such that only dimeric Ci-VSP is able to dephosphorylate the 3-phosphate from PI(3,4,5)P 3 or PI(3,4)P 2 Our results indicate that dimerization plays a significant role in Ci-VSP function. © 2018 Rayaprolu et al.

Characterization of the Functional Domains of a Mammalian Voltage-Sensitive Phosphatase.

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Rosasco, Mario G; Gordon, Sharona E; Bajjalieh, Sandra M

2015-12-15

Voltage-sensitive phosphatases (VSPs) are proteins that directly couple changes in membrane electrical potential to inositol lipid phosphatase activity. VSPs thus couple two signaling pathways that are critical for cellular functioning. Although a number of nonmammalian VSPs have been characterized biophysically, mammalian VSPs are less well understood at both the physiological and biophysical levels. In this study, we aimed to address this gap in knowledge by determining whether the VSP from mouse, Mm-VSP, is expressed in the brain and contains a functional voltage-sensing domain (VSD) and a phosphatase domain. We report that Mm-VSP is expressed in neurons and is developmentally regulated. To address whether the functions of the VSD and phosphatase domain are retained in Mm-VSP, we took advantage of the modular nature of these domains and expressed each independently as a chimeric protein in a heterologous expression system. We found that the Mm-VSP VSD, fused to a viral potassium channel, was able to drive voltage-dependent gating of the channel pore. The Mm-VSP phosphatase domain, fused to the VSD of a nonmammalian VSP, was also functional: activation resulted in PI(4,5)P2 depletion that was sufficient to inhibit the PI(4,5)P2-regulated KCNQ2/3 channels. While testing the functionality of the VSD and phosphatase domain, we observed slight differences between the activities of Mm-VSP-based chimeras and those of nonmammalian VSPs. Although the properties of VSP chimeras may not completely reflect the properties of native VSPs, the differences we observed in voltage-sensing and phosphatase activity provide a starting point for future experiments to investigate the function of Mm-VSP and other mammalian VSPs. In conclusion, our data reveal that both the VSD and the lipid phosphatase domain of Mm-VSP are functional, indicating that Mm-VSP likely plays an important role in mouse neurophysiology. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All

Induction of divalent cation permeability by heterologous expression of a voltage sensor domain.

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Arima, Hiroki; Tsutsui, Hidekazu; Sakamoto, Ayako; Yoshida, Manabu; Okamura, Yasushi

2018-01-06

The voltage sensor domain (VSD) is a protein domain that confers sensitivity to membrane potential in voltage-gated ion channels as well as the voltage-sensing phosphatase. Although VSDs have long been considered to function as regulatory units acting on adjacent effectors, recent studies have revealed the existence of direct ion permeation paths in some mutated VSDs and in the voltage-gated proton channel. In this study, we show that calcium currents are evoked upon membrane hyperpolarization in cells expressing a VSD derived from an ascidian voltage-gated ion channel superfamily. Unlike the previously reported omega-pore in the Shaker K + channel and rNav1.4, mutations are not required. From electrophysiological experiments in heterologous expression systems, we found that the conductance is directly mediated by the VSD itself and is carried by both monovalent and divalent cations. This is the first report of divalent cation permeation through a VSD-like structure. Copyright © 2018 Elsevier B.V. All rights reserved.

Structural basis of lipid-driven conformational transitions in the KvAP voltage-sensing domain.

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Li, Qufei; Wanderling, Sherry; Sompornpisut, Pornthep; Perozo, Eduardo

2014-02-01

Voltage-gated ion channels respond to transmembrane electric fields through reorientations of the positively charged S4 helix within the voltage-sensing domain (VSD). Despite a wealth of structural and functional data, the details of this conformational change remain controversial. Recent electrophysiological evidence showed that equilibrium between the resting ('down') and activated ('up') conformations of the KvAP VSD from Aeropyrum pernix can be biased through reconstitution in lipids with or without phosphate groups. We investigated the structural transition between these functional states, using site-directed spin-labeling and EPR spectroscopic methods. Solvent accessibility and interhelical distance determinations suggest that KvAP gates through S4 movements involving an ∼3-Å upward tilt and simultaneous ∼2-Å axial shift. This motion leads to large accessibly changes in the intracellular water-filled crevice and supports a new model of gating that combines structural rearrangements and electric-field remodeling.

Functional diversity of voltage-sensing phosphatases in two urodele amphibians.

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Mutua, Joshua; Jinno, Yuka; Sakata, Souhei; Okochi, Yoshifumi; Ueno, Shuichi; Tsutsui, Hidekazu; Kawai, Takafumi; Iwao, Yasuhiro; Okamura, Yasushi

2014-07-16

Voltage-sensing phosphatases (VSPs) share the molecular architecture of the voltage sensor domain (VSD) with voltage-gated ion channels and the phosphoinositide phosphatase region with the phosphatase and tensin homolog (PTEN), respectively. VSPs enzymatic activities are regulated by the motions of VSD upon depolarization. The physiological role of these proteins has remained elusive, and insights may be gained by investigating biological variations in different animal species. Urodele amphibians are vertebrates with potent activities of regeneration and also show diverse mechanisms of polyspermy prevention. We cloned cDNAs of VSPs from the testes of two urodeles; Hynobius nebulosus and Cynops pyrrhogaster, and compared their expression and voltage-dependent activation. Their molecular architecture is highly conserved in both Hynobius VSP (Hn-VSP) and Cynops VSP (Cp-VSP), including the positively-charged arginine residues in the S4 segment of the VSD and the enzymatic active site for substrate binding, yet the C-terminal C2 domain of Hn-VSP is significantly shorter than that of Cp-VSP and other VSP orthologs. RT-PCR analysis showed that gene expression pattern was distinct between two VSPs. The voltage sensor motions and voltage-dependent phosphatase activities were investigated electrophysiologically by expression in Xenopus oocytes. Both VSPs showed "sensing" currents, indicating that their voltage sensor domains are functional. The phosphatase activity of Cp-VSP was found to be voltage dependent, as shown by its ability to regulate the conductance of coexpressed GIRK2 channels, but Hn-VSP lacked such phosphatase activity due to the truncation of its C2 domain. © 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Mapping the membrane-aqueous border for the voltage-sensing domain of a potassium channel.

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Neale, Edward J; Rong, Honglin; Cockcroft, Christopher J; Sivaprasadarao, Asipu

2007-12-28

Voltage-sensing domains (VSDs) play diverse roles in biology. As integral components, they can detect changes in the membrane potential of a cell and couple these changes to activity of ion channels and enzymes. As independent proteins, homologues of the VSD can function as voltage-dependent proton channels. To sense voltage changes, the positively charged fourth transmembrane segment, S4, must move across the energetically unfavorable hydrophobic core of the bilayer, which presents a barrier to movement of both charged species and protons. To reduce the barrier to S4 movement, it has been suggested that aqueous crevices may penetrate the protein, reducing the extent of total movement. To investigate this hypothesis in a system containing fully functional channels in a native environment with an intact membrane potential, we have determined the contour of the membrane-aqueous border of the VSD of KvAP in Escherichia coli by examining the chemical accessibility of introduced cysteines. The results revealed the contour of the membrane-aqueous border of the VSD in its activated conformation. The water-inaccessible regions of S1 and S2 correspond to the standard width of the membrane bilayer (~28 A), but those of S3 and S4 are considerably shorter (> or = 40%), consistent with aqueous crevices pervading both the extracellular and intracellular ends. One face of S3b and the entire S3a were water-accessible, reducing the water-inaccessible region of S3 to just 10 residues, significantly shorter than for S4. The results suggest a key role for S3 in reducing the distance S4 needs to move to elicit gating.

Voltage-sensing domain mode shift is coupled to the activation gate by the N-terminal tail of hERG channels.

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

2012-09-01

Human ether-a-go-go-related gene (hERG) potassium channels exhibit unique gating kinetics characterized by unusually slow activation and deactivation. The N terminus of the channel, which contains an amphipathic helix and an unstructured tail, has been shown to be involved in regulation of this slow deactivation. However, the mechanism of how this occurs and the connection between voltage-sensing domain (VSD) return and closing of the gate are unclear. To examine this relationship, we have used voltage-clamp fluorometry to simultaneously measure VSD motion and gate closure in N-terminally truncated constructs. We report that mode shifting of the hERG VSD results in a corresponding shift in the voltage-dependent equilibrium of channel closing and that at negative potentials, coupling of the mode-shifted VSD to the gate defines the rate of channel closure. Deletion of the first 25 aa from the N terminus of hERG does not alter mode shifting of the VSD but uncouples the shift from closure of the cytoplasmic gate. Based on these observations, we propose the N-terminal tail as an adaptor that couples voltage sensor return to gate closure to define slow deactivation gating in hERG channels. Furthermore, because the mode shift occurs on a time scale relevant to the cardiac action potential, we suggest a physiological role for this phenomenon in maximizing current flow through hERG channels during repolarization.

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

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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.

Caution Is Required in Interpretation of Mutations in the Voltage Sensing Domain of Voltage Gated Channels as Evidence for Gating Mechanisms

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Alisher M. Kariev

2015-01-01

Full Text Available The gating mechanism of voltage sensitive ion channels is generally considered to be the motion of the S4 transmembrane segment of the voltage sensing domains (VSD. The primary supporting evidence came from R→C mutations on the S4 transmembrane segment of the VSD, followed by reaction with a methanethiosulfonate (MTS reagent. The cys side chain is –SH (reactive form –S−; the arginine side chain is much larger, leaving space big enough to accommodate the MTS sulfonate head group. The cavity created by the mutation has space for up to seven more water molecules than were present in wild type, which could be displaced irreversibly by the MTS reagent. Our quantum calculations show there is major reorientation of three aromatic residues that face into the cavity in response to proton displacement within the VSD. Two phenylalanines reorient sufficiently to shield/unshield the cysteine from the intracellular and extracellular ends, depending on the proton positions, and a tyrosine forms a hydrogen bond to the cysteine sulfur with its side chain –OH. These could produce the results of the experiments that have been interpreted as evidence for physical motion of the S4 segment, without physical motion of the S4 backbone. The computations strongly suggest that the interpretation of cysteine substitution reaction experiments be re-examined in the light of these considerations.

Electro-chemical coupling in the voltage-dependent phosphatase Ci-VSP

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Kohout, Susy C.; Bell, Sarah C.; Liu, Lijun; Xu, Qiang; Minor, Daniel L.; Isacoff, Ehud Y.

2010-01-01

In the voltage sensing phosphatase, Ci-VSP, a voltage sensing domain (VSD) controls a lipid phosphatase domain (PD). The mechanism by which the domains are allosterically coupled is not well understood. Using an in vivo assay, we find that the inter-domain linker that connects the VSD to the PD is essential for coupling the full-length protein. Biochemical assays show that the linker is also needed for activity in the isolated PD. We identify a late step of VSD motion in the full-length protein that depends on the linker. Strikingly, this VSD motion is found to require PI(4,5)P2, a substrate of Ci-VSP. These results suggest that the voltage-driven motion of the VSD turns the enzyme on by rearranging the linker into an activated conformation, and that this activated conformation is stabilized by PI(4,5)P2. We propose that Ci-VSP activity is self-limited because its decrease of PI(4,5)P2 levels decouples the VSD from the enzyme. PMID:20364128

Domain-to-domain coupling in voltage-sensing phosphatase.

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Sakata, Souhei; Matsuda, Makoto; Kawanabe, Akira; Okamura, Yasushi

2017-01-01

Voltage-sensing phosphatase (VSP) consists of a transmembrane voltage sensor and a cytoplasmic enzyme region. The enzyme region contains the phosphatase and C2 domains, is structurally similar to the tumor suppressor phosphatase PTEN, and catalyzes the dephosphorylation of phosphoinositides. The transmembrane voltage sensor is connected to the phosphatase through a short linker region, and phosphatase activity is induced upon membrane depolarization. Although the detailed molecular characteristics of the voltage sensor domain and the enzyme region have been revealed, little is known how these two regions are coupled. In addition, it is important to know whether mechanism for coupling between the voltage sensor domain and downstream effector function is shared among other voltage sensor domain-containing proteins. Recent studies in which specific amino acid sites were genetically labeled using a fluorescent unnatural amino acid have enabled detection of the local structural changes in the cytoplasmic region of Ciona intestinalis VSP that occur with a change in membrane potential. The results of those studies provide novel insight into how the enzyme activity of the cytoplasmic region of VSP is regulated by the voltage sensor domain.

Voltage-controlled Enzymes: The new Janus Bifrons

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Carlos Alberto Villalba-Galea

2012-09-01

Full Text Available The Ciona intestinalis voltage sensitive phosphatase, Ci-VSP, was the first Voltage-controlled Enzyme (VEnz proven to be under direct command of the membrane potential. The discovery of Ci-VSP conjugated voltage sensitivity and enzymatic activity in a single protein. These two facets of Ci-VSP activity have provided a unique model for studying how membrane potential is sensed by proteins and a novel mechanism for control of enzymatic activity. These facets make Ci-VSP a fascinating and versatile enzyme.Ci-VSP has a voltage sensing domain (VSD that resembles those found in voltage-gated channels (VGC. The VSD resides in the N-terminus and is formed by four putative trans-membrane segments. The fourth segment contains charged residues which are likely involved in voltage sensing. Ci-VSP produces sensing currents in response to changes in potential, within a defined range of voltages. Sensing currents are analogous to gating currents in VGC. As known, these latter proteins contain four VSDs which are entangled in a complex interaction with the pore domain –the effector domain in VGC. This complexity makes studying the basis of voltage sensing in VGC a difficult enterprise. In contrast, Ci-VSP is thought to be monomeric and its catalytic domain –the VSP’s effector domain– can be cleaved off without disrupting the basic electrical functioning of the VSD. For these reasons, VSPs are considered a great model for studying the activity of a VSD in isolation. Finally, VSPs are also phosphoinositide phosphatases. Phosphoinositides are signaling lipids found in eukaryotes and are involved in many processes, including modulation of VGC activity and regulation of cell proliferation. Understanding VSPs as VEnz has been the center of attention in recent years and several reviews has been dedicated to this area. Thus, this review will be focused instead on the other face of this true Janus Bifrons and recapitulate what is known about VSPs as electrically

S1 constrains S4 in the voltage sensor domain of Kv7.1 K+ channels.

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Yoni Haitin

Full Text Available Voltage-gated K(+ channels comprise a central pore enclosed by four voltage-sensing domains (VSDs. While movement of the S4 helix is known to couple to channel gate opening and closing, the nature of S4 motion is unclear. Here, we substituted S4 residues of Kv7.1 channels by cysteine and recorded whole-cell mutant channel currents in Xenopus oocytes using the two-electrode voltage-clamp technique. In the closed state, disulfide and metal bridges constrain residue S225 (S4 nearby C136 (S1 within the same VSD. In the open state, two neighboring I227 (S4 are constrained at proximity while residue R228 (S4 is confined close to C136 (S1 of an adjacent VSD. Structural modeling predicts that in the closed to open transition, an axial rotation (approximately 190 degrees and outward translation of S4 (approximately 12 A is accompanied by VSD rocking. This large sensor motion changes the intra-VSD S1-S4 interaction to an inter-VSD S1-S4 interaction. These constraints provide a ground for cooperative subunit interactions and suggest a key role of the S1 segment in steering S4 motion during Kv7.1 gating.

Expression of the voltage-sensing phosphatase gene in the chick embryonic tissues and in the adult cerebellum.

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Yamaguchi, Shinji; Aoki, Naoya; Kitajima, Takaaki; Okamura, Yasushi; Homma, Koichi J

2014-10-01

Voltage-sensing phosphatase (VSP) consists of a transmembrane voltage sensor domain (VSD) and the cytoplasmic domain with phosphoinositide-phosphatase activities. It operates as the voltage sensor and directly translates membrane potential into phosphoinositide turnover by coupling VSD to the cytoplasmic domain. VSPs are evolutionarily conserved from marine invertebrate up to humans. Recently, we demonstrated that ectopic expression of the chick ortholog of VSP, Gg-VSP, in a fibroblast cell line caused characteristic cell process outgrowths. Co-expression of chick PTEN suppressed such morphological change, suggesting that VSP regulates cell shape by increasing PI(3,4)P2. However, the in vivo function of Gg-VSP remains unclear. Here, we showed that in chick embryos Gg-VSP is expressed in the stomach, mesonephros, pharyngeal arch, limb bud, somites, floor plate of neural tube, and notochord. In addition, both Gg-VSP transcripts and the protein were found in the cerebellar Purkinje neurons. These findings provide an insight into the physiological functions of VSP.

A common pathway for charge transport through voltage-sensing domains.

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Chanda, Baron; Bezanilla, Francisco

2008-02-07

Voltage-gated ion channels derive their voltage sensitivity from the movement of specific charged residues in response to a change in transmembrane potential. Several studies on mechanisms of voltage sensing in ion channels support the idea that these gating charges move through a well-defined permeation pathway. This gating pathway in a voltage-gated ion channel can also be mutated to transport free cations, including protons. The recent discovery of proton channels with sequence homology to the voltage-sensing domains suggests that evolution has perhaps exploited the same gating pathway to generate a bona fide voltage-dependent proton transporter. Here we will discuss implications of these findings on the mechanisms underlying charge (and ion) transport by voltage-sensing domains.

A localized interaction surface for voltage-sensing domains on the pore domain of a K+ channel.

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Li-Smerin, Y; Hackos, D H; Swartz, K J

2000-02-01

Voltage-gated K+ channels contain a central pore domain and four surrounding voltage-sensing domains. How and where changes in the structure of the voltage-sensing domains couple to the pore domain so as to gate ion conduction is not understood. The crystal structure of KcsA, a bacterial K+ channel homologous to the pore domain of voltage-gated K+ channels, provides a starting point for addressing this question. Guided by this structure, we used tryptophan-scanning mutagenesis on the transmembrane shell of the pore domain in the Shaker voltage-gated K+ channel to localize potential protein-protein and protein-lipid interfaces. Some mutants cause only minor changes in gating and when mapped onto the KcsA structure cluster away from the interface between pore domain subunits. In contrast, mutants producing large changes in gating tend to cluster near this interface. These results imply that voltage-sensing domains interact with localized regions near the interface between adjacent pore domain subunits.

A complicated complex: Ion channels, voltage sensing, cell membranes and peptide inhibitors.

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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

Grafting voltage and pharmacological sensitivity in potassium channels.

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Lan, Xi; Fan, Chunyan; Ji, Wei; Tian, Fuyun; Xu, Tao; Gao, Zhaobing

2016-08-01

A classical voltage-gated ion channel consists of four voltage-sensing domains (VSDs). However, the roles of each VSD in the channels remain elusive. We developed a GVTDT (Graft VSD To Dimeric TASK3 channels that lack endogenous VSDs) strategy to produce voltage-gated channels with a reduced number of VSDs. TASK3 channels exhibit a high host tolerance to VSDs of various voltage-gated ion channels without interfering with the intrinsic properties of the TASK3 selectivity filter. The constructed channels, exemplified by the channels grafted with one or two VSDs from Kv7.1 channels, exhibit classical voltage sensitivity, including voltage-dependent opening and closing. Furthermore, the grafted Kv7.1 VSD transfers the potentiation activity of benzbromarone, an activator that acts on the VSDs of the donor channels, to the constructed channels. Our study indicates that one VSD is sufficient to voltage-dependently gate the pore and provides new insight into the roles of VSDs.

Biophysical characterization of the fluorescent protein voltage probe VSFP2.3 based on the voltage-sensing domain of Ci-VSP

DEFF Research Database (Denmark)

Lundby, Alicia; Akemann, Walther; Knöpfel, Thomas

2010-01-01

A voltage sensitive phosphatase was discovered in the ascidian Ciona intestinalis. The phosphatase, Ci-VSP, contains a voltage-sensing domain homologous to those known from voltage-gated ion channels, but unlike ion channels, the voltage-sensing domain of Ci-VSP can reside in the cell membrane...... as a monomer. We fused the voltage-sensing domain of Ci-VSP to a pair of fluorescent reporter proteins to generate a genetically encodable voltage-sensing fluorescent probe, VSFP2.3. VSFP2.3 is a fluorescent voltage probe that reports changes in membrane potential as a FRET (fluorescence resonance energy....... Neutralization of an arginine in S4, previously suggested to be a sensing charge, and measuring associated sensing currents indicate that this charge is likely to reside at the membrane-aqueous interface rather than within the membrane electric field. The data presented give us insights into the voltage-sensing...

Voltage Sensing in Membranes: From Macroscopic Currents to Molecular Motions.

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Freites, J Alfredo; Tobias, Douglas J

2015-06-01

Voltage-sensing domains (VSDs) are integral membrane protein units that sense changes in membrane electric potential, and through the resulting conformational changes, regulate a specific function. VSDs confer voltage-sensitivity to a large superfamily of membrane proteins that includes voltage-gated Na[Formula: see text], K[Formula: see text], Ca[Formula: see text] ,and H[Formula: see text] selective channels, hyperpolarization-activated cyclic nucleotide-gated channels, and voltage-sensing phosphatases. VSDs consist of four transmembrane segments (termed S1 through S4). Their most salient structural feature is the highly conserved positions for charged residues in their sequences. S4 exhibits at least three conserved triplet repeats composed of one basic residue (mostly arginine) followed by two hydrophobic residues. These S4 basic side chains participate in a state-dependent internal salt-bridge network with at least four acidic residues in S1-S3. The signature of voltage-dependent activation in electrophysiology experiments is a transient current (termed gating or sensing current) upon a change in applied membrane potential as the basic side chains in S4 move across the membrane electric field. Thus, the unique structural features of the VSD architecture allow for competing requirements: maintaining a series of stable transmembrane conformations, while allowing charge motion, as briefly reviewed here.

Beyond voltage-gated ion channels: Voltage-operated membrane proteins and cellular processes.

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Zhang, Jianping; Chen, Xingjuan; Xue, Yucong; Gamper, Nikita; Zhang, Xuan

2018-04-18

Voltage-gated ion channels were believed to be the only voltage-sensitive proteins in excitable (and some non-excitable) cells for a long time. Emerging evidence indicates that the voltage-operated model is shared by some other transmembrane proteins expressed in both excitable and non-excitable cells. In this review, we summarize current knowledge about voltage-operated proteins, which are not classic voltage-gated ion channels as well as the voltage-dependent processes in cells for which single voltage-sensitive proteins have yet to be identified. Particularly, we will focus on the following. (1) Voltage-sensitive phosphoinositide phosphatases (VSP) with four transmembrane segments homologous to the voltage sensor domain (VSD) of voltage-gated ion channels; VSPs are the first family of proteins, other than the voltage-gated ion channels, for which there is sufficient evidence for the existence of the VSD domain; (2) Voltage-gated proton channels comprising of a single voltage-sensing domain and lacking an identified pore domain; (3) G protein coupled receptors (GPCRs) that mediate the depolarization-evoked potentiation of Ca 2+ mobilization; (4) Plasma membrane (PM) depolarization-induced but Ca 2+ -independent exocytosis in neurons. (5) Voltage-dependent metabolism of phosphatidylinositol 4,5-bisphosphate (PtdIns[4,5]P 2 , PIP 2 ) in the PM. These recent discoveries expand our understanding of voltage-operated processes within cellular membranes. © 2018 Wiley Periodicals, Inc.

Biophysical characterization of the fluorescent protein voltage probe VSFP2.3 based on the voltage-sensing domain of Ci-VSP.

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Lundby, Alicia; Akemann, Walther; Knöpfel, Thomas

2010-11-01

A voltage sensitive phosphatase was discovered in the ascidian Ciona intestinalis. The phosphatase, Ci-VSP, contains a voltage-sensing domain homologous to those known from voltage-gated ion channels, but unlike ion channels, the voltage-sensing domain of Ci-VSP can reside in the cell membrane as a monomer. We fused the voltage-sensing domain of Ci-VSP to a pair of fluorescent reporter proteins to generate a genetically encodable voltage-sensing fluorescent probe, VSFP2.3. VSFP2.3 is a fluorescent voltage probe that reports changes in membrane potential as a FRET (fluorescence resonance energy transfer) signal. Here we report sensing current measurements from VSFP2.3, and show that VSFP2.3 carries 1.2 e sensing charges, which are displaced within 1.5 ms. The sensing currents become faster at higher temperatures, and the voltage dependence of the decay time constants is temperature dependent. Neutralization of an arginine in S4, previously suggested to be a sensing charge, and measuring associated sensing currents indicate that this charge is likely to reside at the membrane-aqueous interface rather than within the membrane electric field. The data presented give us insights into the voltage-sensing mechanism of Ci-VSP, which will allow us to further improve the sensitivity and kinetics of the family of VSFP proteins.

Independent and cooperative motions of the Kv1.2 channel: voltage sensing and gating.

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Yeheskel, Adva; Haliloglu, Turkan; Ben-Tal, Nir

2010-05-19

Voltage-gated potassium (Kv) channels, such as Kv1.2, are involved in the generation and propagation of action potentials. The Kv channel is a homotetramer, and each monomer is composed of a voltage-sensing domain (VSD) and a pore domain (PD). We analyzed the fluctuations of a model structure of Kv1.2 using elastic network models. The analysis suggested a network of coupled fluctuations of eight rigid structural units and seven hinges that may control the transition between the active and inactive states of the channel. For the most part, the network is composed of amino acids that are known to affect channel activity. The results suggested allosteric interactions and cooperativity between the subunits in the coupling between the motion of the VSD and the selectivity filter of the PD, in accordance with recent empirical data. There are no direct contacts between the VSDs of the four subunits, and the contacts between these and the PDs are loose, suggesting that the VSDs are capable of functioning independently. Indeed, they manifest many inherent fluctuations that are decoupled from the rest of the structure. In general, the analysis suggests that the two domains contribute to the channel function both individually and cooperatively. Copyright 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Structure and hydration of membranes embedded with voltage-sensing domains.

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Krepkiy, Dmitriy; Mihailescu, Mihaela; Freites, J Alfredo; Schow, Eric V; Worcester, David L; Gawrisch, Klaus; Tobias, Douglas J; White, Stephen H; Swartz, Kenton J

2009-11-26

Despite the growing number of atomic-resolution membrane protein structures, direct structural information about proteins in their native membrane environment is scarce. This problem is particularly relevant in the case of the highly charged S1-S4 voltage-sensing domains responsible for nerve impulses, where interactions with the lipid bilayer are critical for the function of voltage-activated ion channels. Here we use neutron diffraction, solid-state nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics simulations to investigate the structure and hydration of bilayer membranes containing S1-S4 voltage-sensing domains. Our results show that voltage sensors adopt transmembrane orientations and cause a modest reshaping of the surrounding lipid bilayer, and that water molecules intimately interact with the protein within the membrane. These structural findings indicate that voltage sensors have evolved to interact with the lipid membrane while keeping energetic and structural perturbations to a minimum, and that water penetrates the membrane, to hydrate charged residues and shape the transmembrane electric field.

Regulation of KV channel voltage-dependent activation by transmembrane β subunits

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Xiaohui eSun

2012-04-01

Full Text Available Voltage-activated K+ (KV channels are important for shaping action potentials and maintaining resting membrane potential in excitable cells. KV channels contain a central pore-gate domain (PGD surrounded by four voltage-sensing domains (VSD. The VSDs will change conformation in response to alterations of the membrane potential thereby inducing the opening of the PGD. Many KV channels are heteromeric protein complexes containing auxiliary β subunits. These β subunits modulate channel expression and activity to increase functional diversity and render tissue specific phenotypes. This review focuses on the KV β subunits that contain transmembrane (TM segments including the KCNE family and the β subunits of large conductance, Ca2+- and voltage-activated K+ (BK channels. These TM β subunits affect the voltage-dependent activation of KV α subunits. Experimental and computational studies have described the structural location of these β subunits in the channel complexes and the biophysical effects on VSD activation, PGD opening and VSD-PGD coupling. These results reveal some common characteristics and mechanistic insights into KV channel modulation by TM β subunits.

Structural interactions between lipids, water and S1-S4 voltage-sensing domains.

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Krepkiy, Dmitriy; Gawrisch, Klaus; Swartz, Kenton J

2012-11-02

Membrane proteins serve crucial signaling and transport functions, yet relatively little is known about their structures in membrane environments or how lipids interact with these proteins. For voltage-activated ion channels, X-ray structures suggest that the mobile voltage-sensing S4 helix would be exposed to the membrane, and functional studies reveal that lipid modification can profoundly alter channel activity. Here, we use solid-state NMR to investigate structural interactions of lipids and water with S1-S4 voltage-sensing domains and to explore whether lipids influence the structure of the protein. Our results demonstrate that S1-S4 domains exhibit extensive interactions with lipids and that these domains are heavily hydrated when embedded in a membrane. We also find evidence for preferential interactions of anionic lipids with S1-S4 domains and that these interactions have lifetimes on the timescale of ≤ 10(-3)s. Arg residues within S1-S4 domains are well hydrated and are positioned in close proximity to lipids, exhibiting local interactions with both lipid headgroups and acyl chains. Comparative studies with a positively charged lipid lacking a phosphodiester group reveal that this lipid modification has only modest effects on the structure and hydration of S1-S4 domains. Taken together, our results demonstrate that Arg residues in S1-S4 voltage-sensing domains reside in close proximity to the hydrophobic interior of the membrane yet are well hydrated, a requirement for carrying charge and driving protein motions in response to changes in membrane voltage. Published by Elsevier Ltd.

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

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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.

Genetically encoded fluorescent voltage sensors using the voltage-sensing domain of Nematostella and Danio phosphatases exhibit fast kinetics.

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Baker, Bradley J; Jin, Lei; Han, Zhou; Cohen, Lawrence B; Popovic, Marko; Platisa, Jelena; Pieribone, Vincent

2012-07-15

A substantial increase in the speed of the optical response of genetically encoded fluorescent protein voltage sensors (FP voltage sensors) was achieved by using the voltage-sensing phosphatase genes of Nematostella vectensis and Danio rerio. A potential N. vectensis voltage-sensing phosphatase was identified in silico. The voltage-sensing domain (S1-S4) of the N. vectensis homolog was used to create an FP voltage sensor called Nema. By replacing the phosphatase with a cerulean/citrine FRET pair, a new FP voltage sensor was synthesized with fast off kinetics (Tau(off)voltage-sensing phosphatase homolog, designated Zahra and Zahra 2, exhibited fast on and off kinetics within 2ms of the time constants observed with the organic voltage-sensitive dye, di4-ANEPPS. Mutagenesis of the S4 region of the Danio FP voltage sensor shifted the voltage dependence to more negative potentials but did not noticeably affect the kinetics of the optical signal. Copyright © 2012 Elsevier B.V. All rights reserved.

Genetically-encoded fluorescent voltage sensors using the voltage-sensing domain of Nematostella and Danio phosphatases exhibit fast kinetics

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Baker, Bradley J.; Jin, Lei; Han, Zhou; Cohen, Lawrence B.; Popovic, Marko; Platisa, Jelena; Pieribone, Vincent

2012-01-01

A substantial increase in the speed of the optical response of genetically-encoded Fluorescent Protein voltage sensors (FP voltage sensors) was achieved by using the voltage-sensing phosphatase genes of Nematostella vectensis and Danio rerio. A potential N. vectensis voltage-sensing phosphatase was identified in silico. The voltage-sensing domain (S1–S4) of the N. vectensis homolog was used to create an FP voltage sensor called Nema. By replacing the phosphatase with a cerulean/citrine FRET pair, a new FP voltage sensor was synthesized with fast off kinetics (Tauoff voltage-sensing phosphatase homolog, designated Zahra and Zahra 2, exhibited fast on and off kinetics within 2 msec of the time constants observed with the organic voltage-sensitive dye, di4-ANEPPS. Mutagenesis of the S4 region of the Danio FP voltage sensor shifted the voltage dependence to more negative potentials but did not noticeably affect the kinetics of the optical signal. PMID:22634212

Structure of Voltage-gated Two-pore Channel TPC1 from Arabidopsis thaliana

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Guo, Jiangtao; Zeng, Weizhong; Chen, Qingfeng; Lee, Changkeun; Chen, Liping; Yang, Yi; Cang, Chunlei; Ren, Dejian; Jiang, Youxing

2015-01-01

Two-pore channels (TPCs) contain two copies of a Shaker-like six-transmembrane (6-TM) domain in each subunit and are ubiquitously expressed in both animals and plants as organellar cation channels. Here, we present the first crystal structure of a vacuolar two-pore channel from Arabidopsis thaliana, AtTPC1, which functions as a homodimer. AtTPC1 activation requires both voltage and cytosolic Ca2+. Ca2+ binding to the cytosolic EF-hand domain triggers conformational changes coupled to the pair of pore-lining inner helices (IS6 helices) from the first 6-TM domains, whereas membrane potential only activates the second voltage-sensing domain (VSD2) whose conformational changes are coupled to the pair of inner helices (IIS6 helices) from the second 6-TM domains. Luminal Ca2+ or Ba2+ can modulate voltage activation by stabilizing VSD2 in the resting state and shifts voltage activation towards more positive potentials. Our Ba2+ bound AtTPC1 structure reveals a voltage sensor in the resting state, providing hitherto unseen structural insight into the general voltage-gating mechanism among voltage-gated channels. PMID:26689363

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

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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.

Sensing voltage across lipid membranes

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Swartz, Kenton J.

2009-01-01

The detection of electrical potentials across lipid bilayers by specialized membrane proteins is required for many fundamental cellular processes such as the generation and propagation of nerve impulses. These membrane proteins possess modular voltage-sensing domains, a notable example being the S1-S4 domains of voltage-activated ion channels. Ground-breaking structural studies on these domains explain how voltage sensors are designed and reveal important interactions with the surrounding lipid membrane. Although further structures are needed to fully understand the conformational changes that occur during voltage sensing, the available data help to frame several key concepts that are fundamental to the mechanism of voltage sensing. PMID:19092925

Intermediate state trapping of a voltage sensor

DEFF Research Database (Denmark)

Lacroix, Jérôme J; Pless, Stephan Alexander; Maragliano, Luca

2012-01-01

Voltage sensor domains (VSDs) regulate ion channels and enzymes by undergoing conformational changes depending on membrane electrical signals. The molecular mechanisms underlying the VSD transitions are not fully understood. Here, we show that some mutations of I241 in the S1 segment of the Shaker...... Kv channel positively shift the voltage dependence of the VSD movement and alter the functional coupling between VSD and pore domains. Among the I241 mutants, I241W immobilized the VSD movement during activation and deactivation, approximately halfway between the resting and active states......, and drastically shifted the voltage activation of the ionic conductance. This phenotype, which is consistent with a stabilization of an intermediate VSD conformation by the I241W mutation, was diminished by the charge-conserving R2K mutation but not by the charge-neutralizing R2Q mutation. Interestingly, most...

A new mechanism of voltage-dependent gating exposed by KV10.1 channels interrupted between voltage sensor and pore.

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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.

Modulating the Voltage-sensitivity of a Genetically Encoded Voltage Indicator.

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Jung, Arong; Rajakumar, Dhanarajan; Yoon, Bong-June; Baker, Bradley J

2017-10-01

Saturation mutagenesis was performed on a single position in the voltage-sensing domain (VSD) of a genetically encoded voltage indicator (GEVI). The VSD consists of four transmembrane helixes designated S1-S4. The V220 position located near the plasma membrane/extracellular interface had previously been shown to affect the voltage range of the optical signal. Introduction of polar amino acids at this position reduced the voltage-dependent optical signal of the GEVI. Negatively charged amino acids slightly reduced the optical signal by 33 percent while positively charge amino acids at this position reduced the optical signal by 80%. Surprisingly, the range of V220D was similar to that of V220K with shifted optical responses towards negative potentials. In contrast, the V220E mutant mirrored the responses of the V220R mutation suggesting that the length of the side chain plays in role in determining the voltage range of the GEVI. Charged mutations at the 219 position all behaved similarly slightly shifting the optical response to more negative potentials. Charged mutations to the 221 position behaved erratically suggesting interactions with the plasma membrane and/or other amino acids in the VSD. Introduction of bulky amino acids at the V220 position increased the range of the optical response to include hyperpolarizing signals. Combining The V220W mutant with the R217Q mutation resulted in a probe that reduced the depolarizing signal and enhanced the hyperpolarizing signal which may lead to GEVIs that only report neuronal inhibition.

alpha-helical structural elements within the voltage-sensing domains of a K(+) channel.

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Li-Smerin, Y; Hackos, D H; Swartz, K J

2000-01-01

Voltage-gated K(+) channels are tetramers with each subunit containing six (S1-S6) putative membrane spanning segments. The fifth through sixth transmembrane segments (S5-S6) from each of four subunits assemble to form a central pore domain. A growing body of evidence suggests that the first four segments (S1-S4) comprise a domain-like voltage-sensing structure. While the topology of this region is reasonably well defined, the secondary and tertiary structures of these transmembrane segments are not. To explore the secondary structure of the voltage-sensing domains, we used alanine-scanning mutagenesis through the region encompassing the first four transmembrane segments in the drk1 voltage-gated K(+) channel. We examined the mutation-induced perturbation in gating free energy for periodicity characteristic of alpha-helices. Our results are consistent with at least portions of S1, S2, S3, and S4 adopting alpha-helical secondary structure. In addition, both the S1-S2 and S3-S4 linkers exhibited substantial helical character. The distribution of gating perturbations for S1 and S2 suggest that these two helices interact primarily with two environments. In contrast, the distribution of perturbations for S3 and S4 were more complex, suggesting that the latter two helices make more extensive protein contacts, possibly interfacing directly with the shell of the pore domain.

α-Helical Structural Elements within the Voltage-Sensing Domains of a K+ Channel

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Li-Smerin, Yingying; Hackos, David H.; Swartz, Kenton J.

2000-01-01

Voltage-gated K+ channels are tetramers with each subunit containing six (S1–S6) putative membrane spanning segments. The fifth through sixth transmembrane segments (S5–S6) from each of four subunits assemble to form a central pore domain. A growing body of evidence suggests that the first four segments (S1–S4) comprise a domain-like voltage-sensing structure. While the topology of this region is reasonably well defined, the secondary and tertiary structures of these transmembrane segments are not. To explore the secondary structure of the voltage-sensing domains, we used alanine-scanning mutagenesis through the region encompassing the first four transmembrane segments in the drk1 voltage-gated K+ channel. We examined the mutation-induced perturbation in gating free energy for periodicity characteristic of α-helices. Our results are consistent with at least portions of S1, S2, S3, and S4 adopting α-helical secondary structure. In addition, both the S1–S2 and S3–S4 linkers exhibited substantial helical character. The distribution of gating perturbations for S1 and S2 suggest that these two helices interact primarily with two environments. In contrast, the distribution of perturbations for S3 and S4 were more complex, suggesting that the latter two helices make more extensive protein contacts, possibly interfacing directly with the shell of the pore domain. PMID:10613917

Expression and testing in plants of ArcLight, a genetically-encoded voltage indicator used in neuroscience research.

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Matzke, Antonius J M; Matzke, Marjori

2015-10-12

It is increasingly appreciated that electrical controls acting at the cellular and supra-cellular levels influence development and initiate rapid responses to environmental cues. An emerging method for non-invasive optical imaging of electrical activity at cell membranes uses genetically-encoded voltage indicators (GEVIs). Developed by neuroscientists to chart neuronal circuits in animals, GEVIs comprise a fluorescent protein that is fused to a voltage-sensing domain. One well-known GEVI, ArcLight, undergoes strong shifts in fluorescence intensity in response to voltage changes in mammalian cells. ArcLight consists of super-ecliptic (SE) pHluorin (pH-sensitive fluorescent protein) with an A227D substitution, which confers voltage sensitivity in neurons, fused to the voltage-sensing domain of the voltage-sensing phosphatase of C iona i ntestinalis (Ci-VSD). In an ongoing effort to adapt tools of optical electrophysiology for plants, we describe here the expression and testing of ArcLight and various derivatives in different membranes of root cells in Arabidopsis thaliana. Transgenic constructs were designed to express ArcLight and various derivatives targeted to the plasma membrane and nuclear membranes of Arabidopsis root cells. In transgenic seedlings, changes in fluorescence intensity of these reporter proteins following extracellular ATP (eATP) application were monitored using a fluorescence microscope equipped with a high speed camera. Coordinate reductions in fluorescence intensity of ArcLight and Ci-VSD-containing derivatives were observed at both the plasma membrane and nuclear membranes following eATP treatments. However, similar responses were observed for derivatives lacking the Ci-VSD. The dispensability of the Ci-VSD suggests that in plants, where H(+) ions contribute substantially to electrical activities, the voltage-sensing ability of ArcLight is subordinate to the pH sensitivity of its SEpHluorin base. The transient reduction of Arc

Spectrally-resolved response properties of the three most advanced FRET based fluorescent protein voltage probes.

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Hiroki Mutoh

Full Text Available Genetically-encoded optical probes for membrane potential hold the promise of monitoring electrical signaling of electrically active cells such as specific neuronal populations in intact brain tissue. The most advanced class of these probes was generated by molecular fusion of the voltage sensing domain (VSD of Ci-VSP with a fluorescent protein (FP pair. We quantitatively compared the three most advanced versions of these probes (two previously reported and one new variant, each involving a spectrally distinct tandem of FPs. Despite these different FP tandems and dissimilarities within the amino acid sequence linking the VSD to the FPs, the amplitude and kinetics of voltage dependent fluorescence changes were surprisingly similar. However, each of these fluorescent probes has specific merits when considering different potential applications.

Microscopic origin of gating current fluctuations in a potassium channel voltage sensor.

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

2012-06-06

Voltage-dependent ion channels open and close in response to changes in membrane electrical potential due to the motion of their voltage-sensing domains (VSDs). VSD charge displacements within the membrane electric field are observed in electrophysiology experiments as gating currents preceding ionic conduction. The elementary charge motions that give rise to the gating current cannot be observed directly, but appear as discrete current pulses that generate fluctuations in gating current measurements. Here we report direct observation of gating-charge displacements in an atomistic molecular dynamics simulation of the isolated VSD from the KvAP channel in a hydrated lipid bilayer on the timescale (10-μs) expected for elementary gating charge transitions. The results reveal that gating-charge displacements are associated with the water-catalyzed rearrangement of salt bridges between the S4 arginines and a set of conserved acidic side chains on the S1-S3 transmembrane segments in the hydrated interior of the VSD. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

MOLECULAR PATHOPHYSIOLOGY AND PHARMACOLOGY OF THE VOLTAGE-SENSING DOMAIN OF NEURONAL ION CHANNELS

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Francesco eMiceli

2015-07-01

Full Text Available Voltage-gated ion channels (VGIC are membrane proteins that switch from a closed to open state in response to changes in membrane potential, thus enabling ion fluxes across the cell membranes. The mechanism that regulate the structural rearrangements occurring in VGIC in response to changes in membrane potential still remains one of the most challenging topic of modern biophysics. Na+, Ca2+ and K+ voltage-gated channels are structurally formed by the assembly of four similar domains, each comprising six transmembrane segments. Each domain can be divided in two main regions: the Pore Module (PM and the Voltage-Sensing Module (VSM. The PM (helices S5 and S6 and intervening linker is responsible for gate opening and ion selectivity; by contrast, the VSM, comprising the first four transmembrane helices (S1-S4, undergoes the first conformational changes in response to membrane voltage. In particular, the S4 segment of each domain, which contains several positively charged residues interspersed with hydrophobic amino acids, is located within the membrane electric field and plays an essential role in voltage sensing. In neurons, specific gating properties of each channel subtype underlie a variety of biological events, ranging from the generation and propagation of electrical impulses, to the secretion of neurotransmitters, to the regulation of gene expression. Given the important functional role played by the VSM in neuronal VGICs, it is not surprising that various VSM mutations affecting the gating process of these channels are responsible for human diseases, and that compounds acting on the VSM have emerged as important investigational tools with great therapeutic potential. In the present review we will briefly describe the most recent discoveries concerning how the VSM exerts its function, how genetically inherited diseases caused by mutations occurring in the VSM affects gating in VGICs, and how several classes of drugs and toxins selectively

Combinatorial mutagenesis of the voltage-sensing domain enables the optical resolution of action potentials firing at 60 Hz by a genetically encoded fluorescent sensor of membrane potential.

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Piao, Hong Hua; Rajakumar, Dhanarajan; Kang, Bok Eum; Kim, Eun Ha; Baker, Bradley J

2015-01-07

ArcLight is a genetically encoded fluorescent voltage sensor using the voltage-sensing domain of the voltage-sensing phosphatase from Ciona intestinalis that gives a large but slow-responding optical signal in response to changes in membrane potential (Jin et al., 2012). Fluorescent voltage sensors using the voltage-sensing domain from other species give faster yet weaker optical signals (Baker et al., 2012; Han et al., 2013). Sequence alignment of voltage-sensing phosphatases from different species revealed conserved polar and charged residues at 7 aa intervals in the S1-S3 transmembrane segments of the voltage-sensing domain, suggesting potential coil-coil interactions. The contribution of these residues to the voltage-induced optical signal was tested using a cassette mutagenesis screen by flanking each transmembrane segment with unique restriction sites to allow for the testing of individual mutations in each transmembrane segment, as well as combinations in all four transmembrane segments. Addition of a counter charge in S2 improved the kinetics of the optical response. A double mutation in the S4 domain dramatically reduced the slow component of the optical signal seen in ArcLight. Combining that double S4 mutant with the mutation in the S2 domain yielded a probe with kinetics voltage-sensing domain could potentially lead to fluorescent sensors capable of optically resolving neuronal inhibition and subthreshold synaptic activity. Copyright © 2015 the authors 0270-6474/15/350372-15$15.00/0.

Functional interactions at the interface between voltage-sensing and pore domains in the Shaker K(v) channel.

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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.

Coupling between the voltage-sensing and phosphatase domains of Ci-VSP.

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Villalba-Galea, Carlos A; Miceli, Francesco; Taglialatela, Maurizio; Bezanilla, Francisco

2009-07-01

The Ciona intestinalis voltage sensor-containing phosphatase (Ci-VSP) shares high homology with the phosphatidylinositol phosphatase enzyme known as PTEN (phosphatase and tensin homologue deleted on chromosome 10). We have taken advantage of the similarity between these proteins to inquire about the coupling between the voltage sensing and the phosphatase domains in Ci-VSP. Recently, it was shown that four basic residues (R11, K13, R14, and R15) in PTEN are critical for its binding onto the membrane, required for its catalytic activity. Ci-VSP has three of the basic residues of PTEN. Here, we show that when R253 and R254 (which are the homologues of R14 and R15 in PTEN) are mutated to alanines in Ci-VSP, phosphatase activity is disrupted, as revealed by a lack of effect on the ionic currents of KCNQ2/3, where current decrease is a measure of phosphatase activity. The enzymatic activity was not rescued by the introduction of lysines, indicating that the binding is an arginine-specific interaction between the phosphatase binding domain and the membrane, presumably through the phosphate groups of the phospholipids. We also found that the kinetics and steady-state voltage dependence of the S4 segment movement are affected when the arginines are not present, indicating that the interaction of R253 and R254 with the membrane, required for the catalytic action of the phosphatase, restricts the movement of the voltage sensor.

Domain cooperativity in the β1a subunit is essential for dihydropyridine receptor voltage sensing in skeletal muscle.

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Dayal, Anamika; Bhat, Vinayakumar; Franzini-Armstrong, Clara; Grabner, Manfred

2013-04-30

The dihydropyridine receptor (DHPR) β1a subunit is crucial for enhancement of DHPR triad expression, assembly of DHPRs in tetrads, and elicitation of DHPRα1S charge movement--the three prerequisites of skeletal muscle excitation-contraction coupling. Despite the ability to fully target α1S into triadic junctions and tetradic arrays, the neuronal isoform β3 was unable to restore considerable charge movement (measure of α1S voltage sensing) upon expression in β1-null zebrafish relaxed myotubes, unlike the other three vertebrate β-isoforms (β1a, β2a, and β4). Thus, we used β3 for chimerization with β1a to investigate whether any of the five distinct molecular regions of β1a is dominantly involved in inducing the voltage-sensing function of α1S. Surprisingly, systematic domain swapping between β1a and β3 revealed a pivotal role of the src homology 3 (SH3) domain and C terminus of β1a in charge movement restoration. More interestingly, β1a SH3 domain and C terminus, when simultaneously engineered into β3 sequence background, were able to fully restore charge movement together with proper intracellular Ca(2+) release, suggesting cooperativity of these two domains in induction of the α1S voltage-sensing function in skeletal muscle excitation-contraction coupling. Furthermore, substitution of a proline by alanine in the putative SH3-binding polyproline motif in the proximal C terminus of β1a (also of β2a and β4) fully obstructed α1S charge movement. Consequently, we postulate a model according to which β subunits, probably via the SH3-C-terminal polyproline interaction, adapt a discrete conformation required to modify the α1S conformation apt for voltage sensing in skeletal muscle.

Relative transmembrane segment rearrangements during BK channel activation resolved by structurally assigned fluorophore–quencher pairing

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Pantazis, Antonios

2012-01-01

Voltage-activated proteins can sense, and respond to, changes in the electric field pervading the cell membrane by virtue of a transmembrane helix bundle, the voltage-sensing domain (VSD). Canonical VSDs consist of four transmembrane helices (S1–S4) of which S4 is considered a principal component because it possesses charged residues immersed in the electric field. Membrane depolarization compels the charges, and by extension S4, to rearrange with respect to the field. The VSD of large-conductance voltage- and Ca-activated K+ (BK) channels exhibits two salient inconsistencies from the canonical VSD model: (1) the BK channel VSD possesses an additional nonconserved transmembrane helix (S0); and (2) it exhibits a “decentralized” distribution of voltage-sensing charges, in helices S2 and S3, in addition to S4. Considering these unique features, the voltage-dependent rearrangements of the BK VSD could differ significantly from the standard model of VSD operation. To understand the mode of operation of this unique VSD, we have optically tracked the relative motions of the BK VSD transmembrane helices during activation, by manipulating the quenching environment of site-directed fluorescent labels with native and introduced Trp residues. Having previously reported that S0 and S4 diverge during activation, in this work we demonstrate that S4 also diverges from S1 and S2, whereas S2, compelled by its voltage-sensing charged residues, moves closer to S1. This information contributes spatial constraints for understanding the BK channel voltage-sensing process, revealing the structural rearrangements in a non-canonical VSD. PMID:22802360

Kv7.1 ion channels require a lipid to couple voltage sensing to pore opening.

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Zaydman, Mark A; Silva, Jonathan R; Delaloye, Kelli; Li, Yang; Liang, Hongwu; Larsson, H Peter; Shi, Jingyi; Cui, Jianmin

2013-08-06

Voltage-gated ion channels generate dynamic ionic currents that are vital to the physiological functions of many tissues. These proteins contain separate voltage-sensing domains, which detect changes in transmembrane voltage, and pore domains, which conduct ions. Coupling of voltage sensing and pore opening is critical to the channel function and has been modeled as a protein-protein interaction between the two domains. Here, we show that coupling in Kv7.1 channels requires the lipid phosphatidylinositol 4,5-bisphosphate (PIP2). We found that voltage-sensing domain activation failed to open the pore in the absence of PIP2. This result is due to loss of coupling because PIP2 was also required for pore opening to affect voltage-sensing domain activation. We identified a critical site for PIP2-dependent coupling at the interface between the voltage-sensing domain and the pore domain. This site is actually a conserved lipid-binding site among different K(+) channels, suggesting that lipids play an important role in coupling in many ion channels.

Gating of the two-pore cation channel AtTPC1 in the plant vacuole is based on a single voltage-sensing domain.

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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.

Structure of a eukaryotic voltage-gated sodium channel at near-atomic resolution.

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Shen, Huaizong; Zhou, Qiang; Pan, Xiaojing; Li, Zhangqiang; Wu, Jianping; Yan, Nieng

2017-03-03

Voltage-gated sodium (Na v ) channels are responsible for the initiation and propagation of action potentials. They are associated with a variety of channelopathies and are targeted by multiple pharmaceutical drugs and natural toxins. Here, we report the cryogenic electron microscopy structure of a putative Na v channel from American cockroach (designated Na v PaS) at 3.8 angstrom resolution. The voltage-sensing domains (VSDs) of the four repeats exhibit distinct conformations. The entrance to the asymmetric selectivity filter vestibule is guarded by heavily glycosylated and disulfide bond-stabilized extracellular loops. On the cytoplasmic side, a conserved amino-terminal domain is placed below VSD I , and a carboxy-terminal domain binds to the III-IV linker. The structure of Na v PaS establishes an important foundation for understanding function and disease mechanism of Na v and related voltage-gated calcium channels. Copyright © 2017, American Association for the Advancement of Science.

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

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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.

Inter-subunit interactions across the upper voltage sensing-pore domain interface contribute to the concerted pore opening transition of Kv channels.

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Tzilhav Shem-Ad

Full Text Available The tight electro-mechanical coupling between the voltage-sensing and pore domains of Kv channels lies at the heart of their fundamental roles in electrical signaling. Structural data have identified two voltage sensor pore inter-domain interaction surfaces, thus providing a framework to explain the molecular basis for the tight coupling of these domains. While the contribution of the intra-subunit lower domain interface to the electro-mechanical coupling that underlies channel opening is relatively well understood, the contribution of the inter-subunit upper interface to channel gating is not yet clear. Relying on energy perturbation and thermodynamic coupling analyses of tandem-dimeric Shaker Kv channels, we show that mutation of upper interface residues from both sides of the voltage sensor-pore domain interface stabilizes the closed channel state. These mutations, however, do not affect slow inactivation gating. We, moreover, find that upper interface residues form a network of state-dependent interactions that stabilize the open channel state. Finally, we note that the observed residue interaction network does not change during slow inactivation gating. The upper voltage sensing-pore interaction surface thus only undergoes conformational rearrangements during channel activation gating. We suggest that inter-subunit interactions across the upper domain interface mediate allosteric communication between channel subunits that contributes to the concerted nature of the late pore opening transition of Kv channels.

Inter-subunit interactions across the upper voltage sensing-pore domain interface contribute to the concerted pore opening transition of Kv channels.

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Shem-Ad, Tzilhav; Irit, Orr; Yifrach, Ofer

2013-01-01

The tight electro-mechanical coupling between the voltage-sensing and pore domains of Kv channels lies at the heart of their fundamental roles in electrical signaling. Structural data have identified two voltage sensor pore inter-domain interaction surfaces, thus providing a framework to explain the molecular basis for the tight coupling of these domains. While the contribution of the intra-subunit lower domain interface to the electro-mechanical coupling that underlies channel opening is relatively well understood, the contribution of the inter-subunit upper interface to channel gating is not yet clear. Relying on energy perturbation and thermodynamic coupling analyses of tandem-dimeric Shaker Kv channels, we show that mutation of upper interface residues from both sides of the voltage sensor-pore domain interface stabilizes the closed channel state. These mutations, however, do not affect slow inactivation gating. We, moreover, find that upper interface residues form a network of state-dependent interactions that stabilize the open channel state. Finally, we note that the observed residue interaction network does not change during slow inactivation gating. The upper voltage sensing-pore interaction surface thus only undergoes conformational rearrangements during channel activation gating. We suggest that inter-subunit interactions across the upper domain interface mediate allosteric communication between channel subunits that contributes to the concerted nature of the late pore opening transition of Kv channels.

Voltage-sensing phosphatase: its molecular relationship with PTEN.

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Okamura, Yasushi; Dixon, Jack E

2011-02-01

Voltage-sensing phosphoinositide phosphatase (VSP) contains voltage sensor and cytoplasmic phosphatase domains. A unique feature of this protein is that depolarization-induced motions of the voltage sensor activate PtdIns(3,4,5)P(3) and PtdIns(4,5)P(2) phosphatase activities. VSP exhibits remarkable structural similarities with PTEN, the phosphatase and tensin homolog deleted on chromosome 10. These similarities include the cytoplasmic phosphatase region, the phosphoinositide binding region, and the putative membrane interacting C2 domain.

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

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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

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

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

2011-05-06

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

Contributions of counter-charge in a potassium channel voltage-sensor domain

DEFF Research Database (Denmark)

Pless, Stephan Alexander; Galpin, Jason D; Niciforovic, Ana P

2011-01-01

Voltage-sensor domains couple membrane potential to conformational changes in voltage-gated ion channels and phosphatases. Highly coevolved acidic and aromatic side chains assist the transfer of cationic side chains across the transmembrane electric field during voltage sensing. We investigated...... the functional contribution of negative electrostatic potentials from these residues to channel gating and voltage sensing with unnatural amino acid mutagenesis, electrophysiology, voltage-clamp fluorometry and ab initio calculations. The data show that neutralization of two conserved acidic side chains...

Arginine side chain interactions and the role of arginine as a gating charge carrier in voltage sensitive ion channels

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Armstrong, Craig T.; Mason, Philip E.; Anderson, J. L. Ross; Dempsey, Christopher E.

2016-02-01

Gating charges in voltage-sensing domains (VSD) of voltage-sensitive ion channels and enzymes are carried on arginine side chains rather than lysine. This arginine preference may result from the unique hydration properties of the side chain guanidinium group which facilitates its movement through a hydrophobic plug that seals the center of the VSD, as suggested by molecular dynamics simulations. To test for side chain interactions implicit in this model we inspected interactions of the side chains of arginine and lysine with each of the 19 non-glycine amino acids in proteins in the protein data bank. The arginine guanidinium interacts with non-polar aromatic and aliphatic side chains above and below the guanidinium plane while hydrogen bonding with polar side chains is restricted to in-plane positions. In contrast, non-polar side chains interact largely with the aliphatic part of the lysine side chain. The hydration properties of arginine and lysine are strongly reflected in their respective interactions with non-polar and polar side chains as observed in protein structures and in molecular dynamics simulations, and likely underlie the preference for arginine as a mobile charge carrier in VSD.

Recording membrane potential changes through photoacoustic voltage sensitive dye

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Zhang, Haichong K.; Kang, Jeeun; Yan, Ping; Abou, Diane S.; Le, Hanh N. D.; Thorek, Daniel L. J.; Kang, Jin U.; Gjedde, Albert; Rahmim, Arman; Wong, Dean F.; Loew, Leslie M.; Boctor, Emad M.

2017-03-01

Monitoring of the membrane potential is possible using voltage sensitive dyes (VSD), where fluorescence intensity changes in response to neuronal electrical activity. However, fluorescence imaging is limited by depth of penetration and high scattering losses, which leads to low sensitivity in vivo systems for external detection. In contrast, photoacoustic (PA) imaging, an emerging modality, is capable of deep tissue, noninvasive imaging by combining near infrared light excitation and ultrasound detection. In this work, we develop the theoretical concept whereby the voltage-dependent quenching of dye fluorescence leads to a reciprocal enhancement of PA intensity. Based on this concept, we synthesized a novel near infrared photoacoustic VSD (PA-VSD) whose PA intensity change is sensitive to membrane potential. In the polarized state, this cyanine-based probe enhances PA intensity while decreasing fluorescence output in a lipid vesicle membrane model. With a 3-9 μM VSD concentration, we measured a PA signal increase in the range of 5.3 % to 18.1 %, and observed a corresponding signal reduction in fluorescence emission of 30.0 % to 48.7 %. A theoretical model successfully accounts for how the experimental PA intensity change depends on fluorescence and absorbance properties of the dye. These results not only demonstrate the voltage sensing capability of the dye, but also indicate the necessity of considering both fluorescence and absorbance spectral sensitivities in order to optimize the characteristics of improved photoacoustic probes. Together, our results demonstrate photoacoustic sensing as a potential new modality for sub-second recording and external imaging of electrophysiological and neurochemical events in the brain.

Localization and Molecular Determinants of the Hanatoxin Receptors on the Voltage-Sensing Domains of a K+ Channel

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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

Probing α-3(10) transitions in a voltage-sensing S4 helix.

Science.gov (United States)

Kubota, Tomoya; Lacroix, Jérôme J; Bezanilla, Francisco; Correa, Ana M

2014-09-02

The S4 helix of voltage sensor domains (VSDs) transfers its gating charges across the membrane electrical field in response to changes of the membrane potential. Recent studies suggest that this process may occur via the helical conversion of the entire S4 between α and 310 conformations. Here, using LRET and FRET, we tested this hypothesis by measuring dynamic changes in the transmembrane length of S4 from engineered VSDs expressed in Xenopus oocytes. Our results suggest that the native S4 from the Ciona intestinalis voltage-sensitive phosphatase (Ci-VSP) does not exhibit extended and long-lived 310 conformations and remains mostly α-helical. Although the S4 of NavAb displays a fully extended 310 conformation in x-ray structures, its transplantation in the Ci-VSP VSD scaffold yielded similar results as the native Ci-VSP S4. Taken together, our study does not support the presence of long-lived extended α-to-310 helical conversions of the S4 in Ci-VSP associated with voltage activation. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Listening to membrane potential: photoacoustic voltage-sensitive dye recording

Science.gov (United States)

Zhang, Haichong K.; Yan, Ping; Kang, Jeeun; Abou, Diane S.; Le, Hanh N. D.; Jha, Abhinav K.; Thorek, Daniel L. J.; Kang, Jin U.; Rahmim, Arman; Wong, Dean F.; Boctor, Emad M.; Loew, Leslie M.

2017-04-01

Voltage-sensitive dyes (VSDs) are designed to monitor membrane potential by detecting fluorescence changes in response to neuronal or muscle electrical activity. However, fluorescence imaging is limited by depth of penetration and high scattering losses, which leads to low sensitivity in vivo systems for external detection. By contrast, photoacoustic (PA) imaging, an emerging modality, is capable of deep tissue, noninvasive imaging by combining near-infrared light excitation and ultrasound detection. Here, we show that voltage-dependent quenching of dye fluorescence leads to a reciprocal enhancement of PA intensity. We synthesized a near-infrared photoacoustic VSD (PA-VSD), whose PA intensity change is sensitive to membrane potential. In the polarized state, this cyanine-based probe enhances PA intensity while decreasing fluorescence output in a lipid vesicle membrane model. A theoretical model accounts for how the experimental PA intensity change depends on fluorescence and absorbance properties of the dye. These results not only demonstrate PA voltage sensing but also emphasize the interplay of both fluorescence and absorbance properties in the design of optimized PA probes. Together, our results demonstrate PA sensing as a potential new modality for recording and external imaging of electrophysiological and neurochemical events in the brain.

Pado, a fluorescent protein with proton channel activity can optically monitor membrane potential, intracellular pH, and map gap junctions.

Science.gov (United States)

Kang, Bok Eum; Baker, Bradley J

2016-04-04

An in silico search strategy was developed to identify potential voltage-sensing domains (VSD) for the development of genetically encoded voltage indicators (GEVIs). Using a conserved charge distribution in the S2 α-helix, a single in silico search yielded most voltage-sensing proteins including voltage-gated potassium channels, voltage-gated calcium channels, voltage-gated sodium channels, voltage-gated proton channels, and voltage-sensing phosphatases from organisms ranging from mammals to bacteria and plants. A GEVI utilizing the VSD from a voltage-gated proton channel identified from that search was able to optically report changes in membrane potential. In addition this sensor was capable of manipulating the internal pH while simultaneously reporting that change optically since it maintains the voltage-gated proton channel activity of the VSD. Biophysical characterization of this GEVI, Pado, demonstrated that the voltage-dependent signal was distinct from the pH-dependent signal and was dependent on the movement of the S4 α-helix. Further investigation into the mechanism of the voltage-dependent optical signal revealed that inhibiting the dimerization of the fluorescent protein greatly reduced the optical signal. Dimerization of the FP thereby enabled the movement of the S4 α-helix to mediate a fluorescent response.

Dicty_cDB: VSD385 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available VS (Link to library) VSD385 (Link to dictyBase) - - - - VSD385E (Link to Original s...ite) VSD385F 523 VSD385Z 639 VSD385P 1162 VSD385E 639 Show VSD385 Library VS (Link to library) Clone ID VSD385 (Link to dict...yBase) Atlas ID - NBRP ID - dictyBase ID - Link to Contig - Original site URL http://dictycd...KTKMNKFIIGFFLCLTVFLTFVNSSEIDHQYSLTSSINGSSSGVSNSTDNTGCGEYTS CGDCREDKGCVWCGSEGICTEGTFYGTKPLNINGACKDFMWMQCKIQGR...ame B: KYKTKMNKFIIGFFLCLTVFLTFVNSSEIDHQYSLTSSINGSSSGVSNSTDNTGCGEYTS CGDCREDKGCVWCGSEGICTEGTFYGTKPLNINGACKDFM

Mutations in the voltage-sensing domain affect the alternative ion permeation pathway in the TRPM3 channel.

Science.gov (United States)

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

Local anesthetics disrupt energetic coupling between the voltage-sensing segments of a sodium channel.

Science.gov (United States)

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.

C-terminal modulatory domain controls coupling of voltage-sensing to pore opening in Cav1.3 L-type Ca(2+) channels.

Science.gov (United States)

Lieb, Andreas; Ortner, Nadine; Striessnig, Jörg

2014-04-01

Activity of voltage-gated Cav1.3 L-type Ca(2+) channels is required for proper hearing as well as sinoatrial node and brain function. This critically depends on their negative activation voltage range, which is further fine-tuned by alternative splicing. Shorter variants miss a C-terminal regulatory domain (CTM), which allows them to activate at even more negative potentials than C-terminally long-splice variants. It is at present unclear whether this is due to an increased voltage sensitivity of the Cav1.3 voltage-sensing domain, or an enhanced coupling of voltage-sensor conformational changes to the subsequent opening of the activation gate. We studied the voltage-dependence of voltage-sensor charge movement (QON-V) and of current activation (ICa-V) of the long (Cav1.3L) and a short Cav1.3 splice variant (Cav1.342A) expressed in tsA-201 cells using whole cell patch-clamp. Charge movement (QON) of Cav1.3L displayed a much steeper voltage-dependence and a more negative half-maximal activation voltage than Cav1.2 and Cav3.1. However, a significantly higher fraction of the total charge had to move for activation of Cav1.3 half-maximal conductance (Cav1.3: 68%; Cav1.2: 52%; Cav3.1: 22%). This indicated a weaker coupling of Cav1.3 voltage-sensor charge movement to pore opening. However, the coupling efficiency was strengthened in the absence of the CTM in Cav1.342A, thereby shifting ICa-V by 7.2 mV to potentials that were more negative without changing QON-V. We independently show that the presence of intracellular organic cations (such as n-methyl-D-glucamine) induces a pronounced negative shift of QON-V and a more negative activation of ICa-V of all three channels. These findings illustrate that the voltage sensors of Cav1.3 channels respond more sensitively to depolarization than those of Cav1.2 or Cav3.1. Weak coupling of voltage sensing to pore opening is enhanced in the absence of the CTM, allowing short Cav1.342A splice variants to activate at lower voltages

The Voltage-Sensing Domain of Kv7.2 Channels as a Molecular Target for Epilepsy-Causing Mutations and Anticonvulsants

Science.gov (United States)

Miceli, Francesco; Soldovieri, Maria Virginia; Iannotti, Fabio Arturo; Barrese, Vincenzo; Ambrosino, Paolo; Martire, Maria; Cilio, Maria Roberta; Taglialatela, Maurizio

2010-01-01

Understanding the molecular mechanisms underlying voltage-dependent gating in voltage-gated ion channels (VGICs) has been a major effort over the last decades. In recent years, changes in the gating process have emerged as common denominators for several genetically determined channelopathies affecting heart rhythm (arrhythmias), neuronal excitability (epilepsy, pain), or skeletal muscle contraction (periodic paralysis). Moreover, gating changes appear as the main molecular mechanism by which several natural toxins from a variety of species affect ion channel function. In this work, we describe the pathophysiological and pharmacological relevance of the gating process in voltage-gated K+ channels encoded by the Kv7 gene family. After reviewing the current knowledge on the molecular mechanisms and on the structural models of voltage-dependent gating in VGICs, we describe the physiological relevance of these channels, with particular emphasis on those formed by Kv7.2–Kv7.5 subunits having a well-established role in controlling neuronal excitability in humans. In fact, genetically determined alterations in Kv7.2 and Kv7.3 genes are responsible for benign familial neonatal convulsions, a rare seizure disorder affecting newborns, and the pharmacological activation of Kv7.2/3 channels can exert antiepileptic activity in humans. Both mutation-triggered channel dysfunction and drug-induced channel activation can occur by impeding or facilitating, respectively, channel sensitivity to membrane voltage and can affect overlapping molecular sites within the voltage-sensing domain of these channels. Thus, understanding the molecular steps involved in voltage-sensing in Kv7 channels will allow to better define the pathogenesis of rare human epilepsy, and to design innovative pharmacological strategies for the treatment of epilepsies and, possibly, other human diseases characterized by neuronal hyperexcitability. PMID:21687499

The voltage-sensing domain of kv7.2 channels as a molecular target for epilepsy-causing mutations and anticonvulsants

Directory of Open Access Journals (Sweden)

Francesco eMiceli

2011-02-01

Full Text Available Understanding the molecular mechanisms underlying voltage-dependent gating in voltage-gated ion channels (VGICs has been a major effort over the last decades. In recent years, changes in the gating process have emerged as common denominators for several genetically-determined channelopathies affecting heart rhythm (arrhythmias, neuronal excitability (epilepsy, pain or skeletal muscle contraction (periodic paralysis. Moreover, gating changes appear as the main molecular mechanism by which several natural toxins from a variety of species affect ion channel function.In this work, we describe the pathophysiological and pharmacological relevance of the gating process in voltage-gated K+ channels encoded by the Kv7 gene family. After reviewing the current knowledge on the molecular mechanisms and on the structural models of voltage-dependent gating in VGICs, we describe the physiological relevance of these channels, with particular emphasis on those formed by Kv7.2-5 subunits having a well-established role in controlling neuronal excitability in humans. In fact, genetically-determined alterations in Kv7.2 and Kv7.3 genes are responsible for benign familial neonatal convulsions, a rare seizure disorder affecting newborns, and the pharmacological activation of Kv7.2/3 channels can exert antiepileptic activity in humans. Both mutation-triggered channel dysfunction and drug-induced channel activation can occur by impeding or facilitating, respectively, channel sensitivity to membrane voltage and can affect overlapping molecular sites within the voltage-sensing domain of these channels. Thus, understanding the molecular steps involved in voltage-sensing in Kv7 channels will allow to better define the pathogenesis of rare human epilepsy, and to design innovative pharmacological strategies for the treatment of epilepsies and, possibly, other human diseases characterized by neuronal hyperexcitability.

Structural refinement of the hERG1 pore and voltage-sensing domains with ROSETTA-membrane and molecular dynamics simulations.

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Subbotina, Julia; Yarov-Yarovoy, Vladimir; Lees-Miller, James; Durdagi, Serdar; Guo, Jiqing; Duff, Henry J; Noskov, Sergei Yu

2010-11-01

The hERG1 gene (Kv11.1) encodes a voltage-gated potassium channel. Mutations in this gene lead to one form of the Long QT Syndrome (LQTS) in humans. Promiscuous binding of drugs to hERG1 is known to alter the structure/function of the channel leading to an acquired form of the LQTS. Expectably, creation and validation of reliable 3D model of the channel have been a key target in molecular cardiology and pharmacology for the last decade. Although many models were built, they all were limited to pore domain. In this work, a full model of the hERG1 channel is developed which includes all transmembrane segments. We tested a template-driven de-novo design with ROSETTA-membrane modeling using side-chain placements optimized by subsequent molecular dynamics (MD) simulations. Although backbone templates for the homology modeled parts of the pore and voltage sensors were based on the available structures of KvAP, Kv1.2 and Kv1.2-Kv2.1 chimera channels, the missing parts are modeled de-novo. The impact of several alignments on the structure of the S4 helix in the voltage-sensing domain was also tested. Herein, final models are evaluated for consistency to the reported structural elements discovered mainly on the basis of mutagenesis and electrophysiology. These structural elements include salt bridges and close contacts in the voltage-sensor domain; and the topology of the extracellular S5-pore linker compared with that established by toxin foot-printing and nuclear magnetic resonance studies. Implications of the refined hERG1 model to binding of blockers and channels activators (potent new ligands for channel activations) are discussed. © 2010 Wiley-Liss, Inc.

A Non-canonical Voltage-Sensing Mechanism Controls Gating in K2P K(+) Channels.

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Schewe, Marcus; Nematian-Ardestani, Ehsan; Sun, Han; Musinszki, Marianne; Cordeiro, Sönke; Bucci, Giovanna; de Groot, Bert L; Tucker, Stephen J; Rapedius, Markus; Baukrowitz, Thomas

2016-02-25

Two-pore domain (K2P) K(+) channels are major regulators of excitability that endow cells with an outwardly rectifying background "leak" conductance. In some K2P channels, strong voltage-dependent activation has been observed, but the mechanism remains unresolved because they lack a canonical voltage-sensing domain. Here, we show voltage-dependent gating is common to most K2P channels and that this voltage sensitivity originates from the movement of three to four ions into the high electric field of an inactive selectivity filter. Overall, this ion-flux gating mechanism generates a one-way "check valve" within the filter because outward movement of K(+) induces filter opening, whereas inward movement promotes inactivation. Furthermore, many physiological stimuli switch off this flux gating mode to convert K2P channels into a leak conductance. These findings provide insight into the functional plasticity of a K(+)-selective filter and also refine our understanding of K2P channels and the mechanisms by which ion channels can sense voltage. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The Voltage-Sensing Domain of K(v)7.2 Channels as a Molecular Target for Epilepsy-Causing Mutations and Anticonvulsants.

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Miceli, Francesco; Soldovieri, Maria Virginia; Iannotti, Fabio Arturo; Barrese, Vincenzo; Ambrosino, Paolo; Martire, Maria; Cilio, Maria Roberta; Taglialatela, Maurizio

2011-01-01

Understanding the molecular mechanisms underlying voltage-dependent gating in voltage-gated ion channels (VGICs) has been a major effort over the last decades. In recent years, changes in the gating process have emerged as common denominators for several genetically determined channelopathies affecting heart rhythm (arrhythmias), neuronal excitability (epilepsy, pain), or skeletal muscle contraction (periodic paralysis). Moreover, gating changes appear as the main molecular mechanism by which several natural toxins from a variety of species affect ion channel function. In this work, we describe the pathophysiological and pharmacological relevance of the gating process in voltage-gated K(+) channels encoded by the K(v)7 gene family. After reviewing the current knowledge on the molecular mechanisms and on the structural models of voltage-dependent gating in VGICs, we describe the physiological relevance of these channels, with particular emphasis on those formed by K(v)7.2-K(v)7.5 subunits having a well-established role in controlling neuronal excitability in humans. In fact, genetically determined alterations in K(v)7.2 and K(v)7.3 genes are responsible for benign familial neonatal convulsions, a rare seizure disorder affecting newborns, and the pharmacological activation of K(v)7.2/3 channels can exert antiepileptic activity in humans. Both mutation-triggered channel dysfunction and drug-induced channel activation can occur by impeding or facilitating, respectively, channel sensitivity to membrane voltage and can affect overlapping molecular sites within the voltage-sensing domain of these channels. Thus, understanding the molecular steps involved in voltage-sensing in K(v)7 channels will allow to better define the pathogenesis of rare human epilepsy, and to design innovative pharmacological strategies for the treatment of epilepsies and, possibly, other human diseases characterized by neuronal hyperexcitability.

Gating transitions in the selectivity filter region of a sodium channel are coupled to the domain IV voltage sensor.

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Capes, Deborah L; Arcisio-Miranda, Manoel; Jarecki, Brian W; French, Robert J; Chanda, Baron

2012-02-14

Voltage-dependent ion channels are crucial for generation and propagation of electrical activity in biological systems. The primary mechanism for voltage transduction in these proteins involves the movement of a voltage-sensing domain (D), which opens a gate located on the cytoplasmic side. A distinct conformational change in the selectivity filter near the extracellular side has been implicated in slow inactivation gating, which is important for spike frequency adaptation in neural circuits. However, it remains an open question whether gating transitions in the selectivity filter region are also actuated by voltage sensors. Here, we examine conformational coupling between each of the four voltage sensors and the outer pore of a eukaryotic voltage-dependent sodium channel. The voltage sensors of these sodium channels are not structurally symmetric and exhibit functional specialization. To track the conformational rearrangements of individual voltage-sensing domains, we recorded domain-specific gating pore currents. Our data show that, of the four voltage sensors, only the domain IV voltage sensor is coupled to the conformation of the selectivity filter region of the sodium channel. Trapping the outer pore in a particular conformation with a high-affinity toxin or disulphide crossbridge impedes the return of this voltage sensor to its resting conformation. Our findings directly establish that, in addition to the canonical electromechanical coupling between voltage sensor and inner pore gates of a sodium channel, gating transitions in the selectivity filter region are also coupled to the movement of a voltage sensor. Furthermore, our results also imply that the voltage sensor of domain IV is unique in this linkage and in the ability to initiate slow inactivation in sodium channels.

Voltage-dependent motion of the catalytic region of voltage-sensing phosphatase monitored by a fluorescent amino acid.

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Sakata, Souhei; Jinno, Yuka; Kawanabe, Akira; Okamura, Yasushi

2016-07-05

The cytoplasmic region of voltage-sensing phosphatase (VSP) derives the voltage dependence of its catalytic activity from coupling to a voltage sensor homologous to that of voltage-gated ion channels. To assess the conformational changes in the cytoplasmic region upon activation of the voltage sensor, we genetically incorporated a fluorescent unnatural amino acid, 3-(6-acetylnaphthalen-2-ylamino)-2-aminopropanoic acid (Anap), into the catalytic region of Ciona intestinalis VSP (Ci-VSP). Measurements of Anap fluorescence under voltage clamp in Xenopus oocytes revealed that the catalytic region assumes distinct conformations dependent on the degree of voltage-sensor activation. FRET analysis showed that the catalytic region remains situated beneath the plasma membrane, irrespective of the voltage level. Moreover, Anap fluorescence from a membrane-facing loop in the C2 domain showed a pattern reflecting substrate turnover. These results indicate that the voltage sensor regulates Ci-VSP catalytic activity by causing conformational changes in the entire catalytic region, without changing their distance from the plasma membrane.

Voltage-dependent motion of the catalytic region of voltage-sensing phosphatase monitored by a fluorescent amino acid

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Sakata, Souhei; Jinno, Yuka; Kawanabe, Akira; Okamura, Yasushi

2016-01-01

The cytoplasmic region of voltage-sensing phosphatase (VSP) derives the voltage dependence of its catalytic activity from coupling to a voltage sensor homologous to that of voltage-gated ion channels. To assess the conformational changes in the cytoplasmic region upon activation of the voltage sensor, we genetically incorporated a fluorescent unnatural amino acid, 3-(6-acetylnaphthalen-2-ylamino)-2-aminopropanoic acid (Anap), into the catalytic region of Ciona intestinalis VSP (Ci-VSP). Measurements of Anap fluorescence under voltage clamp in Xenopus oocytes revealed that the catalytic region assumes distinct conformations dependent on the degree of voltage-sensor activation. FRET analysis showed that the catalytic region remains situated beneath the plasma membrane, irrespective of the voltage level. Moreover, Anap fluorescence from a membrane-facing loop in the C2 domain showed a pattern reflecting substrate turnover. These results indicate that the voltage sensor regulates Ci-VSP catalytic activity by causing conformational changes in the entire catalytic region, without changing their distance from the plasma membrane. PMID:27330112

Cytoplasmic Domains and Voltage-Dependent Potassium Channel Gating

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

2012-01-01

The basic architecture of the voltage-dependent K+ channels (Kv channels) corresponds to a transmembrane protein core in which the permeation pore, the voltage-sensing components and the gating machinery (cytoplasmic facing gate and sensor–gate coupler) reside. Usually, large protein tails are attached to this core, hanging toward the inside of the cell. These cytoplasmic regions are essential for normal channel function and, due to their accessibility to the cytoplasmic environment, constitute obvious targets for cell-physiological control of channel behavior. Here we review the present knowledge about the molecular organization of these intracellular channel regions and their role in both setting and controlling Kv voltage-dependent gating properties. This includes the influence that they exert on Kv rapid/N-type inactivation and on activation/deactivation gating of Shaker-like and eag-type Kv channels. Some illustrative examples about the relevance of these cytoplasmic domains determining the possibilities for modulation of Kv channel gating by cellular components are also considered. PMID:22470342

Improved detection of electrical activity with a voltage probe based on a voltage-sensing phosphatase.

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Tsutsui, Hidekazu; Jinno, Yuka; Tomita, Akiko; Niino, Yusuke; Yamada, Yoshiyuki; Mikoshiba, Katsuhiko; Miyawaki, Atsushi; Okamura, Yasushi

2013-09-15

  One of the most awaited techniques in modern physiology is the sensitive detection of spatiotemporal electrical activity in a complex network of excitable cells. The use of genetically encoded voltage probes has been expected to enable such analysis. However, in spite of recent progress, existing probes still suffer from low signal amplitude and/or kinetics too slow to detect fast electrical activity. Here, we have developed an improved voltage probe named Mermaid2, which is based on the voltage-sensor domain of the voltage-sensing phosphatase from Ciona intestinalis and Förster energy transfer between a pair of fluorescent proteins. In mammalian cells, Mermaid2 permits ratiometric readouts of fractional changes of more than 50% over a physiologically relevant voltage range with fast kinetics, and it was used to follow a train of action potentials at frequencies of up to 150 Hz. Mermaid2 was also able to detect single action potentials and subthreshold voltage responses in hippocampal neurons in vitro, in addition to cortical electrical activity evoked by sound stimuli in single trials in living mice.

Recording membrane potential changes through photoacoustic voltage sensitive dye

DEFF Research Database (Denmark)

Zhang, Haichong K.; Kang, Jeeun; Yan, Ping

2017-01-01

Monitoring of the membrane potential is possible using voltage sensitive dyes (VSD), where fluorescence intensity changes in response to neuronal electrical activity. However, fluorescence imaging is limited by depth of penetration and high scattering losses, which leads to low sensitivity in vivo...... systems for external detection. In contrast, photoacoustic (PA) imaging, an emerging modality, is capable of deep tissue, noninvasive imaging by combining near infrared light excitation and ultrasound detection. In this work, we develop the theoretical concept whereby the voltage-dependent quenching...... the experimental PA intensity change depends on fluorescence and absorbance properties of the dye. These results not only demonstrate the voltage sensing capability of the dye, but also indicate the necessity of considering both fluorescence and absorbance spectral sensitivities in order to optimize...

Voltage-Gated Proton Channels: Molecular Biology, Physiology, and Pathophysiology of the HV Family

Science.gov (United States)

2013-01-01

Voltage-gated proton channels (HV) are unique, in part because the ion they conduct is unique. HV channels are perfectly selective for protons and have a very small unitary conductance, both arguably manifestations of the extremely low H+ concentration in physiological solutions. They open with membrane depolarization, but their voltage dependence is strongly regulated by the pH gradient across the membrane (ΔpH), with the result that in most species they normally conduct only outward current. The HV channel protein is strikingly similar to the voltage-sensing domain (VSD, the first four membrane-spanning segments) of voltage-gated K+ and Na+ channels. In higher species, HV channels exist as dimers in which each protomer has its own conduction pathway, yet gating is cooperative. HV channels are phylogenetically diverse, distributed from humans to unicellular marine life, and perhaps even plants. Correspondingly, HV functions vary widely as well, from promoting calcification in coccolithophores and triggering bioluminescent flashes in dinoflagellates to facilitating killing bacteria, airway pH regulation, basophil histamine release, sperm maturation, and B lymphocyte responses in humans. Recent evidence that hHV1 may exacerbate breast cancer metastasis and cerebral damage from ischemic stroke highlights the rapidly expanding recognition of the clinical importance of hHV1. PMID:23589829

Evidence for functional diversity between the voltage-gated proton channel Hv1 and its closest related protein HVRP1.

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Iris H Kim

Full Text Available The Hv1 channel and voltage-sensitive phosphatases share with voltage-gated sodium, potassium, and calcium channels the ability to detect changes in membrane potential through voltage-sensing domains (VSDs. However, they lack the pore domain typical of these other channels. NaV, KV, and CaV proteins can be found in neurons and muscles, where they play important roles in electrical excitability. In contrast, VSD-containing proteins lacking a pore domain are found in non-excitable cells and are not involved in neuronal signaling. Here, we report the identification of HVRP1, a protein related to the Hv1 channel (from which the name Hv1 Related Protein 1 is derived, which we find to be expressed primarily in the central nervous system, and particularly in the cerebellum. Within the cerebellar tissue, HVRP1 is specifically expressed in granule neurons, as determined by in situ hybridization and immunohistochemistry. Analysis of subcellular distribution via electron microscopy and immunogold labeling reveals that the protein localizes on the post-synaptic side of contacts between glutamatergic mossy fibers and the granule cells. We also find that, despite the similarities in amino acid sequence and structural organization between Hv1 and HVRP1, the two proteins have distinct functional properties. The high conservation of HVRP1 in vertebrates and its cellular and subcellular localizations suggest an important function in the nervous system.

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

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

2015-01-01

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

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

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Frank S Choveau

2012-07-01

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

Interactions between charged residues in the transmembrane segments of the voltage-sensing domain in the hERG channel.

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Zhang, M; Liu, J; Jiang, M; Wu, D-M; Sonawane, K; Guy, H R; Tseng, G-N

2005-10-01

Studies on voltage-gated K channels such as Shaker have shown that positive charges in the voltage-sensor (S4) can form salt bridges with negative charges in the surrounding transmembrane segments in a state-dependent manner, and different charge pairings can stabilize the channels in closed or open states. The goal of this study is to identify such charge interactions in the hERG channel. This knowledge can provide constraints on the spatial relationship among transmembrane segments in the channel's voltage-sensing domain, which are necessary for modeling its structure. We first study the effects of reversing S4's positive charges on channel activation. Reversing positive charges at the outer (K525D) and inner (K538D) ends of S4 markedly accelerates hERG activation, whereas reversing the 4 positive charges in between either has no effect or slows activation. We then use the 'mutant cycle analysis' to test whether D456 (outer end of S2) and D411 (inner end of S1) can pair with K525 and K538, respectively. Other positive charges predicted to be able, or unable, to interact with D456 or D411 are also included in the analysis. The results are consistent with predictions based on the distribution of these charged residues, and confirm that there is functional coupling between D456 and K525 and between D411 and K538.

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

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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.

Piezoelectric self sensing actuators for high voltage excitation

International Nuclear Information System (INIS)

Grasso, E; Totaro, N; Janocha, H; Naso, D

2013-01-01

Self sensing techniques allow the use of a piezoelectric transducer simultaneously as an actuator and as a sensor. Such techniques are based on knowledge of the transducer behaviour and on measurements of electrical quantities, in particular voltage and charge. Past research work has mainly considered the linear behaviour of piezoelectric transducers, consequently restricting the operating driving voltages to low values. In this work a new self sensing technique is proposed which is able to perform self sensing reconstruction both at low and at high driving voltages. This technique, in fact, makes use of a hysteretic model to describe the nonlinear piezoelectric capacitance necessary for self sensing reconstruction. The capacitance can be measured and identified at the antiresonances of a vibrating structure with a good approximation. After providing a mathematical background to deal with the main aspects of self sensing, this technique is compared theoretically and experimentally to a typical linear one by using an aluminum plate with one bonded self sensing transducer and a positive position feedback (PPF) controller to verify the performance in self sensing based vibration control. (paper)

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

Science.gov (United States)

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.

Blue Light-excited Light-Oxygen-Voltage-sensing Domain 2 (LOV2) Triggers a Rearrangement of the Kinase Domain to Induce Phosphorylation Activity in Arabidopsis Phototropin1.

Science.gov (United States)

Oide, Mao; Okajima, Koji; Kashojiya, Sachiko; Takayama, Yuki; Oroguchi, Tomotaka; Hikima, Takaaki; Yamamoto, Masaki; Nakasako, Masayoshi

2016-09-16

Phototropin1 is a blue light (BL) receptor in plants and shows BL-dependent kinase activation. The BL-excited light-oxygen-voltage-sensing domain 2 (LOV2) is primarily responsible for the activation of the kinase domain; however, the molecular mechanism by which conformational changes in LOV2 are transmitted to the kinase domain remains unclear. Here, we investigated BL-induced structural changes of a minimum functional fragment of Arabidopsis phototropin1 composed of LOV2, the kinase domain, and a linker connecting the two domains using small-angle x-ray scattering (SAXS). The fragment existed as a dimer and displayed photoreversible SAXS changes reflected in the radii of gyration of 42.9 Å in the dark and 48.8 Å under BL irradiation. In the dark, the molecular shape reconstructed from the SAXS profiles appeared as two bean-shaped lobes in a twisted arrangement that was 170 Å long, 80 Å wide, and 50 Å thick. The molecular shape under BL became slightly elongated from that in the dark. By fitting the crystal structure of the LOV2 dimer and a homology model of the kinase domain to their inferred shapes, the BL-dependent change could be interpreted as the positional shift in the kinase domain relative to that of the LOV2 dimer. In addition, we found that lysine 475, a functionally important residue, in the N-terminal region of LOV2 plays a critical role in transmitting the structural changes in LOV2 to the kinase domain. The interface between the domains is critical for signaling, suitably changing the structure to activate the kinase in response to conformational changes in the adjoining LOV2. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Fluorescent Protein Voltage Probes Derived from ArcLight that Respond to Membrane Voltage Changes with Fast Kinetics

Science.gov (United States)

Han, Zhou; Jin, Lei; Platisa, Jelena; Cohen, Lawrence B.; Baker, Bradley J.; Pieribone, Vincent A.

2013-01-01

We previously reported the discovery of a fluorescent protein voltage probe, ArcLight, and its derivatives that exhibit large changes in fluorescence intensity in response to changes of plasma membrane voltage. ArcLight allows the reliable detection of single action potentials and sub-threshold activities in individual neurons and dendrites. The response kinetics of ArcLight (τ1-on ~10 ms, τ2-on ~ 50 ms) are comparable with most published genetically-encoded voltage probes. However, probes using voltage-sensing domains other than that from the Ciona intestinalis voltage sensitive phosphatase exhibit faster kinetics. Here we report new versions of ArcLight, in which the Ciona voltage-sensing domain was replaced with those from chicken, zebrafish, frog, mouse or human. We found that the chicken and zebrafish-based ArcLight exhibit faster kinetics, with a time constant (τ) less than 6ms for a 100 mV depolarization. Although the response amplitude of these two probes (8-9%) is not as large as the Ciona-based ArcLight (~35%), they are better at reporting action potentials from cultured neurons at higher frequency. In contrast, probes based on frog, mouse and human voltage sensing domains were either slower than the Ciona-based ArcLight or had very small signals. PMID:24312287

Fluorescent protein voltage probes derived from ArcLight that respond to membrane voltage changes with fast kinetics.

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Zhou Han

Full Text Available We previously reported the discovery of a fluorescent protein voltage probe, ArcLight, and its derivatives that exhibit large changes in fluorescence intensity in response to changes of plasma membrane voltage. ArcLight allows the reliable detection of single action potentials and sub-threshold activities in individual neurons and dendrites. The response kinetics of ArcLight (τ1-on ~10 ms, τ2-on ~ 50 ms are comparable with most published genetically-encoded voltage probes. However, probes using voltage-sensing domains other than that from the Ciona intestinalis voltage sensitive phosphatase exhibit faster kinetics. Here we report new versions of ArcLight, in which the Ciona voltage-sensing domain was replaced with those from chicken, zebrafish, frog, mouse or human. We found that the chicken and zebrafish-based ArcLight exhibit faster kinetics, with a time constant (τ less than 6 ms for a 100 mV depolarization. Although the response amplitude of these two probes (8-9% is not as large as the Ciona-based ArcLight (~35%, they are better at reporting action potentials from cultured neurons at higher frequency. In contrast, probes based on frog, mouse and human voltage sensing domains were either slower than the Ciona-based ArcLight or had very small signals.

Voltage-dependent gating in a "voltage sensor-less" ion channel.

Directory of Open Access Journals (Sweden)

Harley T Kurata

2010-02-01

Full Text Available The voltage sensitivity of voltage-gated cation channels is primarily attributed to conformational changes of a four transmembrane segment voltage-sensing domain, conserved across many levels of biological complexity. We have identified a remarkable point mutation that confers significant voltage dependence to Kir6.2, a ligand-gated channel that lacks any canonical voltage-sensing domain. Similar to voltage-dependent Kv channels, the Kir6.2[L157E] mutant exhibits time-dependent activation upon membrane depolarization, resulting in an outwardly rectifying current-voltage relationship. This voltage dependence is convergent with the intrinsic ligand-dependent gating mechanisms of Kir6.2, since increasing the membrane PIP2 content saturates Po and eliminates voltage dependence, whereas voltage activation is more dramatic when channel Po is reduced by application of ATP or poly-lysine. These experiments thus demonstrate an inherent voltage dependence of gating in a "ligand-gated" K+ channel, and thereby provide a new view of voltage-dependent gating mechanisms in ion channels. Most interestingly, the voltage- and ligand-dependent gating of Kir6.2[L157E] is highly sensitive to intracellular [K+], indicating an interaction between ion permeation and gating. While these two key features of channel function are classically dealt with separately, the results provide a framework for understanding their interaction, which is likely to be a general, if latent, feature of the superfamily of cation channels.

The subtype of VSD and the angiographic differentiation

International Nuclear Information System (INIS)

Choe, Kyu Ok; Sul, Jun Hee; Lee, Sung Kyu; Cho, Bum Koo; Hong, Sung Nok

1985-01-01

VSD is the most common congenital cardiac malformation and the natural history depends not only on the age of patients and the size of defect but the subtype of VSD as well, important factor in clinical management of those patients. In 110 patients, with surgically repaired VSD in Yonsei Medical Center in 1984, the subtype of VSDs evaluated by surgical observation were correlated with LV angiogram findings to verify the incidence of subtype in Korean and the diagnostic accuracy to predict the subtype by angiogram. 1. 110 patients included 64 boys and 46 girls, the age ranged from 3 months to 14 years (average 4.6 years old). 2. Angiographic findings were interpreted as follows; a. Perimembranous defects were profiled in LAO 60 .deg. LV angiogram and located below the aortic valve. In inlet excavation the shunted blood opacified the recess between septal leaflet of tricuspid valve and interventricular septum in early phase, in infundibular excavation opacified the recess between anterior leaflet of TV and anterior free wall of RV and in trabecular excavation the shunted blood traversed anterior portion of TV ring, opacified trabecular portion of RV cavity. b. Subarterial types were profiled in RAO 30 .deg. LV angiogram, just below aortic valve as well as pulmonic valve. Total infundibular defects were profiled in RAO 30 .deg. and LAO 60 .deg. LV angiogram subaortic in location in both views. c. In muscular VSD the profiled angle was varied according to the subtype but the defects were separated from the aortic valve as muscular septum interposed between the aortic valve and the defect. 3. The incidence of subtype of VSDs evaluated by surgical observation were as follows. Subarterial type : 32 cases (29.1%) Total infundibular defect : 5 cases (4.5%) Perimembranous type : 73 cases (66.3%) Infundibular excavation : 32 cases (29.2%) Trabecular excavation : 28 cases (25.5%) Inlet excavation : 10 cases (9.1%) Mixed : 3 cases (2.7%) Muscular type : 1 cases (0.9%) Total 63

Domain IV voltage-sensor movement is both sufficient and rate limiting for fast inactivation in sodium channels.

Science.gov (United States)

Capes, Deborah L; Goldschen-Ohm, Marcel P; Arcisio-Miranda, Manoel; Bezanilla, Francisco; Chanda, Baron

2013-08-01

Voltage-gated sodium channels are critical for the generation and propagation of electrical signals in most excitable cells. Activation of Na(+) channels initiates an action potential, and fast inactivation facilitates repolarization of the membrane by the outward K(+) current. Fast inactivation is also the main determinant of the refractory period between successive electrical impulses. Although the voltage sensor of domain IV (DIV) has been implicated in fast inactivation, it remains unclear whether the activation of DIV alone is sufficient for fast inactivation to occur. Here, we functionally neutralize each specific voltage sensor by mutating several critical arginines in the S4 segment to glutamines. We assess the individual role of each voltage-sensing domain in the voltage dependence and kinetics of fast inactivation upon its specific inhibition. We show that movement of the DIV voltage sensor is the rate-limiting step for both development and recovery from fast inactivation. Our data suggest that activation of the DIV voltage sensor alone is sufficient for fast inactivation to occur, and that activation of DIV before channel opening is the molecular mechanism for closed-state inactivation. We propose a kinetic model of sodium channel gating that can account for our major findings over a wide voltage range by postulating that DIV movement is both necessary and sufficient for fast inactivation.

Identification of an evolutionarily conserved extracellular threonine residue critical for surface expression and its potential coupling of adjacent voltage-sensing and gating domains in voltage-gated potassium channels.

Science.gov (United States)

Mckeown, Lynn; Burnham, Matthew P; Hodson, Charlotte; Jones, Owen T

2008-10-31

The dynamic expression of voltage-gated potassium channels (Kvs) at the cell surface is a fundamental factor controlling membrane excitability. In exploring possible mechanisms controlling Kv surface expression, we identified a region in the extracellular linker between the first and second of the six (S1-S6) transmembrane-spanning domains of the Kv1.4 channel, which we hypothesized to be critical for its biogenesis. Using immunofluorescence microscopy, flow cytometry, patch clamp electrophysiology, and mutagenesis, we identified a single threonine residue at position 330 within the Kv1.4 S1-S2 linker that is absolutely required for cell surface expression. Mutation of Thr-330 to an alanine, aspartate, or lysine prevented surface expression. However, surface expression occurred upon co-expression of mutant and wild type Kv1.4 subunits or mutation of Thr-330 to a serine. Mutation of the corresponding residue (Thr-211) in Kv3.1 to alanine also caused intracellular retention, suggesting that the conserved threonine plays a generalized role in surface expression. In support of this idea, sequence comparisons showed conservation of the critical threonine in all Kv families and in organisms across the evolutionary spectrum. Based upon the Kv1.2 crystal structure, further mutagenesis, and the partial restoration of surface expression in an electrostatic T330K bridging mutant, we suggest that Thr-330 hydrogen bonds to equally conserved outer pore residues, which may include a glutamate at position 502 that is also critical for surface expression. We propose that Thr-330 serves to interlock the voltage-sensing and gating domains of adjacent monomers, thereby yielding a structure competent for the surface expression of functional tetramers.

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

Directory of Open Access Journals (Sweden)

Liora Shamgar

Full Text Available 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.

Molecular mechanism of voltage sensing in voltage-gated proton channels

Science.gov (United States)

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

Word Domain Disambiguation via Word Sense Disambiguation

Energy Technology Data Exchange (ETDEWEB)

Sanfilippo, Antonio P.; Tratz, Stephen C.; Gregory, Michelle L.

2006-06-04

Word subject domains have been widely used to improve the perform-ance of word sense disambiguation al-gorithms. However, comparatively little effort has been devoted so far to the disambiguation of word subject do-mains. The few existing approaches have focused on the development of al-gorithms specific to word domain dis-ambiguation. In this paper we explore an alternative approach where word domain disambiguation is achieved via word sense disambiguation. Our study shows that this approach yields very strong results, suggesting that word domain disambiguation can be ad-dressed in terms of word sense disam-biguation with no need for special purpose algorithms.

Potential role of voltage-sensing phosphatases in regulation of cell structure through the production of PI(3,4)P2.

Science.gov (United States)

Yamaguchi, Shinji; Kurokawa, Tatsuki; Taira, Ikuko; Aoki, Naoya; Sakata, Souhei; Okamura, Yasushi; Homma, Koichi J

2014-04-01

Voltage-sensing phosphatase, VSP, consists of the transmembrane domain, operating as the voltage sensor, and the cytoplasmic domain with phosphoinositide-phosphatase activities. The voltage sensor tightly couples with the cytoplasmic phosphatase and membrane depolarization induces dephosphorylation of several species of phosphoinositides. VSP gene is conserved from urochordate to human. There are some diversities among VSP ortholog proteins; range of voltage of voltage sensor motions as well as substrate selectivity. In contrast with recent understandings of biophysical mechanisms of VSPs, little is known about its physiological roles. Here we report that chick ortholog of VSP (designated as Gg-VSP) induces morphological feature of cell process outgrowths with round cell body in DF-1 fibroblasts upon its forced expression. Expression of the voltage sensor mutant, Gg-VSPR153Q with shifted voltage dependence to a lower voltage led to more frequent changes of cell morphology than the wild-type protein. Coexpression of PTEN that dephosphorylates PI(3,4)P2 suppressed this effect by Gg-VSP, indicating that the increase of PI(3,4)P2 leads to changes of cell shape. In addition, visualization of PI(3,4)P2 with the fluorescent protein fused with the TAPP1-derived pleckstrin homology (PH) domain suggested that Gg-VSP influenced the distribution of PI(3,4)P2 . These findings raise a possibility that one of the VSP's functions could be to regulate cell morphology through voltage-sensitive tuning of phosphoinositide profile. © 2013 Wiley Periodicals, Inc.

The Molecular Basis of Polyunsaturated Fatty Acid Interactions with the Shaker Voltage-Gated Potassium Channel.

Directory of Open Access Journals (Sweden)

Samira Yazdi

2016-01-01

Full Text Available 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.

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

Science.gov (United States)

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.

Gating mechanism of Kv11.1 (hERG) K+ channels without covalent connection between voltage sensor and pore domains.

Science.gov (United States)

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

2018-03-01

Kv11.1 (hERG, KCNH2) is a voltage-gated potassium channel crucial in setting the cardiac rhythm and the electrical behaviour of several non-cardiac cell types. Voltage-dependent gating of Kv11.1 can be reconstructed from non-covalently linked voltage sensing and pore modules (split channels), challenging classical views of voltage-dependent channel activation based on a S4-S5 linker acting as a rigid mechanical lever to open the gate. Progressive displacement of the split position from the end to the beginning of the S4-S5 linker induces an increasing negative shift in activation voltage dependence, a reduced z g value and a more negative ΔG 0 for current activation, an almost complete abolition of the activation time course sigmoid shape and a slowing of the voltage-dependent deactivation. Channels disconnected at the S4-S5 linker near the S4 helix show a destabilization of the closed state(s). Furthermore, the isochronal ion current mode shift magnitude is clearly reduced in the different splits. Interestingly, the progressive modifications of voltage dependence activation gating by changing the split position are accompanied by a shift in the voltage-dependent availability to a methanethiosulfonate reagent of a Cys introduced at the upper S4 helix. Our data demonstrate for the first time that alterations in the covalent connection between the voltage sensor and the pore domains impact on the structural reorganizations of the voltage sensor domain. Also, they support the hypothesis that the S4-S5 linker integrates signals coming from other cytoplasmic domains that constitute either an important component or a crucial regulator of the gating machinery in Kv11.1 and other KCNH channels.

Manual de uso del programa VSD (Video Stereo Digitalizador)

OpenAIRE

Almagro, Antonio; López Hernández, Gerardo

2001-01-01

El Vídeo Estéreo Digitalizador (VSD) de AGH, creado por el profesor J.J. Jachimski y el informático J.M. Zielinski del Departamento de Fotogrametría y Teledetección informática de la Universidad de Minería y Metalurgia de Cracovia, es un estereorrestituidor concebido para la producción de dibujos vectoriales a partir de pares de imágenes fotogramétricas digitales, en blanco y negro o color (estereopares u ortoestereopares). El VSD utiliza imágenes digitales, lo cual se traduce en la posibilid...

Unfolding of a Temperature-Sensitive Domain Controls Voltage-Gated Channel Activation.

Science.gov (United States)

Arrigoni, Cristina; Rohaim, Ahmed; Shaya, David; Findeisen, Felix; Stein, Richard A; Nurva, Shailika Reddy; Mishra, Smriti; Mchaourab, Hassane S; Minor, Daniel L

2016-02-25

Voltage-gated ion channels (VGICs) are outfitted with diverse cytoplasmic domains that impact function. To examine how such elements may affect VGIC behavior, we addressed how the bacterial voltage-gated sodium channel (BacNa(V)) C-terminal cytoplasmic domain (CTD) affects function. Our studies show that the BacNa(V) CTD exerts a profound influence on gating through a temperature-dependent unfolding transition in a discrete cytoplasmic domain, the neck domain, proximal to the pore. Structural and functional studies establish that the BacNa(V) CTD comprises a bi-partite four-helix bundle that bears an unusual hydrophilic core whose integrity is central to the unfolding mechanism and that couples directly to the channel activation gate. Together, our findings define a general principle for how the widespread four-helix bundle cytoplasmic domain architecture can control VGIC responses, uncover a mechanism underlying the diverse BacNa(V) voltage dependencies, and demonstrate that a discrete domain can encode the temperature-dependent response of a channel. Copyright © 2016 Elsevier Inc. All rights reserved.

Voltage-dependent gating of hERG potassium channels

Directory of Open Access Journals (Sweden)

Yen May eCheng

2012-05-01

Full Text Available 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-a-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 voltage-dependent 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.

Voltage-Dependent Gating of hERG Potassium Channels

Science.gov (United States)

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

Construction and validation of a homology model of the human voltage-gated proton channel hHV1.

Science.gov (United States)

Kulleperuma, Kethika; Smith, Susan M E; Morgan, Deri; Musset, Boris; Holyoake, John; Chakrabarti, Nilmadhab; Cherny, Vladimir V; DeCoursey, Thomas E; Pomès, Régis

2013-04-01

The topological similarity of voltage-gated proton channels (H(V)1s) to the voltage-sensing domain (VSD) of other voltage-gated ion channels raises the central question of whether H(V)1s have a similar structure. We present the construction and validation of a homology model of the human H(V)1 (hH(V)1). Multiple structural alignment was used to construct structural models of the open (proton-conducting) state of hH(V)1 by exploiting the homology of hH(V)1 with VSDs of K(+) and Na(+) channels of known three-dimensional structure. The comparative assessment of structural stability of the homology models and their VSD templates was performed using massively repeated molecular dynamics simulations in which the proteins were allowed to relax from their initial conformation in an explicit membrane mimetic. The analysis of structural deviations from the initial conformation based on up to 125 repeats of 100-ns simulations for each system reveals structural features consistently retained in the homology models and leads to a consensus structural model for hH(V)1 in which well-defined external and internal salt-bridge networks stabilize the open state. The structural and electrostatic properties of this open-state model are compatible with proton translocation and offer an explanation for the reversal of charge selectivity in neutral mutants of Asp(112). Furthermore, these structural properties are consistent with experimental accessibility data, providing a valuable basis for further structural and functional studies of hH(V)1. Each Arg residue in the S4 helix of hH(V)1 was replaced by His to test accessibility using Zn(2+) as a probe. The two outermost Arg residues in S4 were accessible to external solution, whereas the innermost one was accessible only to the internal solution. Both modeling and experimental data indicate that in the open state, Arg(211), the third Arg residue in the S4 helix in hH(V)1, remains accessible to the internal solution and is located near the

Remote-sensing image encryption in hybrid domains

Science.gov (United States)

Zhang, Xiaoqiang; Zhu, Guiliang; Ma, Shilong

2012-04-01

Remote-sensing technology plays an important role in military and industrial fields. Remote-sensing image is the main means of acquiring information from satellites, which always contain some confidential information. To securely transmit and store remote-sensing images, we propose a new image encryption algorithm in hybrid domains. This algorithm makes full use of the advantages of image encryption in both spatial domain and transform domain. First, the low-pass subband coefficients of image DWT (discrete wavelet transform) decomposition are sorted by a PWLCM system in transform domain. Second, the image after IDWT (inverse discrete wavelet transform) reconstruction is diffused with 2D (two-dimensional) Logistic map and XOR operation in spatial domain. The experiment results and algorithm analyses show that the new algorithm possesses a large key space and can resist brute-force, statistical and differential attacks. Meanwhile, the proposed algorithm has the desirable encryption efficiency to satisfy requirements in practice.

Applying value sensitive design (VSD) to wind turbines and wind parks: an exploration.

Science.gov (United States)

Oosterlaken, Ilse

2015-04-01

Community acceptance still remains a challenge for wind energy projects. The most popular explanation for local opposition, the Not in My Backyard effect, has received fierce criticism in the past decade. Critics argue that opposition is not merely a matter of selfishness or ignorance, but that moral, ecological and aesthetic values play an important role. In order to better take such values into account, a more bottom-up, participatory decision process is usually proposed. Research on this topic focusses on either stakeholder motivations/attitudes, or their behavior during project implementation. This paper proposes a third research focus, namely the 'objects' which elicit certain behavioral responses and attitudes-the wind turbine and parks. More concretely, this paper explores Value Sensitive Design (VSD) as way to arrive at wind turbines and parks that better embed or reflect key values. After a critical discussion of the notion of acceptance versus acceptability and support, the paper discusses existing literature on ecology and aesthetics in relation to wind turbine/park design, which could serve as 'building blocks' of a more integral VSD approach of the topic. It also discusses the challenge of demarcating wind park projects as VSD projects. A further challenge is that VSD has been applied mainly at the level of technical artifacts, whereas wind parks can best be conceptualized as socio-technical system. This new application would therefore expand the current practice of VSD, and may as a consequence also lead to interesting new insights for the VSD community. The paper concludes that such an outcome-oriented approach of wind turbines and park is worth exploring further, as a supplement to rather than a replacement of the process-oriented approach that is promoted by the current literature on community acceptance of wind parks.

A microcontroller with 96% power-conversion efficiency using stacked voltage domains

NARCIS (Netherlands)

Blutman, K.; Kapoor, A.; Majumdar, A.; Martinez, J.G.; Echeverri, J.; Sevat, L.; Van Der Wel, A.; Fatemi, H.; Pineda de Gyvez, J.; Makinwa, K.

2016-01-01

This paper presents a CMOS 40nm microcontroller where for the first time, stacked voltage domains are used. The system features an ARM Cortex M0+ processor, 4kB ROM, 16kB SRAM, peripherals, and an on-chip switched-capacitor voltage regulator (SCVR). By using voltage stacking the test chip achieves

Percutaneous ASD and VSD closure of 4-month-old infant in the same session

Directory of Open Access Journals (Sweden)

Nazmi Narin

2015-09-01

In conclusion, percutaneous ASD, VSD closure is being done safely in children, but for the first time, percutaneous VSD closure was done in an infant with low body weight in the same session with ASD closure successfully. This case will be an encouraging example for the future.

CONTRIBUTIONS OF INTRACELLULAR IONS TO Kv CHANNEL VOLTAGE SENSOR DYNAMICS.

Directory of Open Access Journals (Sweden)

Samuel eGoodchild

2012-06-01

Full Text Available Voltage sensing domains of Kv channels control ionic conductance through coupling of the movement of charged residues in the S4 segment to conformational changes at the cytoplasmic region of the pore domain, that allow K+ ions to flow. Conformational transitions within the voltage sensing domain caused by changes in the applied voltage across the membrane field are coupled to the conducting pore region and the gating of ionic conductance. However, several other factors not directly linked to the voltage dependent movement of charged residues within the voltage sensor impact the dynamics of the voltage sensor, such as inactivation, ionic conductance, intracellular ion identity and block of the channel by intracellular ligands. The effect of intracellular ions on voltage sensor dynamics is of importance in the interpretation of gating current measurements and the physiology of pore/voltage sensor coupling. There is a significant amount of variability in the reported kinetics of voltage sensor deactivation kinetics of Kv channels attributed to different mechanisms such as open state stabilization, immobilization and relaxation processes of the voltage sensor. Here we separate these factors and focus on the causal role that intracellular ions can play in allosterically modulating the dynamics of Kv voltage sensor deactivation kinetics. These considerations are of critical importance in understanding the molecular determinants of the complete channel gating cycle from activation to deactivation.

Rancang Bangun Inverter SVM Berbasis Mikrokontroler PIC 18F4431 Untuk Sistem VSD

OpenAIRE

Tarmizi; Muyassar

2013-01-01

Sebuah sistem pengaturan kecepatan motor disebut dengan sistem Variable Speed Drives (VSD). Sistem VSD motor induksi menggunakan inverter untuk mengatur frekuensi suplai motor. Untuk mendapatkan frekuensi suplai motor yang mendekati sinusoidal, inveter perlu di switching dengan metode tertentu. Pada penelitian ini, switching inverter 3 fasa menggunakan metode SVM (Space Vector Modulation) yang dikontrol oleh Mikrokontroler PIC18F4431. Sebelum dilakukan ekperimen, inverter SVM ini lakukan si...

Using a Voltage Domain Programmable Technique for Low-Power Management Cell-Based Design

Directory of Open Access Journals (Sweden)

Ching-Hwa Cheng

2011-09-01

Full Text Available The Multi-voltage technique is an effective way to reduce power consumption. In the proposed cell-based voltage domain programmable (VDP technique, the high and low voltages applied to logic gates are programmable. The flexible voltage domain reassignment allows the chip performance and power consumption to be dynamically adjusted. In the proposed technique, the power switches possess the feature of flexible programming after chip manufacturing. This VDP method does not use an external voltage regulator to regulate the supply voltage level from outside of the chip but can be easily integrated within the design. This novel technique is proven by use of a video decoder test chip, which shows 55% and 61% power reductions compared to conventional single-Vdd and low-voltage designs, respectively. This power-aware performance adjusting mechanism shows great power reduction with a good power-performance management mechanism.

PIP2 mediates functional coupling and pharmacology of neuronal KCNQ channels

DEFF Research Database (Denmark)

Kim, Robin Y; Pless, Stephan A; Kurata, Harley T

2017-01-01

Retigabine (RTG) is a first-in-class antiepileptic drug that suppresses neuronal excitability through the activation of voltage-gated KCNQ2-5 potassium channels. Retigabine binds to the pore-forming domain, causing a hyperpolarizing shift in the voltage dependence of channel activation. To elucid......Retigabine (RTG) is a first-in-class antiepileptic drug that suppresses neuronal excitability through the activation of voltage-gated KCNQ2-5 potassium channels. Retigabine binds to the pore-forming domain, causing a hyperpolarizing shift in the voltage dependence of channel activation....... These findings reveal an important role for PIP2 in coupling retigabine binding to altered VSD function. We identify a polybasic motif in the proximal C terminus of retigabine-sensitive KCNQ channels that contributes to VSD-pore coupling via PIP2, and thereby influences the unique gating effects of retigabine....

Ventricular Septal Defect in an Octogenarian: A Case Report of VSD Surgical Repair Concomitant with Coronary Artery Bypass and Valvular Surgery

Directory of Open Access Journals (Sweden)

Eiki Tayama

2012-01-01

Full Text Available Finding an untreated or asymptomatic large ventricular septal defect (VSD in an elderly patient is uncommon. The present case was an 81-year-old man who suffered from acute myocardial infarction due to three-vessel coronary disease, mitral and tricuspid valve insufficiency, and high-flow perimembranous VSD (Qp/Qs 2.3. Although the patient was elderly and the VSD had been asymptomatic for a long time, we considered that high-flow VSD and valve diseases should be repaired simultaneously with coronary disease. Then, he underwent elective surgery, namely, VSD patch repair concomitant with coronary artery bypass grafting, and mitral and tricuspid annuloplasty. His postoperative course was uneventful. We conclude that, even for an octogenarian, surgical repair of VSD is recommendable, if surgical indications are appropriate.

Liquid–Solid Dual-Gate Organic Transistors with Tunable Threshold Voltage for Cell Sensing

KAUST Repository

Zhang, Yu

2017-10-17

Liquid electrolyte-gated organic field effect transistors and organic electrochemical transistors have recently emerged as powerful technology platforms for sensing and simulation of living cells and organisms. For such applications, the transistors are operated at a gate voltage around or below 0.3 V because prolonged application of a higher voltage bias can lead to membrane rupturing and cell death. This constraint often prevents the operation of the transistors at their maximum transconductance or most sensitive regime. Here, we exploit a solid–liquid dual-gate organic transistor structure, where the threshold voltage of the liquid-gated conduction channel is controlled by an additional gate that is separated from the channel by a metal-oxide gate dielectric. With this design, the threshold voltage of the “sensing channel” can be linearly tuned in a voltage window exceeding 0.4 V. We have demonstrated that the dual-gate structure enables a much better sensor response to the detachment of human mesenchymal stem cells. In general, the capability of tuning the optimal sensing bias will not only improve the device performance but also broaden the material selection for cell-based organic bioelectronics.

Liquid-Solid Dual-Gate Organic Transistors with Tunable Threshold Voltage for Cell Sensing.

Science.gov (United States)

Zhang, Yu; Li, Jun; Li, Rui; Sbircea, Dan-Tiberiu; Giovannitti, Alexander; Xu, Junling; Xu, Huihua; Zhou, Guodong; Bian, Liming; McCulloch, Iain; Zhao, Ni

2017-11-08

Liquid electrolyte-gated organic field effect transistors and organic electrochemical transistors have recently emerged as powerful technology platforms for sensing and simulation of living cells and organisms. For such applications, the transistors are operated at a gate voltage around or below 0.3 V because prolonged application of a higher voltage bias can lead to membrane rupturing and cell death. This constraint often prevents the operation of the transistors at their maximum transconductance or most sensitive regime. Here, we exploit a solid-liquid dual-gate organic transistor structure, where the threshold voltage of the liquid-gated conduction channel is controlled by an additional gate that is separated from the channel by a metal-oxide gate dielectric. With this design, the threshold voltage of the "sensing channel" can be linearly tuned in a voltage window exceeding 0.4 V. We have demonstrated that the dual-gate structure enables a much better sensor response to the detachment of human mesenchymal stem cells. In general, the capability of tuning the optimal sensing bias will not only improve the device performance but also broaden the material selection for cell-based organic bioelectronics.

Depression of voltage-activated Ca2+ release in skeletal muscle by activation of a voltage-sensing phosphatase.

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Berthier, Christine; Kutchukian, Candice; Bouvard, Clément; Okamura, Yasushi; Jacquemond, Vincent

2015-04-01

Phosphoinositides act as signaling molecules in numerous cellular transduction processes, and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) regulates the function of several types of plasma membrane ion channels. We investigated the potential role of PtdIns(4,5)P2 in Ca(2+) homeostasis and excitation-contraction (E-C) coupling of mouse muscle fibers using in vivo expression of the voltage-sensing phosphatases (VSPs) Ciona intestinalis VSP (Ci-VSP) or Danio rerio VSP (Dr-VSP). Confocal images of enhanced green fluorescent protein-tagged Dr-VSP revealed a banded pattern consistent with VSP localization within the transverse tubule membrane. Rhod-2 Ca(2+) transients generated by 0.5-s-long voltage-clamp depolarizing pulses sufficient to elicit Ca(2+) release from the sarcoplasmic reticulum (SR) but below the range at which VSPs are activated were unaffected by the presence of the VSPs. However, in Ci-VSP-expressing fibers challenged by 5-s-long depolarizing pulses, the Ca(2+) level late in the pulse (3 s after initiation) was significantly lower at 120 mV than at 20 mV. Furthermore, Ci-VSP-expressing fibers showed a reversible depression of Ca(2+) release during trains, with the peak Ca(2+) transient being reduced by ∼30% after the application of 10 200-ms-long pulses to 100 mV. A similar depression was observed in Dr-VSP-expressing fibers. Cav1.1 Ca(2+) channel-mediated current was unaffected by Ci-VSP activation. In fibers expressing Ci-VSP and a pleckstrin homology domain fused with monomeric red fluorescent protein (PLCδ1PH-mRFP), depolarizing pulses elicited transient changes in mRFP fluorescence consistent with release of transverse tubule-bound PLCδ1PH domain into the cytosol; the voltage sensitivity of these changes was consistent with that of Ci-VSP activation, and recovery occurred with a time constant in the 10-s range. Our results indicate that the PtdIns(4,5)P2 level is tightly maintained in the transverse tubule membrane of the muscle fibers

Mapping of Residues Forming the Voltage Sensor of the Voltage-Dependent Anion-Selective Channel

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Thomas, Lorie; Blachly-Dyson, Elizabeth; Colombini, Marco; Forte, Michael

1993-06-01

Voltage-gated ion-channel proteins contain "voltage-sensing" domains that drive the conformational transitions between open and closed states in response to changes in transmembrane voltage. We have used site-directed mutagenesis to identify residues affecting the voltage sensitivity of a mitochondrial channel, the voltage-dependent anion-selective channel (VDAC). Although charge changes at many sites had no effect, at other sites substitutions that increased positive charge also increased the steepness of voltage dependance and substitutions that decreased positive charge decreased voltage dependance by an appropriate amount. In contrast to the plasma membrane K^+ and Na^+ channels, these residues are distributed over large parts of the VDAC protein. These results have been used to define the conformational transitions that accompany voltage gating of an ion channel. This gating mechanism requires the movement of large portions of the VDAC protein through the membrane.

A low-voltage sense amplifier with two-stage operational amplifier clamping for flash memory

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Guo, Jiarong

2017-04-01

A low-voltage sense amplifier with reference current generator utilizing two-stage operational amplifier clamp structure for flash memory is presented in this paper, capable of operating with minimum supply voltage at 1 V. A new reference current generation circuit composed of a reference cell and a two-stage operational amplifier clamping the drain pole of the reference cell is used to generate the reference current, which avoids the threshold limitation caused by current mirror transistor in the traditional sense amplifier. A novel reference voltage generation circuit using dummy bit-line structure without pull-down current is also adopted, which not only improves the sense window enhancing read precision but also saves power consumption. The sense amplifier was implemented in a flash realized in 90 nm flash technology. Experimental results show the access time is 14.7 ns with power supply of 1.2 V and slow corner at 125 °C. Project supported by the National Natural Science Fundation of China (No. 61376028).

Pharmacology of the Nav1.1 domain IV voltage sensor reveals coupling between inactivation gating processes.

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Osteen, Jeremiah D; Sampson, Kevin; Iyer, Vivek; Julius, David; Bosmans, Frank

2017-06-27

The Na v 1.1 voltage-gated sodium channel is a critical contributor to excitability in the brain, where pathological loss of function leads to such disorders as epilepsy, Alzheimer's disease, and autism. This voltage-gated sodium (Na v ) channel subtype also plays an important role in mechanical pain signaling by primary afferent somatosensory neurons. Therefore, pharmacologic modulation of Na v 1.1 represents a potential strategy for treating excitability disorders of the brain and periphery. Inactivation is a complex aspect of Na v channel gating and consists of fast and slow components, each of which may involve a contribution from one or more voltage-sensing domains. Here, we exploit the Hm1a spider toxin, a Na v 1.1-selective modulator, to better understand the relationship between these temporally distinct modes of inactivation and ask whether they can be distinguished pharmacologically. We show that Hm1a inhibits the gating movement of the domain IV voltage sensor (VSDIV), hindering both fast and slow inactivation and leading to an increase in Na v 1.1 availability during high-frequency stimulation. In contrast, ICA-121431, a small-molecule Na v 1.1 inhibitor, accelerates a subsequent VSDIV gating transition to accelerate entry into the slow inactivated state, resulting in use-dependent block. Further evidence for functional coupling between fast and slow inactivation is provided by a Na v 1.1 mutant in which fast inactivation removal has complex effects on slow inactivation. Taken together, our data substantiate the key role of VSDIV in Na v channel fast and slow inactivation and demonstrate that these gating processes are sequential and coupled through VSDIV. These findings provide insight into a pharmacophore on VSDIV through which modulation of inactivation gating can inhibit or facilitate Na v 1.1 function.

Mural endocarditis caused by Corynebacterium mustelae in a dog with a VSD.

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Winter, Randolph L; Gordon, Sonya G; Zhang, Shuping; Hariu, Crystal D; Miller, Matthew W

2014-01-01

A 6 yr old female spayed large Munsterlander was evaluated following a 3 wk history of lethargy, inappetence, intermittent fever, and a recent change to the timing of her previously diagnosed heart murmur. Physical examination revealed marked dehydration, lethargy, and a grade 5/6 to-and-fro heart murmur that was auscultated best at the right sternal border. The dog was febrile, and echocardiography revealed a large, mobile, vegetative lesion in the right ventricular outflow tract associated with a ventricular septal defect (VSD). Mild aortic insufficiency was present. Corynebacterium mustelae (C. mustelae) was isolated from a pooled blood culture. Treatment of infective endocarditis (IE) was initiated along with supportive care, and the patient was discharged 9 days later. The dog remained without clinical signs 132 days after discharge. VSD is rarely mentioned as a predisposing factor for development of IE in veterinary literature; however, this report highlights that dogs with a VSD may be at risk for IE. To the authors' knowledge, this is the first documented case of a canine infection with C. mustelae. Infection with C. mustelae in this case represents a novel agent for IE in the dog.

Global versus local mechanisms of temperature sensing in ion channels.

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Arrigoni, Cristina; Minor, Daniel L

2018-05-01

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

Ultra-Low Voltage Sixth-Order Low Pass Filter for Sensing the T-Wave Signal in ECGs

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Panagiotis Bertsias

2014-11-01

Full Text Available An ultra-low voltage sixth-order low pass filter topology, suitable for sensing the T-wave signal in an electrocardiogram (ECG, is presented in this paper. This is realized using a cascade connection of second-order building blocks constructed from a sinh-domain two-integrator loop. The performance of the filter has been evaluated using the Cadence Analog Design Environment and the design kit provided by the Austria Mikro Systeme (AMS 0.35-µm CMOS process. The power consumption of filters was 7.21 nW, while a total harmonic distortion (THD level of 4% was observed for an input signal of 220 pA. The RMS value of the input referred noise was 0.43 pA, and the simulated value of the dynamic range (DR was 51.1 dB. A comparison with already published counterparts shows that the proposed topology offers the benefits of 0.5-V supply voltage operation and significantly improved power efficiency.

Outward Rectification of Voltage-Gated K+ Channels Evolved at Least Twice in Life History.

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Janin Riedelsberger

Full Text Available Voltage-gated potassium (K+ channels are present in all living systems. Despite high structural similarities in the transmembrane domains (TMD, this K+ channel type segregates into at least two main functional categories-hyperpolarization-activated, inward-rectifying (Kin and depolarization-activated, outward-rectifying (Kout channels. Voltage-gated K+ channels sense the membrane voltage via a voltage-sensing domain that is connected to the conduction pathway of the channel. It has been shown that the voltage-sensing mechanism is the same in Kin and Kout channels, but its performance results in opposite pore conformations. It is not known how the different coupling of voltage-sensor and pore is implemented. Here, we studied sequence and structural data of voltage-gated K+ channels from animals and plants with emphasis on the property of opposite rectification. We identified structural hotspots that alone allow already the distinction between Kin and Kout channels. Among them is a loop between TMD S5 and the pore that is very short in animal Kout, longer in plant and animal Kin and the longest in plant Kout channels. In combination with further structural and phylogenetic analyses this finding suggests that outward-rectification evolved twice and independently in the animal and plant kingdom.

Effectiveness of several dosage formula of oil and nano emulsion of citronella against vascular streak dieback (VSD) disease on cocoa

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Noveriza, R.; Trisno, J.; Rahma, H.; Yuliani, S.; Reflin; Martinius

2018-02-01

The disease of Vascular streak dieback (VSD) is a deadly disease of cocoa plants, because it attacks the vascular tissue of cocoa at growing point of the plant. In West Sumatra the disease was first reported in 2015 with an incidence of disease range 58.82% - 100% and an intensity of disease range 24.29% - 44.7%. The purpose of this study was to examine the effectiveness of dosage application of oil formula and nano emulsion of citronella formula against Vascular streak dieback (VSD) disease on cocoa plants in West Sumatra (in Padang Pariaman District and Limapuluh Kota District). The results showed that the percentage of VSD disease attacks in both testing sites was 100%. The oil and nano emulsion of citronella formulas can reduce the intensity of VSD disease on cocoa plants in West Sumatra, particularly in Padang Pariaman District and Limapuluh Kota District. The reduction of VSD intensity in Padang Pariaman district ranged from 8.32 to 21.13%; while in Limapuluh Kota district ranged from 4.33 to 11.80%. The nano emulsion of citronella formulation is effective to suppress the intensity of VSD disease on cocoa plants at doses 0.1% (≥ 30% of effectiveness level).

Common molecular determinants of tarantula huwentoxin-IV inhibition of Na+ channel voltage sensors in domains II and IV.

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Xiao, Yucheng; Jackson, James O; Liang, Songping; Cummins, Theodore R

2011-08-05

The voltage sensors of domains II and IV of sodium channels are important determinants of activation and inactivation, respectively. Animal toxins that alter electrophysiological excitability of muscles and neurons often modify sodium channel activation by selectively interacting with domain II and inactivation by selectively interacting with domain IV. This suggests that there may be substantial differences between the toxin-binding sites in these two important domains. Here we explore the ability of the tarantula huwentoxin-IV (HWTX-IV) to inhibit the activity of the domain II and IV voltage sensors. HWTX-IV is specific for domain II, and we identify five residues in the S1-S2 (Glu-753) and S3-S4 (Glu-811, Leu-814, Asp-816, and Glu-818) regions of domain II that are crucial for inhibition of activation by HWTX-IV. These data indicate that a single residue in the S3-S4 linker (Glu-818 in hNav1.7) is crucial for allowing HWTX-IV to interact with the other key residues and trap the voltage sensor in the closed configuration. Mutagenesis analysis indicates that the five corresponding residues in domain IV are all critical for endowing HWTX-IV with the ability to inhibit fast inactivation. Our data suggest that the toxin-binding motif in domain II is conserved in domain IV. Increasing our understanding of the molecular determinants of toxin interactions with voltage-gated sodium channels may permit development of enhanced isoform-specific voltage-gating modifiers.

The Eag domain regulates the voltage-dependent inactivation of rat Eag1 K+ channels.

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Ting-Feng Lin

Full Text Available Eag (Kv10 and Erg (Kv11 belong to two distinct subfamilies of the ether-à-go-go K+ channel family (KCNH. While Erg channels are characterized by an inward-rectifying current-voltage relationship that results from a C-type inactivation, mammalian Eag channels display little or no voltage-dependent inactivation. Although the amino (N-terminal region such as the eag domain is not required for the C-type inactivation of Erg channels, an N-terminal deletion in mouse Eag1 has been shown to produce a voltage-dependent inactivation. To further discern the role of the eag domain in the inactivation of Eag1 channels, we generated N-terminal chimeras between rat Eag (rEag1 and human Erg (hERG1 channels that involved swapping the eag domain alone or the complete cytoplasmic N-terminal region. Functional analyses indicated that introduction of the homologous hERG1 eag domain led to both a fast phase and a slow phase of channel inactivation in the rEag1 chimeras. By contrast, the inactivation features were retained in the reverse hERG1 chimeras. Furthermore, an eag domain-lacking rEag1 deletion mutant also showed the fast phase of inactivation that was notably attenuated upon co-expression with the rEag1 eag domain fragment, but not with the hERG1 eag domain fragment. Additionally, we have identified a point mutation in the S4-S5 linker region of rEag1 that resulted in a similar inactivation phenotype. Biophysical analyses of these mutant constructs suggested that the inactivation gating of rEag1 was distinctly different from that of hERG1. Overall, our findings are consistent with the notion that the eag domain plays a critical role in regulating the inactivation gating of rEag1. We propose that the eag domain may destabilize or mask an inherent voltage-dependent inactivation of rEag1 K+ channels.

3' Phosphatase activity toward phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2] by voltage-sensing phosphatase (VSP).

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Kurokawa, Tatsuki; Takasuga, Shunsuke; Sakata, Souhei; Yamaguchi, Shinji; Horie, Shigeo; Homma, Koichi J; Sasaki, Takehiko; Okamura, Yasushi

2012-06-19

Voltage-sensing phosphatases (VSPs) consist of a voltage-sensor domain and a cytoplasmic region with remarkable sequence similarity to phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a tumor suppressor phosphatase. VSPs dephosphorylate the 5' position of the inositol ring of both phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P(3)] and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)] upon voltage depolarization. However, it is unclear whether VSPs also have 3' phosphatase activity. To gain insights into this question, we performed in vitro assays of phosphatase activities of Ciona intestinalis VSP (Ci-VSP) and transmembrane phosphatase with tensin homology (TPTE) and PTEN homologous inositol lipid phosphatase (TPIP; one human ortholog of VSP) with radiolabeled PI(3,4,5)P(3). TLC assay showed that the 3' phosphate of PI(3,4,5)P(3) was not dephosphorylated, whereas that of phosphatidylinositol 3,4-bisphosphate [PI(3,4)P(2)] was removed by VSPs. Monitoring of PI(3,4)P(2) levels with the pleckstrin homology (PH) domain from tandem PH domain-containing protein (TAPP1) fused with GFP (PH(TAPP1)-GFP) by confocal microscopy in amphibian oocytes showed an increase of fluorescence intensity during depolarization to 0 mV, consistent with 5' phosphatase activity of VSP toward PI(3,4,5)P(3). However, depolarization to 60 mV showed a transient increase of GFP fluorescence followed by a decrease, indicating that, after PI(3,4,5)P(3) is dephosphorylated at the 5' position, PI(3,4)P(2) is then dephosphorylated at the 3' position. These results suggest that substrate specificity of the VSP changes with membrane potential.

The ladder-shaped polyether toxin gambierol anchors the gating machinery of Kv3.1 channels in the resting state

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Kopljar, Ivan; Labro, Alain J.; de Block, Tessa; Rainier, Jon D.; Tytgat, Jan

2013-01-01

Voltage-gated potassium (Kv) and sodium (Nav) channels are key determinants of cellular excitability and serve as targets of neurotoxins. Most marine ciguatoxins potentiate Nav channels and cause ciguatera seafood poisoning. Several ciguatoxins have also been shown to affect Kv channels, and we showed previously that the ladder-shaped polyether toxin gambierol is a potent Kv channel inhibitor. Most likely, gambierol acts via a lipid-exposed binding site, located outside the K+ permeation pathway. However, the mechanism by which gambierol inhibits Kv channels remained unknown. Using gating and ionic current analysis to investigate how gambierol affected S6 gate opening and voltage-sensing domain (VSD) movements, we show that the resting (closed) channel conformation forms the high-affinity state for gambierol. The voltage dependence of activation was shifted by >120 mV in the depolarizing direction, precluding channel opening in the physiological voltage range. The (early) transitions between the resting and the open state were monitored with gating currents, and provided evidence that strong depolarizations allowed VSD movement up to the activated-not-open state. However, for transition to the fully open (ion-conducting) state, the toxin first needed to dissociate. These dissociation kinetics were markedly accelerated in the activated-not-open state, presumably because this state displayed a much lower affinity for gambierol. A tetrameric concatemer with only one high-affinity binding site still displayed high toxin sensitivity, suggesting that interaction with a single binding site prevented the concerted step required for channel opening. We propose a mechanism whereby gambierol anchors the channel’s gating machinery in the resting state, requiring more work from the VSD to open the channel. This mechanism is quite different from the action of classical gating modifier peptides (e.g., hanatoxin). Therefore, polyether toxins open new opportunities in structure�

A Photostable Silicon Rhodamine Platform for Optical Voltage Sensing

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Huang, Yi-Lin; Walker, Alison S.; Miller, Evan W.

2015-01-01

This paper describes the design and synthesis of a photostable, far-red to near-infrared (NIR) platform for optical voltage sensing. We developed a new, sulfonated silicon rhodamine fluorophore and integrated it with a phenylenevinylene molecular wire to create a Berkeley Red Sensor of Transmembrane potential, or BeRST 1 (“burst”). BeRST 1 is the first member of a class of farred to NIR voltage sensitive dyes that make use of a photoinduced electron transfer (PeT) trigger for optical interrogation of membrane voltage. We show that BeRST 1 displays bright, membrane-localized fluorescence in living cells, high photostability, and excellent voltage sensitivity in neurons. Depolarization of the plasma membrane results in rapid fluorescence increases (24% ΔF/F per 100 mV). BeRST 1 can be used in conjunction with fluorescent stains for organelles, Ca2+ indicators, and voltage-sensitive fluorescent proteins. In addition, the red-shifted spectral profile of BeRST 1, relative to commonly employed optogenetic actuators like ChannelRhodopsin2 (ChR2), which require blue light, enables optical electrophysiology in neurons. The high speed, sensitivity, photostability and long-wavelength fluorescence profiles of BeRST 1 make it a useful platform for the non-invasive, optical dissection of neuronal activity. PMID:26237573

Amphipathic motifs in BAR domains are essential for membrane curvature sensing

DEFF Research Database (Denmark)

Bhatia, Vikram K; Madsen, Kenneth L; Bolinger, Pierre-Yves

2009-01-01

BAR (Bin/Amphiphysin/Rvs) domains and amphipathic alpha-helices (AHs) are believed to be sensors of membrane curvature thus facilitating the assembly of protein complexes on curved membranes. Here, we used quantitative fluorescence microscopy to compare the binding of both motifs on single...... nanosized liposomes of different diameters and therefore membrane curvature. Characterization of members of the three BAR domain families showed surprisingly that the crescent-shaped BAR dimer with its positively charged concave face is not able to sense membrane curvature. Mutagenesis on BAR domains showed...... that membrane curvature sensing critically depends on the N-terminal AH and furthermore that BAR domains sense membrane curvature through hydrophobic insertion in lipid packing defects and not through electrostatics. Consequently, amphipathic motifs, such as AHs, that are often associated with BAR domains...

Comparative study of 0° X-cut and Y + 36°-cut lithium niobate high-voltage sensing

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Patel, N.; Branch, D. W.; Schamiloglu, E.; Cular, S.

2015-08-01

A comparison study between Y + 36° and 0° X-cut lithium niobate (LiNbO3) was performed to evaluate the influence of crystal cut on the acoustic propagation to realize a piezoelectric high-voltage sensor. The acoustic time-of-flight for each crystal cut was measured when applying direct current (DC), alternating current (AC), and pulsed voltages. Results show that the voltage-induced shift in the acoustic wave propagation time scaled quadratically with voltage for DC and AC voltages applied to X-cut crystals. For the Y + 36° crystal, the voltage-induced shift scales linearly with DC voltages and quadratically with AC voltages. When applying 5 μs voltage pulses to both crystals, the voltage-induced shift scaled linearly with voltage. For the Y + 36° cut, the voltage-induced shift from applying DC voltages ranged from 10 to 54 ps and 35 to 778 ps for AC voltages at 640 V over the frequency range of 100 Hz-100 kHz. Using the same conditions as the Y + 36° cut, the 0° X-cut crystal sensed a shift of 10-273 ps for DC voltages and 189-813 ps for AC voltage application. For 5 μs voltage pulses, the 0° X-cut crystal sensed a voltage induced shift of 0.250-2 ns and the Y + 36°-cut crystal sensed a time shift of 0.115-1.6 ns. This suggests a frequency sensitive response to voltage where the influence of the crystal cut was not a significant contributor under DC, AC, or pulsed voltage conditions. The measured DC data were compared to a 1-D impedance matrix model where the predicted incremental length changed as a function of voltage. When the voltage source error was eliminated through physical modeling from the uncertainty budget, the combined uncertainty of the sensor (within a 95% confidence interval) decreased to 0.0033% using a Y + 36°-cut crystal and 0.0032% using an X-cut crystal for all the voltage conditions used in this experiment.

Voltage and pH sensing by the voltage-gated proton channel, HV1.

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DeCoursey, Thomas E

2018-04-01

Voltage-gated proton channels are unique ion channels, membrane proteins that allow protons but no other ions to cross cell membranes. They are found in diverse species, from unicellular marine life to humans. In all cells, their function requires that they open and conduct current only under certain conditions, typically when the electrochemical gradient for protons is outwards. Consequently, these proteins behave like rectifiers, conducting protons out of cells. Their activity has electrical consequences and also changes the pH on both sides of the membrane. Here we summarize what is known about the way these proteins sense the membrane potential and the pH inside and outside the cell. Currently, it is hypothesized that membrane potential is sensed by permanently charged arginines (with very high p K a ) within the protein, which results in parts of the protein moving to produce a conduction pathway. The mechanism of pH sensing appears to involve titratable side chains of particular amino acids. For this purpose their p K a needs to be within the operational pH range. We propose a 'counter-charge' model for pH sensing in which electrostatic interactions within the protein are selectively disrupted by protonation of internally or externally accessible groups. © 2018 The Author.

Voltage and pH sensing by the voltage-gated proton channel, HV1

Science.gov (United States)

2018-01-01

Voltage-gated proton channels are unique ion channels, membrane proteins that allow protons but no other ions to cross cell membranes. They are found in diverse species, from unicellular marine life to humans. In all cells, their function requires that they open and conduct current only under certain conditions, typically when the electrochemical gradient for protons is outwards. Consequently, these proteins behave like rectifiers, conducting protons out of cells. Their activity has electrical consequences and also changes the pH on both sides of the membrane. Here we summarize what is known about the way these proteins sense the membrane potential and the pH inside and outside the cell. Currently, it is hypothesized that membrane potential is sensed by permanently charged arginines (with very high pKa) within the protein, which results in parts of the protein moving to produce a conduction pathway. The mechanism of pH sensing appears to involve titratable side chains of particular amino acids. For this purpose their pKa needs to be within the operational pH range. We propose a ‘counter-charge’ model for pH sensing in which electrostatic interactions within the protein are selectively disrupted by protonation of internally or externally accessible groups. PMID:29643227

Asymmetric functional contributions of acidic and aromatic side chains in sodium channel voltage-sensor domains

DEFF Research Database (Denmark)

Pless, Stephan Alexander; Elstone, Fisal D; Niciforovic, Ana P

2014-01-01

largely enigmatic. To this end, natural and unnatural side chain substitutions were made in the S2 hydrophobic core (HC), the extracellular negative charge cluster (ENC), and the intracellular negative charge cluster (INC) of the four VSDs of the skeletal muscle sodium channel isoform (NaV1......Voltage-gated sodium (NaV) channels mediate electrical excitability in animals. Despite strong sequence conservation among the voltage-sensor domains (VSDs) of closely related voltage-gated potassium (KV) and NaV channels, the functional contributions of individual side chains in Nav VSDs remain.......4). The results show that the highly conserved aromatic side chain constituting the S2 HC makes distinct functional contributions in each of the four NaV domains. No obvious cation-pi interaction exists with nearby S4 charges in any domain, and natural and unnatural mutations at these aromatic sites produce...

Discrete-Time Domain Modelling of Voltage Source Inverters in Standalone Applications

DEFF Research Database (Denmark)

Federico, de Bosio; de Sousa Ribeiro, Luiz Antonio; Freijedo Fernandez, Francisco Daniel

2017-01-01

modelling of the LC plant with consideration of delay and sample-and-hold effects on the state feedback cross-coupling decoupling is derived. From this plant formulation, current controllers with wide bandwidth and good relative stability properties are developed. Two controllers based on lead compensation......The decoupling of the capacitor voltage and inductor current has been shown to improve significantly the dynamic performance of voltage source inverters in standalone applications. However, the computation and PWM delays still limit the achievable bandwidth. In this paper a discrete-time domain...

OBSERVATION OF MAGNETIC DOMAINS IN IRRADIATED TRANSITION METALS BY HIGH VOLTAGE ELECTRON MICROSCOPY

OpenAIRE

Ono , F.; Jakubovics , J.; Maeta , H.

1988-01-01

The effect of irradiation on the movement of domain walls was studied in ferromagnetic transition metals by using a high voltage electron microscope. In iron, a domain wall became easily movable at a 300 kV irradiation. The mobility was less affected in cobalt, while in nickel the effect was the greatest.

Sequential injection of domain walls into ferroelectrics at different bias voltages: Paving the way for “domain wall memristors”

Energy Technology Data Exchange (ETDEWEB)

Whyte, J. R.; McQuaid, R. G. P.; Einsle, J. F.; Gregg, J. M., E-mail: m.gregg@qub.ac.uk [Centre for Nanostructured Media (CNM), School of Maths and Physics, Queen' s University Belfast, University Road, Belfast BT7 1NN (United Kingdom); Ashcroft, C. M. [Centre for Nanostructured Media (CNM), School of Maths and Physics, Queen' s University Belfast, University Road, Belfast BT7 1NN (United Kingdom); Department of Physics, Cavendish Laboratory, J. J. Thomson Avenue, Cambridge CB3 0HE (United Kingdom); Canalias, C. [Department of Applied Physics, Royal Institute of Technology, Roslagstullsbacken 21, 10691 Stockholm (Sweden); Gruverman, A. [Department of Physics and Astronomy, University of Nebraska Lincoln, Nebraska 68588–0299 (United States)

2014-08-14

Simple meso-scale capacitor structures have been made by incorporating thin (∼300 nm) single crystal lamellae of KTiOPO{sub 4} (KTP) between two coplanar Pt electrodes. The influence that either patterned protrusions in the electrodes or focused ion beam milled holes in the KTP have on the nucleation of reverse domains during switching was mapped using piezoresponse force microscopy imaging. The objective was to assess whether or not variations in the magnitude of field enhancement at localised “hot-spots,” caused by such patterning, could be used to both control the exact locations and bias voltages at which nucleation events occurred. It was found that both the patterning of electrodes and the milling of various hole geometries into the KTP could allow controlled sequential injection of domain wall pairs at different bias voltages; this capability could have implications for the design and operation of domain wall electronic devices, such as memristors, in the future.

Comparative study of 0° X-cut and Y + 36°-cut lithium niobate high-voltage sensing

International Nuclear Information System (INIS)

Patel, N.; Branch, D. W.; Cular, S.; Schamiloglu, E.

2015-01-01

A comparison study between Y + 36° and 0° X-cut lithium niobate (LiNbO 3 ) was performed to evaluate the influence of crystal cut on the acoustic propagation to realize a piezoelectric high-voltage sensor. The acoustic time-of-flight for each crystal cut was measured when applying direct current (DC), alternating current (AC), and pulsed voltages. Results show that the voltage-induced shift in the acoustic wave propagation time scaled quadratically with voltage for DC and AC voltages applied to X-cut crystals. For the Y + 36° crystal, the voltage-induced shift scales linearly with DC voltages and quadratically with AC voltages. When applying 5 μs voltage pulses to both crystals, the voltage-induced shift scaled linearly with voltage. For the Y + 36° cut, the voltage-induced shift from applying DC voltages ranged from 10 to 54 ps and 35 to 778 ps for AC voltages at 640 V over the frequency range of 100 Hz–100 kHz. Using the same conditions as the Y + 36° cut, the 0° X-cut crystal sensed a shift of 10–273 ps for DC voltages and 189–813 ps for AC voltage application. For 5 μs voltage pulses, the 0° X-cut crystal sensed a voltage induced shift of 0.250–2 ns and the Y + 36°-cut crystal sensed a time shift of 0.115–1.6 ns. This suggests a frequency sensitive response to voltage where the influence of the crystal cut was not a significant contributor under DC, AC, or pulsed voltage conditions. The measured DC data were compared to a 1-D impedance matrix model where the predicted incremental length changed as a function of voltage. When the voltage source error was eliminated through physical modeling from the uncertainty budget, the combined uncertainty of the sensor (within a 95% confidence interval) decreased to 0.0033% using a Y + 36°-cut crystal and 0.0032% using an X-cut crystal for all the voltage conditions used in this experiment

The local domain wall position in ferromagnetic thin wires: simultaneous measurement of resistive and transverse voltages at multiple points

International Nuclear Information System (INIS)

Hanada, R.; Sugawara, H.; Aoki, Y.; Sato, H.; Shigeto, K.; Shinjo, T.; Ono, T.; Miyajima, H.

2002-01-01

We have simultaneously measured the field dependences of voltages at multiple pairs of resistance and transverse voltage probes in ferromagnetic wires (with either magnetic or non-magnetic voltage probes). Both the resistive (through the giant magnetoresistance and anisotropic magnetoresistance) and transverse voltages (through the planar Hall effect) exhibit abrupt jumps, reflecting discrete motion of domain walls or rotations of magnetization. Voltage probes, even if non-magnetic, are found to affect the jump fields depending on the sample conditions. We demonstrate that the specific information on the domain (wall) motion along a thin ferromagnetic wire could be obtained from the jump fields. (author)

Structure of the Nav1.4-β1 Complex from Electric Eel.

Science.gov (United States)

Yan, Zhen; Zhou, Qiang; Wang, Lin; Wu, Jianping; Zhao, Yanyu; Huang, Gaoxingyu; Peng, Wei; Shen, Huaizong; Lei, Jianlin; Yan, Nieng

2017-07-27

Voltage-gated sodium (Na v ) channels initiate and propagate action potentials. Here, we present the cryo-EM structure of EeNa v 1.4, the Na v channel from electric eel, in complex with the β1 subunit at 4.0 Å resolution. The immunoglobulin domain of β1 docks onto the extracellular L5 I and L6 IV loops of EeNa v 1.4 via extensive polar interactions, and the single transmembrane helix interacts with the third voltage-sensing domain (VSD III ). The VSDs exhibit "up" conformations, while the intracellular gate of the pore domain is kept open by a digitonin-like molecule. Structural comparison with closed Na v PaS shows that the outward transfer of gating charges is coupled to the iris-like pore domain dilation through intricate force transmissions involving multiple channel segments. The IFM fast inactivation motif on the III-IV linker is plugged into the corner enclosed by the outer S4-S5 and inner S6 segments in repeats III and IV, suggesting a potential allosteric blocking mechanism for fast inactivation. Copyright © 2017 Elsevier Inc. All rights reserved.

A CMOS Humidity Sensor for Passive RFID Sensing Applications

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Fangming Deng

2014-05-01

Full Text Available This paper presents a low-cost low-power CMOS humidity sensor for passive RFID sensing applications. The humidity sensing element is implemented in standard CMOS technology without any further post-processing, which results in low fabrication costs. The interface of this humidity sensor employs a PLL-based architecture transferring sensor signal processing from the voltage domain to the frequency domain. Therefore this architecture allows the use of a fully digital circuit, which can operate on ultra-low supply voltage and thus achieves low-power consumption. The proposed humidity sensor has been fabricated in the TSMC 0.18 μm CMOS process. The measurements show this humidity sensor exhibits excellent linearity and stability within the relative humidity range. The sensor interface circuit consumes only 1.05 µW at 0.5 V supply voltage and reduces it at least by an order of magnitude compared to previous designs.

A CMOS Humidity Sensor for Passive RFID Sensing Applications

Science.gov (United States)

Deng, Fangming; He, Yigang; Zhang, Chaolong; Feng, Wei

2014-01-01

This paper presents a low-cost low-power CMOS humidity sensor for passive RFID sensing applications. The humidity sensing element is implemented in standard CMOS technology without any further post-processing, which results in low fabrication costs. The interface of this humidity sensor employs a PLL-based architecture transferring sensor signal processing from the voltage domain to the frequency domain. Therefore this architecture allows the use of a fully digital circuit, which can operate on ultra-low supply voltage and thus achieves low-power consumption. The proposed humidity sensor has been fabricated in the TSMC 0.18 μm CMOS process. The measurements show this humidity sensor exhibits excellent linearity and stability within the relative humidity range. The sensor interface circuit consumes only 1.05 μW at 0.5 V supply voltage and reduces it at least by an order of magnitude compared to previous designs. PMID:24841250

A CMOS humidity sensor for passive RFID sensing applications.

Science.gov (United States)

Deng, Fangming; He, Yigang; Zhang, Chaolong; Feng, Wei

2014-05-16

This paper presents a low-cost low-power CMOS humidity sensor for passive RFID sensing applications. The humidity sensing element is implemented in standard CMOS technology without any further post-processing, which results in low fabrication costs. The interface of this humidity sensor employs a PLL-based architecture transferring sensor signal processing from the voltage domain to the frequency domain. Therefore this architecture allows the use of a fully digital circuit, which can operate on ultra-low supply voltage and thus achieves low-power consumption. The proposed humidity sensor has been fabricated in the TSMC 0.18 μm CMOS process. The measurements show this humidity sensor exhibits excellent linearity and stability within the relative humidity range. The sensor interface circuit consumes only 1.05 µW at 0.5 V supply voltage and reduces it at least by an order of magnitude compared to previous designs.

Postinfarct VSD management using 3D computer printing assisted percutaneous closure

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Mohamad Lazkani

2015-11-01

Full Text Available Postinfarct VSD (PIVSD carries a grim prognosis. The mainstay of management has been surgical repair. The advent of septal occluder devices has offered an attractive alternative to surgical repair. Most PIVSD have serpiginous tracts with necrotic tissue, which makes assessing the defect challenging. 3D computer printing has become useful in preprocedure planning of complex surgical procedures in multiple subspecialties.

Time-Domain Voltage Sag State Estimation Based on the Unscented Kalman Filter for Power Systems with Nonlinear Components

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Rafael Cisneros-Magaña

2018-06-01

Full Text Available This paper proposes a time-domain methodology based on the unscented Kalman filter to estimate voltage sags and their characteristics, such as magnitude and duration in power systems represented by nonlinear models. Partial and noisy measurements from the electrical network with nonlinear loads, used as data, are assumed. The characteristics of voltage sags can be calculated in a discrete form with the unscented Kalman filter to estimate all the busbar voltages; being possible to determine the rms voltage magnitude and the voltage sag starting and ending time, respectively. Voltage sag state estimation results can be used to obtain the power quality indices for monitored and unmonitored busbars in the power grid and to design adequate mitigating techniques. The proposed methodology is successfully validated against the results obtained with the time-domain system simulation for the power system with nonlinear components, being the normalized root mean square error less than 3%.

Voltage Drop in a Ferroelectric Single Layer Capacitor by Retarded Domain Nucleation.

Science.gov (United States)

Kim, Yu Jin; Park, Hyeon Woo; Hyun, Seung Dam; Kim, Han Joon; Kim, Keum Do; Lee, Young Hwan; Moon, Taehwan; Lee, Yong Bin; Park, Min Hyuk; Hwang, Cheol Seong

2017-12-13

Ferroelectric (FE) capacitor is a critical electric component in microelectronic devices. Among many of its intriguing properties, the recent finding of voltage drop (V-drop) across the FE capacitor while the positive charges flow in is especially eye-catching. This finding was claimed to be direct evidence that the FE capacitor is in negative capacitance (NC) state, which must be useful for (infinitely) high capacitance and ultralow voltage operation of field-effect transistors. Nonetheless, the NC state corresponds to the maximum energy state of the FE material, so it has been widely accepted in the community that the material alleviates that state by forming ferroelectric domains. This work reports a similar V-drop effect from the 150 nm thick epitaxial BaTiO 3 ferroelectric thin film, but the interpretation was completely disparate; the V-drop can be precisely simulated by the reverse domain nucleation and propagation of which charge effect cannot be fully compensated for by the supplied charge from the external charge source. The disappearance of the V-drop effect was also observed by repeated FE switching only up to 10 cycles, which can hardly be explained by the involvement of the NC effect. The retained reverse domain nuclei even after the subsequent poling can explain such behavior.

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

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RAMÓN LATORRE

2006-01-01

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

Using LDR as Sensing Element for an External Fuzzy Controller Applied in Photovoltaic Pumping Systems with Variable-Speed Drives.

Science.gov (United States)

Maranhão, Geraldo Neves De A; Brito, Alaan Ubaiara; Leal, Anderson Marques; Fonseca, Jéssica Kelly Silva; Macêdo, Wilson Negrão

2015-09-22

In the present paper, a fuzzy controller applied to a Variable-Speed Drive (VSD) for use in Photovoltaic Pumping Systems (PVPS) is proposed. The fuzzy logic system (FLS) used is embedded in a microcontroller and corresponds to a proportional-derivative controller. A Light-Dependent Resistor (LDR) is used to measure, approximately, the irradiance incident on the PV array. Experimental tests are executed using an Arduino board. The experimental results show that the fuzzy controller is capable of operating the system continuously throughout the day and controlling the direct current (DC) voltage level in the VSD with a good performance.

Using LDR as Sensing Element for an External Fuzzy Controller Applied in Photovoltaic Pumping Systems with Variable-Speed Drives

Directory of Open Access Journals (Sweden)

Geraldo Neves De A. Maranhão

2015-09-01

Full Text Available In the present paper, a fuzzy controller applied to a Variable-Speed Drive (VSD for use in Photovoltaic Pumping Systems (PVPS is proposed. The fuzzy logic system (FLS used is embedded in a microcontroller and corresponds to a proportional-derivative controller. A Light-Dependent Resistor (LDR is used to measure, approximately, the irradiance incident on the PV array. Experimental tests are executed using an Arduino board. The experimental results show that the fuzzy controller is capable of operating the system continuously throughout the day and controlling the direct current (DC voltage level in the VSD with a good performance.

Low-voltage analog front-end processor design for ISFET-based sensor and H+ sensing applications

Science.gov (United States)

Chung, Wen-Yaw; Yang, Chung-Huang; Peng, Kang-Chu; Yeh, M. H.

2003-04-01

This paper presents a modular-based low-voltage analog-front-end processor design in a 0.5mm double-poly double-metal CMOS technology for Ion Sensitive Field Effect Transistor (ISFET)-based sensor and H+ sensing applications. To meet the potentiometric response of the ISFET that is proportional to various H+ concentrations, the constant-voltage and constant current (CVCS) testing configuration has been used. Low-voltage design skills such as bulk-driven input pair, folded-cascode amplifier, bootstrap switch control circuits have been designed and integrated for 1.5V supply and nearly rail-to-rail analog to digital signal processing. Core modules consist of an 8-bit two-step analog-digital converter and bulk-driven pre-amplifiers have been developed in this research. The experimental results show that the proposed circuitry has an acceptable linearity to 0.1 pH-H+ sensing conversions with the buffer solution in the range of pH2 to pH12. The processor has a potential usage in battery-operated and portable healthcare devices and environmental monitoring applications.

Realisation of low-voltage square-root-domain all-pass filters

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Farooq A. Khanday

2013-10-01

Full Text Available Novel l ow-voltage first-order and second-order square-root-domain all-pass filters derived systematically by means of transfer function decomposition and state -space synthesis techniques are proposed. The employment of only a few geometric-mean cells and grounded capacitors permits the circuits to absorb shunt parasitic capacitances, which is desirable for production in monolithic form . The circuits enjoy the features of electronic adjustment of frequency characteristics, wider dynamic range and low-voltage environment operation. The filters are employed to design high-order all-pass filters using cascade approach. First-order low-pass and second-order band-pass filters, being the inherited building blocks of the proposed low-order all-pass filters are also discussed. The behaviour of the filters is evaluated through simulations using Taiwan semiconductor manufacturing company 0.25 μm level-3 complementary metal oxide semiconductor process parameters, where the most important performance factors are considered.

Thermal domains in inhomogeneous current-carrying superconductors. Current-voltage characteriscs and dynamics of domain formation after current jumps

International Nuclear Information System (INIS)

Bezuglyj, A.I.; Shklovskij, V.A.

1984-01-01

The static and dynamic behavior of thermal domains in inhomogeneous superconducting films, where the inhomogeneity behaves like a portion of the film with a reduced critical current, have been studied theoretically within the framework of the phenomenological approach, using the heat balance equation and the dependence of the superconductor critical current on temperature. Depending on the size of the inhomogeneity (local or extended) and on the relative values of parameters of the homogeneous and inhomogeneous regions, different types of current-voltage characteristics are obtained. The nonstationary problem of thermal domain formation near the inhomogeneity after a current jump has been solved, and the domain boundary (kink) dynamics at a distance from the inhomogeneity has been analyzed. A combination of the results allows one to describe the whole process of normal phase formation and its spread throughout the superconducting film

Mechanism of electromechanical coupling in voltage-gated potassium channels

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Rikard eBlunck

2012-09-01

Full Text Available 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 3-4 e+ 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

Biochemical and structural analysis of the hyperpolarization-activated K(+) channel MVP.

Science.gov (United States)

Randich, Amelia M; Cuello, Luis G; Wanderling, Sherry S; Perozo, Eduardo

2014-03-18

In contrast to the majority of voltage-gated ion channels, hyperpolarization-activated channels remain closed at depolarizing potentials and are activated at hyperpolarizing potentials. The basis for this reverse polarity is thought to be a result of differences in the way the voltage-sensing domain (VSD) couples to the pore domain. In the absence of structural data, the molecular mechanism of this reverse polarity coupling remains poorly characterized. Here we report the characterization of the structure and local dynamics of the closed activation gate (lower S6 region) of MVP, a hyperpolarization-activated potassium channel from Methanococcus jannaschii, by electron paramagnetic resonance (EPR) spectroscopy. We show that a codon-optimized version of MVP has high expression levels in Escherichia coli, is purified as a stable tetramer, and exhibits expected voltage-dependent activity when reconstituted in liposomes. EPR analysis of the mid to lower S6 region revealed positions exhibiting strong spin-spin coupling, indicating that the activation gate of MVP is closed at 0 mV. A comparison of local environmental parameters along the activation gate for MVP and KcsA indicates that MVP adopts a different closed conformation. These structural details set the stage for future evaluations of reverse electromechanical coupling in MVP.

Biochemical and Structural Analysis of the Hyperpolarization-Activated K+ Channel MVP

Science.gov (United States)

2015-01-01

In contrast to the majority of voltage-gated ion channels, hyperpolarization-activated channels remain closed at depolarizing potentials and are activated at hyperpolarizing potentials. The basis for this reverse polarity is thought to be a result of differences in the way the voltage-sensing domain (VSD) couples to the pore domain. In the absence of structural data, the molecular mechanism of this reverse polarity coupling remains poorly characterized. Here we report the characterization of the structure and local dynamics of the closed activation gate (lower S6 region) of MVP, a hyperpolarization-activated potassium channel from Methanococcus jannaschii, by electron paramagnetic resonance (EPR) spectroscopy. We show that a codon-optimized version of MVP has high expression levels in Escherichia coli, is purified as a stable tetramer, and exhibits expected voltage-dependent activity when reconstituted in liposomes. EPR analysis of the mid to lower S6 region revealed positions exhibiting strong spin–spin coupling, indicating that the activation gate of MVP is closed at 0 mV. A comparison of local environmental parameters along the activation gate for MVP and KcsA indicates that MVP adopts a different closed conformation. These structural details set the stage for future evaluations of reverse electromechanical coupling in MVP. PMID:24490868

Combined distributed Raman and Bragg fiber temperature sensing using incoherent optical frequency domain reflectometry

Directory of Open Access Journals (Sweden)

M. Koeppel

2018-02-01

Full Text Available Optical temperature sensors offer unique features which make them indispensable for key industries such as the energy sector. However, commercially available systems are usually designed to perform either distributed or distinct hot spot temperature measurements since they are restricted to one measurement principle. We have combined two concepts, fiber Bragg grating (FBG temperature sensors and Raman-based distributed temperature sensing (DTS, to overcome these limitations. Using a technique called incoherent optical frequency domain reflectometry (IOFDR, it is possible to cascade several FBGs with the same Bragg wavelength in one fiber and simultaneously perform truly distributed Raman temperature measurements. In our lab we have achieved a standard deviation of 2.5 K or better at a spatial resolution in the order of 1 m with the Raman DTS. We have also carried out a field test in a high-voltage environment with strong magnetic fields where we performed simultaneous Raman and FBG temperature measurements using a single sensor fiber only.

Developing Fast Fluorescent Protein Voltage Sensors by Optimizing FRET Interactions.

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Uhna Sung

Full Text Available FRET (Förster Resonance Energy Transfer-based protein voltage sensors can be useful for monitoring neuronal activity in vivo because the ratio of signals between the donor and acceptor pair reduces common sources of noise such as heart beat artifacts. We improved the performance of FRET based genetically encoded Fluorescent Protein (FP voltage sensors by optimizing the location of donor and acceptor FPs flanking the voltage sensitive domain of the Ciona intestinalis voltage sensitive phosphatase. First, we created 39 different "Nabi1" constructs by positioning the donor FP, UKG, at 8 different locations downstream of the voltage-sensing domain and the acceptor FP, mKO, at 6 positions upstream. Several of these combinations resulted in large voltage dependent signals and relatively fast kinetics. Nabi1 probes responded with signal size up to 11% ΔF/F for a 100 mV depolarization and fast response time constants both for signal activation (~2 ms and signal decay (~3 ms. We improved expression in neuronal cells by replacing the mKO and UKG FRET pair with Clover (donor FP and mRuby2 (acceptor FP to create Nabi2 probes. Nabi2 probes also had large signals and relatively fast time constants in HEK293 cells. In primary neuronal culture, a Nabi2 probe was able to differentiate individual action potentials at 45 Hz.

Smart Sensor for Online Detection of Multiple-Combined Faults in VSD-Fed Induction Motors

Science.gov (United States)

Garcia-Ramirez, Armando G.; Osornio-Rios, Roque A.; Granados-Lieberman, David; Garcia-Perez, Arturo; Romero-Troncoso, Rene J.

2012-01-01

Induction motors fed through variable speed drives (VSD) are widely used in different industrial processes. Nowadays, the industry demands the integration of smart sensors to improve the fault detection in order to reduce cost, maintenance and power consumption. Induction motors can develop one or more faults at the same time that can be produce severe damages. The combined fault identification in induction motors is a demanding task, but it has been rarely considered in spite of being a common situation, because it is difficult to identify two or more faults simultaneously. This work presents a smart sensor for online detection of simple and multiple-combined faults in induction motors fed through a VSD in a wide frequency range covering low frequencies from 3 Hz and high frequencies up to 60 Hz based on a primary sensor being a commercially available current clamp or a hall-effect sensor. The proposed smart sensor implements a methodology based on the fast Fourier transform (FFT), RMS calculation and artificial neural networks (ANN), which are processed online using digital hardware signal processing based on field programmable gate array (FPGA).

VSD a compressor that automatically reduces the power consumption; VSD un compresor que reduce automaticamente el consumo energetico

Energy Technology Data Exchange (ETDEWEB)

De Anda L, Pedro [Atlas Copco, Mexico, D.F. (Mexico)

2001-07-01

With the purpose of verifying the behavior in the demand of air in the different plants Copco Atlas made a sampling of 135 measurements, from which it was concluded, that the air consumption of the plants behaves under three main profiles. In the following graphs the behavior of the demand of air with one color for every day of the week and 24 hours per day. In this sample Profile No. 1 is typical of the industries that work 24 hours a day and have low demand of air at night. This type of profile represents a percentage of 64% of the total of the measurements made. The second profile represents industries that work 5 days per week with two shifts and represents a percentage of 28%. The third profile is typical for applications of fixed consumption during the 5 days of the week, this represents an 8% of the measurements. With the purpose of improving the efficiency in the compressors energy consumption, Atlas Copco has been pioneering in the development of compressors with Variable Speed Drive (VSD), that offers the possibility of adapting with extreme precision the capacity of the compressor to the variable demand of compressed air of the plant. [Spanish] Con la finalidad de verificar el comportamiento en la demanda de aire en las diferentes plantas Atlas Copco realizo un muestreo de 135 mediciones, del cual se concluyo, que el consumo de aire de las plantas se comporta bajo tres perfiles principales. En las siguientes graficas se muestra el comportamiento de la demanda de aire con un color por cada dia de la semana y 24 horas al dia . En esta muestra el Perfil No. 1 es tipico de las Industrias que trabajan las 24 horas del dia y tiene baja demanda de aire en las noches. Este tipo de perfil representa un porcentaje de 64% del total de las mediciones realizadas. El segundo perfil representa industrias que traban 5 dias a la semana con dos turnos y representa un porcentaje de 28%. El tercer perfil estetico para aplicaciones de consumo fijo durante 5 dias a la semana

Frequency-Domain Maximum-Likelihood Estimation of High-Voltage Pulse Transformer Model Parameters

CERN Document Server

Aguglia, D; Martins, C.D.A.

2014-01-01

This paper presents an offline frequency-domain nonlinear and stochastic identification method for equivalent model parameter estimation of high-voltage pulse transformers. Such kinds of transformers are widely used in the pulsed-power domain, and the difficulty in deriving pulsed-power converter optimal control strategies is directly linked to the accuracy of the equivalent circuit parameters. These components require models which take into account electric fields energies represented by stray capacitance in the equivalent circuit. These capacitive elements must be accurately identified, since they greatly influence the general converter performances. A nonlinear frequency-based identification method, based on maximum-likelihood estimation, is presented, and a sensitivity analysis of the best experimental test to be considered is carried out. The procedure takes into account magnetic saturation and skin effects occurring in the windings during the frequency tests. The presented method is validated by experim...

Interfacial evaluation and hydrophobicity of multi-functional Ni-nanopowder/epoxy composites for self-sensing and actuation

International Nuclear Information System (INIS)

Park, Joung-Man; Wang, Zuo-Jia; Kwon, Dong-Jun; Jang, Jung-Hoon; DeVries, K Lawrence

2010-01-01

Electrical and interfacial properties of Ni-nanopowder/epoxy composites were investigated for self-sensing and actuation. Contact resistance and electrical resistivity were measured using a micro-specimen with a gradient grid of electrical contact on its length. The specimens' self-sensing characteristics were monitored reasonably well under applied cyclic loading. Actuation in an electromagnetic field was evaluated by measurement of induced strain for three wavefunction voltages, i.e. sine, triangular and square. Due to the presence of hydrophobic domains on the heterogeneous surface, the static contact angle of Ni-nanopowder/epoxy composites exhibited hydrophobicity. The specimens responded well in both self-sensing and actuation tests, in electromagnetic fields, due to the intrinsic metallic property of Ni-nanopowder. Displacement of the actuator was evaluated to attain optimum performance as functions of wave type, frequency and voltage. The strain response followed the shape of the applied voltages better, and was much smoother and less erratic for applied voltages with sine and triangular waveforms than it was for voltages with a rectangular waveform. This is attributed to the sudden changes in voltage in the latter case. Such self-sensing and actuation, in conductive Ni-nanopowder/epoxy composites, might find uses in multi-functional composite devices such as biomimetic and micro-size generators

Design and Experimental Verification of a 0.19 V 53 μW 65 nm CMOS Integrated Supply-Sensing Sensor With a Supply-Insensitive Temperature Sensor and an Inductive-Coupling Transmitter for a Self-Powered Bio-sensing System Using a Biofuel Cell.

Science.gov (United States)

Kobayashi, Atsuki; Ikeda, Kei; Ogawa, Yudai; Kai, Hiroyuki; Nishizawa, Matsuhiko; Nakazato, Kazuo; Niitsu, Kiichi

2017-12-01

In this paper, we present a self-powered bio-sensing system with the capability of proximity inductive-coupling communication for supply sensing and temperature monitoring. The proposed bio-sensing system includes a biofuel cell as a power source and a sensing frontend that is associated with the CMOS integrated supply-sensing sensor. The sensor consists of a digital-based gate leakage timer, a supply-insensitive time-domain temperature sensor, and a current-driven inductive-coupling transmitter and achieves low-voltage operation. The timer converts the output voltage from a biofuel cell to frequency. The temperature sensor provides a pulse width modulation (PWM) output that is not dependent on the supply voltage, and the associated inductive-coupling transmitter enables proximity communication. A test chip was fabricated in 65 nm CMOS technology and consumed 53 μW with a supply voltage of 190 mV. The low-voltage-friendly design satisfied the performance targets of each integrated sensor without any trimming. The chips allowed us to successfully demonstrate proximity communication with an asynchronous receiver, and the measurement results show the potential for self-powered operation using biofuel cells. The analysis and experimental verification of the system confirmed their robustness.

Giant piezoelectric voltage coefficient in grain-oriented modified PbTiO3 material.

Science.gov (United States)

Yan, Yongke; Zhou, Jie E; Maurya, Deepam; Wang, Yu U; Priya, Shashank

2016-10-11

A rapid surge in the research on piezoelectric sensors is occurring with the arrival of the Internet of Things. Single-phase oxide piezoelectric materials with giant piezoelectric voltage coefficient (g, induced voltage under applied stress) and high Curie temperature (T c ) are crucial towards providing desired performance for sensing, especially under harsh environmental conditions. Here, we report a grain-oriented (with 95% texture) modified PbTiO 3 ceramic that has a high T c (364 °C) and an extremely large g 33 (115 × 10 -3  Vm N -1 ) in comparison with other known single-phase oxide materials. Our results reveal that self-polarization due to grain orientation along the spontaneous polarization direction plays an important role in achieving large piezoelectric response in a domain motion-confined material. The phase field simulations confirm that the large piezoelectric voltage coefficient g 33 originates from maximized piezoelectric strain coefficient d 33 and minimized dielectric permittivity ɛ 33 in [001]-textured PbTiO 3 ceramics where domain wall motions are absent.

Voltage-Gated Potassium Channels: A Structural Examination of Selectivity and Gating

Science.gov (United States)

Kim, Dorothy M.; Nimigean, Crina M.

2016-01-01

Voltage-gated potassium channels play a fundamental role in the generation and propagation of the action potential. The discovery of these channels began with predictions made by early pioneers, and has culminated in their extensive functional and structural characterization by electrophysiological, spectroscopic, and crystallographic studies. With the aid of a variety of crystal structures of these channels, a highly detailed picture emerges of how the voltage-sensing domain reports changes in the membrane electric field and couples this to conformational changes in the activation gate. In addition, high-resolution structural and functional studies of K+ channel pores, such as KcsA and MthK, offer a comprehensive picture on how selectivity is achieved in K+ channels. Here, we illustrate the remarkable features of voltage-gated potassium channels and explain the mechanisms used by these machines with experimental data. PMID:27141052

ASIC3 Channels Integrate Agmatine and Multiple Inflammatory Signals through the Nonproton Ligand Sensing Domain

Directory of Open Access Journals (Sweden)

Cao Hui

2010-12-01

Full Text Available Abstract Background Acid-sensing ion channels (ASICs have long been known to sense extracellular protons and contribute to sensory perception. Peripheral ASIC3 channels represent natural sensors of acidic and inflammatory pain. We recently reported the use of a synthetic compound, 2-guanidine-4-methylquinazoline (GMQ, to identify a novel nonproton sensing domain in the ASIC3 channel, and proposed that, based on its structural similarity with GMQ, the arginine metabolite agmatine (AGM may be an endogenous nonproton ligand for ASIC3 channels. Results Here, we present further evidence for the physiological correlation between AGM and ASIC3. Among arginine metabolites, only AGM and its analog arcaine (ARC activated ASIC3 channels at neutral pH in a sustained manner similar to GMQ. In addition to the homomeric ASIC3 channels, AGM also activated heteromeric ASIC3 plus ASIC1b channels, extending its potential physiological relevance. Importantly, the process of activation by AGM was highly sensitive to mild acidosis, hyperosmolarity, arachidonic acid (AA, lactic acid and reduced extracellular Ca2+. AGM-induced ASIC3 channel activation was not through the chelation of extracellular Ca2+ as occurs with increased lactate, but rather through a direct interaction with the newly identified nonproton ligand sensing domain. Finally, AGM cooperated with the multiple inflammatory signals to cause pain-related behaviors in an ASIC3-dependent manner. Conclusions Nonproton ligand sensing domain might represent a novel mechanism for activation or sensitization of ASIC3 channels underlying inflammatory pain-sensing under in vivo conditions.

High voltage dc-dc converter with dynamic voltage regulation and decoupling during load-generated arcs

Science.gov (United States)

Shimer, Daniel W.; Lange, Arnold C.

1995-01-01

A high-power power supply produces a controllable, constant high voltage output under varying and arcing loads. The power supply includes a voltage regulator, an inductor, an inverter for producing a high frequency square wave current of alternating polarity, an improved inverter voltage clamping circuit, a step up transformer, an output rectifier for producing a dc voltage at the output of each module, and a current sensor for sensing output current. The power supply also provides dynamic response to varying loads by controlling the voltage regulator duty cycle and circuitry is provided for sensing incipient arc currents at the output of the power supply to simultaneously decouple the power supply circuitry from the arcing load. The power supply includes a plurality of discrete switching type dc--dc converter modules.

High voltage dc--dc converter with dynamic voltage regulation and decoupling during load-generated arcs

Science.gov (United States)

Shimer, D.W.; Lange, A.C.

1995-05-23

A high-power power supply produces a controllable, constant high voltage output under varying and arcing loads. The power supply includes a voltage regulator, an inductor, an inverter for producing a high frequency square wave current of alternating polarity, an improved inverter voltage clamping circuit, a step up transformer, an output rectifier for producing a dc voltage at the output of each module, and a current sensor for sensing output current. The power supply also provides dynamic response to varying loads by controlling the voltage regulator duty cycle and circuitry is provided for sensing incipient arc currents at the output of the power supply to simultaneously decouple the power supply circuitry from the arcing load. The power supply includes a plurality of discrete switching type dc--dc converter modules. 5 Figs.

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

Science.gov (United States)

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

2014-12-23

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

Room temperature direct bonding of LiNbO3 crystal layers and its application to high-voltage optical sensing

International Nuclear Information System (INIS)

Tulli, D; Janner, D; Pruneri, V

2011-01-01

LiNbO 3 is a crystal widely used in photonics and acoustics, for example in electro-optic modulation, nonlinear optical frequency conversion, electric field sensing and surface acoustic wave filtering. It often needs to be combined with other materials and used in thin layers to achieve the adequate device performance. In this paper, we investigate direct bonding of LiNbO 3 crystals with other dielectric materials, such as Si and fused silica (SiO 2 ), and we show that specific surface chemical cleaning, together with Ar or O 2 plasma activation, can be used to increase the surface free energy and achieve effective bonding at room temperature. The resulting hybrid material bonding is very strong, making the dicing and grinding of LiNbO 3 layers as thin as 15 µm possible. To demonstrate the application potentials of the proposed bonding technique, we have fabricated and characterized a high-voltage field sensor with high sensitivity in a domain inverted and bonded LiNbO 3 waveguide substrate

Voltage-gated calcium flux mediates Escherichia coli mechanosensation.

Science.gov (United States)

Bruni, Giancarlo N; Weekley, R Andrew; Dodd, Benjamin J T; Kralj, Joel M

2017-08-29

Electrically excitable cells harness voltage-coupled calcium influx to transmit intracellular signals, typically studied in neurons and cardiomyocytes. Despite intense study in higher organisms, investigations of voltage and calcium signaling in bacteria have lagged due to their small size and a lack of sensitive tools. Only recently were bacteria shown to modulate their membrane potential on the timescale of seconds, and little is known about the downstream effects from this modulation. In this paper, we report on the effects of electrophysiology in individual bacteria. A genetically encoded calcium sensor expressed in Escherichia coli revealed calcium transients in single cells. A fusion sensor that simultaneously reports voltage and calcium indicated that calcium influx is induced by voltage depolarizations, similar to metazoan action potentials. Cytoplasmic calcium levels and transients increased upon mechanical stimulation with a hydrogel, and single cells altered protein concentrations dependent on the mechanical environment. Blocking voltage and calcium flux altered mechanically induced changes in protein concentration, while inducing calcium flux reproduced these changes. Thus, voltage and calcium relay a bacterial sense of touch and alter cellular lifestyle. Although the calcium effectors remain unknown, these data open a host of new questions about E. coli , including the identity of the underlying molecular players, as well as other signals conveyed by voltage and calcium. These data also provide evidence that dynamic voltage and calcium exists as a signaling modality in the oldest domain of life, and therefore studying electrophysiology beyond canonical electrically excitable cells could yield exciting new findings.

Crystal structure of the cytoplasmic phosphatase and tensin homolog (PTEN)-like region of Ciona intestinalis voltage-sensing phosphatase provides insight into substrate specificity and redox regulation of the phosphoinositide phosphatase activity.

Science.gov (United States)

Matsuda, Makoto; Takeshita, Kohei; Kurokawa, Tatsuki; Sakata, Souhei; Suzuki, Mamoru; Yamashita, Eiki; Okamura, Yasushi; Nakagawa, Atsushi

2011-07-01

Ciona intestinalis voltage-sensing phosphatase (Ci-VSP) has a transmembrane voltage sensor domain and a cytoplasmic region sharing similarity to the phosphatase and tensin homolog (PTEN). It dephosphorylates phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate upon membrane depolarization. The cytoplasmic region is composed of a phosphatase domain and a putative membrane interaction domain, C2. Here we determined the crystal structures of the Ci-VSP cytoplasmic region in three distinct constructs, wild-type (248-576), wild-type (236-576), and G365A mutant (248-576). The crystal structure of WT-236 and G365A-248 had the disulfide bond between the catalytic residue Cys-363 and the adjacent residue Cys-310. On the other hand, the disulfide bond was not present in the crystal structure of WT-248. These suggest the possibility that Ci-VSP is regulated by reactive oxygen species as found in PTEN. These structures also revealed that the conformation of the TI loop in the active site of the Ci-VSP cytoplasmic region was distinct from the corresponding region of PTEN; Ci-VSP has glutamic acid (Glu-411) in the TI loop, orienting toward the center of active site pocket. Mutation of Glu-411 led to acquirement of increased activity toward phosphatidylinositol 3,5-bisphosphate, suggesting that this site is required for determining substrate specificity. Our results provide the basic information of the enzymatic mechanism of Ci-VSP.

Specific expression of the human voltage-gated proton channel Hv1 in highly metastatic breast cancer cells, promotes tumor progression and metastasis

International Nuclear Information System (INIS)

Wang, Yifan; Li, Shu Jie; Pan, Juncheng; Che, Yongzhe; Yin, Jian; Zhao, Qing

2011-01-01

Highlights: → Hv1 is specifically expressed in highly metastatic human breast tumor tissues. → Hv1 regulates breast cancer cytosolic pH. → Hv1 acidifies extracellular milieu. → Hv1 exacerbates the migratory ability of metastatic cells. -- Abstract: The newly discovered human voltage-gated proton channel Hv1 is essential for proton transfer, which contains a voltage sensor domain (VSD) without a pore domain. We report here for the first time that Hv1 is specifically expressed in the highly metastatic human breast tumor tissues, but not in poorly metastatic breast cancer tissues, detected by immunohistochemistry. Meanwhile, real-time RT-PCR and immunocytochemistry showed that the expression levels of Hv1 have significant differences among breast cancer cell lines, MCF-7, MDA-MB-231, MDA-MB-468, MDA-MB-453, T-47D and SK-BR-3, in which Hv1 is expressed at a high level in highly metastatic human breast cancer cell line MDA-MB-231, but at a very low level in poorly metastatic human breast cancer cell line MCF-7. Inhibition of Hv1 expression in the highly metastatic MDA-MB-231 cells by small interfering RNA (siRNA) significantly decreases the invasion and migration of the cells. The intracellular pH of MDA-MB-231 cells down-regulated Hv1 expression by siRNA is obviously decreased compared with MDA-MB-231 with the scrambled siRNA. The expression of matrix metalloproteinase-2 and gelatinase activity in MDA-MB-231 cells suppressed Hv1 by siRNA were reduced. Our results strongly suggest that Hv1 regulates breast cancer intracellular pH and exacerbates the migratory ability of metastatic cells.

Statistical identification of stimulus-activated network nodes in multi-neuron voltage-sensitive dye optical recordings.

Science.gov (United States)

Fathiazar, Elham; Anemuller, Jorn; Kretzberg, Jutta

2016-08-01

Voltage-Sensitive Dye (VSD) imaging is an optical imaging method that allows measuring the graded voltage changes of multiple neurons simultaneously. In neuroscience, this method is used to reveal networks of neurons involved in certain tasks. However, the recorded relative dye fluorescence changes are usually low and signals are superimposed by noise and artifacts. Therefore, establishing a reliable method to identify which cells are activated by specific stimulus conditions is the first step to identify functional networks. In this paper, we present a statistical method to identify stimulus-activated network nodes as cells, whose activities during sensory network stimulation differ significantly from the un-stimulated control condition. This method is demonstrated based on voltage-sensitive dye recordings from up to 100 neurons in a ganglion of the medicinal leech responding to tactile skin stimulation. Without relying on any prior physiological knowledge, the network nodes identified by our statistical analysis were found to match well with published cell types involved in tactile stimulus processing and to be consistent across stimulus conditions and preparations.

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

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Ana Laura Sanchez-Sandoval

Full Text Available 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.

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

Science.gov (United States)

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

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

Science.gov (United States)

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.

Lipid-protein nanodiscs for cell-free production of integral membrane proteins in a soluble and folded state: comparison with detergent micelles, bicelles and liposomes.

Science.gov (United States)

Lyukmanova, E N; Shenkarev, Z O; Khabibullina, N F; Kopeina, G S; Shulepko, M A; Paramonov, A S; Mineev, K S; Tikhonov, R V; Shingarova, L N; Petrovskaya, L E; Dolgikh, D A; Arseniev, A S; Kirpichnikov, M P

2012-03-01

Production of integral membrane proteins (IMPs) in a folded state is a key prerequisite for their functional and structural studies. In cell-free (CF) expression systems membrane mimicking components could be added to the reaction mixture that promotes IMP production in a soluble form. Here lipid-protein nanodiscs (LPNs) of different lipid compositions (DMPC, DMPG, POPC, POPC/DOPG) have been compared with classical membrane mimicking media such as detergent micelles, lipid/detergent bicelles and liposomes by their ability to support CF synthesis of IMPs in a folded and soluble state. Three model membrane proteins of different topology were used: homodimeric transmembrane (TM) domain of human receptor tyrosine kinase ErbB3 (TM-ErbB3, 1TM); voltage-sensing domain of K(+) channel KvAP (VSD, 4TM); and bacteriorhodopsin from Exiguobacterium sibiricum (ESR, 7TM). Structural and/or functional properties of the synthesized proteins were analyzed. LPNs significantly enhanced synthesis of the IMPs in a soluble form regardless of the lipid composition. A partial disintegration of LPNs composed of unsaturated lipids was observed upon co-translational IMP incorporation. Contrary to detergents the nanodiscs resulted in the synthesis of ~80% active ESR and promoted correct folding of the TM-ErbB3. None of the tested membrane mimetics supported CF synthesis of correctly folded VSD, and the protocol of the domain refolding was developed. The use of LPNs appears to be the most promising approach to CF production of IMPs in a folded state. NMR analysis of (15)N-Ile-TM-ErbB3 co-translationally incorporated into LPNs shows the great prospects of this membrane mimetics for structural studies of IMPs produced by CF systems. Copyright © 2011 Elsevier B.V. All rights reserved.

Large scale 2D spectral compressed sensing in continuous domain

KAUST Repository

Cai, Jian-Feng

2017-06-20

We consider the problem of spectral compressed sensing in continuous domain, which aims to recover a 2-dimensional spectrally sparse signal from partially observed time samples. The signal is assumed to be a superposition of s complex sinusoids. We propose a semidefinite program for the 2D signal recovery problem. Our model is able to handle large scale 2D signals of size 500 × 500, whereas traditional approaches only handle signals of size around 20 × 20.

Large scale 2D spectral compressed sensing in continuous domain

KAUST Repository

Cai, Jian-Feng; Xu, Weiyu; Yang, Yang

2017-01-01

We consider the problem of spectral compressed sensing in continuous domain, which aims to recover a 2-dimensional spectrally sparse signal from partially observed time samples. The signal is assumed to be a superposition of s complex sinusoids. We propose a semidefinite program for the 2D signal recovery problem. Our model is able to handle large scale 2D signals of size 500 × 500, whereas traditional approaches only handle signals of size around 20 × 20.

Bi-Directional Brillouin Optical Time Domain Analyzer System for Long Range Distributed Sensing

Science.gov (United States)

Guo, Nan; Wang, Liang; Wang, Jie; Jin, Chao; Tam, Hwa-Yaw; Zhang, A. Ping; Lu, Chao

2016-01-01

We propose and experimentally demonstrate a novel scheme of bi-directional Brillouin time domain analyzer (BD-BOTDA) to extend the sensing range. By deploying two pump-probe pairs at two different wavelengths, the Brillouin frequency shift (BFS) distribution over each half of the whole fiber can be obtained with the simultaneous detection of Brillouin signals in both channels. Compared to the conventional unidirectional BOTDA system of the same sensing range, the proposed BD-BOTDA scheme enables distributed sensing with a performance level comparable to the conventional one with half of the sensing range and a spatial resolution of 2 m, while maintaining the Brillouin signal-to-noise ratio (SNR) and the BFS uncertainty. Based on this technique, we have achieved distributed temperature sensing with a measurement range of 81.9 km fiber at a spatial resolution of 2 m and BFS uncertainty of ~0.44 MHz without introducing any complicated components or schemes. PMID:27999250

Bi-Directional Brillouin Optical Time Domain Analyzer System for Long Range Distributed Sensing.

Science.gov (United States)

Guo, Nan; Wang, Liang; Wang, Jie; Jin, Chao; Tam, Hwa-Yaw; Zhang, A Ping; Lu, Chao

2016-12-16

We propose and experimentally demonstrate a novel scheme of bi-directional Brillouin time domain analyzer (BD-BOTDA) to extend the sensing range. By deploying two pump-probe pairs at two different wavelengths, the Brillouin frequency shift (BFS) distribution over each half of the whole fiber can be obtained with the simultaneous detection of Brillouin signals in both channels. Compared to the conventional unidirectional BOTDA system of the same sensing range, the proposed BD-BOTDA scheme enables distributed sensing with a performance level comparable to the conventional one with half of the sensing range and a spatial resolution of 2 m, while maintaining the Brillouin signal-to-noise ratio (SNR) and the BFS uncertainty. Based on this technique, we have achieved distributed temperature sensing with a measurement range of 81.9 km fiber at a spatial resolution of 2 m and BFS uncertainty of ~0.44 MHz without introducing any complicated components or schemes.

Assessing Agricultural Drought Vulnerability by a VSD Model: A Case Study in Yunnan Province, China

Directory of Open Access Journals (Sweden)

Jiansheng Wu

2017-05-01

Full Text Available Drought vulnerability of agriculture is significant to economic development and sustainable food production. In this paper, we proposed a framework to evaluate the regional agricultural-eco environment in the face of drought caused by climate change. Based on a vulnerability scoping diagram (VSD model, we built up a comprehensive system to evaluate the agricultural drought vulnerability of Yunnan Province in China. The model highlights the human-land relationship by considering both natural conditions and human activities. Twelve indicators were generated to construct three components of the model: exposure, sensitivity, and adaptive capacity. During the construction of the VSD model, the entropy and the analytic hierarchy process (AHP comprehensive analysis method were adopted to generate the weights and to compute the composite index for each section. Furthermore, the factor analysis method was used to determine the dominant factors of different cities and the main indicators driving the system. The results indicated a spatial pattern that the vulnerability value was high on the eastern and western sides, but low in the middle of Yunnan Province. Most of the vulnerable regions were concentrated in remote areas. Indicators such as population density, irrigation level, annual average precipitation, cultivation land ratio, and difficulty of water supply were the main driving factors. This means that there is a deep connection between agricultural drought vulnerability and urbanization. The evaluation system developed during this research will provide guidance for drought mitigation in regions of complex terrain.

Electrostatic force microscopy with a self-sensing piezoresistive cantilever

International Nuclear Information System (INIS)

Pi, U. H.; Kye, J. I.; Shin, S.; Khim, Z. G.; Hong, J. W.; Yoon, S.

2003-01-01

We present a new method for electrostatic force microscopy (EFM) using a piezoresistive cantilever instead of the conventional cantilever with an optical detector. In EFM with a piezoresistive cantilever, the electrostatic force between the tip and the sample is monitored by sensing the change in the resistance of the piezoresistive cantilever at a frequency of several tens of kHz. A large stray capacitance effect can be rejected by using an appropriate phase tuning of the phase-sensitive detection. We observed the ferroelectric domain images of a triglycine sulfate single crystal. We could also write fine patterns on a lead-zirconate-titanate (PZT) thin film through domain reversal by applying various dc voltages between the tip and the sample. We suggest that the EFM technique using a self-sensing and self-actuating piezoresistive cantilever can be applied to a high-density data storage field

Nanosecond Characterization of Regional Domain Imprint from Fast Domain Switching Currents in Pb(Zr,Ti)O_3 Thin Films

International Nuclear Information System (INIS)

Jun Jiang; An-Quan Jiang

2016-01-01

The traditional imprint characterization of ferroelectric thin films estimates imprint time dependence of the mean coercive voltage of all domains from a polarization-voltage hysteresis loop, which shows a semilogarithmic time dependence above an initial imprint time of τ_0 > 1 μs at room temperature. Below τ_0, the imprint effect is believed to be weak. In consideration of region-by-region domain reversal under a rising pulsed voltage with ordered coercive voltages increasing from zero up to the maximum applied voltage during capacitor charging time, we can estimate the imprinted coercive voltage of each domain from domain switching current transient separately with imprint time as short as 20 ns. In disagreement with the previous observations, all imprinted coercive voltages for the domains in Pt/Pb(Zr_0_._4Ti_0_._6)O_3/Pt thin-film capacitors show step-like increases at two characteristic times of 300 ns and 0.27s. The imprint effect is surprisingly strong enough even at shortened time down to 20 ns without any evidence of weakening. (paper)

Mechanistic studies of the genetically encoded fluorescent protein voltage probe ArcLight.

Directory of Open Access Journals (Sweden)

Zhou Han

Full Text Available ArcLight, a genetically encoded fluorescent protein voltage probe with a large ΔF/ΔV, is a fusion between the voltage sensing domain of the Ciona instestinalis voltage sensitive phosphatase and super ecliptic pHluorin carrying a single mutation (A227D in the fluorescent protein. Without this mutation the probe produces only a very small change in fluorescence in response to voltage deflections (∼ 1%. The large signal afforded by this mutation allows optical detection of action potentials and sub-threshold electrical events in single-trials in vitro and in vivo. However, it is unclear how this single mutation produces a probe with such a large modulation of its fluorescence output with changes in membrane potential. In this study, we identified which residues in super ecliptic pHluorin (vs eGFP are critical for the ArcLight response, as a similarly constructed probe based on eGFP also exhibits large response amplitude if it carries these critical residues. We found that D147 is responsible for determining the pH sensitivity of the fluorescent protein used in these probes but by itself does not result in a voltage probe with a large signal. We also provide evidence that the voltage dependent signal of ArcLight is not simply sensing environmental pH changes. A two-photon polarization microscopy study showed that ArcLight's response to changes in membrane potential includes a reorientation of the super ecliptic pHluorin. We also explored different changes including modification of linker length, deletion of non-essential amino acids in the super ecliptic pHluorin, adding a farnesylation site, using tandem fluorescent proteins and other pH sensitive fluorescent proteins.

Structural Refinement of Proteins by Restrained Molecular Dynamics Simulations with Non-interacting Molecular Fragments.

Directory of Open Access Journals (Sweden)

Rong Shen

2015-10-01

Full Text Available The knowledge of multiple conformational states is a prerequisite to understand the function of membrane transport proteins. Unfortunately, the determination of detailed atomic structures for all these functionally important conformational states with conventional high-resolution approaches is often difficult and unsuccessful. In some cases, biophysical and biochemical approaches can provide important complementary structural information that can be exploited with the help of advanced computational methods to derive structural models of specific conformational states. In particular, functional and spectroscopic measurements in combination with site-directed mutations constitute one important source of information to obtain these mixed-resolution structural models. A very common problem with this strategy, however, is the difficulty to simultaneously integrate all the information from multiple independent experiments involving different mutations or chemical labels to derive a unique structural model consistent with the data. To resolve this issue, a novel restrained molecular dynamics structural refinement method is developed to simultaneously incorporate multiple experimentally determined constraints (e.g., engineered metal bridges or spin-labels, each treated as an individual molecular fragment with all atomic details. The internal structure of each of the molecular fragments is treated realistically, while there is no interaction between different molecular fragments to avoid unphysical steric clashes. The information from all the molecular fragments is exploited simultaneously to constrain the backbone to refine a three-dimensional model of the conformational state of the protein. The method is illustrated by refining the structure of the voltage-sensing domain (VSD of the Kv1.2 potassium channel in the resting state and by exploring the distance histograms between spin-labels attached to T4 lysozyme. The resulting VSD structures are in good

New types of time domain reflectometry sensing waveguides for bridge scour monitoring

Science.gov (United States)

Lin, Chih-Ping; Wang, Kai; Chung, Chih-Chung; Weng, Yu-Wen

2017-07-01

Scour is a major threat to bridge safety, especially in harsh fluvial environments. Real-time monitoring of bridge scour is still very limited due to the lack of robust and economic scour monitoring device. Time domain reflectometry (TDR) is an emerging waveguide-based technique holding great promise to develop more durable scour monitoring devices. This study presents new types of TDR sensing waveguides in forms of either sensing rod or sensing wire, taking into account of the measurement range, durability, and ease of field installation. The sensing rod is composed of a hollow grooved steel rod paired up with a metal strip on the insulating groove, while the sensing wire consists of two steel strands with one of them coated with an insulating jacket. The measurement sensitivity is inevitably sacrificed when other properties such as the measurement range, field durability, and installation easiness are enhanced. Factors affecting the measurement sensitivity were identified and experimentally evaluated for better arranging the waveguide conductors. A data reduction method for scour-depth estimation without the need for identifying the sediment/water reflection and a two-step calibration procedure for rating propagation velocities were proposed to work with the new types of TDR sensing waveguides. Both the calibration procedure and the data reduction method were experimentally validated. The test results indicated that the new TDR sensing waveguide provides accurate scour depth measurements regardless of the sacrificed sensitivity. The insulating coating of the new TDR sensing waveguide was also demonstrated to be effective in extending the measurement range up to at least 15 m.

Mapping the interaction site for the tarantula toxin hainantoxin-IV (β-TRTX-Hn2a) in the voltage sensor module of domain II of voltage-gated sodium channels.

Science.gov (United States)

Cai, Tianfu; Luo, Ji; Meng, Er; Ding, Jiuping; Liang, Songping; Wang, Sheng; Liu, Zhonghua

2015-06-01

Peptide toxins often have pharmacological applications and are powerful tools for investigating the structure-function relationships of voltage-gated sodium channels (VGSCs). Although a group of potential VGSC inhibitors have been reported from tarantula venoms, little is known about the mechanism of their interaction with VGSCs. In this study, we showed that hainantoxin-IV (β-TRTX-Hn2a, HNTX-IV in brief), a 35-residue peptide from Ornithoctonus hainana venom, preferentially inhibited rNav1.2, rNav1.3 and hNav1.7 compared with rNav1.4 and hNav1.5. hNav1.7 was the most sensitive to HNTX-IV (IC50∼21nM). In contrast to many other tarantula toxins that affect VGSCs, HNTX-IV at subsaturating concentrations did not alter activation and inactivation kinetics in the physiological range of voltages, while very large depolarization above +70mV could partially activate toxin-bound hNav1.7 channel, indicating that HNTX-IV acts as a gating modifier rather than a pore blocker. Site-directed mutagenesis indicated that the toxin bound to site 4, which was located on the extracellular S3-S4 linker of hNav1.7 domain II. Mutants E753Q, D816N and E818Q of hNav1.7 decreased toxin affinity for hNav1.7 by 2.0-, 3.3- and 130-fold, respectively. In silico docking indicated that a three-toed claw substructure formed by residues with close contacts in the interface between HNTX-IV and hNav1.7 domain II stabilized the toxin-channel complex, impeding movement of the domain II voltage sensor and inhibiting hNav1.7 activation. Our data provide structural details for structure-based drug design and a useful template for the design of highly selective inhibitors of a specific subtype of VGSCs. Copyright © 2014 Elsevier Inc. All rights reserved.

Optical image encryption using chaos-based compressed sensing and phase-shifting interference in fractional wavelet domain

Science.gov (United States)

Liu, Qi; Wang, Ying; Wang, Jun; Wang, Qiong-Hua

2018-02-01

In this paper, a novel optical image encryption system combining compressed sensing with phase-shifting interference in fractional wavelet domain is proposed. To improve the encryption efficiency, the volume data of original image are decreased by compressed sensing. Then the compacted image is encoded through double random phase encoding in asymmetric fractional wavelet domain. In the encryption system, three pseudo-random sequences, generated by three-dimensional chaos map, are used as the measurement matrix of compressed sensing and two random-phase masks in the asymmetric fractional wavelet transform. It not only simplifies the keys to storage and transmission, but also enhances our cryptosystem nonlinearity to resist some common attacks. Further, holograms make our cryptosystem be immune to noises and occlusion attacks, which are obtained by two-step-only quadrature phase-shifting interference. And the compression and encryption can be achieved in the final result simultaneously. Numerical experiments have verified the security and validity of the proposed algorithm.

High-fidelity optical reporting of neuronal electrical activity with an ultrafast fluorescent voltage sensor

Science.gov (United States)

St-Pierre, François; Marshall, Jesse D; Yang, Ying; Gong, Yiyang; Schnitzer, Mark J; Lin, Michael Z

2015-01-01

Accurate optical reporting of electrical activity in genetically defined neuronal populations is a long-standing goal in neuroscience. Here we describe Accelerated Sensor of Action Potentials 1 (ASAP1), a novel voltage sensor design in which a circularly permuted green fluorescent protein is inserted within an extracellular loop of a voltage-sensing domain, rendering fluorescence responsive to membrane potential. ASAP1 demonstrates on- and off- kinetics of 2.1 and 2.0 ms, reliably detects single action potentials and subthreshold potential changes, and tracks trains of action potential waveforms up to 200 Hz in single trials. With a favorable combination of brightness, dynamic range, and speed, ASAP1 enables continuous monitoring of membrane potential in neurons at KHz frame rates using standard epifluorescence microscopy. PMID:24755780

A voltage-sensitive dye-based assay for the identification of differentiated neurons derived from embryonic neural stem cell cultures.

Directory of Open Access Journals (Sweden)

Richardson N Leão

Full Text Available BACKGROUND: Pluripotent and multipotent stem cells hold great therapeutical promise for the replacement of degenerated tissue in neurological diseases. To fulfill that promise we have to understand the mechanisms underlying the differentiation of multipotent cells into specific types of neurons. Embryonic stem cell (ESC and embryonic neural stem cell (NSC cultures provide a valuable tool to study the processes of neural differentiation, which can be assessed using immunohistochemistry, gene expression, Ca(2+-imaging or electrophysiology. However, indirect methods such as protein and gene analysis cannot provide direct evidence of neuronal functionality. In contrast, direct methods such as electrophysiological techniques are well suited to produce direct evidence of neural functionality but are limited to the study of a few cells on a culture plate. METHODOLOGY/PRINCIPAL FINDINGS: In this study we describe a novel method for the detection of action potential-capable neurons differentiated from embryonic NSC cultures using fast voltage-sensitive dyes (VSD. We found that the use of extracellularly applied VSD resulted in a more detailed labeling of cellular processes compared to calcium indicators. In addition, VSD changes in fluorescence translated precisely to action potential kinetics as assessed by the injection of simulated slow and fast sodium currents using the dynamic clamp technique. We further demonstrate the use of a finite element model of the NSC culture cover slip for optimizing electrical stimulation parameters. CONCLUSIONS/SIGNIFICANCE: Our method allows for a repeatable fast and accurate stimulation of neurons derived from stem cell cultures to assess their differentiation state, which is capable of monitoring large amounts of cells without harming the overall culture.

Cholesterol trafficking and raft-like membrane domain composition mediate scavenger receptor class B type 1-dependent lipid sensing in intestinal epithelial cells.

Science.gov (United States)

Morel, Etienne; Ghezzal, Sara; Lucchi, Géraldine; Truntzer, Caroline; Pais de Barros, Jean-Paul; Simon-Plas, Françoise; Demignot, Sylvie; Mineo, Chieko; Shaul, Philip W; Leturque, Armelle; Rousset, Monique; Carrière, Véronique

2018-02-01

Scavenger receptor Class B type 1 (SR-B1) is a lipid transporter and sensor. In intestinal epithelial cells, SR-B1-dependent lipid sensing is associated with SR-B1 recruitment in raft-like/ detergent-resistant membrane domains and interaction of its C-terminal transmembrane domain with plasma membrane cholesterol. To clarify the initiating events occurring during lipid sensing by SR-B1, we analyzed cholesterol trafficking and raft-like domain composition in intestinal epithelial cells expressing wild-type SR-B1 or the mutated form SR-B1-Q445A, defective in membrane cholesterol binding and signal initiation. These features of SR-B1 were found to influence both apical cholesterol efflux and intracellular cholesterol trafficking from plasma membrane to lipid droplets, and the lipid composition of raft-like domains. Lipidomic analysis revealed likely participation of d18:0/16:0 sphingomyelin and 16:0/0:0 lysophosphatidylethanolamine in lipid sensing by SR-B1. Proteomic analysis identified proteins, whose abundance changed in raft-like domains during lipid sensing, and these included molecules linked to lipid raft dynamics and signal transduction. These findings provide new insights into the role of SR-B1 in cellular cholesterol homeostasis and suggest molecular links between SR-B1-dependent lipid sensing and cell cholesterol and lipid droplet dynamics. Copyright © 2017 Elsevier B.V. All rights reserved.

Field-driven sense elements for chirality-dependent domain wall detection and storage

Energy Technology Data Exchange (ETDEWEB)

Bowden, S. R. [Center for Nanoscale Science and Technology, National Institute of Standards and Technology, Gaithersburg, Maryland 20899 (United States); Maryland Nanocenter, University of Maryland, College Park, Maryland 20742 (United States); Unguris, J. [Center for Nanoscale Science and Technology, National Institute of Standards and Technology, Gaithersburg, Maryland 20899 (United States)

2013-12-14

A method for locally sensing and storing data of transverse domain wall chirality in planar nanowire logic and memory systems is presented. Patterned elements, in close proximity to the nanowires, respond to the asymmetry in the stray field from the domain wall to produce a chirality-dependent response. When a bias field is applied, a stray field-assisted reversal of the element magnetization results in a reversed remanent state, measurable by scanning electron microscopy with polarization analysis (SEMPA). The elements are designed as triangles with tips pointing toward the nanowire, allowing the shape anisotropy to be dominated by the base but having a portion with lower volume and lower energy barrier closest to the domain wall. Micromagnetic modeling assists in the design of the nanowire-triangle systems and experiments using SEMPA confirm the importance of aspect ratio and spacing given a constant bias field magnitude.

Single-channel kinetics of BK (Slo1 channels

Directory of Open Access Journals (Sweden)

Yanyan eGeng

2015-01-01

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

An Amphipathic Helix Directs Cellular Membrane Curvature Sensing and Function of the BAR Domain Protein PICK1.

Science.gov (United States)

Herlo, Rasmus; Lund, Viktor K; Lycas, Matthew D; Jansen, Anna M; Khelashvili, George; Andersen, Rita C; Bhatia, Vikram; Pedersen, Thomas S; Albornoz, Pedro B C; Johner, Niklaus; Ammendrup-Johnsen, Ina; Christensen, Nikolaj R; Erlendsson, Simon; Stoklund, Mikkel; Larsen, Jannik B; Weinstein, Harel; Kjærulff, Ole; Stamou, Dimitrios; Gether, Ulrik; Madsen, Kenneth L

2018-05-15

BAR domains are dimeric protein modules that sense, induce, and stabilize lipid membrane curvature. Here, we show that membrane curvature sensing (MCS) directs cellular localization and function of the BAR domain protein PICK1. In PICK1, and the homologous proteins ICA69 and arfaptin2, we identify an amphipathic helix N-terminal to the BAR domain that mediates MCS. Mutational disruption of the helix in PICK1 impaired MCS without affecting membrane binding per se. In insulin-producing INS-1E cells, super-resolution microscopy revealed that disruption of the helix selectively compromised PICK1 density on insulin granules of high curvature during their maturation. This was accompanied by reduced hormone storage in the INS-1E cells. In Drosophila, disruption of the helix compromised growth regulation. By demonstrating size-dependent binding on insulin granules, our finding highlights the function of MCS for BAR domain proteins in a biological context distinct from their function, e.g., at the plasma membrane during endocytosis. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

An optical fiber Bragg grating and piezoelectric ceramic voltage sensor

Science.gov (United States)

Yang, Qing; He, Yanxiao; Sun, Shangpeng; Luo, Mandan; Han, Rui

2017-10-01

Voltage measurement is essential in many fields like power grids, telecommunications, metallurgy, railways, and oil production. A voltage-sensing unit, consisting of fiber Bragg gratings (FBGs) and piezoelectric ceramics, based on which an optical over-voltage sensor was proposed and fabricated in this paper. No demodulation devices like spectrometer or Fabry-Perot filter were needed to gain the voltage signal, and a relatively large sensing frequency range was acquired in this paper; thus, the cost of the sensing system is more acceptable in engineering application. The voltage to be measured was directly applied to the piezoelectric ceramic, and deformation of the ceramics and the grating would be caused because of the inverse piezoelectric effect. With a reference grating, the output light intensity change will be caused by the FBG center wavelength change; thus, the relationship between the applied voltage and the output light intensity was established. Validation of the sensor was accomplished in the frequency range from 50 Hz to 20 kHz and switching impulse waves with a test platform; good linearity of the input-output characteristic was achieved. A temperature validation test was completed, showing that the sensor maintains good temperature stability. Experimental results show that the optical over-voltage sensor can be used for voltage monitoring, and if applied with a voltage divider, the sensor can be used to measure high voltage.

An optical fiber Bragg grating and piezoelectric ceramic voltage sensor.

Science.gov (United States)

Yang, Qing; He, Yanxiao; Sun, Shangpeng; Luo, Mandan; Han, Rui

2017-10-01

Voltage measurement is essential in many fields like power grids, telecommunications, metallurgy, railways, and oil production. A voltage-sensing unit, consisting of fiber Bragg gratings (FBGs) and piezoelectric ceramics, based on which an optical over-voltage sensor was proposed and fabricated in this paper. No demodulation devices like spectrometer or Fabry-Perot filter were needed to gain the voltage signal, and a relatively large sensing frequency range was acquired in this paper; thus, the cost of the sensing system is more acceptable in engineering application. The voltage to be measured was directly applied to the piezoelectric ceramic, and deformation of the ceramics and the grating would be caused because of the inverse piezoelectric effect. With a reference grating, the output light intensity change will be caused by the FBG center wavelength change; thus, the relationship between the applied voltage and the output light intensity was established. Validation of the sensor was accomplished in the frequency range from 50 Hz to 20 kHz and switching impulse waves with a test platform; good linearity of the input-output characteristic was achieved. A temperature validation test was completed, showing that the sensor maintains good temperature stability. Experimental results show that the optical over-voltage sensor can be used for voltage monitoring, and if applied with a voltage divider, the sensor can be used to measure high voltage.

Poly-benzyl domains grown on porous silicon and their I-V rectification

International Nuclear Information System (INIS)

Chao Jie; Han Huanmei; Xia Bing; Ba Long; Liu Hongbo; Xiao Shoujun

2007-01-01

Microwave-irradiated polymerization of benzyl chloride and triphenyl chloromethane on hydride-terminated porous silicon (PS) was achieved through the use of Zn powder as a catalyst. Transmission infrared Fourier-transform spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses confirmed the poly-benzyl membranes grafted on PS. Topographical images by AFM revealed crystal-like domains rather than homogenous monolayers on the surface. The current-voltage measurements in nano-scale by current sensing atomic force microscopy (CS-AFM) showed the rectification behavior of this polymer membrane. Finally, mechanism of a radical initiation on the surface and a following Friedel-Crafts alkylation was proposed for the covalent assembly of poly-benzyl domains

Low voltage stress-induced leakage current and traps in ultrathin oxide (1.2 2.5 nm) after constant voltage stresses

Science.gov (United States)

Petit, C.; Zander, D.

2007-10-01

It has been shown that the low voltage gate current in ultrathin oxide metal-oxide-semiconductor devices is very sensitive to electrical stresses. Therefore, it can be used as a reliability monitor when the oxide thickness becomes too small for traditional electrical measurements to be used. In this work, we present a study on n-MOSCAP devices at negative gate bias in the direct tunneling (DT) regime. If the low voltage stress-induced leakage current (LVSILC) depends strongly on the low sense voltages, it also depends strongly on the stress voltage magnitude. We show that two LVSILC peaks appear as a function of the sense voltage in the LVSILC region and that their magnitude, one compared to the other, depends strongly on the stress voltage magnitude. One is larger than the other at low stress voltage and smaller at high stress voltage. From our experimental results, different conduction mechanisms are analyzed. To explain LVSILC variations, we propose a model of the conduction through the ultrathin gate oxide based on two distinctly different trap-assisted tunneling mechanisms: inelastic of gate electron (INE) and trap-assisted electron (ETAT).

Characterization and gas sensing properties of CuO synthesized by DC directly applying voltage

International Nuclear Information System (INIS)

Klinbumrung, Arrak; Thongtem, Titipun; Thongtem, Somchai

2014-01-01

Highlights: • CuO as a p-type semiconductor. • It was synthesized by directly applying voltage. • A promising material for ammonia detection. - Abstract: CuO microstructure was successfully synthesized by 50 A and 3.6 V DC directly applying voltage. Crystalline structure was characterized by X-ray diffraction (XRD), morphology by scanning and transmission electron microscopy (SEM, TEM). The sample of the 15 min processing time has an irregular shape with diameter about several hundreds of nanometer. Fourier transform infrared (FTIR) spectroscopy, ultraviolet–visible (UV–vis) absorption spectroscopy and photoluminescence (PL) were used to determine vibrational modes and optical properties of the as-synthesized samples: 529 and 585 cm −1 vibrational modes, 3.95 eV band gap, and 402 nm emitting wavelength in violet region of CuO. X-ray photoelectron (XPS) spectroscopy was used to determine chemical composition, Cu(II)O, of the metal oxide surface. Gas sensing performance exposing to NH 3 mixed with air at various working temperatures and NH 3 concentrations of the as-synthesized CuO has the best response at the optimal working temperature of 250 °C: sensitivity of 56.6% exposed to 5275 ppm NH 3

Voltage-gated sodium channels in taste bud cells

Directory of Open Access Journals (Sweden)

Williams Mark E

2009-03-01

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

Voltage-gated sodium channels in taste bud cells.

Science.gov (United States)

Gao, Na; Lu, Min; Echeverri, Fernando; Laita, Bianca; Kalabat, Dalia; Williams, Mark E; Hevezi, Peter; Zlotnik, Albert; Moyer, Bryan D

2009-03-12

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

The NH2 terminus regulates voltage-dependent gating of CALHM ion channels.

Science.gov (United States)

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

2017-08-01

Calcium homeostasis modulator protein-1 (CALHM1) and its Caenorhabditis elegans (ce) homolog, CLHM-1, belong to a new family of physiologically important ion channels that are regulated by voltage and extracellular Ca 2+ (Ca 2+ o ) but lack a canonical voltage-sensing domain. Consequently, the intrinsic voltage-dependent gating mechanisms for CALHM channels are unknown. Here, we performed voltage-clamp experiments on ceCLHM-1 chimeric, deletion, insertion, and point mutants to assess the role of the NH 2 terminus (NT) in CALHM channel gating. Analyses of chimeric channels in which the ceCLHM-1 and human (h)CALHM1 NH 2 termini were interchanged showed that the hCALHM1 NT destabilized channel-closed states, whereas the ceCLHM-1 NT had a stabilizing effect. In the absence of Ca 2+ o , deletion of up to eight amino acids from the ceCLHM-1 NT caused a hyperpolarizing shift in the conductance-voltage relationship with little effect on voltage-dependent slope. However, deletion of nine or more amino acids decreased voltage dependence and induced a residual conductance at hyperpolarized voltages. Insertion of amino acids into the NH 2 -terminal helix also decreased voltage dependence but did not prevent channel closure. Mutation of ceCLHM-1 valine 9 and glutamine 13 altered half-maximal activation and voltage dependence, respectively, in 0 Ca 2+ In 2 mM Ca 2+ o , ceCLHM-1 NH 2 -terminal deletion and point mutant channels closed completely at hyperpolarized voltages with apparent affinity for Ca 2+ o indistinguishable from wild-type ceCLHM-1, although the ceCLHM-1 valine 9 mutant exhibited an altered conductance-voltage relationship and kinetics. We conclude that the NT plays critical roles modulating voltage dependence and stabilizing the closed states of CALHM channels. Copyright © 2017 the American Physiological Society.

PLZT light transmittance memory driven with an asymmetric voltage pulse

International Nuclear Information System (INIS)

Inoue, Kazuhiko; Morita, Takeshi

2010-01-01

PLZT is a ferroelectric electro-optic material, which has been operated with a constant voltage supply to keep a certain optical property. In this study, we propose an optical transmittance memory effect by controlling the domain conditions. The keypoint is to use an asymmetric voltage pulse. In the positive direction, a sufficiently-large voltage is applied to align the polarization directions. After this operation, a relatively small light transmittance is memorized even after removing the electric field. On the other hand, in the negative direction, the amplitude of the voltage is adjusted to the coercive electric field. In this condition, the domain structure is almost the same as the depolarization state. With this voltage supply, the maximum light transmittance can be kept after removing the electric field. Using these voltage operations, the PLZT can obtain two light transmittance states depending on the domain structure. This memory effect should be useful for innovative optical scanners or shutters in the future.

Energy-minimum sub-threshold self-timed circuits using current-sensing completion detection

DEFF Research Database (Denmark)

Akgun, O. C.; Rodrigues, J. N.; Sparsø, Jens

2011-01-01

This study addresses the design of self-timed energy-minimum circuits, operating in the sub-VT domain and a generic implementation template using bundled-data circuitry and current sensing completion detection (CSCD). Furthermore, a fully decoupled latch controller was developed, which integrates......V. Spice simulations indicate a gain of 52.58% in throughput because of asynchronous operation. By trading the throughput improvement, energy dissipation is reduced by 16.8% at the energy-minimum supply voltage....

Molecular motions that shape the cardiac action potential: Insights from voltage clamp fluorometry.

Science.gov (United States)

Zhu, Wandi; Varga, Zoltan; Silva, Jonathan R

2016-01-01

Very recently, voltage-clamp fluorometry (VCF) protocols have been developed to observe the membrane proteins responsible for carrying the ventricular ionic currents that form the action potential (AP), including those carried by the cardiac Na(+) channel, NaV1.5, the L-type Ca(2+) channel, CaV1.2, the Na(+)/K(+) ATPase, and the rapid and slow components of the delayed rectifier, KV11.1 and KV7.1. This development is significant, because VCF enables simultaneous observation of ionic current kinetics with conformational changes occurring within specific channel domains. The ability gained from VCF, to connect nanoscale molecular movement to ion channel function has revealed how the voltage-sensing domains (VSDs) control ion flux through channel pores, mechanisms of post-translational regulation and the molecular pathology of inherited mutations. In the future, we expect that this data will be of great use for the creation of multi-scale computational AP models that explicitly represent ion channel conformations, connecting molecular, cell and tissue electrophysiology. Here, we review the VCF protocol, recent results, and discuss potential future developments, including potential use of these experimental findings to create novel computational models. Copyright © 2015 Elsevier Ltd. All rights reserved.

Soil-embedded optical fiber sensing cable interrogated by Brillouin optical time-domain reflectometry (B-OTDR) and optical frequency-domain reflectometry (OFDR) for embedded cavity detection and sinkhole warning system

International Nuclear Information System (INIS)

Lanticq, V; Bourgeois, E; Delepine-Lesoille, S; Magnien, P; Dieleman, L; Vinceslas, G; Sang, A

2009-01-01

A soil-embedded optical fiber sensing cable is evaluated for an embedded cavity detection and sinkhole warning system in railway tunnels. Tests were performed on a decametric structure equipped with an embedded 110 m long fiber optic cable. Both Brillouin optical time-domain reflectometry (B-OTDR) and optical frequency-domain reflectometry (OFDR) sensing techniques were used for cable interrogation, yielding results that were in good qualitative agreement with finite-element calculations. Theoretical and experimental comparison enabled physical interpretation of the influence of ground properties, and the analysis of embedded cavity size and position. A 5 mm embedded cavity located 2 m away from the sensing cable was detected. The commercially available sensing cable remained intact after soil collapse. Specificities of each technique are analyzed in view of the application requirements. For tunnel monitoring, the OFDR technique was determined to be more viable than the B-OTDR due to higher spatial resolution, resulting in better detection and size determination of the embedded cavities. Conclusions of this investigation gave outlines for future field use of distributed strain-sensing methods under railways and more precisely enabled designing a warning system suited to the Ebersviller tunnel specificities

Conversion of Dielectric Data from the Time Domain to the Frequency Domain

Directory of Open Access Journals (Sweden)

Vladimir Durman

2005-01-01

Full Text Available Polarisation and conduction processes in dielectric systems can be identified by the time domain or the frequency domain measurements. If the systems is a linear one, the results of the time domain measurements can be transformed into the frequency domain, and vice versa. Commonly, the time domain data of the absorption conductivity are transformed into the frequency domain data of the dielectric susceptibility. In practice, the relaxation are mainly evaluated by the frequency domain data. In the time domain, the absorption current measurement were prefered up to now. Recent methods are based on the recovery voltage measurements. In this paper a new method of the recovery data conversion from the time the frequency domain is proposed. The method is based on the analysis of the recovery voltage transient based on the Maxwell equation for the current density in a dielectric. Unlike the previous published solutions, the Laplace fransform was used to derive a formula suitable for practical purposes. the proposed procedure allows also calculating of the insulation resistance and separating the polarisation and conduction losses.

An Interesting Case Report of Unexpected VSD Device Embolization and its Challenging Percutaneous Retrieval

Directory of Open Access Journals (Sweden)

Vinod Raghunath Revankar

2015-01-01

Full Text Available Device closure of Ventricular septal defect (VSD is gaining popularity as a preferred method of treatment in suitable patients. The decreased morbidity and mortality associated with the procedure as compared to open heart surgery is the main reason behind this. Device embolization is a dreaded complication that occurs rarely with this procedure. While surgical retrieval of the device is preferred at most centres, the device can be retrieved per cutaneously by employing suitable maneuvers. We are reporting a case where we successfully retrieved an embolized ADOII device in our patient. We intend to emphasize the need for thorough pre operative assessment of the patient before proceeding with device closure in order to prevent this complication from occurring.

Characterization and gas sensing properties of CuO synthesized by DC directly applying voltage

Energy Technology Data Exchange (ETDEWEB)

Klinbumrung, Arrak [Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Thongtem, Titipun [Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Materials Science Research Center, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Thongtem, Somchai, E-mail: schthongtem@yahoo.com [Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Materials Science Research Center, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand)

2014-09-15

Highlights: • CuO as a p-type semiconductor. • It was synthesized by directly applying voltage. • A promising material for ammonia detection. - Abstract: CuO microstructure was successfully synthesized by 50 A and 3.6 V DC directly applying voltage. Crystalline structure was characterized by X-ray diffraction (XRD), morphology by scanning and transmission electron microscopy (SEM, TEM). The sample of the 15 min processing time has an irregular shape with diameter about several hundreds of nanometer. Fourier transform infrared (FTIR) spectroscopy, ultraviolet–visible (UV–vis) absorption spectroscopy and photoluminescence (PL) were used to determine vibrational modes and optical properties of the as-synthesized samples: 529 and 585 cm{sup −1} vibrational modes, 3.95 eV band gap, and 402 nm emitting wavelength in violet region of CuO. X-ray photoelectron (XPS) spectroscopy was used to determine chemical composition, Cu(II)O, of the metal oxide surface. Gas sensing performance exposing to NH{sub 3} mixed with air at various working temperatures and NH{sub 3} concentrations of the as-synthesized CuO has the best response at the optimal working temperature of 250 °C: sensitivity of 56.6% exposed to 5275 ppm NH{sub 3}.

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

Science.gov (United States)

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

Inactivation of Mechanically Activated Piezo1 Ion Channels Is Determined by the C-Terminal Extracellular Domain and the Inner Pore Helix

Directory of Open Access Journals (Sweden)

Jason Wu

2017-11-01

Full Text Available Piezo proteins form mechanically activated ion channels that are responsible for our sense of light touch, proprioception, and vascular blood flow. Upon activation by mechanical stimuli, Piezo channels rapidly inactivate in a voltage-dependent manner through an unknown mechanism. Inactivation of Piezo channels is physiologically important, as it modulates overall mechanical sensitivity, gives rise to frequency filtering of repetitive mechanical stimuli, and is itself the target of numerous human disease-related channelopathies that are not well understood mechanistically. Here, we identify the globular C-terminal extracellular domain as a structure that is sufficient to confer the time course of inactivation and a single positively charged lysine residue at the adjacent inner pore helix as being required for its voltage dependence. Our results are consistent with a mechanism for inactivation that is mediated through voltage-dependent conformations of the inner pore helix and allosteric coupling with the C-terminal extracellular domain.

Domain General Mediators of the Relation between Kindergarten Number Sense and First-Grade Mathematics Achievement

Science.gov (United States)

Hassinger-Das, Brenna; Jordan, Nancy C.; Glutting, Joseph; Irwin, Casey; Dyson, Nancy

2013-01-01

Domain general skills that mediate the relation between kindergarten number sense and first-grade mathematics skills were investigated. Participants were 107 children who displayed low number sense in the fall of kindergarten. Controlling for background variables, multiple regression analyses showed that attention problems and executive functioning both were unique predictors of mathematics outcomes. Attention problems were more important for predicting first-grade calculation performance while executive functioning was more important for predicting first-grade performance on applied problems. Moreover, both executive functioning and attention problems were unique partial mediators of the relationship between kindergarten and first-grade mathematics skills. The results provide empirical support for developing interventions that target executive functioning and attention problems in addition to instruction in number skills for kindergartners with initial low number sense. PMID:24237789

Enhanced current and voltage regulators for stand-alone applications

DEFF Research Database (Denmark)

Federico, de Bosio; Pastorelli, Michele; Antonio DeSouza Ribeiro, Luiz

2016-01-01

State feedback decoupling permits to achieve a better dynamic response for Voltage Source in stand-alone applications. The design of current and voltage regulators is performed in the discrete-time domain since it provides better accuracy and allows direct pole placement. As the attainable...... bandwidth of the current loop is mainly limited by computational and PWM delays, a lead compensator structure is proposed to overcome this limitation. The design of the voltage regulator is based on the Nyquist criterion, verifying to guarantee a high sensitivity peak. Discrete-time domain implementation...

Voltage dependence of a stochastic model of activation of an alpha helical S4 sensor in a K channel membrane

Science.gov (United States)

Vaccaro, S. R.

2011-09-01

The voltage dependence of the ionic and gating currents of a K channel is dependent on the activation barriers of a voltage sensor with a potential function which may be derived from the principal electrostatic forces on an S4 segment in an inhomogeneous dielectric medium. By variation of the parameters of a voltage-sensing domain model, consistent with x-ray structures and biophysical data, the lowest frequency of the survival probability of each stationary state derived from a solution of the Smoluchowski equation provides a good fit to the voltage dependence of the slowest time constant of the ionic current in a depolarized membrane, and the gating current exhibits a rising phase that precedes an exponential relaxation. For each depolarizing potential, the calculated time dependence of the survival probabilities of the closed states of an alpha helical S4 sensor are in accord with an empirical model of the ionic and gating currents recorded during the activation process.

On Transform Domain Communication Systems under Spectrum Sensing Mismatch: A Deterministic Analysis.

Science.gov (United States)

Jin, Chuanxue; Hu, Su; Huang, Yixuan; Luo, Qu; Huang, Dan; Li, Yi; Gao, Yuan; Cheng, Shaochi

2017-07-08

Towards the era of mobile Internet and the Internet of Things (IoT), numerous sensors and devices are being introduced and interconnected. To support such an amount of data traffic, traditional wireless communication technologies are facing challenges both in terms of the increasing shortage of spectrum resources and massive multiple access. The transform-domain communication system (TDCS) is considered as an alternative multiple access system, where 5G and mobile IoT are mainly focused. However, previous studies about TDCS are under the assumption that the transceiver has the global spectrum information, without the consideration of spectrum sensing mismatch (SSM). In this paper, we present the deterministic analysis of TDCS systems under arbitrary given spectrum sensing scenarios, especially the influence of the SSM pattern to the signal to noise ratio (SNR) performance. Simulation results show that arbitrary SSM pattern can lead to inferior bit error rate (BER) performance.

Depolarization of the conductance-voltage relationship in the NaV1.5 mutant, E1784K, is due to altered fast inactivation

Science.gov (United States)

Yu, Alec; Zhu, Wandi; Silva, Jonathan R.; Ruben, Peter C.

2017-01-01

E1784K is the most common mixed long QT syndrome/Brugada syndrome mutant in the cardiac voltage-gated sodium channel NaV1.5. E1784K shifts the midpoint of the channel conductance-voltage relationship to more depolarized membrane potentials and accelerates the rate of channel fast inactivation. The depolarizing shift in the midpoint of the conductance curve in E1784K is exacerbated by low extracellular pH. We tested whether the E1784K mutant shifts the channel conductance curve to more depolarized membrane potentials by affecting the channel voltage-sensors. We measured ionic currents and gating currents at pH 7.4 and pH 6.0 in Xenopus laevis oocytes. Contrary to our expectation, the movement of gating charges is shifted to more hyperpolarized membrane potentials by E1784K. Voltage-clamp fluorimetry experiments show that this gating charge shift is due to the movement of the DIVS4 voltage-sensor being shifted to more hyperpolarized membrane potentials. Using a model and experiments on fast inactivation-deficient channels, we show that changes to the rate and voltage-dependence of fast inactivation are sufficient to shift the conductance curve in E1784K. Our results localize the effects of E1784K to DIVS4, and provide novel insight into the role of the DIV-VSD in regulating the voltage-dependencies of activation and fast inactivation. PMID:28898267

Depolarization of the conductance-voltage relationship in the NaV1.5 mutant, E1784K, is due to altered fast inactivation.

Directory of Open Access Journals (Sweden)

Colin H Peters

Full Text Available E1784K is the most common mixed long QT syndrome/Brugada syndrome mutant in the cardiac voltage-gated sodium channel NaV1.5. E1784K shifts the midpoint of the channel conductance-voltage relationship to more depolarized membrane potentials and accelerates the rate of channel fast inactivation. The depolarizing shift in the midpoint of the conductance curve in E1784K is exacerbated by low extracellular pH. We tested whether the E1784K mutant shifts the channel conductance curve to more depolarized membrane potentials by affecting the channel voltage-sensors. We measured ionic currents and gating currents at pH 7.4 and pH 6.0 in Xenopus laevis oocytes. Contrary to our expectation, the movement of gating charges is shifted to more hyperpolarized membrane potentials by E1784K. Voltage-clamp fluorimetry experiments show that this gating charge shift is due to the movement of the DIVS4 voltage-sensor being shifted to more hyperpolarized membrane potentials. Using a model and experiments on fast inactivation-deficient channels, we show that changes to the rate and voltage-dependence of fast inactivation are sufficient to shift the conductance curve in E1784K. Our results localize the effects of E1784K to DIVS4, and provide novel insight into the role of the DIV-VSD in regulating the voltage-dependencies of activation and fast inactivation.

Direct Interaction between the Voltage Sensors Produces Cooperative Sustained Deactivation in Voltage-gated H+ Channel Dimers*

OpenAIRE

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 ?-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 kineti...

Domain-general mediators of the relation between kindergarten number sense and first-grade mathematics achievement.

Science.gov (United States)

Hassinger-Das, Brenna; Jordan, Nancy C; Glutting, Joseph; Irwin, Casey; Dyson, Nancy

2014-02-01

Domain-general skills that mediate the relation between kindergarten number sense and first-grade mathematics skills were investigated. Participants were 107 children who displayed low number sense in the fall of kindergarten. Controlling for background variables, multiple regression analyses showed that both attention problems and executive functioning were unique predictors of mathematics outcomes. Attention problems were more important for predicting first-grade calculation performance, whereas executive functioning was more important for predicting first-grade performance on applied problems. Moreover, both executive functioning and attention problems were unique partial mediators of the relationship between kindergarten and first-grade mathematics skills. The results provide empirical support for developing interventions that target executive functioning and attention problems in addition to instruction in number skills for kindergartners with initial low number sense. Copyright © 2013 Elsevier Inc. All rights reserved.

VKCDB: Voltage-gated potassium channel database

Directory of Open Access Journals (Sweden)

Gallin Warren J

2004-01-01

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

Bio-Inspired Carbon Monoxide Sensors with Voltage-Activated Sensitivity

KAUST Repository

Savagatrup, Suchol; Schroeder, Vera; He, Xin; Lin, Sibo; He, Maggie; Yassine, Omar; Salama, Khaled N.; Zhang, Xixiang; Swager, Timothy M.

2017-01-01

voltage offers a predicted extra dimension for sensing. Specifically, the sensors show a significant increase in sensitivity toward CO when negative gate voltage is applied. The dosimetric sensors are selective to ppm levels of CO and functional in air. UV

Simplicity and Specificity in Language: Domain-General Biases Have Domain-Specific Effects

Science.gov (United States)

Culbertson, Jennifer; Kirby, Simon

2016-01-01

The extent to which the linguistic system—its architecture, the representations it operates on, the constraints it is subject to—is specific to language has broad implications for cognitive science and its relation to evolutionary biology. Importantly, a given property of the linguistic system can be “specific” to the domain of language in several ways. For example, if the property evolved by natural selection under the pressure of the linguistic function it serves then the property is domain-specific in the sense that its design is tailored for language. Equally though, if that property evolved to serve a different function or if that property is domain-general, it may nevertheless interact with the linguistic system in a way that is unique. This gives a second sense in which a property can be thought of as specific to language. An evolutionary approach to the language faculty might at first blush appear to favor domain-specificity in the first sense, with individual properties of the language faculty being specifically linguistic adaptations. However, we argue that interactions between learning, culture, and biological evolution mean any domain-specific adaptations that evolve will take the form of weak biases rather than hard constraints. Turning to the latter sense of domain-specificity, we highlight a very general bias, simplicity, which operates widely in cognition and yet interacts with linguistic representations in domain-specific ways. PMID:26793132

Edge Detection from High Resolution Remote Sensing Images using Two-Dimensional log Gabor Filter in Frequency Domain

International Nuclear Information System (INIS)

Wang, K; Yu, T; Meng, Q Y; Wang, G K; Li, S P; Liu, S H

2014-01-01

Edges are vital features to describe the structural information of images, especially high spatial resolution remote sensing images. Edge features can be used to define the boundaries between different ground objects in high spatial resolution remote sensing images. Thus edge detection is important in the remote sensing image processing. Even though many different edge detection algorithms have been proposed, it is difficult to extract the edge features from high spatial resolution remote sensing image including complex ground objects. This paper introduces a novel method to detect edges from the high spatial resolution remote sensing image based on frequency domain. Firstly, the high spatial resolution remote sensing images are Fourier transformed to obtain the magnitude spectrum image (frequency image) by FFT. Then, the frequency spectrum is analyzed by using the radius and angle sampling. Finally, two-dimensional log Gabor filter with optimal parameters is designed according to the result of spectrum analysis. Finally, dot product between the result of Fourier transform and the log Gabor filter is inverse Fourier transformed to obtain the detections. The experimental result shows that the proposed algorithm can detect edge features from the high resolution remote sensing image commendably

Voltage Dependence of a Neuromodulator-Activated Ionic Current123

Science.gov (United States)

2016-01-01

Abstract The neuromodulatory inward current (IMI) generated by crab Cancer borealis stomatogastric ganglion neurons is an inward current whose voltage dependence has been shown to be crucial in the activation of oscillatory activity of the pyloric network of this system. It has been previously shown that IMI loses its voltage dependence in conditions of low extracellular calcium, but that this effect appears to be regulated by intracellular calmodulin. Voltage dependence is only rarely regulated by intracellular signaling mechanisms. Here we address the hypothesis that the voltage dependence of IMI is mediated by intracellular signaling pathways activated by extracellular calcium. We demonstrate that calmodulin inhibitors and a ryanodine antagonist can reduce IMI voltage dependence in normal Ca2+, but that, in conditions of low Ca2+, calmodulin activators do not restore IMI voltage dependence. Further, we show evidence that CaMKII alters IMI voltage dependence. These results suggest that calmodulin is necessary but not sufficient for IMI voltage dependence. We therefore hypothesize that the Ca2+/calmodulin requirement for IMI voltage dependence is due to an active sensing of extracellular calcium by a GPCR family calcium-sensing receptor (CaSR) and that the reduction in IMI voltage dependence by a calmodulin inhibitor is due to CaSR endocytosis. Supporting this, preincubation with an endocytosis inhibitor prevented W7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride)-induced loss of IMI voltage dependence, and a CaSR antagonist reduced IMI voltage dependence. Additionally, myosin light chain kinase, which is known to act downstream of the CaSR, seems to play a role in regulating IMI voltage dependence. Finally, a Gβγ-subunit inhibitor also affects IMI voltage dependence, in support of the hypothesis that this process is regulated by a G-protein-coupled CaSR. PMID:27257619

A pragmatic approach to voltage stability analysis of large power systems

Energy Technology Data Exchange (ETDEWEB)

Sarmiento, H.G.; Pampin, G. [Inst. de Investigaciones Electricas, Morelos (Mexico); Diaz de Leon, J.A. [American Superconductor, Middleton, WI (United States)

2008-07-01

A methodology for performing voltage stability analyses for large power systems was presented. Modal and time-domain analyses were used for selection and siting solutions for potential voltage instability and collapse. Steady state systems were used to compute the smallest eigenvalues and associated eigenvalues of a reduced Jacobean matrix. The eigenvalues were used to provide a relative measure of proximity to voltage instability. The analysis was applied to provide an indication of a network's proximity to voltage collapse. Negative eigenvalues were representative of voltage instability conditions, while small positive values indicated proximity to voltage instability. The analysis technique was used to identify buses, lines, and generators prone to voltage instabilities for a 10-node network. A comparative analysis of results obtained from modal and time domain analyses were used to identify areas vulnerable to voltage instability conditions. Pre-fault, fault, and post-fault conditions were analyzed statically and dynamically. Results of the study showed that the combined method can be used to identify and place reactive power compensation solutions for voltage collapses in electric networks. 20 refs., 5 tabs., 7 figs.

Three phase voltage measurements with simple open air sensors

NARCIS (Netherlands)

Heesch, van E.J.M.; Caspers, R.; Gulickx, P.F.M.; Jacobs, G.A.P.; Kersten, W.F.J.; Laan, van der P.C.T.

1991-01-01

A low cost, easy to install high-voltage measuring system is described for open air substations and overhead lines. Based on the Differentiating/Integrating (D/I) principle, three free-standing capacitive pickup electrodes are used to sense the three phase to ground voltages. Apart from the

From Plant Infectivity to Growth Patterns: The Role of Blue-Light Sensing in the Prokaryotic World

Directory of Open Access Journals (Sweden)

Aba Losi

2014-01-01

Full Text Available Flavin-based photoreceptor proteins of the LOV (Light, Oxygen, and Voltage and BLUF (Blue Light sensing Using Flavins superfamilies are ubiquitous among the three life domains and are essential blue-light sensing systems, not only in plants and algae, but also in prokaryotes. Here we review their biological roles in the prokaryotic world and their evolution pathways. An unexpected large number of bacterial species possess flavin-based photosensors, amongst which are important human and plant pathogens. Still, few cases are reported where the activity of blue-light sensors could be correlated to infectivity and/or has been shown to be involved in the activation of specific genes, resulting in selective growth patterns. Metagenomics and bio-informatic analysis have only recently been initiated, but signatures are beginning to emerge that allow definition of a bona fide LOV or BLUF domain, aiming at better selection criteria for novel blue-light sensors. We also present here, for the first time, the phylogenetic tree for archaeal LOV domains that have reached a statistically significant number but have not at all been investigated thus far.

Functionalized Fullerene Targeting Human Voltage-Gated Sodium Channel, hNav1.7.

Science.gov (United States)

Hilder, Tamsyn A; Robinson, Anna; Chung, Shin-Ho

2017-08-16

Mutations of hNa v 1.7 that cause its activities to be enhanced contribute to severe neuropathic pain. Only a small number of hNa v 1.7 specific inhibitors have been identified, most of which interact with the voltage-sensing domain of the voltage-activated sodium ion channel. In our previous computational study, we demonstrated that a [Lys 6 ]-C 84 fullerene binds tightly (affinity of 46 nM) to Na v Ab, the voltage-gated sodium channel from the bacterium Arcobacter butzleri. Here, we extend this work and, using molecular dynamics simulations, demonstrate that the same [Lys 6 ]-C 84 fullerene binds strongly (2.7 nM) to the pore of a modeled human sodium ion channel hNa v 1.7. In contrast, the fullerene binds only weakly to a mutated model of hNa v 1.7 (I1399D) (14.5 mM) and a model of the skeletal muscle hNa v 1.4 (3.7 mM). Comparison of one representative sequence from each of the nine human sodium channel isoforms shows that only hNa v 1.7 possesses residues that are critical for binding the fullerene derivative and blocking the channel pore.

Co-occurrence graphs for word sense disambiguation in the biomedical domain.

Science.gov (United States)

Duque, Andres; Stevenson, Mark; Martinez-Romo, Juan; Araujo, Lourdes

2018-05-01

Word sense disambiguation is a key step for many natural language processing tasks (e.g. summarization, text classification, relation extraction) and presents a challenge to any system that aims to process documents from the biomedical domain. In this paper, we present a new graph-based unsupervised technique to address this problem. The knowledge base used in this work is a graph built with co-occurrence information from medical concepts found in scientific abstracts, and hence adapted to the specific domain. Unlike other unsupervised approaches based on static graphs such as UMLS, in this work the knowledge base takes the context of the ambiguous terms into account. Abstracts downloaded from PubMed are used for building the graph and disambiguation is performed using the personalized PageRank algorithm. Evaluation is carried out over two test datasets widely explored in the literature. Different parameters of the system are also evaluated to test robustness and scalability. Results show that the system is able to outperform state-of-the-art knowledge-based systems, obtaining more than 10% of accuracy improvement in some cases, while only requiring minimal external resources. Copyright © 2018 Elsevier B.V. All rights reserved.

Predicting first-grade mathematics achievement: The contributions of domain-general cognitive abilities, nonverbal number sense, and early number competence.

Directory of Open Access Journals (Sweden)

Caroline eHornung

2014-04-01

Full Text Available Early number competence, grounded in number-specific and domain-general cognitive abilities, is theorized to lay the foundation for later math achievement. Few longitudinal studies have tested a comprehensive model for early math development. Using structural equation modeling and mediation analyses, the present work examined the influence of kindergarteners’ nonverbal number sense and domain-general abilities i.e., working memory, fluid intelligence, and receptive vocabulary and their early number competence (i.e., symbolic number skills on first grade math achievement (arithmetic, shape and space skills, and number line estimation assessed one year later. Latent regression models revealed that nonverbal number sense and working memory are central building blocks for developing early number competence in kindergarten and that early number competence is key for first grade math achievement. After controlling for early number competence, fluid intelligence significantly predicted arithmetic and number line estimation while receptive vocabulary significantly predicted shape and space skills. In sum we suggest that early math achievement draws on different constellations of number-specific and domain-general mechanisms.

Grid Filter Design for a Multi-Megawatt Medium-Voltage Voltage Source Inverter

DEFF Research Database (Denmark)

Rockhill, A.A.; Liserre, Marco; Teodorescu, Remus

2011-01-01

This paper describes the design procedure and performance of an LCL grid filter for a medium-voltage neutral point clamped (NPC) converter to be adopted for a multimegawatt wind turbine. The unique filter design challenges in this application are driven by a combination of the medium voltage...... converter, a limited allowable switching frequency, component physical size and weight concerns, and the stringent limits for allowable injected current harmonics. Traditional design procedures of grid filters for lower power and higher switching frequency converters are not valid for a multi......-megawatt filter connecting a medium-voltage converter switching at low frequency to the electric grid. This paper demonstrates a frequency domain model based approach to determine the optimum filter parameters that provide the necessary performance under all operating conditions given the necessary design...

Fourier Domain Sensing

Science.gov (United States)

Feldkhun, Daniel (Inventor); Wagner, Kelvin H. (Inventor)

2013-01-01

Methods and systems are disclosed of sensing an object. A first radiation is spatially modulated to generate a structured second radiation. The object is illuminated with the structured second radiation such that the object produces a third radiation in response. Apart from any spatially dependent delay, a time variation of the third radiation is spatially independent. With a single-element detector, a portion of the third radiation is detected from locations on the object simultaneously. At least one characteristic of a sinusoidal spatial Fourier-transform component of the object is estimated from a time-varying signal from the detected portion of the third radiation.

DISP3, a sterol-sensing domain-containing protein that links thyroid hormone action and cholesterol metabolism

Czech Academy of Sciences Publication Activity Database

Zíková, Martina; Corlett, Alicia; Bendová, Zdeňka; Pajer, Petr; Bartůněk, Petr

2009-01-01

Roč. 23, č. 4 (2009), s. 520-528 ISSN 0888-8809 R&D Projects: GA AV ČR IAA500520705 Grant - others:EC(XE) LSHM-CT-2005-018652 Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50110509 Keywords : thyroid hormone receptor * cholesterol metabolism * sterol-sensing domain Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.257, year: 2009

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

Science.gov (United States)

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

2014-01-01

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

Spin motive forces due to magnetic vortices and domain walls

NARCIS (Netherlands)

Lucassen, M.E.; Kruis, G.C.F.L.; Lavrijsen, R.; Swagten, H.J.M.; Koopmans, B.; Duine, R.A.

2011-01-01

We study spin motive forces, that is, spin-dependent forces and voltages induced by time-dependent magnetization textures, for moving magnetic vortices and domain walls. First, we consider the voltage generated by a one-dimensional field-driven domain wall. Next, we perform detailed calculations on

Circuit and method for controlling the threshold voltage of transistors.

NARCIS (Netherlands)

2008-01-01

A control unit, for controlling a threshold voltage of a circuit unit having transistor devices, includes a reference circuit and a measuring unit. The measuring unit is configured to measure a threshold voltage of at least one sensing transistor of the circuit unit, and to measure a threshold

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

Directory of Open Access Journals (Sweden)

Zhongming Ma

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

An innovative application of time-domain spectroscopy on localized surface plasmon resonance sensing

Science.gov (United States)

Li, Meng-Chi; Chang, Ying-Feng; Wang, Huai-Yi; Lin, Yu-Xen; Kuo, Chien-Cheng; Annie Ho, Ja-An; Lee, Cheng-Chung; Su, Li-Chen

2017-03-01

White-light scanning interferometry (WLSI) is often used to study the surface profiles and properties of thin films because the strength of the technique lies in its ability to provide fast and high resolution measurements. An innovative attempt is made in this paper to apply WLSI as a time-domain spectroscopic system for localized surface plasmon resonance (LSPR) sensing. A WLSI-based spectrometer is constructed with a breadboard of WLSI in combination with a spectral centroid algorithm for noise reduction and performance improvement. Experimentally, the WLSI-based spectrometer exhibits a limit of detection (LOD) of 1.2 × 10-3 refractive index units (RIU), which is better than that obtained with a conventional UV-Vis spectrometer, by resolving the LSPR peak shift. Finally, the bio-applicability of the proposed spectrometer was investigated using the rs242557 tau gene, an Alzheimer’s and Parkinson’s disease biomarker. The LOD was calculated as 15 pM. These results demonstrate that the proposed WLSI-based spectrometer could become a sensitive time-domain spectroscopic biosensing platform.

Enhancement of accuracy in shape sensing of surgical needles using optical frequency domain reflectometry in optical fibers.

Science.gov (United States)

Parent, Francois; Loranger, Sebastien; Mandal, Koushik Kanti; Iezzi, Victor Lambin; Lapointe, Jerome; Boisvert, Jean-Sébastien; Baiad, Mohamed Diaa; Kadoury, Samuel; Kashyap, Raman

2017-04-01

We demonstrate a novel approach to enhance the precision of surgical needle shape tracking based on distributed strain sensing using optical frequency domain reflectometry (OFDR). The precision enhancement is provided by using optical fibers with high scattering properties. Shape tracking of surgical tools using strain sensing properties of optical fibers has seen increased attention in recent years. Most of the investigations made in this field use fiber Bragg gratings (FBG), which can be used as discrete or quasi-distributed strain sensors. By using a truly distributed sensing approach (OFDR), preliminary results show that the attainable accuracy is comparable to accuracies reported in the literature using FBG sensors for tracking applications (~1mm). We propose a technique that enhanced our accuracy by 47% using UV exposed fibers, which have higher light scattering compared to un-exposed standard single mode fibers. Improving the experimental setup will enhance the accuracy provided by shape tracking using OFDR and will contribute significantly to clinical applications.

The pH-sensitive structure of the C-terminal domain of voltage-gated proton channel and the thermodynamic characteristics of Zn{sup 2+} binding to this domain

Energy Technology Data Exchange (ETDEWEB)

Zhao, Qing; Li, Chuanyong; Li, Shu Jie, E-mail: shujieli@nankai.edu.cn

2015-01-02

Highlights: • The α-helical content of the C-terminus is decreased with a pH increase. • The thermostability of the C-terminus is decreased with a pH increase. • Zn{sup 2+} binds to His{sup 244} and His{sup 266} residues within the C-terminal domain. • The binding of Zn{sup 2+} to His{sup 244} residue is an endothermic heat reaction. • The binding of Zn{sup 2+} to His{sup 266} residue is an exothermic heat reaction. - Abstract: The voltage-gated proton channel Hv1 is strongly sensitive to Zn{sup 2+}. The H{sup +} conduction is decreased at a high concentration of Zn{sup 2+} and Hv1 channel closing is slowed by the internal application of Zn{sup 2+}. Although the recent studies demonstrated that Zn{sup 2+} interacts with the intracellular C-terminal domain, the binding sites and details of the interaction remain unknown. Here, we studied the pH-dependent structural stability of the intracellular C-terminal domain of human Hv1 and showed that Zn{sup 2+} binds to His{sup 244} and His{sup 266} residues. The thermodynamics signature of Zn{sup 2+} binding to the two sites was investigated by isothermal titration calorimetry. The binding of Zn{sup 2+} to His{sup 244} (mutant H266A) and His{sup 266} (mutant H244A) were an endothermic heat reaction and an exothermic heat reaction, respectively.

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

Science.gov (United States)

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.

The free energy barrier for arginine gating charge translation is altered by mutations in the voltage sensor domain.

Directory of Open Access Journals (Sweden)

Christine S Schwaiger

Full Text Available The gating of voltage-gated ion channels is controlled by the arginine-rich S4 helix of the voltage-sensor domain moving in response to an external potential. Recent studies have suggested that S4 moves in three to four steps to open the conducting pore, thus visiting several intermediate conformations during gating. However, the exact conformational changes are not known in detail. For instance, it has been suggested that there is a local rotation in the helix corresponding to short segments of a 3(10-helix moving along S4 during opening and closing. Here, we have explored the energetics of the transition between the fully open state (based on the X-ray structure and the first intermediate state towards channel closing (C1, modeled from experimental constraints. We show that conformations within 3 Å of the X-ray structure are obtained in simulations starting from the C1 model, and directly observe the previously suggested sliding 3(10-helix region in S4. Through systematic free energy calculations, we show that the C1 state is a stable intermediate conformation and determine free energy profiles for moving between the states without constraints. Mutations indicate several residues in a narrow hydrophobic band in the voltage sensor contribute to the barrier between the open and C1 states, with F233 in the S2 helix having the largest influence. Substitution for smaller amino acids reduces the transition cost, while introduction of a larger ring increases it, largely confirming experimental activation shift results. There is a systematic correlation between the local aromatic ring rotation, the arginine barrier crossing, and the corresponding relative free energy. In particular, it appears to be more advantageous for the F233 side chain to rotate towards the extracellular side when arginines cross the hydrophobic region.

Voltage-gated proton channel is expressed on phagosomes

International Nuclear Information System (INIS)

Okochi, Yoshifumi; Sasaki, Mari; Iwasaki, Hirohide; Okamura, Yasushi

2009-01-01

Voltage-gated proton channel has been suggested to help NADPH oxidase activity during respiratory burst of phagocytes through its activities of compensating charge imbalance and regulation of pH. In phagocytes, robust production of reactive oxygen species occurs in closed membrane compartments, which are called phagosomes. However, direct evidence for the presence of voltage-gated proton channels in phagosome has been lacking. In this study, the expression of voltage-gated proton channels was studied by Western blot with the antibody specific to the voltage-sensor domain protein, VSOP/Hv1, that has recently been identified as the molecular correlate for the voltage-gated proton channel. Phagosomal membranes of neutrophils contain VSOP/Hv1 in accordance with subunits of NADPH oxidases, gp91, p22, p47 and p67. Superoxide anion production upon PMA activation was significantly reduced in neutrophils from VSOP/Hv1 knockout mice. These are consistent with the idea that voltage-gated proton channels help NADPH oxidase in phagocytes to produce reactive oxygen species.

Current-voltage characteristic of a resonant tunneling diode under electromagnetic radiation

Directory of Open Access Journals (Sweden)

N Hatefi Kargan

2013-09-01

Full Text Available  In this paper, current-voltage characteristic of a resonant tunneling diode under electromagnetic radiation has been calculated and compared with the results when there is no electromagnetic radiation. For calculating current -voltage characteristic, it is required to calculate the transmission coefficient of electrons from the well and barrier structures of this device. For calculating the transmission coefficient of electrons at the presence of electromagnetic radiation, Finite Difference Time Domain (FDTD method has been used and when there is no electromagnetic radiation Transfer Matrix Method (TMM and finite diffirence time domain method have been used. The results show that the presence of electromagnetic radiation causes resonant states other than principal resonant state (without presence of electromagnetic radiation to appear on the transmition coefficient curve where they are in distances from the principal peak and from each other. Also, the presence of electromagnetic radiation causes peaks other than principal peak to appear on the current-voltage characteristics of the device. Under electromagnetic radiation, the number of peaks on the current-voltage curve is smaller than the number of peaks on the current-voltage transmission coefficient. This is due to the fact that current-voltage curve is the result of integration on the energy of electrons, Thus, the sharper and low height peaks on the transmission coefficient do not appear on the current-voltage characteristic curve.

Tarantula huwentoxin-IV inhibits neuronal sodium channels by binding to receptor site 4 and trapping the domain ii voltage sensor in the closed configuration.

Science.gov (United States)

Xiao, Yucheng; Bingham, Jon-Paul; Zhu, Weiguo; Moczydlowski, Edward; Liang, Songping; Cummins, Theodore R

2008-10-03

Peptide toxins with high affinity, divergent pharmacological functions, and isoform-specific selectivity are powerful tools for investigating the structure-function relationships of voltage-gated sodium channels (VGSCs). Although a number of interesting inhibitors have been reported from tarantula venoms, little is known about the mechanism for their interaction with VGSCs. We show that huwentoxin-IV (HWTX-IV), a 35-residue peptide from tarantula Ornithoctonus huwena venom, preferentially inhibits neuronal VGSC subtypes rNav1.2, rNav1.3, and hNav1.7 compared with muscle subtypes rNav1.4 and hNav1.5. Of the five VGSCs examined, hNav1.7 was most sensitive to HWTX-IV (IC(50) approximately 26 nM). Following application of 1 microm HWTX-IV, hNav1.7 currents could only be elicited with extreme depolarizations (>+100 mV). Recovery of hNav1.7 channels from HWTX-IV inhibition could be induced by extreme depolarizations or moderate depolarizations lasting several minutes. Site-directed mutagenesis analysis indicated that the toxin docked at neurotoxin receptor site 4 located at the extracellular S3-S4 linker of domain II. Mutations E818Q and D816N in hNav1.7 decreased toxin affinity for hNav1.7 by approximately 300-fold, whereas the reverse mutations in rNav1.4 (N655D/Q657E) and the corresponding mutations in hNav1.5 (R812D/S814E) greatly increased the sensitivity of the muscle VGSCs to HWTX-IV. Our data identify a novel mechanism for sodium channel inhibition by tarantula toxins involving binding to neurotoxin receptor site 4. In contrast to scorpion beta-toxins that trap the IIS4 voltage sensor in an outward configuration, we propose that HWTX-IV traps the voltage sensor of domain II in the inward, closed configuration.

Lower power by voltage stacking : a fine-grained system design approach

NARCIS (Netherlands)

Blutman, K.; Kapoor, A.; Martinez, J.G.; Fatemi, S.H.; Pineda de Gyvez, J.

2016-01-01

Stacking voltage domains on top of each other is a design approach that is getting the attention of engineering communities due to the implicit high efficiency of the power delivery. Previous works have shown voltage stacking at the core level only. In this paper we present a more involved approach

Two separate interfaces between the voltage sensor and pore are required for the function of voltage-dependent K(+ channels.

Directory of Open Access Journals (Sweden)

Seok-Yong Lee

2009-03-01

Full Text Available Voltage-dependent K(+ (Kv channels gate open in response to the membrane voltage. To further our understanding of how cell membrane voltage regulates the opening of a Kv channel, we have studied the protein interfaces that attach the voltage-sensor domains to the pore. In the crystal structure, three physical interfaces exist. Only two of these consist of amino acids that are co-evolved across the interface between voltage sensor and pore according to statistical coupling analysis of 360 Kv channel sequences. A first co-evolved interface is formed by the S4-S5 linkers (one from each of four voltage sensors, which form a cuff surrounding the S6-lined pore opening at the intracellular surface. The crystal structure and published mutational studies support the hypothesis that the S4-S5 linkers convert voltage-sensor motions directly into gate opening and closing. A second co-evolved interface forms a small contact surface between S1 of the voltage sensor and the pore helix near the extracellular surface. We demonstrate through mutagenesis that this interface is necessary for the function and/or structure of two different Kv channels. This second interface is well positioned to act as a second anchor point between the voltage sensor and the pore, thus allowing efficient transmission of conformational changes to the pore's gate.

Effect of electric and magnetic fields on current-voltage characteristics of a lyotropic liquid crystal

International Nuclear Information System (INIS)

Minasyants, M.Kh.; Badalyan, G. G.; Shahinian, A. A.

1997-01-01

The effect of electric and magnetic fields on current-voltage characteristics is studied for the lamellar phase in the lyotropic liquid-crystal sodium pentadecylsulfonate (SPDS)-water and lecithin-water systems. It has been found that the current-voltage characteristics of both systems have hysteresis. In the case of ionogenic SPDS, the hysteresis is formed due to ion current caused by the spatial reorientation of domains consisting of parallel lamellar fragments; in the case of lecithin, whose molecules contain dipoles, the hysteresis is formed due to the spatial reorientation of domains caused by the interaction of the resultant dipole moment of the domains with the electric field. It is shown that the introduction into lamellae of cetylpyridine bromide, which has an intrinsic magnetic moment, changes the resultant magnetic moment of domains and, thus, also the hysteresis loop of the current-voltage characteristic. The systems studied show the 'memory' effect with respect to both the electric and magnetic fields. Field-induced processes of domain reorientation were recorded by the method of small-angle x-ray scattering

Hybridization of Sensing Methods of the Search Domain and Adaptive Weighted Sum in the Pareto Approximation Problem

Directory of Open Access Journals (Sweden)

A. P. Karpenko

2015-01-01

Full Text Available We consider the relatively new and rapidly developing class of methods to solve a problem of multi-objective optimization, based on the preliminary built finite-dimensional approximation of the set, and thereby, the Pareto front of this problem as well. The work investigates the efficiency of several modifications of the method of adaptive weighted sum (AWS. This method proposed in the paper of Ryu and Kim Van (JH. Ryu, S. Kim, H. Wan is intended to build Pareto approximation of the multi-objective optimization problem.The AWS method uses quadratic approximation of the objective functions in the current sub-domain of the search space (the area of trust based on the gradient and Hessian matrix of the objective functions. To build the (quadratic meta objective functions this work uses methods of the experimental design theory, which involves calculating the values of these functions in the grid nodes covering the area of trust (a sensing method of the search domain. There are two groups of the sensing methods under consideration: hypercube- and hyper-sphere-based methods. For each of these groups, a number of test multi-objective optimization tasks has been used to study the efficiency of the following grids: "Latin Hypercube"; grid, which is uniformly random for each measurement; grid, based on the LP  sequences.

Control and Protection Cooperation Strategy for Voltage Instability

DEFF Research Database (Denmark)

Liu, Zhou; Chen, Zhe; Sun, Haishun

2012-01-01

Most cascaded blackouts are caused by unexpected backup relay operations due to low voltage or overload state caused by post fault load restoration dynamics. If such state can be sensed and adjusted appropriately prior to those relay actions, system stability might be sustained. This paper proposed...... a control and protection cooperation strategy to prevent post fault voltage instability. The multi-agent technology is applied for the strategy implementation; the criteria based on wide area measured apparent impedances are defined to choose the control strategy, such as tap changer adjusting or load...

Battery Cell Voltage Sensing and Balancing Using Addressable Transformers

Science.gov (United States)

Davies, Francis

2009-01-01

A document discusses the use of saturating transformers in a matrix arrangement to address individual cells in a high voltage battery. This arrangement is able to monitor and charge individual cells while limiting the complexity of circuitry in the battery. The arrangement has inherent galvanic isolation, low cell leakage currents, and allows a single bad cell in a battery of several hundred cells to be easily spotted.

Temporary formation of highly conducting domain walls for non-destructive read-out of ferroelectric domain-wall resistance switching memories

Science.gov (United States)

Jiang, Jun; Bai, Zi Long; Chen, Zhi Hui; He, Long; Zhang, David Wei; Zhang, Qing Hua; Shi, Jin An; Park, Min Hyuk; Scott, James F.; Hwang, Cheol Seong; Jiang, An Quan

2018-01-01

Erasable conductive domain walls in insulating ferroelectric thin films can be used for non-destructive electrical read-out of the polarization states in ferroelectric memories. Still, the domain-wall currents extracted by these devices have not yet reached the intensity and stability required to drive read-out circuits operating at high speeds. This study demonstrated non-destructive read-out of digital data stored using specific domain-wall configurations in epitaxial BiFeO3 thin films formed in mesa-geometry structures. Partially switched domains, which enable the formation of conductive walls during the read operation, spontaneously retract when the read voltage is removed, reducing the accumulation of mobile defects at the domain walls and potentially improving the device stability. Three-terminal memory devices produced 14 nA read currents at an operating voltage of 5 V, and operated up to T = 85 °C. The gap length can also be smaller than the film thickness, allowing the realization of ferroelectric memories with device dimensions far below 100 nm.

Rectification of terahertz radiation in semiconductor superlattices in the absence of domains

International Nuclear Information System (INIS)

Isohätälä, J; Alekseev, K N

2012-01-01

We study theoretically the dynamical rectification of a terahertz AC electric field, i.e. the DC current and voltage response to the incident radiation, in strongly coupled semiconductor superlattices. We address the problem of stability against electric field domains: a spontaneous DC voltage is known to appear exactly for parameters for which a spatially homogeneous electron distribution is unstable. We show that by applying a weak direct current bias the rectifier can be switched from a state with zero DC voltage to one with a finite voltage in full absence of domains. The switching occurs near the conditions of dynamical symmetry breaking of an unbiased semiconductor superlattice. Therefore our scheme allows for the generation of DC voltages that would otherwise be unreachable due to domain instabilities. Furthermore, for realistic, highly doped wide miniband superlattices at room temperature, the generated DC field can be nearly quantized, that is, be approximately proportional to an integer multiple of ħω/ea where a is the superlattice period and ω is the AC field frequency. (paper)

Non-contact current and voltage sensing method using a clamshell housing and a ferrite cylinder

Science.gov (United States)

Carpenter, Gary D.; El-Essawy, Wael; Ferreira, Alexandre Peixoto; Keller, Thomas Walter; Rubio, Juan C.; Schappert, Michael

2016-04-26

A method of measurement using a detachable current and voltage sensor provides an isolated and convenient technique for to measuring current passing through a conductor such as an AC branch circuit wire, as well as providing an indication of an electrostatic potential on the wire, which can be used to indicate the phase of the voltage on the wire, and optionally a magnitude of the voltage. The device includes a housing that contains the current and voltage sensors, which may be a ferrite cylinder with a hall effect sensor disposed in a gap along the circumference to measure current, or alternative a winding provided through the cylinder along its axis and a capacitive plate or wire disposed adjacent to, or within, the ferrite cylinder to provide the indication of the voltage.

Structural and sensing characteristics of Gd2Ti2O7, Er2TiO5 and Lu2Ti2O7 sensing membrane electrolyte–insulator–semiconductor for bio-sensing applications

International Nuclear Information System (INIS)

Pan, Tung-Ming; Liao, Pei-You; Chang, Kung-Yuan; Chi, Lifeng

2013-01-01

Highlights: ► The structural and sensing properties of Gd 2 Ti 2 O 7 , Er 2 TiO 5 and Lu 2 Ti 2 O 7 sensing films grown on Si substrates by reactive co-sputtering. ► The EIS device incorporating a Lu 2 Ti 2 O 7 sensing film exhibited a higher sensitivity, a larger drift rate, a higher hysteresis voltage, and a larger hysteresis gap than other sensing films. ► The impedance effect of EIS sensors has been investigated using C–V method. -- Abstract: This paper describes the structural and sensing characteristics of Gd 2 Ti 2 O 7 , Er 2 TiO 5 , and Lu 2 Ti 2 O 7 sensing membranes deposited on Si substrates through reactive co-sputtering for electrolyte–insulator–semiconductor (EIS) pH sensors. In this work, the structural properties of Gd 2 Ti 2 O 7 , Er 2 TiO 5 , and Lu 2 Ti 2 O 7 membranes were investigated by X-ray diffraction, atomic force microscopy and X-ray photoelectron spectroscopy. The observed structural properties were then correlated with the resulting pH sensing performances. The EIS device incorporating a Lu 2 Ti 2 O 7 sensing film exhibited a higher sensitivity (59.32 mV pH −1 ), a larger drift rate (0.55 mV h −1 ), a higher hysteresis voltage (5 mV), and a larger hysteresis gap (∼70 mV) compared to those of the other sensing films. This result is attributed to the higher surface roughness and the formation of a thicker interfacial layer at the oxide–Si interface. Furthermore, the impedance effect of EIS sensors has been investigated using capacitance–voltage (C–V) method (frequency-dependent C–V curves). From the impedance spectroscopy analysis, we find that the diameter of a semicircle of an EIS sensor becomes smaller due to a gradual decrease in the bulk resistance of the device with degree of pH value

Charge immobilization of the voltage sensor in domain IV is independent of sodium current inactivation.

Science.gov (United States)

Sheets, Michael F; Hanck, Dorothy A

2005-02-15

Recovery from fast inactivation in voltage-dependent Na+ channels is associated with a slow component in the time course of gating charge during repolarization (i.e. charge immobilization), which results from the slow movement of the S4 segments in domains III and IV (S4-DIII and S4-DIV). Previous studies have shown that the non-specific removal of fast inactivation by the proteolytic enzyme pronase eliminated charge immobilization, while the specific removal of fast inactivation (by intracellular MTSET modification of a cysteine substituted for the phenylalanine in the IFM motif, ICMMTSET, in the inactivation particle formed by the linker between domains III and IV) only reduced the amount of charge immobilization by nearly one-half. To investigate the molecular origin of the remaining slow component of charge immobilization we studied the human cardiac Na+ channel (hH1a) in which the outermost arginine in the S4-DIV, which contributes approximately 20% to total gating charge (Qmax), was mutated to a cysteine (R1C-DIV). Gating charge could be fully restored in R1C-DIV by exposure to extracellular MTSEA, a positively charged methanethiosulphonate reagent. The RIC-DIV mutation was combined with ICMMTSET to remove fast inactivation, and the gating currents of R1C-DIV-ICM(MTSET) were recorded before and after modification with MTSEAo. Prior to MTSEAo, the time course of the gating charge during repolarization (off-charge) was best described by a single fast time constant. After MTSEA, the off-charge had both fast and slow components, with the slow component accounting for nearly 35% of Qmax. These results demonstrate that the slow movement of the S4-DIV during repolarization is not dependent upon the normal binding of the inactivation particle.

Binding modes and functional surface of anti-mammalian scorpion α-toxins to sodium channels.

Science.gov (United States)

Chen, Rong; Chung, Shin-Ho

2012-10-02

Scorpion α-toxins bind to the voltage-sensing domains of voltage-gated sodium (Na(V)) channels and interfere with the inactivation mechanisms. The functional surface of α-toxins has been shown to contain an NC-domain consisting of the five-residue turn (positions 8-12) and the C-terminus (positions 56-64) and a core-domain centered on the residue 18. The NC- and core-domains are interconnected by the linker-domain (positions 8-18). Here with atomistic molecular dynamics simulations, we examine the binding modes between two α-toxins, the anti-mammalian AahII and the anti-insect LqhαIT, and the voltage-sensing domain of rat Na(V)1.2, a subtype of Na(V) channels expressed in nerve cells. Both toxins are docked to the extracellular side of the voltage-sensing domain of Na(V)1.2 using molecular dynamics simulations, with the linker-domain assumed to wedge into the binding pocket. Several salt bridges and hydrophobic clusters are observed to form between the NC- and core-domains of the toxins and Na(V)1.2 and stabilize the toxin-channel complexes. The binding modes predicted are consistent with available mutagenesis data and can readily explain the relative affinities of AahII and LqhαIT for Na(V)1.2. The dissociation constants for the two toxin-channel complexes are derived, which compare favorably with experiment. Our models demonstrate that the functional surface of anti-mammalian scorpion α-toxins is centered on the linker-domain, similar to that of β-toxins.

Readout Distance Enhancement of the Passive Wireless Multi-Parameter Sensing System Using a Repeater Coil

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Lifeng Wang

2018-01-01

Full Text Available A repeater coil is used to extend the detection distance of a passive wireless multi-parameter sensing system. The passive wireless sensing system has the ability of simultaneously monitoring three parameters by using backscatter modulation together with channel multiplexing. Two different repeater coils are designed and fabricated for readout distance enhancement of the sensing system: one is a PCB (printed circuit board repeater coil, and the other is a copper wire repeater coil. Under the conditions of fixed voltage and adjustable voltage, the maximum readout distance of the sensing system with and without a repeater coil is measured. Experimental results show that larger power supply voltage can help further increase the readout distance. The maximum readout distance of the sensing system with a PCB repeater coil has been extended 2.3 times, and the one with a copper wire repeater coil has been extended 3 times. Theoretical analysis and experimental results both indicate that the high Q factor repeater coil can extend the readout distance more. With the copper wire repeater coil as well as a higher power supply voltage, the passive wireless multi-parameter sensing system finally achieves a maximum readout distance of 13.5 cm.

A 32 kb 9T near-threshold SRAM with enhanced read ability at ultra-low voltage operation

Science.gov (United States)

Kim, Tony Tae-Hyoung; Lee, Zhao Chuan; Do, Anh Tuan

2018-01-01

Ultra-low voltage SRAMs are highly sought-after in energy-limited systems such as battery-powered and self-harvested SoCs. However, ultra-low voltage operation diminishes SRAM read bitline (RBL) sensing margin significantly. This paper tackles this issue by presenting a novel 9T cell with data-independent RBL leakage in combination with an RBL boosting technique for enhancing the sensing margin. The proposed technique automatically tracks process, temperature and voltage (PVT) variations for robust sensing margin enhancement. A test chip fabricated in 65 nm CMOS technology shows that the proposed scheme significantly enlarges the sensing margin compared to the conventional bitline sensing scheme. It also achieves the minimum operating voltage of 0.18 V and the minimum energy consumption of 0.92 J/access at 0.4 V. He received 2016 International Low Power Design Contest Award from ISLPED, a best paper award at 2014 and 2011 ISOCC, 2008 AMD/CICC Student Scholarship Award, 2008 Departmental Research Fellowship from Univ. of Minnesota, 2008 DAC/ISSCC Student Design Contest Award, 2008, 2001, and 1999 Samsung Humantec Thesis Award and, 2005 ETRI Journal Paper of the Year Award. He is an author/co-author of +100 journal and conference papers and has 17 US and Korean patents registered. His current research interests include low power and high performance digital, mixed- mode, and memory circuit design, ultra-low voltage circuits and systems design, variation and aging tolerant circuits and systems, and circuit techniques for 3D ICs. He serves as an associate editor of IEEE Transactions on VLSI Systems. He is an IEEE senior member and the Chair of IEEE Solid-State Circuits Society Singapore Chapter. He has served numerous conferences as a committee member.

Real-time monitoring of luminescent lifetime changes of PtOEP oxygen sensing film with LED/photodiode-based time-domain lifetime device.

Science.gov (United States)

Ji, Shaomin; Wu, Wanhua; Wu, Yubo; Zhao, Taiyang; Zhou, Fuke; Yang, Yubin; Zhang, Xin; Liang, Xiaofen; Wu, Wenting; Chi, Lina; Wang, Zhonggang; Zhao, Jianzhang

2009-05-01

A cost-effective LED/photodiode(PD)-based time-domain luminescent lifetime measuring device with rugged electronics and simplified algorithms was assembled and successfully used to characterize oxygen sensing films, by continuously monitoring phosphorescence lifetime changes of phosphorescent platinum octaethylporphyrin (PtOEP) in cardo poly(aryl ether ketone) polymer (IMPEK-C) vs. variation of the oxygen partial pressure in a gas mixture (O(2)/N(2)). The results determined by both phosphorescence lifetime and intensity monitoring were compared and the lifetime mode gave results which are in good agreement with the intensity mode. The lifetime-based linear Stern-Volmer plot indicates that the PtOEP molecules are nearly homogeneously distributed in the sensing film. The phosphorescent lifetime of the PtOEP film changes from 75 micros in neat N(2) to less than 2 micros in neat O(2). The sensing system (by combination of the PtOEP sensing film with the home-assembled lifetime device) gives a high lifetime-based O(2) sensing resolution, e.g. about 2 micros Torr(-1) for low O(2) concentration (below 3.5% O(2), V/V). This feasible lifetime device configuration is affordable to most sensor laboratories and the device may facilitate the study of O(2) sensing material with the continuous lifetime monitoring method.

Studies of alpha-helicity and intersegmental interactions in voltage-gated Na+ channels: S2D4.

Directory of Open Access Journals (Sweden)

Zhongming Ma

2009-11-01

Full Text Available Much data, including crystallographic, support structural models of sodium and potassium channels consisting of S1-S4 transmembrane segments (the "voltage-sensing domain" clustered around a central pore-forming region (S5-S6 segments and the intervening loop. Voltage gated sodium channels have four non-identical domains which differentiates them from the homotetrameric potassium channels that form the basis for current structural models. Since potassium and sodium channels also exhibit many different functional characteristics and the fourth domain (D4 of sodium channels differs in function from other domains (D1-D3, we have explored its structure in order to determine whether segments in D4 of sodium channels differ significantly from that determined for potassium channels. We have probed the secondary and tertiary structure and the role of the individual amino acid residues of the S2D4 of Na(v1.4 by employing cysteine-scanning mutagenesis (with tryptophan and glutamine substituted for native cysteine. A Fourier transform power spectrum of perturbations in free energy of steady-state inactivation gating (using midpoint potentials and slopes of Boltzmann equation fits of channel availability, h(infinity-V plots indicates a substantial amount of alpha-helical structure in S2D4 (peak at 106 degrees, alpha-Periodicity Index (alpha-PI of 3.10, This conclusion is supported by alpha-PI values of 3.28 and 2.84 for the perturbations in rate constants of entry into (beta and exit from (alpha fast inactivation at 0 mV for mutant channels relative to WT channels assuming a simple two-state model for transition from the open to inactivated state. The results of cysteine substitution at the two most sensitive sites of the S2D4 alpha-helix (N1382 and E1392C support the existence of electrostatic network interactions between S2 and other transmembrane segments within Na(v1.4D4 similar to but not identical to those proposed for K+ channels.

Ferroelectric Negative Capacitance Domain Dynamics

OpenAIRE

Hoffmann, Michael; Khan, Asif Islam; Serrao, Claudy; Lu, Zhongyuan; Salahuddin, Sayeef; Pešić, Milan; Slesazeck, Stefan; Schroeder, Uwe; Mikolajick, Thomas

2017-01-01

Transient negative capacitance effects in epitaxial ferroelectric Pb(Zr$_{0.2}$Ti$_{0.8}$)O$_3$ capacitors are investigated with a focus on the dynamical switching behavior governed by domain nucleation and growth. Voltage pulses are applied to a series connection of the ferroelectric capacitor and a resistor to directly measure the ferroelectric negative capacitance during switching. A time-dependent Ginzburg-Landau approach is used to investigate the underlying domain dynamics. The transien...

Semantic neology in the domain of videogames in Spanish

Directory of Open Access Journals (Sweden)

Inmaculada Álvarez de Mon Rego

2013-04-01

Full Text Available The aim of this paper is to discuss the meaning of five neologisms in the domain of videogames in Spanish: título, aventura, personaje, plataforma, and rol. Our study focuses on a special type of neologism since the Spanish terms we deal with here are not strictly new words; they are what have been called sense neologisms or neosemanticisms, that is, old words taking a new sense in a different domain. These words were identified as new concepts after a process of analysis based on contextual evidence. This study of neology is based on the analysis of a corpus of press articles evaluating videogames published by the Spanish newspaper El País from 1998 to 2008. The analysis of the instances of use of domain specific terms in the corpus revealed that they acquired new senses different to those they have in other domains where they are also used. The paper explains the process of discovering the specialized meaning these words have developed in the domain of videogames and how the analysis of collocational behavior helps in the process of discovering the new sense and in the design of the definition provided.

Power grid current harmonics mitigation drawn on low voltage rated switching devices with effortless control

Energy Technology Data Exchange (ETDEWEB)

Marques, Hugo S.; Anunciada, Victor; Borges, Beatriz V. [Power Electronics Group, Instituto de Telecomunicacoes, Lisbon (Portugal); Instituto Superior Tecnico - Universidade Tecnica de Lisboa, Lisbon (Portugal)

2010-01-15

The great majority of the existing hybrid active power filter solutions is normally focused in 3{phi} systems and, in general, concentrates its domain of application in specific loads with deterministic behavior. Because common use grids do not exhibit these characteristics, it is mandatory to develop solutions for more generic scenarios, encouraging the use of less classical hybrid solutions. In fact, due to the widely use of switch mode converters in a great variety of consumer electronics, the problematic of mains current harmonic mitigation is no longer an exclusive matter of 3{phi} systems. The contribution of this paper is to present a shunt hybrid active power filter topology, initially conceived to work in 1{phi} domestic grids, able to operate the inverter at a voltage rate that can be lower than 10% of the mains voltage magnitude, even under nonspecific working conditions. In addition, the results shown in this paper demonstrate that this topology can, without lack of generality, be suitable to medium voltage (1{phi} or 3{phi}) systems. A new control approach for the proposed topology is discussed in this paper. The control method exhibits an extremely simple architecture requiring single point current sensing only, with no need for any kind of reference. Its practical implementation can be fulfilled by using very few, common use, operational amplifiers. The principle of operation, design criteria, simulation predictions and experimental results are presented and discussed. (author)

Mobile Autonomous Sensing Unit (MASU: A Framework That Supports Distributed Pervasive Data Sensing

Directory of Open Access Journals (Sweden)

Esunly Medina

2016-07-01

Full Text Available Pervasive data sensing is a major issue that transverses various research areas and application domains. It allows identifying people’s behaviour and patterns without overwhelming the monitored persons. Although there are many pervasive data sensing applications, they are typically focused on addressing specific problems in a single application domain, making them difficult to generalize or reuse. On the other hand, the platforms for supporting pervasive data sensing impose restrictions to the devices and operational environments that make them unsuitable for monitoring loosely-coupled or fully distributed work. In order to help address this challenge this paper present a framework that supports distributed pervasive data sensing in a generic way. Developers can use this framework to facilitate the implementations of their applications, thus reducing complexity and effort in such an activity. The framework was evaluated using simulations and also through an empirical test, and the obtained results indicate that it is useful to support such a sensing activity in loosely-coupled or fully distributed work scenarios.

Analysis of time domain active sensing data from CX-100 wind turbine blade fatigue tests for damage assessment

Energy Technology Data Exchange (ETDEWEB)

Choi, Mi Jin [Dept. of Aerospace Engineering and LANL-CBNU Engineering Institute, Chunbuk National University, Jeonju (Korea, Republic of); Jung, Hwee Kwon; Park, Gyu Hae [School of Mechanical Engineering, Chonnam National University, Gwangju (Korea, Republic of); Taylor, Stuart G.; Farinholt, Kevin M. [The Engineering Institute, Los Alamos National Laboratory, Los Alamos (United States)

2016-04-15

This paper presents the results obtained using time-series-based methods for structural damage assessment. The methods are applied to a wind turbine blade structure subjected to fatigue loads. A 9 m CX-100 (carbon experimental 100 kW) blade is harmonically excited at its first natural frequency to introduce a failure mode. Consequently, a through-thickness fatigue crack is visually identified at 8.5 million cycles. The time domain data from the piezoelectric active-sensing techniques are measured during the fatigue loadings and used to detect incipient damage. The damage-sensitive features, such as the first four moments and a normality indicator, are extracted from the time domain data. Time series autoregressive models with exogenous inputs are also implemented. These features could efficiently detect a fatigue crack and are less sensitive to operational variations than the other methods.

Apo-states of calmodulin and CaBP1 control CaV1 voltage-gated calcium channel function through direct competition for the IQ domain

Science.gov (United States)

Findeisen, Felix; Rumpf, Christine; Minor, Daniel L.

2013-01-01

In neurons, binding of calmodulin (CaM) or calcium-binding protein 1 (CaBP1) to the CaV1 (L-type) voltage-gated calcium channel IQ domain endows the channel with diametrically opposed properties. CaM causes calcium-dependent inactivation (CDI) and limits calcium entry, whereas CaBP1 blocks CDI and allows sustained calcium influx. Here, we combine isothermal titration calorimetry (ITC) with cell-based functional measurements and mathematical modeling to show that these calcium sensors behave in a competitive manner that is explained quantitatively by their apo-state binding affinities for the IQ domain. This competition can be completely blocked by covalent tethering of CaM to the channel. Further, we show that Ca2+/CaM has a sub-picomolar affinity for the IQ domain that is achieved without drastic alteration of calcium binding properties. The observation that the apo-forms of CaM and CaBP1 compete with each other demonstrates a simple mechanism for direct modulation of CaV1 function and suggests a means by which excitable cells may dynamically tune CaV activity. PMID:23811053

Apo states of calmodulin and CaBP1 control CaV1 voltage-gated calcium channel function through direct competition for the IQ domain.

Science.gov (United States)

Findeisen, Felix; Rumpf, Christine H; Minor, Daniel L

2013-09-09

In neurons, binding of calmodulin (CaM) or calcium-binding protein 1 (CaBP1) to the CaV1 (L-type) voltage-gated calcium channel IQ domain endows the channel with diametrically opposed properties. CaM causes calcium-dependent inactivation and limits calcium entry, whereas CaBP1 blocks calcium-dependent inactivation (CDI) and allows sustained calcium influx. Here, we combine isothermal titration calorimetry with cell-based functional measurements and mathematical modeling to show that these calcium sensors behave in a competitive manner that is explained quantitatively by their apo-state binding affinities for the IQ domain. This competition can be completely blocked by covalent tethering of CaM to the channel. Further, we show that Ca(2+)/CaM has a sub-picomolar affinity for the IQ domain that is achieved without drastic alteration of calcium-binding properties. The observation that the apo forms of CaM and CaBP1 compete with each other demonstrates a simple mechanism for direct modulation of CaV1 function and suggests a means by which excitable cells may dynamically tune CaV activity. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Voltage Control Support and Coordination between Renewable Generation Plants in MV Distribution Systems

DEFF Research Database (Denmark)

Petersen, Lennart; Iov, Florin; Hansen, Anca Daniela

2016-01-01

This paper focusses on voltage control support and coordination between renewable generation plants in medium voltage distribution systems. An exemplary benchmark grid in Denmark, including a number of flexible ReGen plants providing voltage control functionality, is used as a base case. First......, voltage sensitivity analysis is performed to quantify node voltage variations due to injections of reactive power for given operational points of the network. The results are then used to develop an adaptive voltage droop control method, where various droop settings are allocated to each ReGen plant...... according to the sensitivity indices of corresponding node voltages and the location of respective ReGen plants in the distribution system. Case studies are performed in time-domain to analyze the impact of voltage fluctuations due to active power variations of ReGen plants in order to verify...

Voltage Quench Dynamics of a Kondo System.

Science.gov (United States)

Antipov, Andrey E; Dong, Qiaoyuan; Gull, Emanuel

2016-01-22

We examine the dynamics of a correlated quantum dot in the mixed valence regime. We perform numerically exact calculations of the current after a quantum quench from equilibrium by rapidly applying a bias voltage in a wide range of initial temperatures. The current exhibits short equilibration times and saturates upon the decrease of temperature at all times, indicating Kondo behavior both in the transient regime and in the steady state. The time-dependent current saturation temperature connects the equilibrium Kondo temperature to a substantially increased value at voltages outside of the linear response. These signatures are directly observable by experiments in the time domain.

Bio-Inspired Carbon Monoxide Sensors with Voltage-Activated Sensitivity

KAUST Repository

Savagatrup, Suchol

2017-09-27

Carbon monoxide (CO) outcompetes oxygen when binding to the iron center of hemeproteins, leading to a reduction in blood oxygen level and acute poisoning. Harvesting the strong specific interaction between CO and the iron porphyrin provides a highly selective and customizable sensor. We report the development of chemiresistive sensors with voltage-activated sensitivity for the detection of CO comprising iron porphyrin and functionalized single-walled carbon nanotubes (F-SWCNTs). Modulation of the gate voltage offers a predicted extra dimension for sensing. Specifically, the sensors show a significant increase in sensitivity toward CO when negative gate voltage is applied. The dosimetric sensors are selective to ppm levels of CO and functional in air. UV/Vis spectroscopy, differential pulse voltammetry, and density functional theory reveal that the in situ reduction of FeIII to FeII enhances the interaction between the F-SWCNTs and CO. Our results illustrate a new mode of sensors wherein redox active recognition units are voltage-activated to give enhanced and highly specific responses.

Research on uncertainty evaluation measure and method of voltage sag severity

Science.gov (United States)

Liu, X. N.; Wei, J.; Ye, S. Y.; Chen, B.; Long, C.

2018-01-01

Voltage sag is an inevitable serious problem of power quality in power system. This paper focuses on a general summarization and reviews on the concepts, indices and evaluation methods about voltage sag severity. Considering the complexity and uncertainty of influencing factors, damage degree, the characteristics and requirements of voltage sag severity in the power source-network-load sides, the measure concepts and their existing conditions, evaluation indices and methods of voltage sag severity have been analyzed. Current evaluation techniques, such as stochastic theory, fuzzy logic, as well as their fusion, are reviewed in detail. An index system about voltage sag severity is provided for comprehensive study. The main aim of this paper is to propose thought and method of severity research based on advanced uncertainty theory and uncertainty measure. This study may be considered as a valuable guide for researchers who are interested in the domain of voltage sag severity.

Sensing the gas metal arc welding process

Science.gov (United States)

Carlson, N. M.; Johnson, J. A.; Smartt, H. B.; Watkins, A. D.; Larsen, E. D.; Taylor, P. L.; Waddoups, M. A.

1994-01-01

Control of gas metal arc welding (GMAW) requires real-time sensing of the process. Three sensing techniques for GMAW are being developed at the Idaho National Engineering Laboratory (INEL). These are (1) noncontacting ultrasonic sensing using a laser/EMAT (electromagnetic acoustic transducer) to detect defects in the solidified weld on a pass-by-pass basis, (2) integrated optical sensing using a CCD camera and a laser stripe to obtain cooling rate and weld bead geometry information, and (3) monitoring fluctuations in digitized welding voltage data to detect the mode of metal droplet transfer and assure that the desired mass input is achieved.

Light-induced conformational changes of LOV1 (light oxygen voltage-sensing domain 1) and LOV2 relative to the kinase domain and regulation of kinase activity in Chlamydomonas phototropin.

Science.gov (United States)

Okajima, Koji; Aihara, Yusuke; Takayama, Yuki; Nakajima, Mihoko; Kashojiya, Sachiko; Hikima, Takaaki; Oroguchi, Tomotaka; Kobayashi, Amane; Sekiguchi, Yuki; Yamamoto, Masaki; Suzuki, Tomomi; Nagatani, Akira; Nakasako, Masayoshi; Tokutomi, Satoru

2014-01-03

Phototropin (phot), a blue light (BL) receptor in plants, has two photoreceptive domains named LOV1 and LOV2 as well as a Ser/Thr kinase domain (KD) and acts as a BL-regulated protein kinase. A LOV domain harbors a flavin mononucleotide that undergoes a cyclic photoreaction upon BL excitation via a signaling state in which the inhibition of the kinase activity by LOV2 is negated. To understand the molecular mechanism underlying the BL-dependent activation of the kinase, the photochemistry, kinase activity, and molecular structure were studied with the phot of Chlamydomonas reinhardtii. Full-length and LOV2-KD samples of C. reinhardtii phot showed cyclic photoreaction characteristics with the activation of LOV- and BL-dependent kinase. Truncation of LOV1 decreased the photosensitivity of the kinase activation, which was well explained by the fact that the signaling state lasted for a shorter period of time compared with that of the phot. Small angle x-ray scattering revealed monomeric forms of the proteins in solution and detected BL-dependent conformational changes, suggesting an extension of the global molecular shapes of both samples. Constructed molecular model of full-length phot based on the small angle x-ray scattering data proved the arrangement of LOV1, LOV2, and KD for the first time that showed a tandem arrangement both in the dark and under BL irradiation. The models suggest that LOV1 alters its position relative to LOV2-KD under BL irradiation. This finding demonstrates that LOV1 may interact with LOV2 and modify the photosensitivity of the kinase activation through alteration of the duration of the signaling state in LOV2.

Development of a Piezoelectric Vacuum Sensing Component for a Wide Pressure Range

Directory of Open Access Journals (Sweden)

Bing-Yu Wang

2014-11-01

Full Text Available In this study, we develop a clamped–clamped beam-type piezoelectric vacuum pressure sensing element. The clamped–clamped piezoelectric beam is composed of a PZT layer and a copper substrate. A pair of electrodes is set near each end. An input voltage is applied to a pair of electrodes to vibrate the piezoelectric beam, and the output voltage is measured at the other pair. Because the viscous forces on the piezoelectric beam vary at different air pressures, the vibration of the beam depends on the vacuum pressure. The developed pressure sensor can sense a wide range of pressure, from 6.5 × 10−6 to 760 Torr. The experimental results showed that the output voltage is inversely proportional to the gas damping ratio, and thus, the vacuum pressure was estimated from the output voltage.

High Voltage Coil Current Sensor for DC-DC Converters Employing DDCC

Directory of Open Access Journals (Sweden)

M. Drinovsky

2015-12-01

Full Text Available Current sensor is an integral part of every switching converter. It is used for over-current protection, regulation and in case of multiphase converters for balancing. A new high voltage current sensor for coil-based current sensing in DC-DC converters is presented. The sensor employs DDCC with high voltage input stage and gain trimming. The circuit has been simulated and implemented in 0.35 um BCD technology as part of a multiphase DC-DC converter where its function has been verified. The circuit is able to sustain common mode voltage on the input up to 40 V, it occupies 0.387*0.345 mm2 and consumes 3.2 mW typically.

PMU-Aided Voltage Security Assessment for a Wind Power Plant: Preprint

Energy Technology Data Exchange (ETDEWEB)

Jiang, H.; Zhang, Y. C.; Zhang, J. J.; Muljadi, E.

2015-04-08

Because wind power penetration levels in electric power systems are continuously increasing, voltage stability is a critical issue for maintaining power system security and operation. The traditional methods to analyze voltage stability can be classified into two categories: dynamic and steady-state. Dynamic analysis relies on time-domain simulations of faults at different locations; however, this method needs to exhaust faults at all locations to find the security region for voltage at a single bus. With the widely located phasor measurement units (PMUs), the Thevenin equivalent matrix can be calculated by the voltage and current information collected by the PMUs. This paper proposes a method based on a Thevenin equivalent matrix to identify system locations that will have the greatest impact on the voltage at the wind power plant’s point of interconnection. The number of dynamic voltage stability analysis runs is greatly reduced by using the proposed method. The numerical results demonstrate the feasibility, effectiveness, and robustness of the proposed approach for voltage security assessment for a wind power plant.

Measurement and analysis of time-domain characteristics of corona-generated radio interference from a single positive corona source

Science.gov (United States)

Li, Xuebao; Li, Dayong; Chen, Bo; Cui, Xiang; Lu, Tiebing; Li, Yinfei

2018-04-01

The corona-generated electromagnetic interference commonly known as radio interference (RI) has become a limiting factor for the design of high voltage direct current transmission lines. In this paper, a time-domain measurement system is developed to measure the time-domain characteristics of corona-generated RI from a single corona source under a positive corona source. In the experiments, the corona current pulses are synchronously measured through coupling capacitors. The one-to-one relationship between the corona current pulse and measured RI voltage pulse is observed. The statistical characteristics of pulse parameters are analyzed, and the correlations between the corona current pulse and RI voltage pulse in the time-domain and frequency-domain are analyzed. Depending on the measured corona current pulses, the time-domain waveform of corona-generated RI is calculated on the basis of the propagation model of corona current on the conductor, the dipolar model for electric field calculation, and the antenna model for inducing voltage calculation. The well matched results between measured and simulated waveforms of RI voltage can show the validity of the measurement and calculation method presented in this paper, which also further show the close correlation between corona current and corona-generated RI.

On some aspects of high voltage electron microscopy

International Nuclear Information System (INIS)

Jouffrey, B.; Trinquier, J.

1987-01-01

The present paper deals with high voltage electron microscopy (HVEM). It is an overview on this domain due to the pionneer work of G. Dupouy which has permitted to perform a new kind of electron microscopy. Since this time, HVEM has shown its interest in high resolution, irradiations, chemical analysis, in situ experiments

Modular organization of α-toxins from scorpion venom mirrors domain structure of their targets, sodium channels.

Science.gov (United States)

Chugunov, Anton O; Koromyslova, Anna D; Berkut, Antonina A; Peigneur, Steve; Tytgat, Jan; Polyansky, Anton A; Pentkovsky, Vladimir M; Vassilevski, Alexander A; Grishin, Eugene V; Efremov, Roman G

2013-06-28

To gain success in the evolutionary "arms race," venomous animals such as scorpions produce diverse neurotoxins selected to hit targets in the nervous system of prey. Scorpion α-toxins affect insect and/or mammalian voltage-gated sodium channels (Na(v)s) and thereby modify the excitability of muscle and nerve cells. Although more than 100 α-toxins are known and a number of them have been studied into detail, the molecular mechanism of their interaction with Na(v)s is still poorly understood. Here, we employ extensive molecular dynamics simulations and spatial mapping of hydrophobic/hydrophilic properties distributed over the molecular surface of α-toxins. It is revealed that despite the small size and relatively rigid structure, these toxins possess modular organization from structural, functional, and evolutionary perspectives. The more conserved and rigid "core module" is supplemented with the "specificity module" (SM) that is comparatively flexible and variable and determines the taxon (mammal versus insect) specificity of α-toxin activity. We further show that SMs in mammal toxins are more flexible and hydrophilic than in insect toxins. Concomitant sequence-based analysis of the extracellular loops of Na(v)s suggests that α-toxins recognize the channels using both modules. We propose that the core module binds to the voltage-sensing domain IV, whereas the more versatile SM interacts with the pore domain in repeat I of Na(v)s. These findings corroborate and expand the hypothesis on different functional epitopes of toxins that has been reported previously. In effect, we propose that the modular structure in toxins evolved to match the domain architecture of Na(v)s.

small signal analysis of load angle governing and excitation control

African Journals Online (AJOL)

Dr Obe

system stabilizers (PSS) or using terminal voltage for control of exciter and speed signal for governor. ... Vfd= generator field voltage. Xd, Xq ... each other in the frequency domain, and therefore ..... angle sensing equipment, relays and.

Ion Concentration- and Voltage-Dependent Push and Pull Mechanisms of Potassium Channel Ion Conduction.

Directory of Open Access Journals (Sweden)

Kota Kasahara

Full Text Available The mechanism of ion conduction by potassium channels is one of the central issues in physiology. In particular, it is still unclear how the ion concentration and the membrane voltage drive ion conduction. We have investigated the dynamics of the ion conduction processes in the Kv1.2 pore domain, by molecular dynamics (MD simulations with several different voltages and ion concentrations. By focusing on the detailed ion movements through the pore including selectivity filter (SF and cavity, we found two major conduction mechanisms, called the III-IV-III and III-II-III mechanisms, and the balance between the ion concentration and the voltage determines the mechanism preference. In the III-IV-III mechanism, the outermost ion in the pore is pushed out by a new ion coming from the intracellular fluid, and four-ion states were transiently observed. In the III-II-III mechanism, the outermost ion is pulled out first, without pushing by incoming ions. Increases in the ion concentration and voltage accelerated ion conductions, but their mechanisms were different. The increase in the ion concentrations facilitated the III-IV-III conductions, while the higher voltages increased the III-II-III conductions, indicating that the pore domain of potassium channels permeates ions by using two different driving forces: a push by intracellular ions and a pull by voltage.

Functional roles of the amino terminal domain in determining biophysical properties of Cx50 gap junction channels

Directory of Open Access Journals (Sweden)

Li eXin

2013-12-01

Full Text Available Communication through gap junction channels is essential for synchronized and coordinated cellular activities. The gap junction channel pore size, its switch control for opening/closing, and the modulations by chemicals can be different depending on the connexin subtypes that compose the channel. Recent structural and functional studies provide compelling evidence that the amino terminal (NT domains of several connexins line the pore of gap junction channels and play an important role in single channel conductance (γj and transjunctional voltage-dependent gating (Vj-gating. This article reviews recent studies conducted on a series of mutations/chimeras in the NT domain of connexin50 (Cx50. Functional examination of the gap junction channels formed by these mutants/chimeras shows the net charge number at the NT domain to be an important factor in γj and in Vj-gating. Furthermore, with an increase in the net negative charge at the NT domain, we observed an increase in the γj, as well as changes in the parameters of the Boltzmann fit of the normalized steady-state conductance and Vj relationship. Our data are consistent with a structural model where the NT domain of Cx50 lines the gap junction pore and plays an important role in sensing Vj and in the subsequent conformational changes leading to gating, as well as in limiting the rate of ion permeation.

E-beam high voltage switching power supply

Science.gov (United States)

Shimer, Daniel W.; Lange, Arnold C.

1997-01-01

A high power, solid state power supply is described for producing a controllable, constant high voltage output under varying and arcing loads suitable for powering an electron beam gun or other ion source. The present power supply is most useful for outputs in a range of about 100-400 kW or more. The power supply is comprised of a plurality of discrete switching type dc-dc converter modules, each comprising a voltage regulator, an inductor, an inverter for producing a high frequency square wave current of alternating polarity, an improved inverter voltage clamping circuit, a step up transformer, and an output rectifier for producing a dc voltage at the output of each module. The inputs to the converter modules are fed from a common dc rectifier/filter and are linked together in parallel through decoupling networks to suppress high frequency input interactions. The outputs of the converter modules are linked together in series and connected to the input of the transmission line to the load through a decoupling and line matching network. The dc-dc converter modules are phase activated such that for n modules, each module is activated equally 360.degree./n out of phase with respect to a successive module. The phased activation of the converter modules, combined with the square current waveforms out of the step up transformers, allows the power supply to operate with greatly reduced output capacitance values which minimizes the stored energy available for discharge into an electron beam gun or the like during arcing. The present power supply also provides dynamic response to varying loads by controlling the voltage regulator duty cycle using simulated voltage feedback signals and voltage feedback loops. Circuitry is also provided for sensing incipient arc currents reflected at the output of the power supply and for simultaneously decoupling the power supply circuitry from the arcing load.

E-beam high voltage switching power supply

International Nuclear Information System (INIS)

Shimer, D.W.; Lange, A.C.

1997-01-01

A high power, solid state power supply is described for producing a controllable, constant high voltage output under varying and arcing loads suitable for powering an electron beam gun or other ion source. The present power supply is most useful for outputs in a range of about 100-400 kW or more. The power supply is comprised of a plurality of discrete switching type dc-dc converter modules, each comprising a voltage regulator, an inductor, an inverter for producing a high frequency square wave current of alternating polarity, an improved inverter voltage clamping circuit, a step up transformer, and an output rectifier for producing a dc voltage at the output of each module. The inputs to the converter modules are fed from a common dc rectifier/filter and are linked together in parallel through decoupling networks to suppress high frequency input interactions. The outputs of the converter modules are linked together in series and connected to the input of the transmission line to the load through a decoupling and line matching network. The dc-dc converter modules are phase activated such that for n modules, each module is activated equally 360 degree/n out of phase with respect to a successive module. The phased activation of the converter modules, combined with the square current waveforms out of the step up transformers, allows the power supply to operate with greatly reduced output capacitance values which minimizes the stored energy available for discharge into an electron beam gun or the like during arcing. The present power supply also provides dynamic response to varying loads by controlling the voltage regulator duty cycle using simulated voltage feedback signals and voltage feedback loops. Circuitry is also provided for sensing incipient arc currents reflected at the output of the power supply and for simultaneously decoupling the power supply circuitry from the arcing load. 7 figs

Tarantula toxins use common surfaces for interacting with Kv and ASIC ion channels.

Science.gov (United States)

Gupta, Kanchan; Zamanian, Maryam; Bae, Chanhyung; Milescu, Mirela; Krepkiy, Dmitriy; Tilley, Drew C; Sack, Jon T; Yarov-Yarovoy, Vladimir; Kim, Jae Il; Swartz, Kenton J

2015-05-07

Tarantula toxins that bind to voltage-sensing domains of voltage-activated ion channels are thought to partition into the membrane and bind to the channel within the bilayer. While no structures of a voltage-sensor toxin bound to a channel have been solved, a structural homolog, psalmotoxin (PcTx1), was recently crystalized in complex with the extracellular domain of an acid sensing ion channel (ASIC). In the present study we use spectroscopic, biophysical and computational approaches to compare membrane interaction properties and channel binding surfaces of PcTx1 with the voltage-sensor toxin guangxitoxin (GxTx-1E). Our results show that both types of tarantula toxins interact with membranes, but that voltage-sensor toxins partition deeper into the bilayer. In addition, our results suggest that tarantula toxins have evolved a similar concave surface for clamping onto α-helices that is effective in aqueous or lipidic physical environments.

Heat-pump performance: voltage dip/sag, under-voltage and over-voltage

Directory of Open Access Journals (Sweden)

William J.B. Heffernan

2014-12-01

Full Text Available Reverse cycle air-source heat-pumps are an increasingly significant load in New Zealand and in many other countries. This has raised concern over the impact wide-spread use of heat-pumps may have on the grid. The characteristics of the loads connected to the power system are changing because of heat-pumps. Their performance during under-voltage events such as voltage dips has the potential to compound the event and possibly cause voltage collapse. In this study, results from testing six heat-pumps are presented to assess their performance at various voltages and hence their impact on voltage stability.

Mobile Sensing Systems

Science.gov (United States)

Macias, Elsa; Suarez, Alvaro; Lloret, Jaime

2013-01-01

Rich-sensor smart phones have made possible the recent birth of the mobile sensing research area as part of ubiquitous sensing which integrates other areas such as wireless sensor networks and web sensing. There are several types of mobile sensing: individual, participatory, opportunistic, crowd, social, etc. The object of sensing can be people-centered or environment-centered. The sensing domain can be home, urban, vehicular… Currently there are barriers that limit the social acceptance of mobile sensing systems. Examples of social barriers are privacy concerns, restrictive laws in some countries and the absence of economic incentives that might encourage people to participate in a sensing campaign. Several technical barriers are phone energy savings and the variety of sensors and software for their management. Some existing surveys partially tackle the topic of mobile sensing systems. Published papers theoretically or partially solve the above barriers. We complete the above surveys with new works, review the barriers of mobile sensing systems and propose some ideas for efficiently implementing sensing, fusion, learning, security, privacy and energy saving for any type of mobile sensing system, and propose several realistic research challenges. The main objective is to reduce the learning curve in mobile sensing systems where the complexity is very high. PMID:24351637

Mobile sensing systems.

Science.gov (United States)

Macias, Elsa; Suarez, Alvaro; Lloret, Jaime

2013-12-16

Rich-sensor smart phones have made possible the recent birth of the mobile sensing research area as part of ubiquitous sensing which integrates other areas such as wireless sensor networks and web sensing. There are several types of mobile sensing: individual, participatory, opportunistic, crowd, social, etc. The object of sensing can be people-centered or environment-centered. The sensing domain can be home, urban, vehicular… Currently there are barriers that limit the social acceptance of mobile sensing systems. Examples of social barriers are privacy concerns, restrictive laws in some countries and the absence of economic incentives that might encourage people to participate in a sensing campaign. Several technical barriers are phone energy savings and the variety of sensors and software for their management. Some existing surveys partially tackle the topic of mobile sensing systems. Published papers theoretically or partially solve the above barriers. We complete the above surveys with new works, review the barriers of mobile sensing systems and propose some ideas for efficiently implementing sensing, fusion, learning, security, privacy and energy saving for any type of mobile sensing system, and propose several realistic research challenges. The main objective is to reduce the learning curve in mobile sensing systems where the complexity is very high.

Mobile Sensing Systems

Directory of Open Access Journals (Sweden)

Elsa Macias

2013-12-01

Full Text Available Rich-sensor smart phones have made possible the recent birth of the mobile sensing research area as part of ubiquitous sensing which integrates other areas such as wireless sensor networks and web sensing. There are several types of mobile sensing: individual, participatory, opportunistic, crowd, social, etc. The object of sensing can be people-centered or environment-centered. The sensing domain can be home, urban, vehicular… Currently there are barriers that limit the social acceptance of mobile sensing systems. Examples of social barriers are privacy concerns, restrictive laws in some countries and the absence of economic incentives that might encourage people to participate in a sensing campaign. Several technical barriers are phone energy savings and the variety of sensors and software for their management. Some existing surveys partially tackle the topic of mobile sensing systems. Published papers theoretically or partially solve the above barriers. We complete the above surveys with new works, review the barriers of mobile sensing systems and propose some ideas for efficiently implementing sensing, fusion, learning, security, privacy and energy saving for any type of mobile sensing system, and propose several realistic research challenges. The main objective is to reduce the learning curve in mobile sensing systems where the complexity is very high.

A voltage regulator system with dynamic bandwidth boosting for passive UHF RFID transponders

International Nuclear Information System (INIS)

Shen Jinpeng; Wang Xin'an; Liu Shan; Li Shoucheng; Ruan Zhengkun

2013-01-01

This paper presents a voltage regulator system for passive UHF RFID transponders, which contains a rectifier, a limiter, and a regulator. The rectifier achieves power by rectifying the incoming RF energy. Due to the huge variation of the rectified voltage, a limiter at the rectifier output is used to clamp the rectified voltage. In this paper, the design of a limiter circuit is discussed in detail, which can provide a stable limiting voltage with low sensitivity to temperature variation and process dispersion. The key aspect of the voltage regulator system is the dynamic bandwidth boosting in the regulator. By sensing the excess current that is bypassed in the limiter during periods of excess energy, the bias current as well as the bandwidth of the regulator are increased, the output supply voltage can recover quickly from line transients during the periods of no RF energy to a full blast of RF energy. This voltage regulator system is implemented in a 0.18 μm CMOS process. (semiconductor integrated circuits)

Mitigation of Unbalanced Voltage Sags and Voltage Unbalance in CIGRE Low Voltage Distribution Network

DEFF Research Database (Denmark)

Mustafa, Ghullam; Bak-Jensen, Birgitte; Mahat, Pukar

2013-01-01

Any problem with voltage in a power network is undesirable as it aggravates the quality of the power. Power electronic devices such as Voltage Source Converter (VSC) based Static Synchronous Compensator (STATCOM) etc. can be used to mitigate the voltage problems in the distribution system...... to unbalanced faults. The compensation of unbalanced voltage sags and voltage unbalance in the CIGRE distribution network is done by using the four STATCOM compensators already existing in the test grid. The simulations are carried out in DIgSILENT power factory software version 15.0........ The voltage problems dealt with in this paper are to show how to mitigate unbalanced voltage sags and voltage unbalance in the CIGRE Low Voltage (LV) test network and net-works like this. The voltage unbalances, for the tested cases in the CIGRE LV test network are mainly due to single phase loads and due...

Stapled Voltage-Gated Calcium Channel (CaV) α-Interaction Domain (AID) Peptides Act As Selective Protein-Protein Interaction Inhibitors of CaV Function.

Science.gov (United States)

Findeisen, Felix; Campiglio, Marta; Jo, Hyunil; Abderemane-Ali, Fayal; Rumpf, Christine H; Pope, Lianne; Rossen, Nathan D; Flucher, Bernhard E; DeGrado, William F; Minor, Daniel L

2017-06-21

For many voltage-gated ion channels (VGICs), creation of a properly functioning ion channel requires the formation of specific protein-protein interactions between the transmembrane pore-forming subunits and cystoplasmic accessory subunits. Despite the importance of such protein-protein interactions in VGIC function and assembly, their potential as sites for VGIC modulator development has been largely overlooked. Here, we develop meta-xylyl (m-xylyl) stapled peptides that target a prototypic VGIC high affinity protein-protein interaction, the interaction between the voltage-gated calcium channel (Ca V ) pore-forming subunit α-interaction domain (AID) and cytoplasmic β-subunit (Ca V β). We show using circular dichroism spectroscopy, X-ray crystallography, and isothermal titration calorimetry that the m-xylyl staples enhance AID helix formation are structurally compatible with native-like AID:Ca V β interactions and reduce the entropic penalty associated with AID binding to Ca V β. Importantly, electrophysiological studies reveal that stapled AID peptides act as effective inhibitors of the Ca V α 1 :Ca V β interaction that modulate Ca V function in an Ca V β isoform-selective manner. Together, our studies provide a proof-of-concept demonstration of the use of protein-protein interaction inhibitors to control VGIC function and point to strategies for improved AID-based Ca V modulator design.

Maneuver from the Air Domain

Science.gov (United States)

2016-05-26

Overload From the previous discussion, cognitive maneuver seeks to degrade the enemy’s capacity for...in all domains, the ability to maneuver from the air domain in the cognitive sense, comes primarily from air power’s unique ability to overload the... cognitive maneuver mechanisms developed in the 1980s as part of broader maneuver warfare theory. The result is a proposed definition of maneuver from

Airship Sparse Array Antenna Radar Real Aperture Imaging Based on Compressed Sensing and Sparsity in Transform Domain

Directory of Open Access Journals (Sweden)

Li Liechen

2016-02-01

Full Text Available A conformal sparse array based on combined Barker code is designed for airship platform. The performance of the designed array such as signal-to-noise ratio is analyzed. Using the hovering characteristics of the airship, interferometry operation can be applied on the real aperture imaging results of two pulses, which can eliminate the random backscatter phase and make the image sparse in the transform domain. Building the relationship between echo and transform coefficients, the Compressed Sensing (CS theory can be introduced to solve the formula and achieving imaging. The image quality of the proposed method can reach the image formed by the full array imaging. The simulation results show the effectiveness of the proposed method.

Compressed sensing & sparse filtering

CERN Document Server

Carmi, Avishy Y; Godsill, Simon J

2013-01-01

This book is aimed at presenting concepts, methods and algorithms ableto cope with undersampled and limited data. One such trend that recently gained popularity and to some extent revolutionised signal processing is compressed sensing. Compressed sensing builds upon the observation that many signals in nature are nearly sparse (or compressible, as they are normally referred to) in some domain, and consequently they can be reconstructed to within high accuracy from far fewer observations than traditionally held to be necessary. Apart from compressed sensing this book contains other related app

Optimized expression and purification of NavAb provide the structural insight into the voltage dependence.

Science.gov (United States)

Irie, Katsumasa; Haga, Yukari; Shimomura, Takushi; Fujiyoshi, Yoshinori

2018-01-01

Voltage-gated sodium channels are crucial for electro-signalling in living systems. Analysis of the molecular mechanism requires both fine electrophysiological evaluation and high-resolution channel structures. Here, we optimized a dual expression system of NavAb, which is a well-established standard of prokaryotic voltage-gated sodium channels, for E. coli and insect cells using a single plasmid vector to analyse high-resolution protein structures and measure large ionic currents. Using this expression system, we evaluated the voltage dependence and determined the crystal structures of NavAb wild-type and two mutants, E32Q and N49K, whose voltage dependence were positively shifted and essential interactions were lost in voltage sensor domain. The structural and functional comparison elucidated the molecular mechanisms of the voltage dependence of prokaryotic voltage-gated sodium channels. © 2017 Federation of European Biochemical Societies.

A Neutron View of Proteins in Lipid Bilayers

Science.gov (United States)

White, Stephen

2012-02-01

Despite the growing number of atomic-resolution membrane protein structures, direct structural information about proteins in their native membrane environment is scarce. This problem is particularly relevant in the case of the highly-charged S1-S4 voltage- sensing domains responsible for nerve impulses, where interactions with the lipid bilayer are critical for the function of voltage-activated potassium channels. We have used neutron diffraction, solid-state nuclear magnetic resonance spectroscopy, and molecular dynamics simulations to investigate the structure and hydration of bilayer membranes containing S1-S4 voltage-sensing domains. Our results show that voltage sensors adopt transmembrane orientations, cause a modest reshaping of the surrounding lipid bilayer, and that water molecules intimately interact with the protein within the membrane. These structural findings reveal that voltage sensors have evolved to interact with the lipid membrane while keeping the energetic and structural perturbations to a minimum, and that water penetrates into the membrane to hydrate charged residues and shape the transmembrane electric field.

Ultrasonic guided wave sensing characteristics of large area thin piezo coating

Science.gov (United States)

Rathod, V. T.; Jeyaseelan, A. Antony; Dutta, Soma; Mahapatra, D. Roy

2017-10-01

This paper reports on the characterization method and performance enhancement of thin piezo coating for ultrasonic guided wave sensing applications. We deposited the coatings by an in situ slurry coating method and studied their guided wave sensing properties on a one-dimensional metallic beam as a substrate waveguide. The developed piezo coatings show good sensitivity to the longitudinal and flexural modes of guided waves. Sensing voltage due to the guided waves at various different ultrasonic frequencies shows a linear dependence on the thickness of the coating. The coatings also exhibit linear sensor output voltage with respect to the induced dynamic strain magnitude. Diameter/size of the piezo coatings strongly influences the voltage response in relation to the wavelength. The proposed method used a characterization set-up involving coated sensors, reference transducers and an analytical model to estimate the piezoelectric coefficient of the piezo coating. The method eliminates the size dependent effect on the piezo property accurately and gives further insight to design better sensors/filters with respect to frequency/wavelength of interest. The developed coatings will have interesting applications in structural health monitoring (SHM) and internet of things (IOT).

Voltage Control of Antiferromagnetic Phases at Near-Terahertz Frequencies

Science.gov (United States)

Barra, Anthony; Domann, John; Kim, Ki Wook; Carman, Greg

2018-03-01

A method to control antiferromagnetism using voltage-induced strain is proposed and theoretically examined. Voltage-induced magnetoelastic anisotropy is shown to provide sufficient torque to switch an antiferromagnetic domain 90° either from out of plane to in plane or between in-plane axes. Numerical results indicate that strain-mediated antiferromagnetic switching can occur in an 80-nm nanopatterned disk at frequencies approaching 1 THz but that the switching speed heavily depends on the system's mechanical design. Furthermore, the energy cost to induce magnetic switching is only 450 aJ, indicating that magnetoelastic control of antiferromagnetism is substantially more energy efficient than other approaches.

An impact analysis of the fault impedance on voltage sags

Energy Technology Data Exchange (ETDEWEB)

Ramos, Alessandro Candido Lopes [CELG - Companhia Energetica de Goias, Goiania, GO (Brazil). Generation and Transmission. System' s Operation Center], E-mail: alessandro.clr@celg.com.br; Batista, Adalberto Jose [Federal University of Goias (UFG), Goiania, GO (Brazil)], E-mail: batista@eee.ufg.br; Leborgne, Roberto Chouhy [Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil)], E-mail: rcl@ece.ufrgs.br; Emiliano, Pedro Henrique Mota, E-mail: ph@phph.com.br

2009-07-01

This paper presents an impact analysis of the fault impedance, in terms of its module and angle, on voltage sags caused by faults. Symmetrical and asymmetrical faults are simulated, at transmission and distribution lines, by using a frequency-domain fault simulation software called ANAFAS. Voltage sags are monitored at buses where sensitive end-users are connected. In order to overcome some intrinsic limitations of this software concerning its automatic execution for several cases, a computational tool was developed in Java programming language. This solution allows the automatic simulation of cases including the effect of the fault position, the fault type, and the proper fault impedance. The main conclusion is that the module and angle of the fault impedance can have a significant influence on voltage sag depending on the fault characteristics. (author)

Capacitive Sensing of Glucose in Electrolytes Using Graphene Quantum Capacitance Varactors.

Science.gov (United States)

Zhang, Yao; Ma, Rui; Zhen, Xue V; Kudva, Yogish C; Bühlmann, Philippe; Koester, Steven J

2017-11-08

A novel graphene-based variable capacitor (varactor) that senses glucose based on the quantum capacitance effect was successfully developed. The sensor utilizes a metal-oxide-graphene varactor device structure that is inherently compatible with passive wireless sensing, a key advantage for in vivo glucose sensing. The graphene varactors were functionalized with pyrene-1-boronic acid (PBA) by self-assembly driven by π-π interactions. Successful surface functionalization was confirmed by both Raman spectroscopy and capacitance-voltage characterization of the devices. Through glucose binding to the PBA, the glucose concentration in the buffer solutions modulates the level of electrostatic doping of the graphene surface to different degrees, which leads to capacitance changes and Dirac voltage shifts. These responses to the glucose concentration were shown to be reproducible and reversible over multiple measurement cycles, suggesting promise for eventual use in wireless glucose monitoring.

Lamellar multilayer hexadecylaniline-modified gold nanoparticle ...

Indian Academy of Sciences (India)

standard Wilhelmy plate was used for surface pressure sensing. Multilayer ... carried out on a JEOL model 1200EX instrument operated at an accelerating voltage of ... the gold nanoparticles within domains (and reorganization of the domains ...

Nonlinear current-voltage behavior in PZT thin films

Energy Technology Data Exchange (ETDEWEB)

Xiao, Mi; Zhang, Weikang; Zhang, Zebin; Li, Shida; Zhang, Ping; Lan, Kuibo [Tianjin University, School of Electrical and Information Engineering, Tianjin (China)

2017-05-15

In this paper, Pb(Zr{sub 0.52}Ti{sub 0.48})O{sub 3} (PZT) thin films were prepared by sol-gel synthesis and characterized by X-ray diffraction, field emission scanning electron microscopy and current-voltage measurements. Here, we demonstrate that in addition to the outstanding ferroelectric and dielectric properties, the PZT films also have remarkably nonlinear current-voltage characteristics. Considering the contact of semi-conductive grains in the PZT films, a double Schottky barrier (DSB) model may be responsible for such phenomena. The test results show that with the decrease of annealing temperature and the increase of the film thickness, the threshold voltages (V{sub th}) increase obviously. The maximum V{sub th} value of 60.95 V and the minimum value of 6.9 V in our experiments were obtained from the five-layered samples annealed at 600 C and the two-layered samples annealed at 700 C, respectively. As a result, PZT thin film may lead to efficient switching and sensing devices. (orig.)

Ferroelectric negative capacitance domain dynamics

Science.gov (United States)

Hoffmann, Michael; Khan, Asif Islam; Serrao, Claudy; Lu, Zhongyuan; Salahuddin, Sayeef; Pešić, Milan; Slesazeck, Stefan; Schroeder, Uwe; Mikolajick, Thomas

2018-05-01

Transient negative capacitance effects in epitaxial ferroelectric Pb(Zr0.2Ti0.8)O3 capacitors are investigated with a focus on the dynamical switching behavior governed by domain nucleation and growth. Voltage pulses are applied to a series connection of the ferroelectric capacitor and a resistor to directly measure the ferroelectric negative capacitance during switching. A time-dependent Ginzburg-Landau approach is used to investigate the underlying domain dynamics. The transient negative capacitance is shown to originate from reverse domain nucleation and unrestricted domain growth. However, with the onset of domain coalescence, the capacitance becomes positive again. The persistence of the negative capacitance state is therefore limited by the speed of domain wall motion. By changing the applied electric field, capacitor area or external resistance, this domain wall velocity can be varied predictably over several orders of magnitude. Additionally, detailed insights into the intrinsic material properties of the ferroelectric are obtainable through these measurements. A new method for reliable extraction of the average negative capacitance of the ferroelectric is presented. Furthermore, a simple analytical model is developed, which accurately describes the negative capacitance transient time as a function of the material properties and the experimental boundary conditions.

Scorpion β-toxin interference with NaV channel voltage sensor gives rise to excitatory and depressant modes

Science.gov (United States)

Leipold, Enrico; Borges, Adolfo

2012-01-01

Scorpion β toxins, peptides of ∼70 residues, specifically target voltage-gated sodium (NaV) channels to cause use-dependent subthreshold channel openings via a voltage–sensor trapping mechanism. This excitatory action is often overlaid by a not yet understood depressant mode in which NaV channel activity is inhibited. Here, we analyzed these two modes of gating modification by β-toxin Tz1 from Tityus zulianus on heterologously expressed NaV1.4 and NaV1.5 channels using the whole cell patch-clamp method. Tz1 facilitated the opening of NaV1.4 in a use-dependent manner and inhibited channel opening with a reversed use dependence. In contrast, the opening of NaV1.5 was exclusively inhibited without noticeable use dependence. Using chimeras of NaV1.4 and NaV1.5 channels, we demonstrated that gating modification by Tz1 depends on the specific structure of the voltage sensor in domain 2. Although residue G658 in NaV1.4 promotes the use-dependent transitions between Tz1 modification phenotypes, the equivalent residue in NaV1.5, N803, abolishes them. Gating charge neutralizations in the NaV1.4 domain 2 voltage sensor identified arginine residues at positions 663 and 669 as crucial for the outward and inward movement of this sensor, respectively. Our data support a model in which Tz1 can stabilize two conformations of the domain 2 voltage sensor: a preactivated outward position leading to NaV channels that open at subthreshold potentials, and a deactivated inward position preventing channels from opening. The results are best explained by a two-state voltage–sensor trapping model in that bound scorpion β toxin slows the activation as well as the deactivation kinetics of the voltage sensor in domain 2. PMID:22450487

Handheld Frequency Domain Vector EMI Sensing for UXO Discrimination

Science.gov (United States)

2010-07-01

MATERIALS AND METHODS: GEM-3D+ SOFTWARE 4.6 NSMS Modeling of GEM-3D+ and HAP Method parametrized by a Pasion Oldenburg type model and/or combined with...Sens., 39:1286–1293, June 2001. 33, 38 [9] Leonard R. Pasion and Douglas W. Oldenburg. A discrimination algorithm for UXO using time domain...Oct. 1969. 52, 69 [39] Nicolas Lhomme, Leonard R. Pasion , Stephen D. Billings, and Douglas W. Oldenburg. Inversion of frequency domain data

A genetically encoded tool kit for manipulating and monitoring membrane phosphatidylinositol 4,5-bisphosphate in intact cells.

Science.gov (United States)

Hertel, Fabian; Switalski, Agathe; Mintert-Jancke, Elisa; Karavassilidou, Katharina; Bender, Kirsten; Pott, Lutz; Kienitz, Marie-Cécile

2011-01-01

Most ion channels are regulated by phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)) in the cell membrane by diverse mechanisms. Important molecular tools to study ion channel regulation by PtdIns(4,5)P(2) in living cells have been developed in the past. These include fluorescent PH-domains as sensors for Förster resonance energy transfer (FRET), to monitor changes in plasma membrane(.) For controlled and reversible depletion of PtdIns(4,5)P(2), voltage-sensing phosphoinositide phosphatases (VSD) have been demonstrated as a superior tool, since they are independent of cellular signaling pathways. Combining these methods in intact cells requires multiple transfections. We used self-cleaving viral 2A-peptide sequences for adenovirus driven expression of the PH-domain of phospholipase-Cδ1 (PLCδ1) fused to ECFP and EYFP respectively and Ciona intestinalis VSP (Ci-VSP), from a single open reading frame (ORF) in adult rat cardiac myocytes. Expression and correct targeting of ECFP-PH-PLCδ1(,) EYFP-PH-PLCδ1, and Ci-VSP from a single tricistronic vector containing 2A-peptide sequences first was demonstrated in HEK293 cells by voltage-controlled FRET measurements and Western blotting. Adult rat cardiac myocytes expressed Ci-VSP and the two fluorescent PH-domains within 4 days after gene transfer using the vector integrated into an adenoviral construct. Activation of Ci-VSP by depolarization resulted in rapid changes in FRET ratio indicating depletion of PtdIns(4,5)P(2) in the plasma membrane. This was paralleled by inhibition of endogenous G protein activated K(+) (GIRK) current. By comparing changes in FRET and current, a component of GIRK inhibition by adrenergic receptors unrelated to depletion of PtdIns(4,5)P(2) was identified. Expression of a FRET sensor pair and Ci-VSP from a single ORF provides a useful approach to study regulation of ion channels by phosphoinositides in cell lines and transfection-resistant postmitotic cells. Generally, adenoviral

A genetically encoded tool kit for manipulating and monitoring membrane phosphatidylinositol 4,5-bisphosphate in intact cells.

Directory of Open Access Journals (Sweden)

Fabian Hertel

Full Text Available BACKGROUND: Most ion channels are regulated by phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5P(2 in the cell membrane by diverse mechanisms. Important molecular tools to study ion channel regulation by PtdIns(4,5P(2 in living cells have been developed in the past. These include fluorescent PH-domains as sensors for Förster resonance energy transfer (FRET, to monitor changes in plasma membrane(. For controlled and reversible depletion of PtdIns(4,5P(2, voltage-sensing phosphoinositide phosphatases (VSD have been demonstrated as a superior tool, since they are independent of cellular signaling pathways. Combining these methods in intact cells requires multiple transfections. We used self-cleaving viral 2A-peptide sequences for adenovirus driven expression of the PH-domain of phospholipase-Cδ1 (PLCδ1 fused to ECFP and EYFP respectively and Ciona intestinalis VSP (Ci-VSP, from a single open reading frame (ORF in adult rat cardiac myocytes. METHODS AND RESULTS: Expression and correct targeting of ECFP-PH-PLCδ1(, EYFP-PH-PLCδ1, and Ci-VSP from a single tricistronic vector containing 2A-peptide sequences first was demonstrated in HEK293 cells by voltage-controlled FRET measurements and Western blotting. Adult rat cardiac myocytes expressed Ci-VSP and the two fluorescent PH-domains within 4 days after gene transfer using the vector integrated into an adenoviral construct. Activation of Ci-VSP by depolarization resulted in rapid changes in FRET ratio indicating depletion of PtdIns(4,5P(2 in the plasma membrane. This was paralleled by inhibition of endogenous G protein activated K(+ (GIRK current. By comparing changes in FRET and current, a component of GIRK inhibition by adrenergic receptors unrelated to depletion of PtdIns(4,5P(2 was identified. CONCLUSIONS: Expression of a FRET sensor pair and Ci-VSP from a single ORF provides a useful approach to study regulation of ion channels by phosphoinositides in cell lines and transfection

Ontology-based classification of remote sensing images using spectral rules

Science.gov (United States)

Andrés, Samuel; Arvor, Damien; Mougenot, Isabelle; Libourel, Thérèse; Durieux, Laurent

2017-05-01

Earth Observation data is of great interest for a wide spectrum of scientific domain applications. An enhanced access to remote sensing images for "domain" experts thus represents a great advance since it allows users to interpret remote sensing images based on their domain expert knowledge. However, such an advantage can also turn into a major limitation if this knowledge is not formalized, and thus is difficult for it to be shared with and understood by other users. In this context, knowledge representation techniques such as ontologies should play a major role in the future of remote sensing applications. We implemented an ontology-based prototype to automatically classify Landsat images based on explicit spectral rules. The ontology is designed in a very modular way in order to achieve a generic and versatile representation of concepts we think of utmost importance in remote sensing. The prototype was tested on four subsets of Landsat images and the results confirmed the potential of ontologies to formalize expert knowledge and classify remote sensing images.

Taste sensing FET (TSFET)

Energy Technology Data Exchange (ETDEWEB)

Toko, K.; Yasuda, R.; Ezaki, S. [Kyushu University, Fukuoka (Japan); Fujiyoshi, T. [Kumamoto University, Kumamoto (Japan). Faculty of Engineering

1997-12-20

Taste can be quantified using a multichannel taste sensor with lipid/polymer membranes. Its sensitivity and stability are superior to those of humans. A present study is concerned with the first step of miniaturization and integration of the taste sensor with lipid/polymer membranes using FET. As a result, it was found that gate-source voltage of the taste sensing FET showed the same behaviors as the conventional taste sensor utilizing the membrane-potential change due to five kinds of taste substances. Discrimination of foodstuffs was very easy. A thin lipid membrane formed using LB technique was also tried. These results will open doors to fabrication of a miniaturized, integrated taste sensing system. 12 refs., 6 figs.

System for improving measurement accuracy of transducer by measuring transducer temperature and resistance change using thermoelectric voltages

Science.gov (United States)

Anderson, Karl F. (Inventor); Parker, Allen R., Jr. (Inventor)

1993-01-01

A constant current loop measuring system measures a property including the temperature of a sensor responsive to an external condition being measured. The measuring system includes thermocouple conductors connected to the sensor, sensing first and second induced voltages responsive to the external condition. In addition, the measuring system includes a current generator and reverser generating a constant current, and supplying the constant current to the thermocouple conductors in forward and reverse directions generating first and second measured voltages, and a determining unit receiving the first and second measured voltages from the current generator and reverser, and determining the temperature of the sensor responsive to the first and second measured voltages.

Apparatus for sensing radiation and providing electrical read out

International Nuclear Information System (INIS)

Michon, G.J.; Burke, H.K.

1975-01-01

In an array of radiation sensing devices each including a pair of closely coupled conductor-insulator-semiconductor cells on a common substrate, each of the devices is addressed in sequence for read out. Read out of a device is accomplished by reducing the amplitudes of the voltages on the cells of the device in sequence to inject charge stored in the cells into the substrate and by sensing such injected charge. The device is reset for the next cycle of operation by reestablishing voltages in sequence on the cells. Means are provided in the bulk of the substrate to collect injected charge to avoid recollection by the cells of the device of such charge which has not had sufficient time to recombine or diffuse in the substrate away from the vicinity of the cells. (auth)

Lower-Order Compensation Chain Threshold-Reduction Technique for Multi-Stage Voltage Multipliers.

Science.gov (United States)

Dell' Anna, Francesco; Dong, Tao; Li, Ping; Wen, Yumei; Azadmehr, Mehdi; Casu, Mario; Berg, Yngvar

2018-04-17

This paper presents a novel threshold-compensation technique for multi-stage voltage multipliers employed in low power applications such as passive and autonomous wireless sensing nodes (WSNs) powered by energy harvesters. The proposed threshold-reduction technique enables a topological design methodology which, through an optimum control of the trade-off among transistor conductivity and leakage losses, is aimed at maximizing the voltage conversion efficiency (VCE) for a given ac input signal and physical chip area occupation. The conducted simulations positively assert the validity of the proposed design methodology, emphasizing the exploitable design space yielded by the transistor connection scheme in the voltage multiplier chain. An experimental validation and comparison of threshold-compensation techniques was performed, adopting 2N5247 N-channel junction field effect transistors (JFETs) for the realization of the voltage multiplier prototypes. The attained measurements clearly support the effectiveness of the proposed threshold-reduction approach, which can significantly reduce the chip area occupation for a given target output performance and ac input signal.

Structural properties and sensing characteristics of high-k Ho2O3 sensing film-based electrolyte-insulator-semiconductor

International Nuclear Information System (INIS)

Pan, Tung-Ming; Huang, Ming-De

2011-01-01

Highlights: → We report the structural properties and sensing characteristics of Ho 2 O 3 sensing membranes deposited on Si substrates by reactive sputtering. → We applied X-ray diffraction, X-ray photoelectron spectroscopy, and atomic force microscopy to study the structural and morphological features of these films after they had been subjected to annealing at various temperatures (700 deg. C, 800 deg. C, and 900 deg. C). → The Ho 2 O 3 electrolyte-insulator-semiconductor device annealed at 800 deg. C exhibited a higher sensitivity, a lower hysteresis voltage, and a smaller drift rate than other annealing temperatures. - Abstract: In this study, we report a Ho 2 O 3 electrolyte-insulator-semiconductor (EIS) device films deposited on Si substrates through reactive sputtering. The effect of thermal annealing (700, 800, and 900 deg. C) on the structural and surface properties of Ho 2 O 3 sensing film was investigated by X-ray diffraction, X-ray photoelectron spectroscopy, and atomic force microscopy. We found that the EIS device with a Ho 2 O 3 sensing film annealed at 800 deg. C exhibited a higher sensitivity of ∼57 mV/pH, a lower hysteresis voltage of 2.68 mV, and a smaller drift rate of 2.83 mV h -1 compared to those at other annealing conditions. This improvement can be attributed to the well-crystallized Ho 2 O 3 structure and the large surface roughness.

Coordinated Voltage Control of Distributed PV Inverters for Voltage Regulation in Low Voltage Distribution Networks

DEFF Research Database (Denmark)

Nainar, Karthikeyan; Pokhrel, Basanta Raj; Pillai, Jayakrishnan Radhakrishna

2017-01-01

This paper reviews and analyzes the existing voltage control methods of distributed solar PV inverters to improve the voltage regulation and thereby the hosting capacity of a low-voltage distribution network. A novel coordinated voltage control method is proposed based on voltage sensitivity...... optimization. The proposed method is used to calculate the voltage bands and droop settings of PV inverters at each node by the supervisory controller. The local controller of each PV inverter implements the volt/var control and if necessary, the active power curtailment as per the received settings and based...... on measured local voltages. The advantage of the proposed method is that the calculated reactive power and active power droop settings enable fair contribution of the PV inverters at each node to the voltage regulation. Simulation studies are conducted using DigSilent Power factory software on a simplified...

Detecting Power Voltage Dips using Tracking Filters - A Comparison against Kalman

Directory of Open Access Journals (Sweden)

STANCIU, I.-R.

2012-11-01

Full Text Available Due of its significant economical impact, Power-Quality (PQ analysis is an important domain today. Severe voltage distortions affect the consumers and disturb their activity. They may be caused by short circuits (in this case the voltage drops significantly or by varying loads (with a smaller drop. These two types are the PQ currently issues. Monitoring these phenomena (called dips or sags require powerful techniques. Digital Signal Processing (DSP algorithms are currently employed to fulfill this task. Discrete Wavelet Transforms, (and variants, Kalman filters, and S-Transform are currently proposed by researchers to detect voltage dips. This paper introduces and examines a new tool to detect voltage dips: the so-called tracking filters. Discovered and tested during the cold war, they can estimate a parameter of interest one-step-ahead based on the previously observed values. Two filters are implemented. Their performance is assessed by comparison against the Kalman filter?s results.

Interaction of C-70 fullerene with the Kv1.2 potassium channel

DEFF Research Database (Denmark)

Monticelli, L.; Barnoud, J.; Orlowskid, A.

2012-01-01

, both in the water-exposed loops and in the transmembrane helices. The tilt angle of transmembrane helices in the voltage-sensing domain appears to be affected by direct contact with fullerene, but a generic effect due to the small increase in membrane thickness might also play a role. A small rotation...... of the S3 and S4 helices in the voltage-sensing domain is noticed when C-70 is embedded in the membrane. The interpretation of the observed conformational changes is not straightforward due to the associated time scales, which are difficult to sample with state-of-the-art computing resources. We cannot...

Inversion of time-domain induced polarization data based on time-lapse concept

Science.gov (United States)

Kim, Bitnarae; Nam, Myung Jin; Kim, Hee Joon

2018-05-01

Induced polarization (IP) surveys, measuring overvoltage phenomena of the medium, are widely and increasingly performed not only for exploration of mineral resources but also for engineering applications. Among several IP survey methods such as time-domain, frequency-domain and spectral IP surveys, this study introduces a noble inversion method for time-domain IP data to recover the chargeability structure of target medium. The inversion method employs the concept of 4D inversion of time-lapse resistivity data sets, considering the fact that measured voltage in time-domain IP survey is distorted by IP effects to increase from the instantaneous voltage measured at the moment the source current injection starts. Even though the increase is saturated very fast, we can consider the saturated and instantaneous voltages as a time-lapse data set. The 4D inversion method is one of the most powerful method for inverting time-lapse resistivity data sets. Using the developed IP inversion algorithm, we invert not only synthetic but also field IP data to show the effectiveness of the proposed method by comparing the recovered chargeability models with those from linear inversion that was used for the inversion of the field data in a previous study. Numerical results confirm that the proposed inversion method generates reliable chargeability models even though the anomalous bodies have large IP effects.

The tarantula toxins ProTx-II and huwentoxin-IV differentially interact with human Nav1.7 voltage sensors to inhibit channel activation and inactivation.

Science.gov (United States)

Xiao, Yucheng; Blumenthal, Kenneth; Jackson, James O; Liang, Songping; Cummins, Theodore R

2010-12-01

The voltage-gated sodium channel Na(v)1.7 plays a crucial role in pain, and drugs that inhibit hNa(v)1.7 may have tremendous therapeutic potential. ProTx-II and huwentoxin-IV (HWTX-IV), cystine knot peptides from tarantula venoms, preferentially block hNa(v)1.7. Understanding the interactions of these toxins with sodium channels could aid the development of novel pain therapeutics. Whereas both ProTx-II and HWTX-IV have been proposed to preferentially block hNa(v)1.7 activation by trapping the domain II voltage-sensor in the resting configuration, we show that specific residues in the voltage-sensor paddle of domain II play substantially different roles in determining the affinities of these toxins to hNa(v)1.7. The mutation E818C increases ProTx-II's and HWTX-IV's IC(50) for block of hNa(v)1.7 currents by 4- and 400-fold, respectively. In contrast, the mutation F813G decreases ProTx-II affinity by 9-fold but has no effect on HWTX-IV affinity. It is noteworthy that we also show that ProTx-II, but not HWTX-IV, preferentially interacts with hNa(v)1.7 to impede fast inactivation by trapping the domain IV voltage-sensor in the resting configuration. Mutations E1589Q and T1590K in domain IV each decreased ProTx-II's IC(50) for impairment of fast inactivation by ~6-fold. In contrast mutations D1586A and F1592A in domain-IV increased ProTx-II's IC(50) for impairment of fast inactivation by ~4-fold. Our results show that whereas ProTx-II and HWTX-IV binding determinants on domain-II may overlap, domain II plays a much more crucial role for HWTX-IV, and contrary to what has been proposed to be a guiding principle of sodium channel pharmacology, molecules do not have to exclusively target the domain IV voltage-sensor to influence sodium channel inactivation.

Stress induced modulation of magnetic domain diffraction of single crystalline yttrium iron garnet

Science.gov (United States)

Mito, Shinichiro; Yoshihara, Yuki; Takagi, Hiroyuki; Inoue, Mitsuteru

2018-05-01

Stress induced modulation of the diffraction angle and efficiency of the light reflected from a stripe-domain magnetic garnet was demonstrated. The spacing of the magnetic domain was changed using the inverse magnetostriction effect. The sample structure was a piezo actuator/Al reflection layer/magnetic garnet substrate. A diffraction angle between the 0th and 1st ordered light was changed from 9.12 deg. to 10.20 deg. This result indicates that the domain spacing was changed from 3.3 μm to 3.0 μm. The change of the diffraction angle was irreversible for the voltage. However, reversible, linear and continuous change of the diffraction efficiency was observed. These results could be applicable for a voltage-driven optical solid state light deflector with low power consumption and high switching speed.

Mitigation of Voltage Sags in CIGRE Low Voltage Distribution Network

DEFF Research Database (Denmark)

Mustafa, Ghullam; Bak-Jensen, Birgitte; Mahat, Pukar

2013-01-01

Any problem in voltage in a power network is undesirable as it aggravates the quality of the power. Power electronic devices such as Voltage Source Converter (VSC) based Static Synchronous Compensator (STATCOM), Dynamic Voltage Restorer (DVR) etc. are commonly used for the mitigation of voltage p....... The compensation of voltage sags in the different parts of CIGRE distribution network is done by using the four STATCOM compensators already existing in the test grid. The simulations are carried out in DIgSILENT power factory software version 15.0.......Any problem in voltage in a power network is undesirable as it aggravates the quality of the power. Power electronic devices such as Voltage Source Converter (VSC) based Static Synchronous Compensator (STATCOM), Dynamic Voltage Restorer (DVR) etc. are commonly used for the mitigation of voltage...... problems in the distribution system. The voltage problems dealt with in this paper are to show how to mitigate voltage sags in the CIGRE Low Voltage (LV) test network and networks like this. The voltage sags, for the tested cases in the CIGRE LV test network are mainly due to three phase faults...

Development of a New Cascade Voltage-Doubler for Voltage Multiplication

OpenAIRE

Toudeshki, Arash; Mariun, Norman; Hizam, Hashim; Abdul Wahab, Noor Izzri

2014-01-01

For more than eight decades, cascade voltage-doubler circuits are used as a method to produce DC output voltage higher than the input voltage. In this paper, the topological developments of cascade voltage-doublers are reviewed. A new circuit configuration for cascade voltage-doubler is presented. This circuit can produce a higher value of the DC output voltage and better output quality compared to the conventional cascade voltage-doubler circuits, with the same number of stages.

Suppressing voltage transients in high voltage power supplies

International Nuclear Information System (INIS)

Lickel, K.F.; Stonebank, R.

1979-01-01

A high voltage power supply for an X-ray tubes includes voltage adjusting means, a high voltage transformer, switch means connected to make and interrupt the primary current of the transformer, and over-voltage suppression means to suppress the voltage transient produced when the current is switched on. In order to reduce the power losses in the suppression means, an impedance is connected in the transformer primary circuit on operation of the switch means and is subsequently short-circuited by a switch controlled by a timer after a period which is automatically adjusted to the duration of the transient overvoltage. (U.K.)

Accuracy of Voltage Signal Measurement During Radiofrequency Delivery Through the SMARTTOUCH Catheter.

Science.gov (United States)

Safavi-Naeini, Payam; Zafar-Awan, Dreema; Zhu, Hongjian; Zablah, Gerardo; Ganapathy, Anand V; Rasekh, Abdi; Saeed, Mohammad; Razavi, Joanna Esther Molina; Razavi, Mehdi

2017-01-01

Current methods for measuring voltage during radiofrequency (RF) ablation (RFA) necessitate turning off the ablation catheter. If voltage could be accurately read without signal attenuation during RFA, turning off the catheter would be unnecessary, allowing continuous ablation. We evaluated the accuracy of the Thermocool SMARTTOUCH catheter for measuring voltage while RF traverses the catheter. We studied 26 patients undergoing RFA for arrhythmias. A 7.5F SMARTTOUCH catheter was used for sensing voltage and performing RFA. Data were collected from the Carto-3 3-dimensional mapping system. Voltages were measured during ablation (RF-ON) and immediately before or after ablation (RF-OFF). In evaluating the accuracy of RF-ON measurements, we utilized the RF-OFF measure as the gold standard. We measured 465 voltage signals. The median values were 0.2900 and 0.3100 for RF-ON and RF-OFF, respectively. Wilcoxon signed rank testing showed no significant difference in these values (P = 0.608). The intraclass correlation coefficient (ICC) was 0.96, indicating that voltage measurements were similarly accurate during RF-OFF versus RF-ON. Five patients had baseline atrial fibrillation (AF), for whom 82 ablation points were measured; 383 additional ablation points were measured for the remaining patients. The voltages measured during RF-ON versus RF-OFF were similar in the presence of AF (P = 0.800) versus non-AF rhythm (P = 0.456) (ICC, 0.96 for both). Voltage signal measurement was similarly accurate during RF-ON versus RF-OFF independent of baseline rhythm. Physicians should consider not turning off the SMARTTOUCH ablation catheter when measuring voltage during RFA. © 2016 Wiley Periodicals, Inc.

Illuminating the early signaling pathway of a fungal light-oxygen-voltage photoreceptor.

Science.gov (United States)

Peter, Emanuel; Dick, Bernhard; Baeurle, Stephan A

2012-02-01

Circadian clocks are molecular timekeepers encountered in a wide variety of organisms, which allow to adapt the cell's metabolism and behavior to the daily and seasonal periods. Their function is regulated by light-sensing proteins, among which Vivid, a light-oxygen-voltage (LOV) sensitive domain of the fungus Neurospora crassa, constitutes one of the most prominent examples. Although the major photochemical and structural changes during the photocycle of this photosensor have been elucidated through experimental means, its signal transduction pathway is still poorly resolved at the molecular level. In this article, we show through molecular dynamics simulation that the primary steps after adduct formation involve a switch of Gln182 in vicinity of the chromophore FAD (flavin-adenine-dinucleotide), followed by a coupling between the Iβ- and Hβ-strands through H-bond formation between Gln182 and Asn161 as well as subsequent weakening of the H-bonding interaction between the Iβ- and Aβ-strands. These processes then induce a reorientation of the Aβ-Bβ-loop with respect to the protein core as well as a simultaneous contraction of the partially unfolded α-helix onto the α-Aβ-linker at the Ncap. Finally, we demonstrate through additional dimer simulations that the light-induced conformational changes, observed in the monomeric case, play a decisive role in controlling the dimerization tendency of Vivid with its partner domains and that the light-state homodimer shows a much larger affinity for aggregation than the dark state. Copyright © 2011 Wiley Periodicals, Inc.

Fast Coordinated Control of DFIG Wind Turbine Generators for Low and High Voltage Ride-Through

Directory of Open Access Journals (Sweden)

Yun Wang

2014-06-01

Full Text Available This paper presents a fast coordinated control scheme of the rotor side converter (RSC, the Direct Current (DC chopper and the grid side converter (GSC of doubly fed induction generator (DFIG wind turbine generators (WTGs to improve the low voltage ride through (LVRT and high voltage ride through (HVRT capability of the DFIG WTGs. The characteristics of DFIG WTGs under voltage sags and swells were studied focusing on the DFIG WTG stator flux and rotor voltages during the transient periods of grid voltage changes. The protection schemes of the rotor crowbar circuit and the DC chopper circuit were proposed considering the characteristics of the DFIG WTGs during voltage changes. The fast coordinated control of RSC and GSC were developed based on the characteristic analysis in order to realize efficient LVRT and HVRT of the DFIG WTGs. The proposed fast coordinated control schemes were verified by time domain simulations using Matlab-Simulink.

Cholesterol-induced conformational changes in the sterol-sensing domain of the Scap protein suggest feedback mechanism to control cholesterol synthesis.

Science.gov (United States)

Gao, Yansong; Zhou, Yulian; Goldstein, Joseph L; Brown, Michael S; Radhakrishnan, Arun

2017-05-26

Scap is a polytopic protein of endoplasmic reticulum (ER) membranes that transports sterol regulatory element-binding proteins to the Golgi complex for proteolytic activation. Cholesterol accumulation in ER membranes prevents Scap transport and decreases cholesterol synthesis. Previously, we provided evidence that cholesterol inhibition is initiated when cholesterol binds to loop 1 of Scap, which projects into the ER lumen. Within cells, this binding causes loop 1 to dissociate from loop 7, another luminal Scap loop. However, we have been unable to demonstrate this dissociation when we added cholesterol to isolated complexes of loops 1 and 7. We therefore speculated that the dissociation requires a conformational change in the intervening polytopic sequence separating loops 1 and 7. Here we demonstrate such a change using a protease protection assay in sealed membrane vesicles. In the absence of cholesterol, trypsin or proteinase K cleaved cytosolic loop 4, generating a protected fragment that we visualized with a monoclonal antibody against loop 1. When cholesterol was added to these membranes, cleavage in loop 4 was abolished. Because loop 4 is part of the so-called sterol-sensing domain separating loops 1 and 7, these results support the hypothesis that cholesterol binding to loop 1 alters the conformation of the sterol-sensing domain. They also suggest that this conformational change helps transmit the cholesterol signal from loop 1 to loop 7, thereby allowing separation of the loops and facilitating the feedback inhibition of cholesterol synthesis. These insights suggest a new structural model for cholesterol-mediated regulation of Scap activity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Electric-field-induced magnetic domain writing in a Co wire

Science.gov (United States)

Tanaka, Yuki; Hirai, Takamasa; Koyama, Tomohiro; Chiba, Daichi

2018-05-01

We have demonstrated that the local magnetization in a Co microwire can be switched by an application of a gate voltage without using any external magnetic fields. The electric-field-induced reversible ferromagnetic phase transition was used to realize this. An internal stray field from a ferromagnetic gate electrode assisted the local domain reversal in the Co wire. This new concept of electrical domain switching may be useful for dramatically reducing the power consumption of writing information in a magnetic racetrack memory, in which a shift of a magnetic domain by electric current is utilized.

Lower-Order Compensation Chain Threshold-Reduction Technique for Multi-Stage Voltage Multipliers

Directory of Open Access Journals (Sweden)

Francesco Dell’ Anna

2018-04-01

Full Text Available This paper presents a novel threshold-compensation technique for multi-stage voltage multipliers employed in low power applications such as passive and autonomous wireless sensing nodes (WSNs powered by energy harvesters. The proposed threshold-reduction technique enables a topological design methodology which, through an optimum control of the trade-off among transistor conductivity and leakage losses, is aimed at maximizing the voltage conversion efficiency (VCE for a given ac input signal and physical chip area occupation. The conducted simulations positively assert the validity of the proposed design methodology, emphasizing the exploitable design space yielded by the transistor connection scheme in the voltage multiplier chain. An experimental validation and comparison of threshold-compensation techniques was performed, adopting 2N5247 N-channel junction field effect transistors (JFETs for the realization of the voltage multiplier prototypes. The attained measurements clearly support the effectiveness of the proposed threshold-reduction approach, which can significantly reduce the chip area occupation for a given target output performance and ac input signal.

Optical fibre sensing of plasmas

International Nuclear Information System (INIS)

Woolsey, G.A.; Scelsi, G.B.

2000-01-01

The progress of optical fiber technology for communications has induced an interest in, among others, the sensing of a wide range of physical, and chemical quantities. Any application of optical fibers that are crucial for communication are significant for sensing, e.g. small dimension, insulating materials, immunity to high voltage field etc. In the present paper basic points of optical fiber sensing are summarized. It is noted optical fiber sensors come in two forms, intrinsic and extrinsic. In the former the fiber itself works as sensing element, in addition to data transmission lines. In an intrinsic sensor, a single fiber transmits the light from the source to the detector and the light is modulated while it is in the fiber. On the other hand, in the extrinsic sensor, the light leaves the input fiber to be modulated before being collected by the second output fiber. Characteristic of the light that can be modulated are amplitude, phase, polarization, and wavelength. The paper describes the modulation in some details. (author)

Optical fibre sensing of plasmas

Energy Technology Data Exchange (ETDEWEB)

Woolsey, G.A.; Scelsi, G.B. [School of Physical Sciences and Engineering, Univ. of New England, Armidale, NSW (Australia)

2000-03-01

The progress of optical fiber technology for communications has induced an interest in, among others, the sensing of a wide range of physical, and chemical quantities. Any application of optical fibers that are crucial for communication are significant for sensing, e.g. small dimension, insulating materials, immunity to high voltage field etc. In the present paper basic points of optical fiber sensing are summarized. It is noted optical fiber sensors come in two forms, intrinsic and extrinsic. In the former the fiber itself works as sensing element, in addition to data transmission lines. In an intrinsic sensor, a single fiber transmits the light from the source to the detector and the light is modulated while it is in the fiber. On the other hand, in the extrinsic sensor, the light leaves the input fiber to be modulated before being collected by the second output fiber. Characteristic of the light that can be modulated are amplitude, phase, polarization, and wavelength. The paper describes the modulation in some details. (author)

Method and apparatus for controlling LCL converters using asymmetric voltage cancellation techniques

Science.gov (United States)

Wu, Hunter; Sealy, Kylee Devro; Sharp, Bryan Thomas; Gilchrist, Aaron

2016-01-26

A method and apparatus for LCL resonant converter control utilizing Asymmetric Voltage Cancellation is described. The methods to determine the optimal trajectory of the control variables are discussed. Practical implementations of sensing load parameters are included. Simple PI, PID and fuzzy logic controllers are included with AVC for achieving good transient response characteristics with output current regulation.

Transient voltage sharing in series-coupled high voltage switches

Directory of Open Access Journals (Sweden)

Editorial Office

1992-07-01

Full Text Available For switching voltages in excess of the maximum blocking voltage of a switching element (for example, thyristor, MOSFET or bipolar transistor such elements are often coupled in series - and additional circuitry has to be provided to ensure equal voltage sharing. Between each such series element and system ground there is a certain parasitic capacitance that may draw a significant current during high-speed voltage transients. The "open" switch is modelled as a ladder network. Analy­sis reveals an exponential progression in the distribution of the applied voltage across the elements. Overstressing thus oc­curs in some of the elements at levels of the total voltage that are significantly below the design value. This difficulty is overcome by grading the voltage sharing circuitry, coupled in parallel with each element, in a prescribed manner, as set out here.

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

Science.gov (United States)

Chowdhury, Sandipan

2013-01-01

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

Power conditioning using dynamic voltage restorers under different voltage sag types.

Science.gov (United States)

Saeed, Ahmed M; Abdel Aleem, Shady H E; Ibrahim, Ahmed M; Balci, Murat E; El-Zahab, Essam E A

2016-01-01

Voltage sags can be symmetrical or unsymmetrical depending on the causes of the sag. At the present time, one of the most common procedures for mitigating voltage sags is by the use of dynamic voltage restorers (DVRs). By definition, a DVR is a controlled voltage source inserted between the network and a sensitive load through a booster transformer injecting voltage into the network in order to correct any disturbance affecting a sensitive load voltage. In this paper, modelling of DVR for voltage correction using MatLab software is presented. The performance of the device under different voltage sag types is described, where the voltage sag types are introduced using the different types of short-circuit faults included in the environment of the MatLab/Simulink package. The robustness of the proposed device is evaluated using the common voltage sag indices, while taking into account voltage and current unbalance percentages, where maintaining the total harmonic distortion percentage of the load voltage within a specified range is desired. Finally, several simulation results are shown in order to highlight that the DVR is capable of effective correction of the voltage sag while minimizing the grid voltage unbalance and distortion, regardless of the fault type.

The S4-S5 linker acts as a signal integrator for HERG K+ channel activation and deactivation gating.

Directory of Open Access Journals (Sweden)

Chai Ann Ng

Full Text Available 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.

Low Voltage Ride-Through Capability Solutions for Permanent Magnet Synchronous Wind Generators

Directory of Open Access Journals (Sweden)

Victor F. Mendes

2016-01-01

Full Text Available Due to the increasing number of wind power plants, several countries have modified their grid codes to include specific requirements for the connection of this technology to the power system. One of the requirements is the ride-through fault capability (RTFC, i.e., the system capability to sustain operation during voltage sags. In this sense, the present paper intends to investigate the behavior of a full-converter wind generator with a permanent magnet synchronous machine during symmetrical and asymmetrical voltage sags. Two solutions to improve the low voltage ride-through capability (LVRT of this technology are analyzed: discharging resistors (brake chopper and resonant controllers (RCs. The design and limitations of these solutions and the others proposed in the literature are discussed. Experimental results in a 34 kW test bench, which represents a scaled prototype of a real 2 MW wind conversion system, are presented.

Study of electric field distorted by space charges under positive lightning impulse voltage

Science.gov (United States)

Wang, Zezhong; Geng, Yinan

2018-03-01

Actually, many insulation problems are related to electric fields. And measuring electric fields is an important research topic of high-voltage engineering. In particular, the electric field distortion caused by space charge is the basis of streamer theory, and thus quantitatively measuring the Poisson electric field caused by space charge is significant to researching the mechanism of air gap discharge. In this paper, we used our photoelectric integrated sensor to measure the electric field distribution in a 1-m rod-plane gap under positive lightning impulse voltage. To verify the reliability of this quantitative measurement, we compared the measured results with calculated results from a numerical simulation. The electric-field time domain waveforms on the axis of the 1-m rod-plane out of the space charge zone were measured with various electrodes. The Poisson electric fields generated by space charge were separated from the Laplace electric field generated by applied voltages, and the amplitudes and variations were measured for various applied voltages and at various locations. This work also supplies the feasible basis for directly measuring strong electric field under high voltage.

Mitigation of voltage sags in the distribution system with dynamic voltage restorer

International Nuclear Information System (INIS)

Viglas, D.; Belan, A.

2012-01-01

Dynamic voltage restorer is a custom power device that is used to improve voltage sags or swells in electrical distribution system. The components of the Dynamic Voltage Restorer consist of injection transformers, voltage source inverter, passive filters and energy storage. The main function of the Dynamic voltage restorer is used to inject three phase voltage in series and in synchronism with the grid voltages in order to compensate voltage disturbances. This article deals with mitigation of voltage sags caused by three-phase short circuit. Dynamic voltage restorer is modelled in MATLAB/Simulink. (Authors)

A conserved glutamine plays a central role in LOV domain signal transmission and duration

Science.gov (United States)

Nash, Abigail I.; Ko, Wen-Huang; Harper, Shannon M.; Gardner, Kevin H.

2009-01-01

Light is a key stimulus for plant biological functions, several of which are controlled by light-activated kinases known as phototropins, a group of kinases that contain two light-sensing domains (LOV, Light-Oxygen-Voltage domains) and a C-terminal serine/threonine kinase domain. The second sensory domain, LOV2, plays a key role in regulating kinase enzymatic activity via the photochemical formation of a covalent adduct between a LOV2 cysteine residue and an internally-bound flavin mononucleotide (FMN) chromophore. Subsequent conformational changes in LOV2 lead to the unfolding of a peripheral Jα helix, and ultimately, phototropin kinase activation. To date, the mechanism coupling bond formation and helix dissociation has remained unclear. Previous studies found that a conserved glutamine residue (Q513 in the Avena sativa phototropin 1 LOV2 (AsLOV2) domain) switches its hydrogen-bonding pattern with FMN upon light stimulation. Located in the immediate vicinity of the FMN binding site, this Gln residue is provided by the Iβ strand that interacts with the Jα helix, suggesting a route for signal propagation from the core of the LOV domain to its peripheral Jα helix. To test whether Q513 plays a key role in tuning the photochemical and transduction properties of AsLOV2, we designed two point mutations, Q513L and Q513N, and monitored the effects on the chromophore and protein using a combination of UV-visible absorbance and circular dichroism spectroscopy, limited proteolysis, and solution NMR. The results show that these mutations significantly dampen the changes between the dark and lit state AsLOV2 structures, leaving the protein in a pseudo-dark state (Q513L) or a pseudo-lit state (Q513N) conformation. Further, both mutations changed the photochemical properties of this receptor, particularly the lifetime of the photoexcited signaling states. Together, these data establish that this residue plays a central role in both spectral tuning and signal propagation from

Designing sparse sensing matrix for compressive sensing to reconstruct high resolution medical images

Directory of Open Access Journals (Sweden)

Vibha Tiwari

2015-12-01

Full Text Available Compressive sensing theory enables faithful reconstruction of signals, sparse in domain $ \\Psi $, at sampling rate lesser than Nyquist criterion, while using sampling or sensing matrix $ \\Phi $ which satisfies restricted isometric property. The role played by sensing matrix $ \\Phi $ and sparsity matrix $ \\Psi $ is vital in faithful reconstruction. If the sensing matrix is dense then it takes large storage space and leads to high computational cost. In this paper, effort is made to design sparse sensing matrix with least incurred computational cost while maintaining quality of reconstructed image. The design approach followed is based on sparse block circulant matrix (SBCM with few modifications. The other used sparse sensing matrix consists of 15 ones in each column. The medical images used are acquired from US, MRI and CT modalities. The image quality measurement parameters are used to compare the performance of reconstructed medical images using various sensing matrices. It is observed that, since Gram matrix of dictionary matrix ($ \\Phi \\Psi \\mathrm{} $ is closed to identity matrix in case of proposed modified SBCM, therefore, it helps to reconstruct the medical images of very good quality.

EIT-based fabric pressure sensing.

Science.gov (United States)

Yao, A; Yang, C L; Seo, J K; Soleimani, M

2013-01-01

This paper presents EIT-based fabric sensors that aim to provide a pressure mapping using the current carrying and voltage sensing electrodes attached to the boundary of the fabric patch. Pressure-induced shape change over the sensor area makes a change in the conductivity distribution which can be conveyed to the change of boundary current-voltage data. This boundary data is obtained through electrode measurements in EIT system. The corresponding inverse problem is to reconstruct the pressure and deformation map from the relationship between the applied current and the measured voltage on the fabric boundary. Taking advantage of EIT in providing dynamical images of conductivity changes due to pressure induced shape change, the pressure map can be estimated. In this paper, the EIT-based fabric sensor was presented for circular and rectangular sensor geometry. A stretch sensitive fabric was used in circular sensor with 16 electrodes and a pressure sensitive fabric was used in a rectangular sensor with 32 electrodes. A preliminary human test was carried out with the rectangular sensor for foot pressure mapping showing promising results.

EIT-Based Fabric Pressure Sensing

Directory of Open Access Journals (Sweden)

A. Yao

2013-01-01

Full Text Available This paper presents EIT-based fabric sensors that aim to provide a pressure mapping using the current carrying and voltage sensing electrodes attached to the boundary of the fabric patch. Pressure-induced shape change over the sensor area makes a change in the conductivity distribution which can be conveyed to the change of boundary current-voltage data. This boundary data is obtained through electrode measurements in EIT system. The corresponding inverse problem is to reconstruct the pressure and deformation map from the relationship between the applied current and the measured voltage on the fabric boundary. Taking advantage of EIT in providing dynamical images of conductivity changes due to pressure induced shape change, the pressure map can be estimated. In this paper, the EIT-based fabric sensor was presented for circular and rectangular sensor geometry. A stretch sensitive fabric was used in circular sensor with 16 electrodes and a pressure sensitive fabric was used in a rectangular sensor with 32 electrodes. A preliminary human test was carried out with the rectangular sensor for foot pressure mapping showing promising results.

Voltage regulating circuit

NARCIS (Netherlands)

2005-01-01

A voltage regulating circuit comprising a rectifier (2) for receiving an AC voltage (Vmains) and for generating a rectified AC voltage (vrec), and a capacitor (3) connected in parallel with said rectified AC voltage for providing a DC voltage (VDC) over a load (5), characterized by a unidirectional

Performance evaluation of wideband bio-impedance spectroscopy using constant voltage source and constant current source

International Nuclear Information System (INIS)

Mohamadou, Youssoufa; Oh, Tong In; Wi, Hun; Sohal, Harsh; Farooq, Adnan; Woo, Eung Je; McEwan, Alistair Lee

2012-01-01

Current sources are widely used in bio-impedance spectroscopy (BIS) measurement systems to maximize current injection for increased signal to noise while keeping within medical safety specifications. High-performance current sources based on the Howland current pump with optimized impedance converters are able to minimize stray capacitance of the cables and setup. This approach is limited at high frequencies primarily due to the deteriorated output impedance of the constant current source when situated in a real measurement system. For this reason, voltage sources have been suggested, but they require a current sensing resistor, and the SNR reduces at low impedance loads due to the lower current required to maintain constant voltage. In this paper, we compare the performance of a current source-based BIS and a voltage source-based BIS, which use common components. The current source BIS is based on a Howland current pump and generalized impedance converters to maintain a high output impedance of more than 1 MΩ at 2 MHz. The voltage source BIS is based on voltage division between an internal current sensing resistor (R s ) and an external sample. To maintain high SNR, R s is varied so that the source voltage is divided more or less equally. In order to calibrate the systems, we measured the transfer function of the BIS systems with several known resistor and capacitor loads. From this we may estimate the resistance and capacitance of biological tissues using the least-squares method to minimize error between the measured transimpedance excluding the system transfer function and that from an impedance model. When tested on realistic loads including discrete resistors and capacitors, and saline and agar phantoms, the voltage source-based BIS system had a wider bandwidth of 10 Hz to 2.2 MHz with less than 1% deviation from the expected spectra compared to more than 10% with the current source. The voltage source also showed an SNR of at least 60 dB up to 2.2 MHz

Calibration of TAMA300 in time domain

International Nuclear Information System (INIS)

Telada, Souichi; Tatsumi, Daisuke; Akutsu, Tomomi; Ando, Masaki; Kanda, Nobuyuki

2005-01-01

We could reconstruct the strain of gravitational wave signals from acquired data in the time domain by using the infinite impulse response filter technique in TAMA300. We would like to analyse the waveform in the time domain for burst-like signal, merger phase waveform of binary neutron stars, and so on. We established the way to make a continuous time-series gravitational wave strain signal. We compared the time-domain reconstruction with the Fourier-space reconstruction. Both coincided within 3% in the observation range. We could also produce the voltage signal which would be recorded by the data-acquisition system from a simulated gravitational wave. This is useful for some analyses of simulations and signal injections. We could extract the waveform of the hardware injection signal in an observational run in the time domain. The extracted waveform was similar to the injection signal

Monitoring voltage-dependent charge displacement of Shaker B-IR K+ ion channels using radio frequency interrogation.

Directory of Open Access Journals (Sweden)

Sameera Dharia

2011-02-01

Full Text Available Here we introduce a new technique that probes voltage-dependent charge displacements of excitable membrane-bound proteins using extracellularly applied radio frequency (RF, 500 kHz electric fields. Xenopus oocytes were used as a model cell for these experiments, and were injected with cRNA encoding Shaker B-IR (ShB-IR K(+ ion channels to express large densities of this protein in the oocyte membranes. Two-electrode voltage clamp (TEVC was applied to command whole-cell membrane potential and to measure channel-dependent membrane currents. Simultaneously, RF electric fields were applied to perturb the membrane potential about the TEVC level and to measure voltage-dependent RF displacement currents. ShB-IR expressing oocytes showed significantly larger changes in RF displacement currents upon membrane depolarization than control oocytes. Voltage-dependent changes in RF displacement currents further increased in ShB-IR expressing oocytes after ∼120 µM Cu(2+ addition to the external bath. Cu(2+ is known to bind to the ShB-IR ion channel and inhibit Shaker K(+ conductance, indicating that changes in the RF displacement current reported here were associated with RF vibration of the Cu(2+-linked mobile domain of the ShB-IR protein. Results demonstrate the use of extracellular RF electrodes to interrogate voltage-dependent movement of charged mobile protein domains--capabilities that might enable detection of small changes in charge distribution associated with integral membrane protein conformation and/or drug-protein interactions.

Monitoring voltage-dependent charge displacement of Shaker B-IR K+ ion channels using radio frequency interrogation.

Science.gov (United States)

Dharia, Sameera; Rabbitt, Richard D

2011-02-28

Here we introduce a new technique that probes voltage-dependent charge displacements of excitable membrane-bound proteins using extracellularly applied radio frequency (RF, 500 kHz) electric fields. Xenopus oocytes were used as a model cell for these experiments, and were injected with cRNA encoding Shaker B-IR (ShB-IR) K(+) ion channels to express large densities of this protein in the oocyte membranes. Two-electrode voltage clamp (TEVC) was applied to command whole-cell membrane potential and to measure channel-dependent membrane currents. Simultaneously, RF electric fields were applied to perturb the membrane potential about the TEVC level and to measure voltage-dependent RF displacement currents. ShB-IR expressing oocytes showed significantly larger changes in RF displacement currents upon membrane depolarization than control oocytes. Voltage-dependent changes in RF displacement currents further increased in ShB-IR expressing oocytes after ∼120 µM Cu(2+) addition to the external bath. Cu(2+) is known to bind to the ShB-IR ion channel and inhibit Shaker K(+) conductance, indicating that changes in the RF displacement current reported here were associated with RF vibration of the Cu(2+)-linked mobile domain of the ShB-IR protein. Results demonstrate the use of extracellular RF electrodes to interrogate voltage-dependent movement of charged mobile protein domains--capabilities that might enable detection of small changes in charge distribution associated with integral membrane protein conformation and/or drug-protein interactions.

Microwave-Induced Magneto-Oscillations and Signatures of Zero-Resistance States in Phonon-Drag Voltage in Two-Dimensional Electron Systems.

Science.gov (United States)

Levin, A D; Momtaz, Z S; Gusev, G M; Raichev, O E; Bakarov, A K

2015-11-13

We observe the phonon-drag voltage oscillations correlating with the resistance oscillations under microwave irradiation in a two-dimensional electron gas in perpendicular magnetic field. This phenomenon is explained by the influence of dissipative resistivity modified by microwaves on the phonon-drag voltage perpendicular to the phonon flux. When the lowest-order resistance minima evolve into zero-resistance states, the phonon-drag voltage demonstrates sharp features suggesting that current domains associated with these states can exist in the absence of external dc driving.

Frequency-domain Harman technique for rapid characterization of bulk and thin film thermoelectric materials

Science.gov (United States)

Moran, Samuel

Nanostructured thermoelectrics, often in the form of thin films, may potentially improve the generally poor efficiency of bulk thermoelectric power generators and coolers. In order to characterize the efficiency of these new materials it is necessary to measure their thermoelectric figure of merit, ZT. The only direct measurement of ZT is based on the Harman technique and relies on measuring the voltage drop across a sample subjected to a passing continuous current. Application of this technique to thin films is currently carried out as a time-domain measurement of the voltage as the thermal component decays after switching off an applied voltage. This work develops a technique for direct simultaneous measurement of figure of merit and Seebeck coefficient from the harmonic response of a thermoelectric material under alternating current excitation. A thermocouple mounted on the top surface measures voltage across the device as the frequency of the applied voltage is varied. A thermal model allows the sample thermal conductivity to also be determined and shows good agreement with measurements. This technique provides improved signal-to-noise ratio and accuracy compared to time-domain ZT measurements for comparable conditions while simultaneously measuring Seebeck coefficient. The technique is applied to both bulk and thin film thermoelectric samples.

Self-Sensing Ionic Polymer Actuators: A Review

Directory of Open Access Journals (Sweden)

Karl Kruusamäe

2015-03-01

Full Text Available Ionic electromechanically active polymers (IEAP are laminar composites that can be considered attractive candidates for soft actuators. Their outstanding properties such as low operating voltage, easy miniaturization, and noiseless operation are, however, marred by issues related to the repeatability in the production and operation of these materials. Implementing closed-loop control for IEAP actuators is a viable option for overcoming these issues. Since IEAP laminates also behave as mechanoelectrical sensors, it is advantageous to combine the actuating and sensing functionalities of a single device to create a so-called self-sensing actuator. This review article systematizes the state of the art in producing self-sensing ionic polymer actuators. The IEAPs discussed in this paper are conducting (or conjugated polymers actuators (CPA, ionic polymer-metal composite (IPMC, and carbonaceous polymer laminates.

Individual hollow and mesoporous aero-graphitic microtube based devices for gas sensing applications

Science.gov (United States)

Lupan, Oleg; Postica, Vasile; Marx, Janik; Mecklenburg, Matthias; Mishra, Yogendra K.; Schulte, Karl; Fiedler, Bodo; Adelung, Rainer

2017-06-01

In this work, individual hollow and mesoporous graphitic microtubes were integrated into electronic devices using a FIB/SEM system and were investigated as gas and vapor sensors by applying different bias voltages (in the range of 10 mV-1 V). By increasing the bias voltage, a slight current enhancement is observed, which is mainly attributed to the self-heating effect. A different behavior of ammonia NH3 vapor sensing by increasing the applied bias voltage for hollow and mesoporous microtubes with diameters down to 300 nm is reported. In the case of the hollow microtube, an increase in the response was observed, while a reverse effect has been noticed for the mesoporous microtube. It might be explained on the basis of the higher specific surface area (SSA) of the mesoporous microtube compared to the hollow one. Thus, at room temperature when the surface chemical reaction rate (k) prevails on the gas diffusion rate (DK) the structures with a larger SSA possess a higher response. By increasing the bias voltage, i.e., the overall temperature of the structure, DK becomes a limiting step in the gas response. Therefore, at higher bias voltages the larger pores will facilitate an enhanced gas diffusion, i.e., a higher gas response. The present study demonstrates the importance of the material porosity towards gas sensing applications.

Cross domains Arabic named entity recognition system

Science.gov (United States)

Al-Ahmari, S. Saad; Abdullatif Al-Johar, B.

2016-07-01

Named Entity Recognition (NER) plays an important role in many Natural Language Processing (NLP) applications such as; Information Extraction (IE), Question Answering (QA), Text Clustering, Text Summarization and Word Sense Disambiguation. This paper presents the development and implementation of domain independent system to recognize three types of Arabic named entities. The system works based on a set of domain independent grammar-rules along with Arabic part of speech tagger in addition to gazetteers and lists of trigger words. The experimental results shown, that the system performed as good as other systems with better results in some cases of cross-domains corpora.

Magnetic domain-wall motion study under an electric field in a Finemet{sup ®} thin film on flexible substrate

Energy Technology Data Exchange (ETDEWEB)

Lan, Ngo Thi [Laboratoire des Sciences des Procédés et des Matériaux, CNRS-Université Paris XIII, 93430 Villetaneuse (France); Mercone, Silvana, E-mail: silvana.mercone@univ-paris13.fr [Laboratoire des Sciences des Procédés et des Matériaux, CNRS-Université Paris XIII, 93430 Villetaneuse (France); Moulin, Johan [Institut d' Electronique Fondamentale, UMR 8622 Université Paris Sud/CNRS, Orsay (France); Bahoui, Anouar El; Faurie, Damien; Zighem, Fatih; Belmeguenai, Mohamed; Haddadi, Halim [Laboratoire des Sciences des Procédés et des Matériaux, CNRS-Université Paris XIII, 93430 Villetaneuse (France)

2015-01-01

We study the influence of applied in-plane elastic strains on the static magnetic configuration of a 530 nm magnetostrictive FeCuNbSiB (Finemet{sup ®}) thin film. The in-plane strains are induced via the application of a voltage to a piezoelectric actuator on which the film/substrate system was glued. A quantitative characterization of the voltage dependence of the induced-strain at the surface of the film was performed using a digital image correlation technique. Magnetic Force Microscopy (MFM) images at remanence (H=0 Oe and U=0 V) clearly reveal the presence of weak stripe domains. The effect of the voltage-induced strain shows the existence of a voltage threshold value for the strike configuration break. For a maximum strain of ε{sub XX}∼0.5×10{sup −3} we succeed in destabilizing the stripes configuration helping the setting up of a complete homogeneous magnetic pattern. - Highlights: • Elastic strain effect on the magnetic domain structure of a Finemet/Kapton is investigated. • External loading is applied thanks to a piezo-actuator on which the sample is glued. • The amount of strains was measured by the Digital Image Correlation technique. • Magnetic Force Microscopy showed high mobility of magnetic stripes domains. • Bending, curving and branching of domains go into maze-like pattern.

Making Sense of the Abstraction Hierarchy in the Power Plant Domain

DEFF Research Database (Denmark)

Lind, Morten

2003-01-01

The paper discusses the abstraction hierarchy proposed by Rasmussen [(1986) Information processing and human-machine interaction, North-Holland] for design of human-machine interfaces for supervisory control. The purpose of the abstraction hierarchy is to represent a work domain by multiple levels...... of means-end and part-whole abstractions. It is argued in the paper that the abstraction hierarchy suffers from both methodological and conceptual problems. A cluster of selected problems are analyzed and illustrated by concrete examples from the power plant domain. It is concluded that the semantics...... in the model-building process. It is also pointed out that attempts to clarify the semantics of the abstraction hierarchy will invariably reduce the range of work domains where it can be applied....

Mapping organizational members' sense of fit

OpenAIRE

Billsberry, Jon; Marsh, Philip; Moss-Jones, John

2004-01-01

Despite its importance in the organizational behavior literature, person–organization (P–O) fit remains an elusive construct. One reason for this is the lack of research about organizational members’ own sense of their P–O fit. In this paper we report an empirical study that explored organizational members’ own sense of fit using storytelling and causal mapping techniques. The results suggest that organizational members categorize their perceptions of their fit into five discrete domains (job...

Stray voltage mitigation

Energy Technology Data Exchange (ETDEWEB)

Jamali, B.; Piercy, R.; Dick, P. [Kinetrics Inc., Toronto, ON (Canada). Transmission and Distribution Technologies

2008-04-09

This report discussed issues related to farm stray voltage and evaluated mitigation strategies and costs for limiting voltage to farms. A 3-phase, 3-wire system with no neutral ground was used throughout North America before the 1930s. Transformers were connected phase to phase without any electrical connection between the primary and secondary sides of the transformers. Distribution voltage levels were then increased and multi-grounded neutral wires were added. The earth now forms a parallel return path for the neutral current that allows part of the neutral current to flow continuously through the earth. The arrangement is responsible for causing stray voltage. Stray voltage causes uneven milk production, increased incidences of mastitis, and can create a reluctance to drink water amongst cows when stray voltages are present. Off-farm sources of stray voltage include phase unbalances, undersized neutral wire, and high resistance splices on the neutral wire. Mitigation strategies for reducing stray voltage include phase balancing; conversion from single to 3-phase; increasing distribution voltage levels, and changing pole configurations. 22 refs., 5 tabs., 13 figs.

Quantum Sensing for High Energy Physics

Energy Technology Data Exchange (ETDEWEB)

Ahmed, Zeeshan; et al.

2018-03-29

Report of the first workshop to identify approaches and techniques in the domain of quantum sensing that can be utilized by future High Energy Physics applications to further the scientific goals of High Energy Physics.

Reliability of supply of switchgear for auxiliary low voltage in substations extra high voltage to high voltage

Directory of Open Access Journals (Sweden)

Perić Dragoslav M.

2015-01-01

Full Text Available Switchgear for auxiliary low voltage in substations (SS of extra high voltages (EHV to high voltage (HV - SS EHV/HV kV/kV is of special interest for the functioning of these important SS, as it provides a supply for system of protection and other vital functions of SS. The article addresses several characteristic examples involving MV lines with varying degrees of independence of their supply, and the possible application of direct transformation EHV/LV through special voltage transformers. Auxiliary sources such as inverters and diesel generators, which have limited power and expensive energy, are also used for the supply of switchgear for auxiliary low voltage. Corresponding reliability indices are calculated for all examples including mean expected annual engagement of diesel generators. The applicability of certain solutions of switchgear for auxiliary low voltage SS EHV/HV, taking into account their reliability, feasibility and cost-effectiveness is analyzed too. In particular, the analysis of applications of direct transformation EHV/LV for supply of switchgear for auxiliary low voltage, for both new and existing SS EHV/HV.

Charge-pump voltage converter

Science.gov (United States)

Brainard, John P [Albuquerque, NM; Christenson, Todd R [Albuquerque, NM

2009-11-03

A charge-pump voltage converter for converting a low voltage provided by a low-voltage source to a higher voltage. Charge is inductively generated on a transfer rotor electrode during its transit past an inductor stator electrode and subsequently transferred by the rotating rotor to a collector stator electrode for storage or use. Repetition of the charge transfer process leads to a build-up of voltage on a charge-receiving device. Connection of multiple charge-pump voltage converters in series can generate higher voltages, and connection of multiple charge-pump voltage converters in parallel can generate higher currents. Microelectromechanical (MEMS) embodiments of this invention provide a small and compact high-voltage (several hundred V) voltage source starting with a few-V initial voltage source. The microscale size of many embodiments of this invention make it ideally suited for MEMS- and other micro-applications where integration of the voltage or charge source in a small package is highly desirable.

Preparation of Power Distribution System for High Penetration of Renewable Energy Part I. Dynamic Voltage Restorer for Voltage Regulation Pat II. Distribution Circuit Modeling and Validation

Science.gov (United States)

Khoshkbar Sadigh, Arash

by simulation and experimental tests under various conditions considering all possible cases such as different amounts of voltage sag depth (VSD), different amounts of point-on-wave (POW) at which voltage sag occurs, harmonic distortion, line frequency variation, and phase jump (PJ). Furthermore, the ripple amount of fundamental voltage amplitude calculated by the proposed method and its error is analyzed considering the line frequency variation together with harmonic distortion. The best and worst detection time of proposed method were measured 1ms and 8.8ms, respectively. Finally, the proposed method has been compared with other voltage sag detection methods available in literature. Part 2: Power System Modeling for Renewable Energy Integration: As power distribution systems are evolving into more complex networks, electrical engineers have to rely on software tools to perform circuit analysis. There are dozens of powerful software tools available in the market to perform the power system studies. Although their main functions are similar, there are differences in features and formatting structures to suit specific applications. This creates challenges for transferring power system circuit models data (PSCMD) between different software and rebuilding the same circuit in the second software environment. The objective of this part of thesis is to develop a Unified Platform (UP) to facilitate transferring PSCMD among different software packages and relieve the challenges of the circuit model conversion process. UP uses a commonly available spreadsheet file with a defined format, for any home software to write data to and for any destination software to read data from, via a script-based application called PSCMD transfer application. The main considerations in developing the UP are to minimize manual intervention and import a one-line diagram into the destination software or export it from the source software, with all details to allow load flow, short circuit and

High voltage systems

International Nuclear Information System (INIS)

Martin, M.

1991-01-01

Industrial processes usually require electrical power. This power is used to drive motors, to heat materials, or in electrochemical processes. Often the power requirements of a plant require the electric power to be delivered at high voltage. In this paper high voltage is considered any voltage over 600 V. This voltage could be as high as 138,000 V for some very large facilities. The characteristics of this voltage and the enormous amounts of power being transmitted necessitate special safety considerations. Safety must be considered during the four activities associated with a high voltage electrical system. These activities are: Design; Installation; Operation; and Maintenance

Surface potential domains on lamellar P3OT structures

Energy Technology Data Exchange (ETDEWEB)

Perez-GarcIa, B [Departamento Fisica, Facultad de Quimica (Campus Espinardo), Universidad de Murcia, E-30100 Murcia (Spain); Abad, J [Departamento Fisica, Facultad de Quimica (Campus Espinardo), Universidad de Murcia, E-30100 Murcia (Spain); Urbina, A [Departamento Electronica, TecnologIa de Computadoras y Proyectos, Universidad Politecnica de Cartagena, E-30202 Cartagena (Spain); Colchero, J [Departamento Fisica, Facultad de Quimica (Campus Espinardo), Universidad de Murcia, E-30100 Murcia (Spain); Palacios-Lidon, E [Departamento Fisica, Facultad de Quimica (Campus Espinardo), Universidad de Murcia, E-30100 Murcia (Spain)

2008-02-13

In this work the electrostatic properties of poly(3-octylthiophene) thin films have been studied on a nanometer scale by means of electrostatic force microscopy and Kelvin probe microscopy (KPM). The KPM images reveal that different surface contact potential domains coexist on the polymer surface. This result, together with additional capacitance measurements, indicates that the potential domains are related to the existence of dipoles due to different molecular arrangements. Finally, capacitance measurements as a function of the tip-sample bias voltage show that in all regions large band bending effects take place.

Surface potential domains on lamellar P3OT structures

International Nuclear Information System (INIS)

Perez-GarcIa, B; Abad, J; Urbina, A; Colchero, J; Palacios-Lidon, E

2008-01-01

In this work the electrostatic properties of poly(3-octylthiophene) thin films have been studied on a nanometer scale by means of electrostatic force microscopy and Kelvin probe microscopy (KPM). The KPM images reveal that different surface contact potential domains coexist on the polymer surface. This result, together with additional capacitance measurements, indicates that the potential domains are related to the existence of dipoles due to different molecular arrangements. Finally, capacitance measurements as a function of the tip-sample bias voltage show that in all regions large band bending effects take place

Prediction Reweighting for Domain Adaptation.

Science.gov (United States)

Shuang Li; Shiji Song; Gao Huang

2017-07-01

There are plenty of classification methods that perform well when training and testing data are drawn from the same distribution. However, in real applications, this condition may be violated, which causes degradation of classification accuracy. Domain adaptation is an effective approach to address this problem. In this paper, we propose a general domain adaptation framework from the perspective of prediction reweighting, from which a novel approach is derived. Different from the major domain adaptation methods, our idea is to reweight predictions of the training classifier on testing data according to their signed distance to the domain separator, which is a classifier that distinguishes training data (from source domain) and testing data (from target domain). We then propagate the labels of target instances with larger weights to ones with smaller weights by introducing a manifold regularization method. It can be proved that our reweighting scheme effectively brings the source and target domains closer to each other in an appropriate sense, such that classification in target domain becomes easier. The proposed method can be implemented efficiently by a simple two-stage algorithm, and the target classifier has a closed-form solution. The effectiveness of our approach is verified by the experiments on artificial datasets and two standard benchmarks, a visual object recognition task and a cross-domain sentiment analysis of text. Experimental results demonstrate that our method is competitive with the state-of-the-art domain adaptation algorithms.

Piezoelectric self-sensing actuator for active vibration control of motorized spindle based on adaptive signal separation

Science.gov (United States)

He, Ye; Chen, Xiaoan; Liu, Zhi; Qin, Yi

2018-06-01

The motorized spindle is the core component of CNC machine tools, and the vibration of it reduces the machining precision and service life of the machine tools. Owing to the fast response, large output force, and displacement of the piezoelectric stack, it is often used as the actuator in the active vibration control of the spindle. A piezoelectric self-sensing actuator (SSA) can reduce the cost of the active vibration control system and simplify the structure by eliminating the use of a sensor, because a SSA can have both actuating and sensing functions at the same time. The signal separation method of a SSA based on a bridge circuit is widely applied because of its simple principle and easy implementation. However, it is difficult to maintain dynamic balance of the circuit. Prior research has used adaptive algorithm to balance of the bridge circuit on the flexible beam dynamically, but those algorithms need no correlation between sensing and control voltage, which limit the applications of SSA in the vibration control of the rotor-bearing system. Here, the electromechanical coupling model of the piezoelectric stack is established, followed by establishment of the dynamic model of the spindle system. Next, a new adaptive signal separation method based on the bridge circuit is proposed, which can separate relative small sensing voltage from related mixed voltage adaptively. The experimental results show that when the self-sensing signal obtained from the proposed method is used as a displacement signal, the vibration of the motorized spindle can be suppressed effectively through a linear quadratic Gaussian (LQG) algorithm.

Investigating ion channel conformational changes using voltage clamp fluorometry.