Exploration of genetically encoded voltage indicators based on a chimeric voltage sensing domain.

Science.gov (United States)

Mishina, Yukiko; Mutoh, Hiroki; Song, Chenchen; Knöpfel, Thomas

2014-01-01

Deciphering how the brain generates cognitive function from patterns of electrical signals is one of the ultimate challenges in neuroscience. To this end, it would be highly desirable to monitor the activities of very large numbers of neurons while an animal engages in complex behaviors. Optical imaging of electrical activity using genetically encoded voltage indicators (GEVIs) has the potential to meet this challenge. Currently prevalent GEVIs are based on the voltage-sensitive fluorescent protein (VSFP) prototypical design or on the voltage-dependent state transitions of microbial opsins. We recently introduced a new VSFP design in which the voltage-sensing domain (VSD) is sandwiched between a fluorescence resonance energy transfer pair of fluorescent proteins (termed VSFP-Butterflies) and also demonstrated a series of chimeric VSD in which portions of the VSD of Ciona intestinalis voltage-sensitive phosphatase are substituted by homologous portions of a voltage-gated potassium channel subunit. These chimeric VSD had faster sensing kinetics than that of the native Ci-VSD. Here, we describe a new set of VSFPs that combine chimeric VSD with the Butterfly structure. We show that these chimeric VSFP-Butterflies can report membrane voltage oscillations of up to 200 Hz in cultured cells and report sensory evoked cortical population responses in living mice. This class of GEVIs may be suitable for imaging of brain rhythms in behaving mammalians.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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

Atomistic Modeling of Ion Conduction through the Voltage-Sensing Domain of the Shaker K+ Ion Channel.

Science.gov (United States)

Wood, Mona L; Freites, J Alfredo; Tombola, Francesco; Tobias, Douglas J

2017-04-20

Voltage-sensing domains (VSDs) sense changes in the membrane electrostatic potential and, through conformational changes, regulate a specific function. The VSDs of wild-type voltage-dependent K + , Na + , and Ca 2+ channels do not conduct ions, but they can become ion-permeable through pathological mutations in the VSD. Relatively little is known about the underlying mechanisms of conduction through VSDs. The most detailed studies have been performed on Shaker K + channel variants in which ion conduction through the VSD is manifested in electrophysiology experiments as a voltage-dependent inward current, the so-called omega current, which appears when the VSDs are in their resting state conformation. Only monovalent cations appear to permeate the Shaker VSD via a pathway that is believed to be, at least in part, the same as that followed by the S4 basic side chains during voltage-dependent activation. We performed μs-time scale atomistic molecular dynamics simulations of a cation-conducting variant of the Shaker VSD under applied electric fields in an experimentally validated resting-state conformation, embedded in a lipid bilayer surrounded by solutions containing guanidinium chloride or potassium chloride. Our simulations provide insights into the Shaker VSD permeation pathway, the protein-ion interactions that control permeation kinetics, and the mechanism of voltage-dependent activation of voltage-gated ion channels.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Regulation of Na+ channel inactivation by the DIII and DIV voltage-sensing domains.

Science.gov (United States)

Hsu, Eric J; Zhu, Wandi; Schubert, Angela R; Voelker, Taylor; Varga, Zoltan; Silva, Jonathan R

2017-03-06

Functional eukaryotic voltage-gated Na + (Na V ) channels comprise four domains (DI-DIV), each containing six membrane-spanning segments (S1-S6). Voltage sensing is accomplished by the first four membrane-spanning segments (S1-S4), which together form a voltage-sensing domain (VSD). A critical Na V channel gating process, inactivation, has previously been linked to activation of the VSDs in DIII and DIV. Here, we probe this interaction by using voltage-clamp fluorometry to observe VSD kinetics in the presence of mutations at locations that have been shown to impair Na V channel inactivation. These locations include the DIII-DIV linker, the DIII S4-S5 linker, and the DIV S4-S5 linker. Our results show that, within the 10-ms timeframe of fast inactivation, the DIV-VSD is the primary regulator of inactivation. However, after longer 100-ms pulses, the DIII-DIV linker slows DIII-VSD deactivation, and the rate of DIII deactivation correlates strongly with the rate of recovery from inactivation. Our results imply that, over the course of an action potential, DIV-VSDs regulate the onset of fast inactivation while DIII-VSDs determine its recovery. © 2017 Hsu et al.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

The voltage-sensing domain of a phosphatase gates the pore of a potassium channel.

Science.gov (United States)

Arrigoni, Cristina; Schroeder, Indra; Romani, Giulia; Van Etten, James L; Thiel, Gerhard; Moroni, Anna

2013-03-01

The modular architecture of voltage-gated K(+) (Kv) channels suggests that they resulted from the fusion of a voltage-sensing domain (VSD) to a pore module. Here, we show that the VSD of Ciona intestinalis phosphatase (Ci-VSP) fused to the viral channel Kcv creates Kv(Synth1), a functional voltage-gated, outwardly rectifying K(+) channel. Kv(Synth1) displays the summed features of its individual components: pore properties of Kcv (selectivity and filter gating) and voltage dependence of Ci-VSP (V(1/2) = +56 mV; z of ~1), including the depolarization-induced mode shift. The degree of outward rectification of the channel is critically dependent on the length of the linker more than on its amino acid composition. This highlights a mechanistic role of the linker in transmitting the movement of the sensor to the pore and shows that electromechanical coupling can occur without coevolution of the two domains.

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

Directory of Open Access Journals (Sweden)

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.

Science.gov (United States)

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.

Science.gov (United States)

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.

Science.gov (United States)

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.

Engineering of a genetically encodable fluorescent voltage sensor exploiting fast Ci-VSP voltage-sensing movements

DEFF Research Database (Denmark)

Lundby, Alicia; Mutoh, Hiroki; Dimitrov, Dimitar

2008-01-01

Ci-VSP contains a voltage-sensing domain (VSD) homologous to that of voltage-gated potassium channels. Using charge displacement ('gating' current) measurements we show that voltage-sensing movements of this VSD can occur within 1 ms in mammalian membranes. Our analysis lead to development...

Expression, purification, and reconstitution of the voltage-sensing domain from Ci-VSP.

Science.gov (United States)

Li, Qufei; Jogini, Vishwanath; Wanderling, Sherry; Cortes, D Marien; Perozo, Eduardo

2012-10-16

The voltage-sensing domain (VSD) is the common scaffold responsible for the functional behavior of voltage-gated ion channels, voltage sensitive enzymes, and proton channels. Because of the position of the voltage dependence of the available VSD structures, at present, they all represent the activated state of the sensor. Yet in the absence of a consensus resting state structure, the mechanistic details of voltage sensing remain controversial. The voltage dependence of the VSD from Ci-VSP (Ci-VSD) is dramatically right shifted, so that at 0 mV it presumably populates the putative resting state. Appropriate biochemical methods are an essential prerequisite for generating sufficient amounts of Ci-VSD protein for high-resolution structural studies. Here, we present a simple and robust protocol for the expression of eukaryotic Ci-VSD in Escherichia coli at milligram levels. The protein is pure, homogeneous, monodisperse, and well-folded after solubilization in Anzergent 3-14 at the analyzed concentration (~0.3 mg/mL). Ci-VSD can be reconstituted into liposomes of various compositions, and initial site-directed spin labeling and electron paramagnetic resonance (EPR) spectroscopic measurements indicate its first transmembrane segment folds into an α-helix, in agreement with the homologous region of other VSDs. On the basis of our results and enhanced relaxation EPR spectroscopy measurement, Ci-VSD reconstitutes essentially randomly in proteoliposomes, precluding straightforward application of transmembrane voltages in combination with spectroscopic methods. Nevertheless, these results represent an initial step that makes the resting state of a VSD accessible to a variety of biophysical and structural approaches, including X-ray crystallography, spectroscopic methods, and electrophysiology in lipid bilayers.

Expression, Purification and Reconstitution of the Voltage Sensing Domain from Ci-VSP

Science.gov (United States)

Li, Qufei; Jogini, Vishwanath; Wanderling, Sherry; Cortes, D. Marien; Perozo, Eduardo

2013-01-01

The voltage-sensing domain (VSD) is the common scaffold responsible for the functional behavior of voltage gated ion channels, voltage sensitive enzymes and proton channels. Because of the position of the voltage dependence of the available VSD structures, at present, they all represent the activated state of the sensor. Yet, in the absence of a consensus resting state structure, the mechanistic details of voltage sensing remain controversial. The voltage dependence of the VSD from Ci-VSP (Ci-VSD) is dramatically right shifted, so that at 0 mV It presumably populates the putative resting state. Appropriate biochemical methods are an essential prerequisite to generate sufficient amounts of Ci-VSD protein for high-resolution structural studies. Here, we present a simple and robust protocol for the Escherichia coli expression of eukaryotic Ci-VSD at milligram levels. The protein is pure, homogeneous, mono-disperse and well folded after solubilization in Anzergent 3-14 at the analyzed concentration (~ 0.3 mg/mL). Ci-VSD can be reconstituted into liposomes of various compositions and initial site-directed spin labeling and EPR spectroscopic measurements indicate its first transmembrane segment folds into an α-helix, in agreement to the homologous region of other VSDs. Based on current results and enhanced relaxation EPR spectroscopy measurement, Ci-VSD reconstitutes essentially randomly in proteo-liposomes, precluding straightforward application of transmembrane voltages in combination with spectroscopic methods. Nevertheless, the present results represent an initial step that makes the resting state of a VSD accessible to a variety of biophysical and structural approaches, including X-ray crystallography, spectroscopic methods and electrophysiology in lipid bilayers. PMID:22989304

Sensing charges of the Ciona intestinalis voltage-sensing phosphatase.

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Engineering of a genetically encodable fluorescent voltage sensor exploiting fast Ci-VSP voltage-sensing movements.

Science.gov (United States)

Lundby, Alicia; Mutoh, Hiroki; Dimitrov, Dimitar; Akemann, Walther; Knöpfel, Thomas

2008-06-25

Ci-VSP contains a voltage-sensing domain (VSD) homologous to that of voltage-gated potassium channels. Using charge displacement ('gating' current) measurements we show that voltage-sensing movements of this VSD can occur within 1 ms in mammalian membranes. Our analysis lead to development of a genetically encodable fluorescent protein voltage sensor (VSFP) in which the fast, voltage-dependent conformational changes of the Ci-VSP voltage sensor are transduced to similarly fast fluorescence read-outs.

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

Science.gov (United States)

Nakajo, Koichi; Kubo, Yoshihiro

2015-06-15

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

Engineering of a genetically encodable fluorescent voltage sensor exploiting fast Ci-VSP voltage-sensing movements.

Directory of Open Access Journals (Sweden)

Alicia Lundby

2008-06-01

Full Text Available Ci-VSP contains a voltage-sensing domain (VSD homologous to that of voltage-gated potassium channels. Using charge displacement ('gating' current measurements we show that voltage-sensing movements of this VSD can occur within 1 ms in mammalian membranes. Our analysis lead to development of a genetically encodable fluorescent protein voltage sensor (VSFP in which the fast, voltage-dependent conformational changes of the Ci-VSP voltage sensor are transduced to similarly fast fluorescence read-outs.

Enzyme domain affects the movement of the voltage sensor in ascidian and zebrafish voltage-sensing phosphatases.

Science.gov (United States)

Hossain, Md Israil; Iwasaki, Hirohide; Okochi, Yoshifumi; Chahine, Mohamed; Higashijima, Shinichi; Nagayama, Kuniaki; Okamura, Yasushi

2008-06-27

The ascidian voltage-sensing phosphatase (Ci-VSP) consists of the voltage sensor domain (VSD) and a cytoplasmic phosphatase region that has significant homology to the phosphatase and tensin homolog deleted on chromosome TEN (PTEN). The phosphatase activity of Ci-VSP is modified by the conformational change of the VSD. In many proteins, two protein modules are bidirectionally coupled, but it is unknown whether the phosphatase domain could affect the movement of the VSD in VSP. We addressed this issue by whole-cell patch recording of gating currents from a teleost VSP (Dr-VSP) cloned from Danio rerio expressed in tsA201 cells. Replacement of a critical cysteine residue, in the phosphatase active center of Dr-VSP, by serine sharpened both ON- and OFF-gating currents. Similar changes were produced by treatment with phosphatase inhibitors, pervanadate and orthovanadate, that constitutively bind to cysteine in the active catalytic center of phosphatases. The distinct kinetics of gating currents dependent on enzyme activity were not because of altered phosphatidylinositol 4,5-bisphosphate levels, because the kinetics of gating current did not change by depletion of phosphatidylinositol 4,5-bisphosphate, as reported by coexpressed KCNQ2/3 channels. These results indicate that the movement of the VSD is influenced by the enzymatic state of the cytoplasmic domain, providing an important clue for understanding mechanisms of coupling between the VSD and its effector.

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

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

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.

Science.gov (United States)

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.

Science.gov (United States)

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.

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

Science.gov (United States)

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

2011-05-06

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

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...

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

Science.gov (United States)

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

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

Science.gov (United States)

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.

Two distinct voltage-sensing domains control voltage sensitivity and kinetics of current activation in CaV1.1 calcium channels.

Science.gov (United States)

Tuluc, Petronel; Benedetti, Bruno; Coste de Bagneaux, Pierre; Grabner, Manfred; Flucher, Bernhard E

2016-06-01

Alternative splicing of the skeletal muscle CaV1.1 voltage-gated calcium channel gives rise to two channel variants with very different gating properties. The currents of both channels activate slowly; however, insertion of exon 29 in the adult splice variant CaV1.1a causes an ∼30-mV right shift in the voltage dependence of activation. Existing evidence suggests that the S3-S4 linker in repeat IV (containing exon 29) regulates voltage sensitivity in this voltage-sensing domain (VSD) by modulating interactions between the adjacent transmembrane segments IVS3 and IVS4. However, activation kinetics are thought to be determined by corresponding structures in repeat I. Here, we use patch-clamp analysis of dysgenic (CaV1.1 null) myotubes reconstituted with CaV1.1 mutants and chimeras to identify the specific roles of these regions in regulating channel gating properties. Using site-directed mutagenesis, we demonstrate that the structure and/or hydrophobicity of the IVS3-S4 linker is critical for regulating voltage sensitivity in the IV VSD, but by itself cannot modulate voltage sensitivity in the I VSD. Swapping sequence domains between the I and the IV VSDs reveals that IVS4 plus the IVS3-S4 linker is sufficient to confer CaV1.1a-like voltage dependence to the I VSD and that the IS3-S4 linker plus IS4 is sufficient to transfer CaV1.1e-like voltage dependence to the IV VSD. Any mismatch of transmembrane helices S3 and S4 from the I and IV VSDs causes a right shift of voltage sensitivity, indicating that regulation of voltage sensitivity by the IVS3-S4 linker requires specific interaction of IVS4 with its corresponding IVS3 segment. In contrast, slow current kinetics are perturbed by any heterologous sequences inserted into the I VSD and cannot be transferred by moving VSD I sequences to VSD IV. Thus, CaV1.1 calcium channels are organized in a modular manner, and control of voltage sensitivity and activation kinetics is accomplished by specific molecular mechanisms

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.

Allosteric substrate switching in a voltage-sensing lipid phosphatase.

Science.gov (United States)

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

Science.gov (United States)

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

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

The Voltage-Sensing Domain of K(v)7.2 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

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.

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

Science.gov (United States)

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.

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

NMR investigation of the isolated second voltage-sensing domain of human Nav1.4 channel.

Science.gov (United States)

Paramonov, A S; Lyukmanova, E N; Myshkin, M Yu; Shulepko, M A; Kulbatskii, D S; Petrosian, N S; Chugunov, A O; Dolgikh, D A; Kirpichnikov, M P; Arseniev, A S; Shenkarev, Z O

2017-03-01

Voltage-gated Na + channels are essential for the functioning of cardiovascular, muscular, and nervous systems. The α-subunit of eukaryotic Na + channel consists of ~2000 amino acid residues and encloses 24 transmembrane (TM) helices, which form five membrane domains: four voltage-sensing (VSD) and one pore domain. The structural complexity significantly impedes recombinant production and structural studies of full-sized Na + channels. Modular organization of voltage-gated channels gives an idea for studying of the isolated second VSD of human skeletal muscle Nav1.4 channel (VSD-II). Several variants of VSD-II (~150a.a., four TM helices) with different N- and C-termini were produced by cell-free expression. Screening of membrane mimetics revealed low stability of VSD-II samples in media containing phospholipids (bicelles, nanodiscs) associated with the aggregation of electrically neutral domain molecules. The almost complete resonance assignment of 13 C, 15 N-labeled VSD-II was obtained in LPPG micelles. The secondary structure of VSD-II showed similarity with the structures of bacterial Na + channels. The fragment of S4 TM helix between the first and second conserved Arg residues probably adopts 3 10 -helical conformation. Water accessibility of S3 helix, observed by the Mn 2+ titration, pointed to the formation of water-filled crevices in the micelle embedded VSD-II. 15 N relaxation data revealed characteristic pattern of μs-ms time scale motions in the VSD-II regions sharing expected interhelical contacts. VSD-II demonstrated enhanced mobility at ps-ns time scale as compared to isolated VSDs of K + channels. These results validate structural studies of isolated VSDs of Na + channels and show possible pitfalls in application of this 'divide and conquer' approach. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

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

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

Science.gov (United States)

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

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...

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)

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Science.gov (United States)

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

Science.gov (United States)

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

Voltage-controlled Enzymes: The new Janus Bifrons

Directory of Open Access Journals (Sweden)

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

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

Science.gov (United States)

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.

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.

Cytoplasmic Domains and Voltage-Dependent Potassium Channel Gating

Science.gov (United States)

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.

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

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.

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.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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

2015-01-01

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

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...

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

Science.gov (United States)

Cheng, Lan; Sanguinetti, Michael C

2009-05-01

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

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

Science.gov (United States)

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.

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.

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

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.

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

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

Science.gov (United States)

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

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.

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.

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.

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.

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

Science.gov (United States)

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.

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.

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

Directory of Open Access Journals (Sweden)

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.

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

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

Science.gov (United States)

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

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.

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

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.

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.

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.

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

Directory of Open Access Journals (Sweden)

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%.

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.

Science.gov (United States)

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

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

Science.gov (United States)

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

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

Science.gov (United States)

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

Science.gov (United States)

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.

Science.gov (United States)

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.

Global versus local mechanisms of temperature sensing in ion channels.

Science.gov (United States)

Arrigoni, Cristina; Minor, Daniel L

2018-05-01

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

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

Directory of Open Access Journals (Sweden)

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.

Directory of Open Access Journals (Sweden)

Janin Riedelsberger

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

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

Science.gov (United States)

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

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

Science.gov (United States)

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

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

Science.gov (United States)

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.

Directory of Open Access Journals (Sweden)

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).

Science.gov (United States)

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.

A Photostable Silicon Rhodamine Platform for Optical Voltage Sensing

Science.gov (United States)

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...

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

Science.gov (United States)

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.

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...

Mechanism of electromechanical coupling in voltage-gated potassium channels

Directory of Open Access Journals (Sweden)

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

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.

Dynamic hysteretic sensing model of bending-mode Galfenol transducer

International Nuclear Information System (INIS)

Cao, Shuying; Zheng, Jiaju; Sang, Jie; Zhang, Pengfei; Wang, Bowen; Huang, Wenmei

2015-01-01

A dynamic hysteretic sensing model has been developed to predict the dynamic responses of the magnetic induction, the stress, and the output voltage for a bending-mode Galfenol unimorph transducer subjected simultaneously to acceleration and bias magnetic field. This model is obtained by coupling the hysteretic Armstrong model and the structural dynamic model of the Galfenol unimorph beam. The structural dynamic model of the beam is founded based on the Euler-Bernouli beam theory, the nonlinear constitutive equations, and the Faraday law of electromagnetic induction. Comparisons between the calculated and measured results show the model can describe dynamic nonlinear voltage characteristics of the device, and can predict hysteretic behaviors between the magnetic induction and the stress. Moreover, the model can effectively analyze the effects of the bias magnetic field, the acceleration amplitude, and frequency on the root mean square voltage of the device

Dynamic hysteretic sensing model of bending-mode Galfenol transducer

Energy Technology Data Exchange (ETDEWEB)

Cao, Shuying, E-mail: shuying-cao@hebut.edu.cn; Zheng, Jiaju; Sang, Jie; Zhang, Pengfei; Wang, Bowen; Huang, Wenmei [Province-Ministry Joint Key Laboratory of Electromagnetic Field and Electrical Apparatus Reliability, Hebei University of Technology, Tianjin 300130 (China)

2015-05-07

A dynamic hysteretic sensing model has been developed to predict the dynamic responses of the magnetic induction, the stress, and the output voltage for a bending-mode Galfenol unimorph transducer subjected simultaneously to acceleration and bias magnetic field. This model is obtained by coupling the hysteretic Armstrong model and the structural dynamic model of the Galfenol unimorph beam. The structural dynamic model of the beam is founded based on the Euler-Bernouli beam theory, the nonlinear constitutive equations, and the Faraday law of electromagnetic induction. Comparisons between the calculated and measured results show the model can describe dynamic nonlinear voltage characteristics of the device, and can predict hysteretic behaviors between the magnetic induction and the stress. Moreover, the model can effectively analyze the effects of the bias magnetic field, the acceleration amplitude, and frequency on the root mean square voltage of the device.

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)

A CMOS Humidity Sensor for Passive RFID Sensing Applications

Directory of Open Access Journals (Sweden)

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.

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.

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.

Grafting voltage and pharmacological sensitivity in potassium channels.

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

RAMÓN LATORRE

2006-01-01

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

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

Science.gov (United States)

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.

Unified Impedance Model of Grid-Connected Voltage-Source Converters

DEFF Research Database (Denmark)

Wang, Xiongfei; Harnefors, Lennart; Blaabjerg, Frede

2018-01-01

This paper proposes a unified impedance model of grid-connected voltage-source converters for analyzing dynamic influences of the Phase-Locked Loop (PLL) and current control. The mathematical relations between the impedance models in the different domains are first explicitly revealed by means...... of complex transfer functions and complex space vectors. A stationary (αβ-) frame impedance model is then proposed, which not only predicts the stability impact of the PLL, but reveals also its frequency coupling effect explicitly. Furthermore, the impedance shaping effect of the PLL on the current control...... results and theoretical analysis confirm the effectiveness of the stationary-frame impedance model....

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.

Characterization of non-linear household loads for frequency domain modeling

Directory of Open Access Journals (Sweden)

Miguel Fernando Romero

2015-06-01

Full Text Available Component-based harmonic studies in public Low Voltage grids require realistic models of individual loads as well as their typical penetration ratios. As fundamental basis for the development of comprehensive models for residential users, this paper identifies the most commonly used household loads in Colombia. The loads are classified according to their Power Factor Correction (PFC circuit topology in no-PFC, passive-PFC and active-PFC devices, and a comprehensive set of loads is selected. Their behavior in terms of harmonic emission is characterized by intensive lab measurements with systematically varied supply voltage distortion. Based on several indices, the suitability of different frequency-domain modeling approaches (e.g. constant current source, decoupled and coupled Norton models is assessed.

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

Directory of Open Access Journals (Sweden)

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

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.

A Unified Impedance Model of Voltage-Source Converters with Phase-Locked Loop Effect

DEFF Research Database (Denmark)

Wang, Xiongfei; Harnefors, Lennart; Blaabjerg, Frede

2016-01-01

This paper proposes a unified impedance model for analyzing the effect of Phase-Locked Loop (PLL) on the stability of grid-connected voltage-source converters. In the approach, the dq-frame impedance model is transformed into the stationary αβ-frame by means of complex transfer functions...... and complex space vectors, which not only predicts the stability impact of the PLL, but reveals also its frequency coupling effect in the phase domain. Thus, the impedance models previously developed in the different domains can be unified. Moreover, the impedance shaping effects of PLL are structurally...... characterized for the current control in the rotating dq-frame and the stationary αβ-frame. Case studies based on the unified impedance model are presented, which are then verified in the time-domain simulations and experiments. The results closely correlate with the impedance-based analysis....

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

Directory of Open Access Journals (Sweden)

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.

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.

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.

Modeling charge polarization voltage for large lithium-ion batteries in electric vehicles

Directory of Open Access Journals (Sweden)

Yan Jiang

2013-06-01

Full Text Available Purpose: Polarization voltage of the lithium-ion battery is an important parameter that has direct influence on battery performance. The paper aims to analyze the impedance characteristics of the lithium-ion battery based on EIS data. Design/methodology/approach: The effects of currents, initial SOC of the battery on charge polarization voltage are investigated, which is approximately linear function of charge current. The change of charge polarization voltage is also analyzed with the gradient analytical method in the SOC domain. The charge polarization model with two RC networks is presented, and parts of model parameters like Ohmic resistance and charge transfer impedance are estimated by both EIS method and battery constant current testing method. Findings: This paper reveals that the Ohmic resistance accounts for much contribution to battery total polarization compared to charge transfer impedance. Practical implications: Experimental results demonstrate the efficacy of the model with the proposed identification method, which provides the foundation for battery charging optimization. Originality/value: The paper analyzed the impedance characteristics of the lithium-ion battery based on EIS data, presented a charge polarization model with two RC networks, and estimated parameters like Ohmic resistance and charge transfer impedance.

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

Science.gov (United States)

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.

Developing Fast Fluorescent Protein Voltage Sensors by Optimizing FRET Interactions.

Directory of Open Access Journals (Sweden)

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.

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.

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.

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).

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.

Evapotranspiration Within the Groundwater Model Domain of the Tuba City, Arizona, Disposal Site Interim Report

Energy Technology Data Exchange (ETDEWEB)

None, None

2015-03-01

The revised groundwater model includes estimates of evapotranspiration (ET). The types of vegetation and the influences of ET on groundwater hydrology vary within the model domain. Some plant species within the model domain, classified as phreatophytes, survive by extracting groundwater. ET within these plant communities can result in a net discharge of groundwater if ET exceeds precipitation. Other upland desert plants within the model domain survive on meteoric water, potentially limiting groundwater recharge if ET is equivalent to precipitation. For all plant communities within the model domain, excessive livestock grazing or other disturbances can tip the balance to a net groundwater recharge. This task characterized and mapped vegetation within the groundwater model domain at the Tuba City, Arizona, Site, and then applied a remote sensing algorithm to estimate ET for each vegetation type. The task was designed to address five objectives: 1. Characterize and delineate different vegetation or ET zones within the groundwater model domain, focusing on the separation of plant communities with phreatophytes that survive by tapping groundwater and upland plant communities that are dependent on precipitation. 2. Refine a remote sensing method, developed to estimate ET at the Monument Valley site, for application at the Tuba City site. 3. Estimate recent seasonal and annual ET for all vegetation zones, separating phreatophytic and upland plant communities within the Tuba City groundwater model domain. 4. For selected vegetation zones, estimate ET that might be achieved given a scenario of limited livestock grazing. 5. Analyze uncertainty of ET estimates for each vegetation zone and for the entire groundwater model domain.

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

Science.gov (United States)

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

Modeling and control of a self-sensing polymer metal composite actuator

International Nuclear Information System (INIS)

Nam, Doan Ngoc Chi; Ahn, Kyoung Kwan

2014-01-01

An ion polymer metal composite (IPMC) is an electro-active polymer (EAP) that bends in response to a small applied electrical field as a result of mobility of cations in the polymer network and vice versa. One drawback in the use of an IPMC is the sensing problem for such a small size actuator. The aim of this paper is to develop a physical model for a self-sensing IPMC actuator and to verify its applicability for practical position control. Firstly, ion dynamics inside a polymer membrane is investigated with an asymmetric solution in the presence of distributed surface resistance. Based on this analysis, a modified equivalent circuit and a simple configuration to realize the self-sensing IPMC actuator are proposed. Mathematical modelling and experimental evaluation indicate that the bending curvature can be obtained accurately using several feedback voltage signals along with the IPMC length. Finally, the controllability of the developed self-sensing IPMC actuator is investigated using a robust position control. Experimental results prove that the self-sensing characteristics can be applied in engineering control problems to provide a more convenient sensing method for IPMC actuating systems. (paper)

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

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

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.

Modeling and Simulation of Low Voltage Arcs

NARCIS (Netherlands)

Ghezzi, L.; Balestrero, A.

2010-01-01

Modeling and Simulation of Low Voltage Arcs is an attempt to improve the physical understanding, mathematical modeling and numerical simulation of the electric arcs that are found during current interruptions in low voltage circuit breakers. An empirical description is gained by refined electrical

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.

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

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

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...

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.

Estimation of Transmittance of Solar Radiation in the Visible Domain Based on Remote Sensing: Evaluation of Models Using In Situ Data

Science.gov (United States)

Zoffoli, M. Laura; Lee, Zhongping; Ondrusek, Michael; Lin, Junfang; Kovach, Charles; Wei, Jianwei; Lewis, Marlon

2017-11-01

The transmittance of solar radiation in the oceanic water column plays an important role in heat transfer and photosynthesis, with implications for the global carbon cycle, global circulation, and climate. Globally, the transmittance of solar radiation in the visible domain (˜400-700 nm) (TRVIS) through the water column, which determines the vertical distribution of visible light, has to be based on remote sensing products. There are models centered on chlorophyll-a (Chl) concentration or Inherent Optical Properties (IOPs) as both can be derived from ocean color measurements. We present evaluations of both schemes with field data from clear oceanic and from coastal waters. Here five models were evaluated: (1) Morel and Antoine (1994) (MA94), (2) Ohlmann and Siegel (2000) (OS00), (3) Murtugudde et al. (2002) (MU02), (4) Manizza et al. (2005) (MA05), and (5) Lee et al. ([Lee, Z., 2005]) (IOPs05), where the first four are Chl-based and the last one is IOPs-based, with all inputs derived from remote sensing reflectance. It is found that the best performing model is the IOPs05, with Unbiased Absolute Percent Difference (UAPD) ˜23%, while Chl-based models show higher uncertainties (UAPD for MA94: ˜54%, OS00: ˜133%, MU02: ˜56%, and MA05: ˜39%). The IOPs-based model was insensitive to the type of water, allowing it to be applied in most marine environments; whereas some of the Chl-based models (MU02 and MA05) show much higher sensitivities in coastal turbid waters (higher Chl waters). These results highlight the applicablity of using IOPs products for such applications.

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.

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

Directory of Open Access Journals (Sweden)

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.

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.

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.

Spatial pattern evaluation of a calibrated national hydrological model - a remote-sensing-based diagnostic approach

Science.gov (United States)

Mendiguren, Gorka; Koch, Julian; Stisen, Simon

2017-11-01

Distributed hydrological models are traditionally evaluated against discharge stations, emphasizing the temporal and neglecting the spatial component of a model. The present study widens the traditional paradigm by highlighting spatial patterns of evapotranspiration (ET), a key variable at the land-atmosphere interface, obtained from two different approaches at the national scale of Denmark. The first approach is based on a national water resources model (DK-model), using the MIKE-SHE model code, and the second approach utilizes a two-source energy balance model (TSEB) driven mainly by satellite remote sensing data. Ideally, the hydrological model simulation and remote-sensing-based approach should present similar spatial patterns and driving mechanisms of ET. However, the spatial comparison showed that the differences are significant and indicate insufficient spatial pattern performance of the hydrological model.The differences in spatial patterns can partly be explained by the fact that the hydrological model is configured to run in six domains that are calibrated independently from each other, as it is often the case for large-scale multi-basin calibrations. Furthermore, the model incorporates predefined temporal dynamics of leaf area index (LAI), root depth (RD) and crop coefficient (Kc) for each land cover type. This zonal approach of model parameterization ignores the spatiotemporal complexity of the natural system. To overcome this limitation, this study features a modified version of the DK-model in which LAI, RD and Kc are empirically derived using remote sensing data and detailed soil property maps in order to generate a higher degree of spatiotemporal variability and spatial consistency between the six domains. The effects of these changes are analyzed by using empirical orthogonal function (EOF) analysis to evaluate spatial patterns. The EOF analysis shows that including remote-sensing-derived LAI, RD and Kc in the distributed hydrological model adds

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.

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.

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.

High-Resolution Remote Sensing Image Building Extraction Based on Markov Model

Science.gov (United States)

Zhao, W.; Yan, L.; Chang, Y.; Gong, L.

2018-04-01

With the increase of resolution, remote sensing images have the characteristics of increased information load, increased noise, more complex feature geometry and texture information, which makes the extraction of building information more difficult. To solve this problem, this paper designs a high resolution remote sensing image building extraction method based on Markov model. This method introduces Contourlet domain map clustering and Markov model, captures and enhances the contour and texture information of high-resolution remote sensing image features in multiple directions, and further designs the spectral feature index that can characterize "pseudo-buildings" in the building area. Through the multi-scale segmentation and extraction of image features, the fine extraction from the building area to the building is realized. Experiments show that this method can restrain the noise of high-resolution remote sensing images, reduce the interference of non-target ground texture information, and remove the shadow, vegetation and other pseudo-building information, compared with the traditional pixel-level image information extraction, better performance in building extraction precision, accuracy and completeness.

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.

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.

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

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.

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.

Direct model-based predictive control scheme without cost function for voltage source inverters with reduced common-mode voltage

Science.gov (United States)

Kim, Jae-Chang; Moon, Sung-Ki; Kwak, Sangshin

2018-04-01

This paper presents a direct model-based predictive control scheme for voltage source inverters (VSIs) with reduced common-mode voltages (CMVs). The developed method directly finds optimal vectors without using repetitive calculation of a cost function. To adjust output currents with the CMVs in the range of -Vdc/6 to +Vdc/6, the developed method uses voltage vectors, as finite control resources, excluding zero voltage vectors which produce the CMVs in the VSI within ±Vdc/2. In a model-based predictive control (MPC), not using zero voltage vectors increases the output current ripples and the current errors. To alleviate these problems, the developed method uses two non-zero voltage vectors in one sampling step. In addition, the voltage vectors scheduled to be used are directly selected at every sampling step once the developed method calculates the future reference voltage vector, saving the efforts of repeatedly calculating the cost function. And the two non-zero voltage vectors are optimally allocated to make the output current approach the reference current as close as possible. Thus, low CMV, rapid current-following capability and sufficient output current ripple performance are attained by the developed method. The results of a simulation and an experiment verify the effectiveness of the developed method.

Vector spin modeling for magnetic tunnel junctions with voltage dependent effects

International Nuclear Information System (INIS)

Manipatruni, Sasikanth; Nikonov, Dmitri E.; Young, Ian A.

2014-01-01

Integration and co-design of CMOS and spin transfer devices requires accurate vector spin conduction modeling of magnetic tunnel junction (MTJ) devices. A physically realistic model of the MTJ should comprehend the spin torque dynamics of nanomagnet interacting with an injected vector spin current and the voltage dependent spin torque. Vector spin modeling allows for calculation of 3 component spin currents and potentials along with the charge currents/potentials in non-collinear magnetic systems. Here, we show 4-component vector spin conduction modeling of magnetic tunnel junction devices coupled with spin transfer torque in the nanomagnet. Nanomagnet dynamics, voltage dependent spin transport, and thermal noise are comprehended in a self-consistent fashion. We show comparison of the model with experimental magnetoresistance (MR) of MTJs and voltage degradation of MR with voltage. Proposed model enables MTJ circuit design that comprehends voltage dependent spin torque effects, switching error rates, spin degradation, and back hopping effects

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

Predicting detection performance with model observers: Fourier domain or spatial domain?

Science.gov (United States)

Chen, Baiyu; Yu, Lifeng; Leng, Shuai; Kofler, James; Favazza, Christopher; Vrieze, Thomas; McCollough, Cynthia

2016-02-27

The use of Fourier domain model observer is challenged by iterative reconstruction (IR), because IR algorithms are nonlinear and IR images have noise texture different from that of FBP. A modified Fourier domain model observer, which incorporates nonlinear noise and resolution properties, has been proposed for IR and needs to be validated with human detection performance. On the other hand, the spatial domain model observer is theoretically applicable to IR, but more computationally intensive than the Fourier domain method. The purpose of this study is to compare the modified Fourier domain model observer to the spatial domain model observer with both FBP and IR images, using human detection performance as the gold standard. A phantom with inserts of various low contrast levels and sizes was repeatedly scanned 100 times on a third-generation, dual-source CT scanner at 5 dose levels and reconstructed using FBP and IR algorithms. The human detection performance of the inserts was measured via a 2-alternative-forced-choice (2AFC) test. In addition, two model observer performances were calculated, including a Fourier domain non-prewhitening model observer and a spatial domain channelized Hotelling observer. The performance of these two mode observers was compared in terms of how well they correlated with human observer performance. Our results demonstrated that the spatial domain model observer correlated well with human observers across various dose levels, object contrast levels, and object sizes. The Fourier domain observer correlated well with human observers using FBP images, but overestimated the detection performance using IR images.

Method of controlling illumination device based on current-voltage model

DEFF Research Database (Denmark)

2013-01-01

The present invention relates to an illumination device comprising a number of LEDs, means for receiving an input signal, means for generating an activation signal for at least one of the LEDs based on the input signal. The illumination device comprises further means for obtaining the voltage...... and the colorimetric properties of said light emitted by LED. The present invention relates also to a method of controlling and a meted of calibrating such illumination device....... across and current through the LED and the means for generating the activation signal is adapted to generate the activating signal based on the voltage, the current and a current- voltage model related to LED. The current-voltage model defines a relationship between the current, the voltage...

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

Directory of Open Access Journals (Sweden)

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.

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

Impedance based time-domain modeling of lithium-ion batteries: Part I

Science.gov (United States)

Gantenbein, Sophia; Weiss, Michael; Ivers-Tiffée, Ellen

2018-03-01

This paper presents a novel lithium-ion cell model, which simulates the current voltage characteristic as a function of state of charge (0%-100%) and temperature (0-30 °C). It predicts the cell voltage at each operating point by calculating the total overvoltage from the individual contributions of (i) the ohmic loss η0, (ii) the charge transfer loss of the cathode ηCT,C, (iii) the charge transfer loss and the solid electrolyte interface loss of the anode ηSEI/CT,A, and (iv) the solid state and electrolyte diffusion loss ηDiff,A/C/E. This approach is based on a physically meaningful equivalent circuit model, which is parametrized by electrochemical impedance spectroscopy and time domain measurements, covering a wide frequency range from MHz to μHz. The model is exemplarily parametrized to a commercial, high-power 350 mAh graphite/LiNiCoAlO2-LiCoO2 pouch cell and validated by continuous discharge and charge curves at varying temperature. For the first time, the physical background of the model allows the operator to draw conclusions about the performance-limiting factor at various operating conditions. Not only can the model help to choose application-optimized cell characteristics, but it can also support the battery management system when taking corrective actions during operation.

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.

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

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....

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

Threshold voltage roll-off modelling of bilayer graphene field-effect transistors

International Nuclear Information System (INIS)

Saeidmanesh, M; Ismail, Razali; Khaledian, M; Karimi, H; Akbari, E

2013-01-01

An analytical model is presented for threshold voltage roll-off of double gate bilayer graphene field-effect transistors. To this end, threshold voltage models of short- and long-channel states have been developed. In the short-channel case, front and back gate potential distributions have been modelled and used. In addition, the tunnelling probability is modelled and its effect is taken into consideration in the potential distribution model. To evaluate the accuracy of the potential model, FlexPDE software is employed with proper boundary conditions and a good agreement is observed. Using the proposed models, the effect of several structural parameters on the threshold voltage and its roll-off are studied at room temperature. (paper)

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.

Generic domain models in software engineering

Science.gov (United States)

Maiden, Neil

1992-01-01

This paper outlines three research directions related to domain-specific software development: (1) reuse of generic models for domain-specific software development; (2) empirical evidence to determine these generic models, namely elicitation of mental knowledge schema possessed by expert software developers; and (3) exploitation of generic domain models to assist modelling of specific applications. It focuses on knowledge acquisition for domain-specific software development, with emphasis on tool support for the most important phases of software development.

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 ...

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.

Distributed electrical time domain reflectometry (ETDR) structural sensors: design models and proof-of-concept experiments

Science.gov (United States)

Stastny, Jeffrey A.; Rogers, Craig A.; Liang, Chen

1993-07-01

A parametric design model has been created to optimize the sensitivity of the sensing cable in a distributed sensing system. The system consists of electrical time domain reflectometry (ETDR) signal processing equipment and specially designed sensing cables. The ETDR equipment sends a high-frequency electric pulse (in the giga hertz range) along the sensing cable. Some portion of the electric pulse will be reflected back to the ETDR equipment as a result of the variation of the cable impedance. The electric impedance variation in the sensing cable can be related to its mechanical deformation, such as cable elongation (change in the resistance), shear deformation (change in the capacitance), corrosion of the cable or the materials around the cable (change in inductance and capacitance), etc. The time delay, amplitude, and shape of the reflected pulse provides the means to locate, determine the magnitude, and indicate the nature of the change in the electrical impedance, which is then related to the distributed structural deformation. The sensing cables are an essential part of the health-monitoring system. By using the parametric design model, the optimum cable parameters can be determined for specific deformation. Proof-of-concept experiments also are presented in the paper to demonstrate the utility of an electrical TDR system in distributed sensing applications.

Time-domain modeling of electromagnetic diffusion with a frequency-domain code

NARCIS (Netherlands)

Mulder, W.A.; Wirianto, M.; Slob, E.C.

2007-01-01

We modeled time-domain EM measurements of induction currents for marine and land applications with a frequency-domain code. An analysis of the computational complexity of a number of numerical methods shows that frequency-domain modeling followed by a Fourier transform is an attractive choice if a

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}.

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.

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

Directory of Open Access Journals (Sweden)

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.

Design of the robust synchronous generator stator voltage regulator based on the interval plant model

Directory of Open Access Journals (Sweden)

Stojić Đorđe

2013-01-01

Full Text Available In this paper a novel method for the stator voltage regulator of a synchronous generator based on the interval plant mode, is presented. Namely, it is shown in the literature that, in order to design a controller for the first-order compensator, the limited number of interval plants needs to be examined. Consequently, the intervals of the plant model parameter variations used to calculate the four extreme interval plants required for the sequential PI controller design are determined. The controller is designed using frequency-domain-based techniques, while its robust performance is examined using simulation tests.

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.

A model for voltage collapse study considering load characteristics

Energy Technology Data Exchange (ETDEWEB)

Aguiar, L B [Companhia de Energia Eletrica da Bahia (COELBA), Salvador, BA (Brazil)

1994-12-31

This paper presents a model for analysis of voltage collapse and instability problem considering the load characteristics. The model considers fundamentally the transmission lines represented by exact from through the generalized constants A, B, C, D and the loads as function of the voltage, emphasizing the cases of constant power, constant current and constant impedance. the study treats of the system behavior on steady state and presents illustrative graphics about the problem. (author) 12 refs., 4 figs.

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

Analytical drift-current threshold voltage model of long-channel double-gate MOSFETs

International Nuclear Information System (INIS)

Shih, Chun-Hsing; Wang, Jhong-Sheng

2009-01-01

This paper presents a new, physical threshold voltage model to solve the ambiguity in determining the threshold voltage of double-gate (DG) MOSFETs. To avoid the difficulties of the conventional 2ψ B model in nearly undoped DG MOSFETs, this study proposes to define the on–off switching based on the actual roles of the drift and diffusion components in the total drain current. The drift current strongly enhances beyond the threshold voltage, while the diffusion current plays a major role in the subthreshold. The threshold voltage is defined as the drift component that exceeds the diffusion counterpart. From the solutions of Poisson's equation, the drift and diffusion currents of DG MOSFETs are separately formulated to derive the analytical expressions of the threshold voltage and associated threshold current. This model provides a comprehensive description of the switching behavior of DG MOSFET devices, and offers a physical onset threshold current to determine the threshold voltage in practical extraction

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...

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.

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

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...

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.

Detection of Subtle Context-Dependent Model Inaccuracies in High-Dimensional Robot Domains.

Science.gov (United States)

Mendoza, Juan Pablo; Simmons, Reid; Veloso, Manuela

2016-12-01

Autonomous robots often rely on models of their sensing and actions for intelligent decision making. However, when operating in unconstrained environments, the complexity of the world makes it infeasible to create models that are accurate in every situation. This article addresses the problem of using potentially large and high-dimensional sets of robot execution data to detect situations in which a robot model is inaccurate-that is, detecting context-dependent model inaccuracies in a high-dimensional context space. To find inaccuracies tractably, the robot conducts an informed search through low-dimensional projections of execution data to find parametric Regions of Inaccurate Modeling (RIMs). Empirical evidence from two robot domains shows that this approach significantly enhances the detection power of existing RIM-detection algorithms in high-dimensional spaces.

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.

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.

TENCompetence Domain Model

NARCIS (Netherlands)

2006-01-01

This is the version 1.1 of the TENCompetence Domain Model (version 1.0 released at 19-6-2006; version 1.1 at 9-11-2008). It contains several files: a) a pdf with the model description, b) three jpg files with class models (also in the pdf), c) a MagicDraw zip file with the model itself, d) a release

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.

A micromagnetic study of domain structure modeling

International Nuclear Information System (INIS)

Matsuo, Tetsuji; Mimuro, Naoki; Shimasaki, Masaaki

2008-01-01

To develop a mesoscopic model for magnetic-domain behavior, a domain structure model (DSM) was examined and compared with a micromagnetic simulation. The domain structure of this model is given by several domains with uniform magnetization vectors and domain walls. The directions of magnetization vectors and the locations of domain walls are determined so as to minimize the magnetic total energy of the magnetic material. The DSM was modified to improve its representation capability for domain behavior. The domain wall energy is multiplied by a vanishing factor to represent the disappearance of magnetic domain. The sequential quadratic programming procedure is divided into two steps to improve an energy minimization process. A comparison with micromagnetic simulation shows that the modified DSM improves the representation accuracy of the magnetization process

Domain-Specific Modelling Languages in Bigraphs

DEFF Research Database (Denmark)

Perrone, Gian David

" of models, in order to improve the utility of the models we build, and to ease the process of model construction by moving the languages we use to express such models closer to their respective domains. This thesis is concerned with the study of bigraphical reactive systems as a host for domain...... for deciding reaction rule causation. Finally, we provide a mechanism for the modular construction of domain-specic modelling languages as bigraphical reactive systems, exploring the relationship between vertical renement and language specialisation in this setting. The thesis is composed of several...

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

Current-voltage model of LED light sources

DEFF Research Database (Denmark)

Beczkowski, Szymon; Munk-Nielsen, Stig

2012-01-01

Amplitude modulation is rarely used for dimming light-emitting diodes in polychromatic luminaires due to big color shifts caused by varying magnitude of LED driving current and nonlinear relationship between intensity of a diode and driving current. Current-voltage empirical model of light...

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

Time-domain modeling for shielding effectiveness of materials against electromagnetic pulse based on system identification

International Nuclear Information System (INIS)

Chen, Xiang; Chen, Yong Guang; Wei, Ming; Hu, Xiao Feng

2013-01-01

Shielding effectiveness (SE) of materials against electromagnetic pulse (EMP) cannot be well estimated by traditional test method of SE of materials which only consider the amplitude-frequency characteristic of materials, but ignore the phase-frequency ones. In order to solve this problem, the model of SE of materials against EMP was established based on system identification (SI) method with time-domain linear cosine frequency sweep signal. The feasibility of the method in this paper was examined depending on infinite planar material and the simulation research of coaxial test method and windowed semi-anechoic box of materials. The results show that the amplitude-frequency and phase-frequency information of each frequency can be fully extracted with this method. SE of materials against strong EMP can be evaluated with time-domain low field strength (voltage) of cosine frequency sweep signal. And SE of materials against a variety EMP will be predicted by the model.

Recording membrane potential changes through photoacoustic voltage sensitive dye

Science.gov (United States)

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.

New business models: the Agents and Inter-Agents in a neuroscientific domain

Directory of Open Access Journals (Sweden)

Michela Balconi

2017-04-01

Full Text Available Agency has been classically defined as the ability to sense and judge ourselves as the generators of an action and of its effects. In interactions, the ability to sense and consciously recognize that we – me and you – are the ones that are generating an action and causing its effects has been instead defined inter-agency or joint-agency. The implications of having developed good agency-related skills and of being aware of such processes become crucially important when we think at complex situations that characterize the real-life professional domain. Based on the crucial role of relationship with other social agents, cooperation and team-work for business and management activities, novel business models might benefit from an increased awareness of the way we and our co-workers plan, behave, make decisions, and manage action outcomes.

Analytic sensing for multi-layer spherical models with application to EEG source imaging

OpenAIRE

Kandaswamy, Djano; Blu, Thierry; Van De Ville, Dimitri

2013-01-01

Source imaging maps back boundary measurements to underlying generators within the domain; e. g., retrieving the parameters of the generating dipoles from electrical potential measurements on the scalp such as in electroencephalography (EEG). Fitting such a parametric source model is non-linear in the positions of the sources and renewed interest in mathematical imaging has led to several promising approaches. One important step in these methods is the application of a sensing principle that ...

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.

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

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.

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...

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

Science.gov (United States)

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.

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.

A new SOI high-voltage device with a step-thickness drift region and its analytical model for the electric field and breakdown voltage

International Nuclear Information System (INIS)

Luo Xiaorong; Zhang Wei; Zhang Bo; Li Zhaoji; Yang Shouguo; Zhan Zhan; Fu Daping

2008-01-01

A new SOI high-voltage device with a step-thickness drift region (ST SOI) and its analytical model for the two-dimension electric field distribution and the breakdown voltage are proposed. The electric field in the drift region is modulated and that of the buried layer is enhanced by the variable thickness SOI layer, thereby resulting in the enhancement of the breakdown voltage. Based on the Poisson equation, the expression for the two-dimension electric field distribution is presented taking the modulation effect into account, from which the RESURF (REduced SURface Field) condition and the approximate but explicit expression for the maximal breakdown voltage are derived. The analytical model can explain the effects of the device parameters, such as the step height and the step length of the SOI layer, the doping concentration and the buried oxide thickness, on the electric field distribution and the breakdown voltage. The validity of this model is demonstrated by a comparison with numerical simulations. Improvement on both the breakdown voltage and the on-resistance (R on ) for the ST SOI is obtained due to the variable thickness SOI layer

PSpice modeling of broadband RF cavities for transient and frequency domain simulations

Energy Technology Data Exchange (ETDEWEB)

Harzheim, Jens [Institut fuer Theorie Elektromagnetischer Felder, Fachgebiet Beschleunigertechnik, TU Darmstadt (Germany)

2016-07-01

In the future accelerator facility FAIR, Barrier-Bucket Systems will play an important role for different longitudinal beam manipulations. As the function of this type of system is to provide single sine gap voltages, the components of the system have to operate in a broad frequency range. To investigate the different effects and to design the different system components, the whole Barrier-Bucket System is to be modeled in PSpice. While for low power signals, the system shows linear behavior, nonlinear effects arise at higher amplitudes. Therefore, simulations in both, frequency and time domain are needed. The highly frequency dependent magnetic alloy ring cores of the future Barrier-Bucket cavity have been mod eled in a first step and based on these models, the whole cavity was analyzed in PSpice. The simulation results show good agreement with former measurements.

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.

Modeling Global Urbanization Supported by Nighttime Light Remote Sensing

Science.gov (United States)

Zhou, Y.

2015-12-01

Urbanization, a major driver of global change, profoundly impacts our physical and social world, for example, altering carbon cycling and climate. Understanding these consequences for better scientific insights and effective decision-making unarguably requires accurate information on urban extent and its spatial distributions. In this study, we developed a cluster-based method to estimate the optimal thresholds and map urban extents from the nighttime light remote sensing data, extended this method to the global domain by developing a computational method (parameterization) to estimate the key parameters in the cluster-based method, and built a consistent 20-year global urban map series to evaluate the time-reactive nature of global urbanization (e.g. 2000 in Fig. 1). Supported by urban maps derived from nightlights remote sensing data and socio-economic drivers, we developed an integrated modeling framework to project future urban expansion by integrating a top-down macro-scale statistical model with a bottom-up urban growth model. With the models calibrated and validated using historical data, we explored urban growth at the grid level (1-km) over the next two decades under a number of socio-economic scenarios. The derived spatiotemporal information of historical and potential future urbanization will be of great value with practical implications for developing adaptation and risk management measures for urban infrastructure, transportation, energy, and water systems when considered together with other factors such as climate variability and change, and high impact weather events.

Improved model predictive control for high voltage quality in microgrid applications

DEFF Research Database (Denmark)

Dragicevic, T.; Al hasheem, Mohamed; Lu, M.

2017-01-01

This paper proposes an improvement of the finite control set model predictive control (FCS-MPC) strategy for enhancing the voltage regulation performance of a voltage source converter (VSC) used for standalone microgrid and uninterrupted power supply (UPS) applications. The modification is based...

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

Science.gov (United States)

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.

A Review of Domain Modelling and Domain Imaging Techniques in Ferroelectric Crystals

Directory of Open Access Journals (Sweden)

John E. Huber

2011-02-01

Full Text Available The present paper reviews models of domain structure in ferroelectric crystals, thin films and bulk materials. Common crystal structures in ferroelectric materials are described and the theory of compatible domain patterns is introduced. Applications to multi-rank laminates are presented. Alternative models employing phase-field and related techniques are reviewed. The paper then presents methods of observing ferroelectric domain structure, including optical, polarized light, scanning electron microscopy, X-ray and neutron diffraction, atomic force microscopy and piezo-force microscopy. Use of more than one technique for unambiguous identification of the domain structure is also described.

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.

Computational optogenetics: empirically-derived voltage- and light-sensitive channelrhodopsin-2 model.

Directory of Open Access Journals (Sweden)

John C Williams

Full Text Available Channelrhodospin-2 (ChR2, a light-sensitive ion channel, and its variants have emerged as new excitatory optogenetic tools not only in neuroscience, but also in other areas, including cardiac electrophysiology. An accurate quantitative model of ChR2 is necessary for in silico prediction of the response to optical stimulation in realistic tissue/organ settings. Such a model can guide the rational design of new ion channel functionality tailored to different cell types/tissues. Focusing on one of the most widely used ChR2 mutants (H134R with enhanced current, we collected a comprehensive experimental data set of the response of this ion channel to different irradiances and voltages, and used these data to develop a model of ChR2 with empirically-derived voltage- and irradiance- dependence, where parameters were fine-tuned via simulated annealing optimization. This ChR2 model offers: 1 accurate inward rectification in the current-voltage response across irradiances; 2 empirically-derived voltage- and light-dependent kinetics (activation, deactivation and recovery from inactivation; and 3 accurate amplitude and morphology of the response across voltage and irradiance settings. Temperature-scaling factors (Q10 were derived and model kinetics was adjusted to physiological temperatures. Using optical action potential clamp, we experimentally validated model-predicted ChR2 behavior in guinea pig ventricular myocytes. The model was then incorporated in a variety of cardiac myocytes, including human ventricular, atrial and Purkinje cell models. We demonstrate the ability of ChR2 to trigger action potentials in human cardiomyocytes at relatively low light levels, as well as the differential response of these cells to light, with the Purkinje cells being most easily excitable and ventricular cells requiring the highest irradiance at all pulse durations. This new experimentally-validated ChR2 model will facilitate virtual experimentation in neural and

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

Model Predictive Voltage Control of Wind Power Plants

DEFF Research Database (Denmark)

Zhao, Haoran; Wu, Qiuwei

2018-01-01

the efficacy of the proposed WFVC, two case scenarios were designed: the wind farm is under normal operating conditions and the internal wind power fluctuation is considered; and besides internal power fluctuation, the impact of the external grid on the wind farm is considered.......This chapter proposes an autonomous wind farm voltage controller (WFVC) based on model predictive control (MPC). It also introduces the analytical expressions for the voltage sensitivity to tap positions of a transformer. The chapter then describes the discrete models for the wind turbine...... generators (WTGs) and static var compensators (SVCs)/static var generators (SVGs). Next, it describes the implementation of the on‐load tap changing (OLTC) in the MPC. Furthermore, the chapter examines the cost function as well as the constraints of the MPC‐based WFVC for both control modes. In order to test...

The SHOCT domain: a widespread domain under-represented in model organisms.

Directory of Open Access Journals (Sweden)

Ruth Y Eberhardt

Full Text Available We have identified a new protein domain, which we have named the SHOCT domain (Short C-terminal domain. This domain is widespread in bacteria with over a thousand examples. But we found it is missing from the most commonly studied model organisms, despite being present in closely related species. It's predominantly C-terminal location, co-occurrence with numerous other domains and short size is reminiscent of the Gram-positive anchor motif, however it is present in a much wider range of species. We suggest several hypotheses about the function of SHOCT, including oligomerisation and nucleic acid binding. Our initial experiments do not support its role as an oligomerisation domain.

Multi-Domain Modeling Based on Modelica

Directory of Open Access Journals (Sweden)

Liu Jun

2016-01-01

Full Text Available With the application of simulation technology in large-scale and multi-field problems, multi-domain unified modeling become an effective way to solve these problems. This paper introduces several basic methods and advantages of the multidisciplinary model, and focuses on the simulation based on Modelica language. The Modelica/Mworks is a newly developed simulation software with features of an object-oriented and non-casual language for modeling of the large, multi-domain system, which makes the model easier to grasp, develop and maintain.It This article shows the single degree of freedom mechanical vibration system based on Modelica language special connection mechanism in Mworks. This method that multi-domain modeling has simple and feasible, high reusability. it closer to the physical system, and many other advantages.

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.)

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).

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

Enhanced Voltage Control of VSC-HVDC Connected Offshore Wind Farms Based on Model Predictive Control

DEFF Research Database (Denmark)

Guo, Yifei; Gao, Houlei; Wu, Qiuwei

2018-01-01

This paper proposes an enhanced voltage control strategy (EVCS) based on model predictive control (MPC) for voltage source converter based high voltage direct current (VSCHVDC) connected offshore wind farms (OWFs). In the proposed MPC based EVCS, all wind turbine generators (WTGs) as well...... as the wind farm side VSC are optimally coordinated to keep voltages within the feasible range and reduce system power losses. Considering the high ratio of the OWF collector system, the effects of active power outputs of WTGs on voltage control are also taken into consideration. The predictive model of VSC...

Modeling generalized interline power-flow controller (GIPFC using 48-pulse voltage source converters

Directory of Open Access Journals (Sweden)

Amir Ghorbani

2018-05-01

Full Text Available Generalized interline power-flow controller (GIPFC is one of the voltage-source controller (VSC-based flexible AC transmission system (FACTS controllers that can independently regulate the power-flow over each transmission line of a multiline system. This paper presents the modeling and performance analysis of GIPFC based on 48-pulsed voltage-source converters. This paper deals with a cascaded multilevel converter model, which is a 48-pulse (three levels voltage source converter. The voltage source converter described in this paper is a harmonic neutralized, 48-pulse GTO converter. The GIPFC controller is based on d-q orthogonal coordinates. The algorithm is verified using simulations in MATLAB/Simulink environment. Comparisons between unified power flow controller (UPFC and GIPFC are also included. Keywords: Generalized interline power-flow controller (GIPFC, Voltage source converter (VCS, 48-pulse GTO converter

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

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.

Torsion sensing based on patterned piezoelectric beams

Science.gov (United States)

Cha, Youngsu; You, Hangil

2018-03-01

In this study, we investigated the sensing characteristics of piezoelectric beams under torsional loads. We used partially patterned piezoelectric beams to sense torsion. In particular, the piezoelectric patches are located symmetrically with respect to the line of the shear center of the beam. The patterned piezoelectric beam is modeled as a slender beam, and its electrical responses are obtained by piezoelectric electromechanical equations. To validate the modeling framework, experiments are performed using a setup that forces pure torsional deformation. Three different geometric configurations of the patterned piezoelectric layer are used for the experiments. The frequency and amplitude of the forced torsional load are systematically varied in order to study the behavior of the piezoelectric sensor. Experimental results demonstrate that two voltage outputs of the piezoelectric beam are approximately out of phase with identical amplitude. Moreover, the length of the piezoelectric layers has a significant influence on the sensing properties. Our theoretical predictions using the model support the experimental findings.

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

General Voltage Feedback Circuit Model in the Two-Dimensional Networked Resistive Sensor Array

Directory of Open Access Journals (Sweden)

JianFeng Wu

2015-01-01

Full Text Available To analyze the feature of the two-dimensional networked resistive sensor array, we firstly proposed a general model of voltage feedback circuits (VFCs such as the voltage feedback non-scanned-electrode circuit, the voltage feedback non-scanned-sampling-electrode circuit, and the voltage feedback non-scanned-sampling-electrode circuit. By analyzing the general model, we then gave a general mathematical expression of the effective equivalent resistor of the element being tested in VFCs. Finally, we evaluated the features of VFCs with simulation and test experiment. The results show that the expression is applicable to analyze the VFCs’ performance of parameters such as the multiplexers’ switch resistors, the nonscanned elements, and array size.

Small--radiation-amplitude dynamical voltage model of an irradiated, externally unbiased Josephson tunnel junction

International Nuclear Information System (INIS)

McAdory, R.T. Jr.

1988-01-01

A theory is presented for the nonequilibrium voltage states of an irradiated Josephson junction shunted by an external resistor but with no external current or voltage biasing. This device, referred to as a free-running Josephson junction, is modeled in a small--radiation-amplitude, deterministic regime extending the previous work of Shenoy and Agarwal. The time-averaged induced voltage is treated as a dynamical variable, the external radiation is modeled as a current source, and the induced junction-radiation vector potential, with and without a mode structure, is treated to first order in the driving currents. A dynamical equation for the time-averaged induced voltage yields a (nonequilibrium) steady-state relation between the time-averaged induced voltage and the incident radiation amplitude valid for a wide range of voltages, including zero. Regions of bistability occur in the voltage--versus--incident-amplitude curves, some of which are dependent on the external resistor. The zero-voltage state breaks down, as the external radiation amplitude is increased, at a critical value of the incident-radiation amplitude inversely proportional to the external resistance

Neutral-point voltage dynamic model of three-level NPC inverter for reactive load

DEFF Research Database (Denmark)

Maheshwari, Ram Krishan; Munk-Nielsen, Stig; Busquets-Monge, Sergio

2012-01-01

A three-level neutral-point-clamped inverter needs a controller for the neutral-point voltage. Typically, the controller design is based on a dynamic model. The dynamic model of the neutral-point voltage depends on the pulse width modulation technique used for the inverter. A pulse width modulati...

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)

Work domain constraints for modelling surgical performance.

Science.gov (United States)

Morineau, Thierry; Riffaud, Laurent; Morandi, Xavier; Villain, Jonathan; Jannin, Pierre

2015-10-01

Three main approaches can be identified for modelling surgical performance: a competency-based approach, a task-based approach, both largely explored in the literature, and a less known work domain-based approach. The work domain-based approach first describes the work domain properties that constrain the agent's actions and shape the performance. This paper presents a work domain-based approach for modelling performance during cervical spine surgery, based on the idea that anatomical structures delineate the surgical performance. This model was evaluated through an analysis of junior and senior surgeons' actions. Twenty-four cervical spine surgeries performed by two junior and two senior surgeons were recorded in real time by an expert surgeon. According to a work domain-based model describing an optimal progression through anatomical structures, the degree of adjustment of each surgical procedure to a statistical polynomial function was assessed. Each surgical procedure showed a significant suitability with the model and regression coefficient values around 0.9. However, the surgeries performed by senior surgeons fitted this model significantly better than those performed by junior surgeons. Analysis of the relative frequencies of actions on anatomical structures showed that some specific anatomical structures discriminate senior from junior performances. The work domain-based modelling approach can provide an overall statistical indicator of surgical performance, but in particular, it can highlight specific points of interest among anatomical structures that the surgeons dwelled on according to their level of expertise.

A hierarchical model predictive voltage control for NPC/H-bridge converters with a reduced computational burden

DEFF Research Database (Denmark)

Gong, Zheng; Dai, Peng; Wu, Xiaojie

2017-01-01

In recent years, voltage source multilevel converters are very popular in medium/high-voltage industrial applications, among which the NPC/H-Bridge converter is a popular solution to the medium/high-voltage drive systems. The conventional finite control set model predictive control (FCS-MPC) stra......In recent years, voltage source multilevel converters are very popular in medium/high-voltage industrial applications, among which the NPC/H-Bridge converter is a popular solution to the medium/high-voltage drive systems. The conventional finite control set model predictive control (FCS......-MPC) strategy is not practical for multilevel converters due to their substantial calculation requirements, especially under high number of voltage levels. To solve this problem, a hierarchical model predictive voltage control (HMPVC) strategy with referring to the implementation of g-h coordinate space vector...... and experiments with a down-scaled NPC/H-Bridge converter prototype under various conditions, which validate the proposed HMPVC strategy....

Modelling of Context: Designing Mobile Systems from Domain-Dependent Models

DEFF Research Database (Denmark)

Nielsen, Peter Axel; Stage, Jan

2009-01-01

Modelling of domain-dependent aspects is a key prerequisite for the design of software for mobile systems. Most mobile systems include a more or less advanced model of selected aspects of the domain in which they are used. This paper discusses the creation of such a model and its relevance for te...

Modelling a single phase voltage controlled rectifier using Laplace transforms

Science.gov (United States)

Kraft, L. Alan; Kankam, M. David

1992-01-01

The development of a 20 kHz, AC power system by NASA for large space projects has spurred a need to develop models for the equipment which will be used on these single phase systems. To date, models for the AC source (i.e., inverters) have been developed. It is the intent of this paper to develop a method to model the single phase voltage controlled rectifiers which will be attached to the AC power grid as an interface for connected loads. A modified version of EPRI's HARMFLO program is used as the shell for these models. The results obtained from the model developed in this paper are quite adequate for the analysis of problems such as voltage resonance. The unique technique presented in this paper uses the Laplace transforms to determine the harmonic content of the load current of the rectifier rather than a curve fitting technique. Laplace transforms yield the coefficient of the differential equations which model the line current to the rectifier directly.

A systemic domain model for ambient pervasive persuasive games

OpenAIRE

Eglin, Roger; Eyles, Mark; Dansey, Neil

2008-01-01

By the development of the system domain model it is hoped that a greater conceptual and theoretical clarity may be brought to understanding the complex and multifaceted nature of pervasive and ambient computer games. This paper presents a conceptual model, the system domain model, to illustrate domain areas that exist in a console, pervasive or ambient game. It is implicit that the regions that the systemic domain model describes are contextually dependent. By developing this model it is poss...

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

Streamer model for high voltage water switches

International Nuclear Information System (INIS)

Sazama, F.J.; Kenyon, V.L. III

1979-01-01

An electrical switch model for high voltage water switches has been developed which predicts streamer-switching effects that correlate well with water-switch data from Casino over the past four years and with switch data from recent Aurora/AMP experiments. Preclosure rounding and postclosure resistive damping of pulseforming line voltage waveforms are explained in terms of spatially-extensive, capacitive-coupling of the conducting streamers as they propagate across the gap and in terms of time-dependent streamer resistance and inductance. The arc resistance of the Casino water switch and of a gas switch under test on Casino was determined by computer fit to be 0.5 +- 0.1 ohms and 0.3 +- 0.06 ohms respectively, during the time of peak current in the power pulse. Energy lost in the water switch during the first pulse is 18% of that stored in the pulseforming line while similar energy lost in the gas switch is 11%. The model is described, computer transient analyses are compared with observed water and gas switch data and the results - switch resistance, inductance and energy loss during the primary power pulse - are presented

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.

Maintenance Optimization of High Voltage Substation Model

Directory of Open Access Journals (Sweden)

Radim Bris

2008-01-01

Full Text Available The real system from practice is selected for optimization purpose in this paper. We describe the real scheme of a high voltage (HV substation in different work states. Model scheme of the HV substation 22 kV is demonstrated within the paper. The scheme serves as input model scheme for the maintenance optimization. The input reliability and cost parameters of all components are given: the preventive and corrective maintenance costs, the actual maintenance period (being optimized, the failure rate and mean time to repair - MTTR.

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.

Grid workflow validation using ontology-based tacit knowledge: A case study for quantitative remote sensing applications

Science.gov (United States)

Liu, Jia; Liu, Longli; Xue, Yong; Dong, Jing; Hu, Yingcui; Hill, Richard; Guang, Jie; Li, Chi

2017-01-01

Workflow for remote sensing quantitative retrieval is the ;bridge; between Grid services and Grid-enabled application of remote sensing quantitative retrieval. Workflow averts low-level implementation details of the Grid and hence enables users to focus on higher levels of application. The workflow for remote sensing quantitative retrieval plays an important role in remote sensing Grid and Cloud computing services, which can support the modelling, construction and implementation of large-scale complicated applications of remote sensing science. The validation of workflow is important in order to support the large-scale sophisticated scientific computation processes with enhanced performance and to minimize potential waste of time and resources. To research the semantic correctness of user-defined workflows, in this paper, we propose a workflow validation method based on tacit knowledge research in the remote sensing domain. We first discuss the remote sensing model and metadata. Through detailed analysis, we then discuss the method of extracting the domain tacit knowledge and expressing the knowledge with ontology. Additionally, we construct the domain ontology with Protégé. Through our experimental study, we verify the validity of this method in two ways, namely data source consistency error validation and parameters matching error validation.

Modelling of V-Hz and vector controlled ASDs in PSCAD/EMTDC for voltage sag studies

Energy Technology Data Exchange (ETDEWEB)

Vegunta, S.C. [TNEI Services Ltd, Manchester M1 2PW (United Kingdom); Milanovic, J.V. [School of Electrical and Electronic Engineering of The University of Manchester, PO Box 88, Manchester M60 1QD (United Kingdom); Djokic, S.Z. [School of Engineering of The University of Edinburgh, The King' s Buildings, Mayfield Road, Edinburgh EH9 3JL (United Kingdom)

2010-01-15

This paper deals with modelling and performance of adjustable speed drives (ASDs) subjected to voltage disturbances in electric supply. The aim of this study was to develop appropriate models of typical ASD and investigate their sensitivity to voltage disturbances under various practical modes of operation and control. Accordingly, scalar controlled open and closed loop volts-hertz (V-Hz) and vector controlled closed loop ASDs are modelled in PSCAD/EMTDC environment, and their performance in the presence of voltage disturbances is investigated under typical operating and loading conditions. The drive sensitivity to three-phase, two-phase and single-phase voltage sags and short interruptions was assessed, and the findings are discussed in the paper. Depending on the type of drive control, type of voltage sag, applied load torque and adjusted speed, various sensitivity curves were established and analyzed. (author)

Prediction of breakdown voltages in novel gases for high voltage insulation

International Nuclear Information System (INIS)

Koch, M.

2015-01-01

This thesis submitted to the Swiss Federal Institute of Technology ETH in Zurich examines the use of sulphur hexafluoride (SF_6) and similar gases as important insulation media for high voltage equipment. Due to its superior insulation properties, SF_6 is widely used in gas-insulated switchgear. However, the gas also has a very high global warming potential and the content of SF_6 in the atmosphere is constantly increasing. The search for new insulation gases using classical breakdown experiments is discussed. A model for SF_6 based on the stepped leader model is described. This calculates the breakdown voltages in arbitrary electrode configurations and under standard voltage waveforms. Thus, the thesis provides a method for the prediction of breakdown voltages of arbitrary field configurations under standard voltage waveforms for gases with electron-attaching properties. With this, further gases can be characterized for usage as high voltage insulation media

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.

Evaluation of HVDC interconnection models for considering its impact in real-time voltage stability assessment

DEFF Research Database (Denmark)

Perez, Angel; Jóhannsson, Hjörtur; Lund, P.

2015-01-01

An approach to evaluate the HVDC interconnectionsmodels to be used in real-time voltage stability assessment is proposed.The existing models for the HVDC interconnections, thatare based on voltage source converter, were studied selecting theones that are suitable for its application in Thevenin...... equivalent ´methods for voltage stability assessment. The proposed methodis to evaluate the validity of the models by using synthetizedPMU measurements from simulations and from PMUs connectedto the danish system. Wide-area measurements are used toestimate the HVDC model parameters which are needed...

Current-voltage relation for thin tunnel barriers: Parabolic barrier model

DEFF Research Database (Denmark)

Hansen, Kim; Brandbyge, Mads

2004-01-01

We derive a simple analytic result for the current-voltage curve for tunneling of electrons through a thin uniform insulating layer modeled by a parabolic barrier. Our model, which goes beyond the Wentzel–Kramers–Brillouin approximation, is applicable also in the limit of highly transparant...

Stochastic lattice model of synaptic membrane protein domains.

Science.gov (United States)

Li, Yiwei; Kahraman, Osman; Haselwandter, Christoph A

2017-05-01

Neurotransmitter receptor molecules, concentrated in synaptic membrane domains along with scaffolds and other kinds of proteins, are crucial for signal transmission across chemical synapses. In common with other membrane protein domains, synaptic domains are characterized by low protein copy numbers and protein crowding, with rapid stochastic turnover of individual molecules. We study here in detail a stochastic lattice model of the receptor-scaffold reaction-diffusion dynamics at synaptic domains that was found previously to capture, at the mean-field level, the self-assembly, stability, and characteristic size of synaptic domains observed in experiments. We show that our stochastic lattice model yields quantitative agreement with mean-field models of nonlinear diffusion in crowded membranes. Through a combination of analytic and numerical solutions of the master equation governing the reaction dynamics at synaptic domains, together with kinetic Monte Carlo simulations, we find substantial discrepancies between mean-field and stochastic models for the reaction dynamics at synaptic domains. Based on the reaction and diffusion properties of synaptic receptors and scaffolds suggested by previous experiments and mean-field calculations, we show that the stochastic reaction-diffusion dynamics of synaptic receptors and scaffolds provide a simple physical mechanism for collective fluctuations in synaptic domains, the molecular turnover observed at synaptic domains, key features of the observed single-molecule trajectories, and spatial heterogeneity in the effective rates at which receptors and scaffolds are recycled at the cell membrane. Our work sheds light on the physical mechanisms and principles linking the collective properties of membrane protein domains to the stochastic dynamics that rule their molecular components.

Latent domain models for statistical machine translation

NARCIS (Netherlands)

Hoàng, C.

2017-01-01

A data-driven approach to model translation suffers from the data mismatch problem and demands domain adaptation techniques. Given parallel training data originating from a specific domain, training an MT system on the data would result in a rather suboptimal translation for other domains. But does

Prediction of breakdown voltages in novel gases for high voltage insulation

Energy Technology Data Exchange (ETDEWEB)

Koch, M.

2015-07-01

This thesis submitted to the Swiss Federal Institute of Technology ETH in Zurich examines the use of sulphur hexafluoride (SF{sub 6}) and similar gases as important insulation media for high voltage equipment. Due to its superior insulation properties, SF{sub 6} is widely used in gas-insulated switchgear. However, the gas also has a very high global warming potential and the content of SF{sub 6} in the atmosphere is constantly increasing. The search for new insulation gases using classical breakdown experiments is discussed. A model for SF{sub 6} based on the stepped leader model is described. This calculates the breakdown voltages in arbitrary electrode configurations and under standard voltage waveforms. Thus, the thesis provides a method for the prediction of breakdown voltages of arbitrary field configurations under standard voltage waveforms for gases with electron-attaching properties. With this, further gases can be characterized for usage as high voltage insulation media.

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.

Biomimicry of quorum sensing using bacterial lifecycle model.

Science.gov (United States)

Niu, Ben; Wang, Hong; Duan, Qiqi; Li, Li

2013-01-01

Recent microbiologic studies have shown that quorum sensing mechanisms, which serve as one of the fundamental requirements for bacterial survival, exist widely in bacterial intra- and inter-species cell-cell communication. Many simulation models, inspired by the social behavior of natural organisms, are presented to provide new approaches for solving realistic optimization problems. Most of these simulation models follow population-based modelling approaches, where all the individuals are updated according to the same rules. Therefore, it is difficult to maintain the diversity of the population. In this paper, we present a computational model termed LCM-QS, which simulates the bacterial quorum-sensing (QS) mechanism using an individual-based modelling approach under the framework of Agent-Environment-Rule (AER) scheme, i.e. bacterial lifecycle model (LCM). LCM-QS model can be classified into three main sub-models: chemotaxis with QS sub-model, reproduction and elimination sub-model and migration sub-model. The proposed model is used to not only imitate the bacterial evolution process at the single-cell level, but also concentrate on the study of bacterial macroscopic behaviour. Comparative experiments under four different scenarios have been conducted in an artificial 3-D environment with nutrients and noxious distribution. Detailed study on bacterial chemotatic processes with quorum sensing and without quorum sensing are compared. By using quorum sensing mechanisms, artificial bacteria working together can find the nutrient concentration (or global optimum) quickly in the artificial environment. Biomimicry of quorum sensing mechanisms using the lifecycle model allows the artificial bacteria endowed with the communication abilities, which are essential to obtain more valuable information to guide their search cooperatively towards the preferred nutrient concentrations. It can also provide an inspiration for designing new swarm intelligence optimization algorithms

Gating of Connexin Channels by transjunctional-voltage: Conformations and models of open and closed states.

Science.gov (United States)

Bargiello, Thaddeus A; Oh, Seunghoon; Tang, Qingxiu; Bargiello, Nicholas K; Dowd, Terry L; Kwon, Taekyung

2018-01-01

Voltage is an important physiologic regulator of channels formed by the connexin gene family. Connexins are unique among ion channels in that both plasma membrane inserted hemichannels (undocked hemichannels) and intercellular channels (aggregates of which form gap junctions) have important physiological roles. The hemichannel is the fundamental unit of gap junction voltage-gating. Each hemichannel displays two distinct voltage-gating mechanisms that are primarily sensitive to a voltage gradient formed along the length of the channel pore (the transjunctional voltage) rather than sensitivity to the absolute membrane potential (V m or V i-o ). These transjunctional voltage dependent processes have been termed V j - or fast-gating and loop- or slow-gating. Understanding the mechanism of voltage-gating, defined as the sequence of voltage-driven transitions that connect open and closed states, first and foremost requires atomic resolution models of the end states. Although ion channels formed by connexins were among the first to be characterized structurally by electron microscopy and x-ray diffraction in the early 1980's, subsequent progress has been slow. Much of the current understanding of the structure-function relations of connexin channels is based on two crystal structures of Cx26 gap junction channels. Refinement of crystal structure by all-atom molecular dynamics and incorporation of charge changing protein modifications has resulted in an atomic model of the open state that arguably corresponds to the physiologic open state. Obtaining validated atomic models of voltage-dependent closed states is more challenging, as there are currently no methods to solve protein structure while a stable voltage gradient is applied across the length of an oriented channel. It is widely believed that the best approach to solve the atomic structure of a voltage-gated closed ion channel is to apply different but complementary experimental and computational methods and to use

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....

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.

Coordinated Voltage Control of a Wind Farm based on Model Predictive Control

DEFF Research Database (Denmark)

Zhao, Haoran; Wu, Qiuwei; Guo, Qinglai

2016-01-01

This paper presents an autonomous wind farm voltage controller based on Model Predictive Control (MPC). The reactive power compensation and voltage regulation devices of the wind farm include Static Var Compensators (SVCs), Static Var Generators (SVGs), Wind Turbine Generators (WTGs) and On...... are calculated based on an analytical method to improve the computation efficiency and overcome the convergence problem. Two control modes are designed for both voltage violated and normal operation conditions. A wind farm with 20 wind turbines was used to conduct case studies to verify the proposed coordinated...

Simple and accurate model for voltage-dependent resistance of metallic carbon nanotube interconnects: An ab initio study

International Nuclear Information System (INIS)

Yamacli, Serhan; Avci, Mutlu

2009-01-01

In this work, development of a voltage dependent resistance model for metallic carbon nanotubes is aimed. Firstly, the resistance of metallic carbon nanotube interconnects are obtained from ab initio simulations and then the voltage dependence of the resistance is modeled through regression. Self-consistent non-equilibrium Green's function formalism combined with density functional theory is used for calculating the voltage dependent resistance of metallic carbon nanotubes. It is shown that voltage dependent resistances of carbon nanotubes can be accurately modeled as a polynomial function which enables rapid integration of carbon nanotube interconnect models into electronic design automation tools.

Modeling, Simulation, and Analysis of Novel Threshold Voltage Definition for Nano-MOSFET

Directory of Open Access Journals (Sweden)

Yashu Swami

2017-01-01

Full Text Available Threshold voltage (VTH is the indispensable vital parameter in MOSFET designing, modeling, and operation. Diverse expounds and extraction methods exist to model the on-off transition characteristics of the device. The governing gauge for efficient threshold voltage definition and extraction method can be itemized as clarity, simplicity, precision, and stability throughout the operating conditions and technology node. The outcomes of extraction methods diverge from the exact values due to various short-channel effects (SCEs and nonidealities present in the device. A new approach to define and extract the real value of VTH of MOSFET is proposed in the manuscript. The subsequent novel enhanced SCE-independent VTH extraction method named “hybrid extrapolation VTH extraction method” (HEEM is elaborated, modeled, and compared with few prevalent MOSFET threshold voltage extraction methods for validation of the results. All the results are verified by extensive 2D TCAD simulation and confirmed analytically at various technology nodes.

Semi-empirical model for the threshold voltage of a double implanted MOSFET and its temperature dependence

Energy Technology Data Exchange (ETDEWEB)

Arora, N D

1987-05-01

A simple and accurate semi-empirical model for the threshold voltage of a small geometry double implanted enhancement type MOSFET, especially useful in a circuit simulation program like SPICE, has been developed. The effect of short channel length and narrow width on the threshold voltage has been taken into account through a geometrical approximation, which involves parameters whose values can be determined from the curve fitting experimental data. A model for the temperature dependence of the threshold voltage for the implanted devices has also been presented. The temperature coefficient of the threshold voltage was found to change with decreasing channel length and width. Experimental results from various device sizes, both short and narrow, show very good agreement with the model. The model has been implemented in SPICE as part of the complete dc model.

Analytical modeling of Schottky tunneling source impact ionization MOSFET with reduced breakdown voltage

Directory of Open Access Journals (Sweden)

Sangeeta Singh

2016-03-01

Full Text Available In this paper, we have investigated a novel Schottky tunneling source impact ionization MOSFET (STS-IMOS to lower the breakdown voltage of conventional impact ionization MOS (IMOS and developed an analytical model for the same. In STS-IMOS there is an accumulative effect of both impact ionization and source induced barrier tunneling. The silicide source offers very low parasitic resistance, the outcome of which is an increment in voltage drop across the intrinsic region for the same applied bias. This reduces operating voltage and hence, it exhibits a significant reduction in both breakdown and threshold voltage. STS-IMOS shows high immunity against hot electron damage. As a result of this the device reliability increases magnificently. The analytical model for impact ionization current (Iii is developed based on the integration of ionization integral (M. Similarly, to get Schottky tunneling current (ITun expression, Wentzel–Kramers–Brillouin (WKB approximation is employed. Analytical models for threshold voltage and subthreshold slope is optimized against Schottky barrier height (ϕB variation. The expression for the drain current is computed as a function of gate-to-drain bias via integral expression. It is validated by comparing it with the technology computer-aided design (TCAD simulation results as well. In essence, this analytical framework provides the physical background for better understanding of STS-IMOS and its performance estimation.

Fuzzy Controller for a Voltage-Regulated Solar-Powered MPPT System for Hybrid Power System Applications

Directory of Open Access Journals (Sweden)

Jaw-Kuen Shiau

2015-04-01

Full Text Available This paper presents the design of a fuzzy-logic-based voltage-regulated solar power maximum power point tracking (MPPT system for applications involving hybrid power systems. The system contains a solar power system and battery as the primary and secondary power sources, respectively. The solar system alone supplies power to the electric motor and maintains the output voltage at a predetermined level when it has sufficient power. When the solar power is insufficient, the solar system is operated at its maximum power point (MPP and the battery is engaged to compensate for the insufficiency. First, a variant of the incremental conductance MPP condition was established. Under the MPP condition, the voltage-regulated MPPT system was formulated as a feedback control system, where the MPP condition and voltage regulation requirements were used as the system inputs. Next, a fuzzy controller was developed to perform the voltage-regulated MPPT function for the hybrid power system. A simulation model based on Matrix laboratory (MATLAB/SIMULINK (a block diagram environment for multi-domain simulation and model-based design and a piecewise linear electric circuit simulation (PLECS tool for controlling the dc motor velocity was developed to verify the voltage-regulated solar power MPPT system.

Model Development for Current–Voltage and Transconductance Characteristics of Normally-off AlN/GaN MOSHEMT

International Nuclear Information System (INIS)

Swain, R.; Jena, K.; Lenka, T. R.

2016-01-01

In this paper, an AlN/GaN-based MOSHEMT is proposed, in accordance to this, a charge control model has been developed analytically and simulated with MATLAB to predict the characteristics of threshold voltage, drain currents and transconductance. The physics based models for 2DEG density, threshold voltage and quantum capacitance in the channel has been put forward. By using these developed models, the drain current for both linear and saturation models is derived. The predicted threshold voltage with the variation of barrier thickness has been plotted. A positive threshold voltage can be obtained by decreasing the barrier thickness which builds up the foundation for enhancement mode MOSHEMT devices. The predicted I_d–V_g_s, I_d–V_d_s and transconductance characteristics show an excellent agreement with the experimental results and hence validate the model.

Local sparsity enhanced compressed sensing magnetic resonance imaging in uniform discrete curvelet domain

International Nuclear Information System (INIS)

Yang, Bingxin; Yuan, Min; Ma, Yide; Zhang, Jiuwen; Zhan, Kun

2015-01-01

Compressed sensing(CS) has been well applied to speed up imaging by exploring image sparsity over predefined basis functions or learnt dictionary. Firstly, the sparse representation is generally obtained in a single transform domain by using wavelet-like methods, which cannot produce optimal sparsity considering sparsity, data adaptivity and computational complexity. Secondly, most state-of-the-art reconstruction models seldom consider composite regularization upon the various structural features of images and transform coefficients sub-bands. Therefore, these two points lead to high sampling rates for reconstructing high-quality images. In this paper, an efficient composite sparsity structure is proposed. It learns adaptive dictionary from lowpass uniform discrete curvelet transform sub-band coefficients patches. Consistent with the sparsity structure, a novel composite regularization reconstruction model is developed to improve reconstruction results from highly undersampled k-space data. It is established via minimizing spatial image and lowpass sub-band coefficients total variation regularization, transform sub-bands coefficients l 1 sparse regularization and constraining k-space measurements fidelity. A new augmented Lagrangian method is then introduced to optimize the reconstruction model. It updates representation coefficients of lowpass sub-band coefficients over dictionary, transform sub-bands coefficients and k-space measurements upon the ideas of constrained split augmented Lagrangian shrinkage algorithm. Experimental results on in vivo data show that the proposed method obtains high-quality reconstructed images. The reconstructed images exhibit the least aliasing artifacts and reconstruction error among current CS MRI methods. The proposed sparsity structure can fit and provide hierarchical sparsity for magnetic resonance images simultaneously, bridging the gap between predefined sparse representation methods and explicit dictionary. The new augmented

Domain Endurants: An Analysis and Description Process Model

DEFF Research Database (Denmark)

Bjørner, Dines

2014-01-01

We present a summary, Sect. 2, of a structure of domain analysis and description concepts: techniques and tools. And we link, in Sect. 3, these concepts, embodied in domain analysis prompts and domain description prompts, in a model of how a diligent domain analyser cum describer would use them. We...

Modeling Network Traffic in Wavelet Domain

Directory of Open Access Journals (Sweden)

Sheng Ma

2004-12-01

Full Text Available This work discovers that although network traffic has the complicated short- and long-range temporal dependence, the corresponding wavelet coefficients are no longer long-range dependent. Therefore, a "short-range" dependent process can be used to model network traffic in the wavelet domain. Both independent and Markov models are investigated. Theoretical analysis shows that the independent wavelet model is sufficiently accurate in terms of the buffer overflow probability for Fractional Gaussian Noise traffic. Any model, which captures additional correlations in the wavelet domain, only improves the performance marginally. The independent wavelet model is then used as a unified approach to model network traffic including VBR MPEG video and Ethernet data. The computational complexity is O(N for developing such wavelet models and generating synthesized traffic of length N, which is among the lowest attained.

Modeling ion sensing in molecular electronics

International Nuclear Information System (INIS)

Chen, Caroline J.; Smeu, Manuel; Ratner, Mark A.

2014-01-01

We examine the ability of molecules to sense ions by measuring the change in molecular conductance in the presence of such charged species. The detection of protons (H + ), alkali metal cations (M + ), calcium ions (Ca 2+ ), and hydronium ions (H 3 O + ) is considered. Density functional theory (DFT) is used within the Keldysh non-equilibrium Green's function framework (NEGF) to model electron transport properties of quinolinedithiol (QDT, C 9 H 7 NS 2 ), bridging Al electrodes. The geometry of the transport region is relaxed with DFT. The transport properties of the device are modeled with NEGF-DFT to determine if this device can distinguish among the M + + QDT species containing monovalent cations, where M + = H + , Li + , Na + , or K + . Because of the asymmetry of QDT in between the two electrodes, both positive and negative biases are considered. The electron transmission function and conductance properties are simulated for electrode biases in the range from −0.5 V to 0.5 V at increments of 0.1 V. Scattering state analysis is used to determine the molecular orbitals that are the main contributors to the peaks in the transmission function near the Fermi level of the electrodes, and current-voltage relationships are obtained. The results show that QDT can be used as a proton detector by measuring transport through it and can conceivably act as a pH sensor in solutions. In addition, QDT may be able to distinguish among different monovalent species. This work suggests an approach to design modern molecular electronic conductance sensors with high sensitivity and specificity using well-established quantum chemistry

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.

Harmonic current prediction by impedance modeling of grid-tied inverters

DEFF Research Database (Denmark)

Pereira, Heverton A.; Freijedo, Francisco D.; Silva, M. M.

2017-01-01

and harmonic voltage profiles. Results reinforce that impedance models can represent with relatively accuracy the harmonic current emitted by the PV plants at the point of common coupling (PCC). Lastly, a stress test is performed to show how a variation in the harmonic voltage phase angle impacts the PV plant...... impedance models when used in harmonic integration studies. It is aimed to estimate the harmonic current contribution as a function of the background harmonic voltages components. Time domain simulations based on detailed and average models are compared with the impedance model developed in frequency domain....... In grids with harmonic voltages, impedance models can predict the current distortion for all active power injection scenarios. Furthermore, measurements in a 1.4 MW PV plant connected in a distributed grid are used to validate the simulation based on impedance models during different power injections...

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.

Modelling voltage sag mitigation using dynamic voltage restorer and analyzing power quality issue

Science.gov (United States)

Ismail, Nor Laili; Hidzir, Hizrin Dayana Mohd; Thanakodi, Suresh; Nazar, Nazatul Shiema Moh; Ibrahim, Pungut; Ali, Che Ku Muhammad Sabri Che Ku

2018-02-01

Power quality problem which are arise due to a fault or a pulsed load can have caused an interruption of critical load. The modern power systems are becoming more sensitive to the quality of the power supplied by the utility company. Voltage sags and swells, flicker, interruptions, harmonic distortion and other distortion to the sinusoidal waveform are the examples of the power quality problems. The most affected due to these problems is industrial customers who use a lot of sensitive equipment. There has suffered a huge loss to these problems. Resulting of broken or damage equipment if voltage sag exceeds the sensitive threshold of the equipment. Thus, device such as Static Synchronous Compensator (STATCOM) and Dynamic Voltage Restorer (DVR) has been created to solve this problem among users. DVR is a custom power device that most effective and efficient. This paper intended to report the DVR operations during voltage sag compensation.

The current-voltage relation of a pore and its asymptotic behavior in a Nernst-Planck model

Directory of Open Access Journals (Sweden)

Marius Birlea

2012-08-01

Full Text Available A model for current-voltage nonlinearity and asymmetry is a good starting point for explaining the electrical behavior of the nanopores in synthetic or biological membranes. Using a Nernst-Planck model, we found three behaviors for the current density in a membrane's pore as a function of voltage: a quasi-ohmic, slow rising linear current at low voltages, a nonlinear current at intermediate voltages, and a non-ohmic, fast rising linear current at large voltages. The slope of the quasi-ohmic current depends mainly on the height of energy barrier inside the pore, w, through an exponential term, ew. The magnitude of the non-ohmic linear current is controlled by the potential energy gradient at the pore entrance, w/r. The current-voltage relation is asymmetric if the ion's potential energy inside the pore has an asymmetric triangular profile. The model has only two assumed parameters, the energy barrier height, w, and the relative size of the entrance region of the pore, r, which is a useful feature for fitting and interpreting experimental data.

Vibration sensing in flexible structures using a distributed-effect modal domain optical fiber sensor

Science.gov (United States)

Reichard, Karl M.; Lindner, Douglas K.; Claus, Richard O.

1991-01-01

Modal domain optical fiber sensors have recently been employed in the implementation of system identification algorithms and the closed-loop control of vibrations in flexible structures. The mathematical model of the modal domain optical fiber sensor used in these applications, however, only accounted for the effects of strain in the direction of the fiber's longitudinal axis. In this paper, we extend this model to include the effects of arbitrary stress. Using this sensor model, we characterize the sensor's sensitivity and dynamic range.

Making sense of the Sense Model: translation priming with Japanese-English bilinguals

OpenAIRE

Allen, David; Conklin, Kathy; Van Heuven, Walter J.B.

2015-01-01

Many studies have reported that first language (L1) translation primes speed responses to second language (L2) targets, whereas L2 translation primes generally do not speed up responses to L1 targets in lexical decision. According to the Sense Model (Finkbeiner, Forster, Nicol & Nakamura, 2004) this asymmetry is due to the proportion of senses activated by the prime. Because L2 primes activate only a subset of the L1 translations senses, priming is not observed. In this study we test the pred...

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.

Mechanisms for integration of information models across related domains

Science.gov (United States)

Atkinson, Rob

2010-05-01

It is well recognised that there are opportunities and challenges in cross-disciplinary data integration. A significant barrier, however, is creating a conceptual model of the combined domains and the area of integration. For example, a groundwater domain application may require information from several related domains: geology, hydrology, water policy, etc. Each domain may have its own data holdings and conceptual models, but these will share various common concepts (eg. The concept of an aquifer). These areas of semantic overlap present significant challenges, firstly to choose a single representation (model) of a concept that appears in multiple disparate models,, then to harmonise these other models with the single representation. In addition, models may exist at different levels of abstraction depending on how closely aligned they are with a particular implementation. This makes it hard for modellers in one domain to introduce elements from another domain without either introducing a specific style of implementation, or conversely dealing with a set of abstract patterns that are hard to integrate with existing implementations. Models are easier to integrate if they are broken down into small units, with common concepts implemented using common models from well-known, and predictably managed shared libraries. This vision however requires development of a set of mechanisms (tools and procedures) for implementing and exploiting libraries of model components. These mechanisms need to handle publication, discovery, subscription, versioning and implementation of models in different forms. In this presentation a coherent suite of such mechanisms is proposed, using a scenario based on re-use of geosciences models. This approach forms the basis of a comprehensive strategy to empower domain modellers to create more interoperable systems. The strategy address a range of concerns and practice, and includes methodologies, an accessible toolkit, improvements to available

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.

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.

Domain Specific Language for Modeling Waste Management Systems

DEFF Research Database (Denmark)

Zarrin, Bahram

environmental technologies i.e. solid waste management systems. Flow-based programming is used to support concurrent execution of the processes, and provides a model-integration language for composing processes from homogeneous or heterogeneous domains. And a domain-specific language is used to define atomic......In order to develop sustainable waste management systems with considering life cycle perspective, scientists and domain experts in environmental science require readily applicable tools for modeling and evaluating the life cycle impacts of the waste management systems. Practice has proved...... a domain specific language for modeling of waste-management systems on the basis of our framework. We evaluate the language by providing a set of case studies. The contributions of this thesis are; addressing separation of concerns in Flow-based programming and providing the formal specification of its...

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

Model Based Optimization of Integrated Low Voltage DC-DC Converter for Energy Harvesting Applications

Science.gov (United States)

Jayaweera, H. M. P. C.; Muhtaroğlu, Ali

2016-11-01

A novel model based methodology is presented to determine optimal device parameters for the fully integrated ultra low voltage DC-DC converter for energy harvesting applications. The proposed model feasibly contributes to determine the maximum efficient number of charge pump stages to fulfill the voltage requirement of the energy harvester application. The proposed DC-DC converter based power consumption model enables the analytical derivation of the charge pump efficiency when utilized simultaneously with the known LC tank oscillator behavior under resonant conditions, and voltage step up characteristics of the cross-coupled charge pump topology. The verification of the model has been done using a circuit simulator. The optimized system through the established model achieves more than 40% maximum efficiency yielding 0.45 V output with single stage, 0.75 V output with two stages, and 0.9 V with three stages for 2.5 kΩ, 3.5 kΩ and 5 kΩ loads respectively using 0.2 V input.

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.

A DNA-based semantic fusion model for remote sensing data.

Directory of Open Access Journals (Sweden)

Heng Sun

Full Text Available Semantic technology plays a key role in various domains, from conversation understanding to algorithm analysis. As the most efficient semantic tool, ontology can represent, process and manage the widespread knowledge. Nowadays, many researchers use ontology to collect and organize data's semantic information in order to maximize research productivity. In this paper, we firstly describe our work on the development of a remote sensing data ontology, with a primary focus on semantic fusion-driven research for big data. Our ontology is made up of 1,264 concepts and 2,030 semantic relationships. However, the growth of big data is straining the capacities of current semantic fusion and reasoning practices. Considering the massive parallelism of DNA strands, we propose a novel DNA-based semantic fusion model. In this model, a parallel strategy is developed to encode the semantic information in DNA for a large volume of remote sensing data. The semantic information is read in a parallel and bit-wise manner and an individual bit is converted to a base. By doing so, a considerable amount of conversion time can be saved, i.e., the cluster-based multi-processes program can reduce the conversion time from 81,536 seconds to 4,937 seconds for 4.34 GB source data files. Moreover, the size of result file recording DNA sequences is 54.51 GB for parallel C program compared with 57.89 GB for sequential Perl. This shows that our parallel method can also reduce the DNA synthesis cost. In addition, data types are encoded in our model, which is a basis for building type system in our future DNA computer. Finally, we describe theoretically an algorithm for DNA-based semantic fusion. This algorithm enables the process of integration of the knowledge from disparate remote sensing data sources into a consistent, accurate, and complete representation. This process depends solely on ligation reaction and screening operations instead of the ontology.

A DNA-based semantic fusion model for remote sensing data.

Science.gov (United States)

Sun, Heng; Weng, Jian; Yu, Guangchuang; Massawe, Richard H

2013-01-01

Semantic technology plays a key role in various domains, from conversation understanding to algorithm analysis. As the most efficient semantic tool, ontology can represent, process and manage the widespread knowledge. Nowadays, many researchers use ontology to collect and organize data's semantic information in order to maximize research productivity. In this paper, we firstly describe our work on the development of a remote sensing data ontology, with a primary focus on semantic fusion-driven research for big data. Our ontology is made up of 1,264 concepts and 2,030 semantic relationships. However, the growth of big data is straining the capacities of current semantic fusion and reasoning practices. Considering the massive parallelism of DNA strands, we propose a novel DNA-based semantic fusion model. In this model, a parallel strategy is developed to encode the semantic information in DNA for a large volume of remote sensing data. The semantic information is read in a parallel and bit-wise manner and an individual bit is converted to a base. By doing so, a considerable amount of conversion time can be saved, i.e., the cluster-based multi-processes program can reduce the conversion time from 81,536 seconds to 4,937 seconds for 4.34 GB source data files. Moreover, the size of result file recording DNA sequences is 54.51 GB for parallel C program compared with 57.89 GB for sequential Perl. This shows that our parallel method can also reduce the DNA synthesis cost. In addition, data types are encoded in our model, which is a basis for building type system in our future DNA computer. Finally, we describe theoretically an algorithm for DNA-based semantic fusion. This algorithm enables the process of integration of the knowledge from disparate remote sensing data sources into a consistent, accurate, and complete representation. This process depends solely on ligation reaction and screening operations instead of the ontology.

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.

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

Sequence Domain Harmonic Modeling of Type-IV Wind Turbines

DEFF Research Database (Denmark)

Guest, Emerson; Jensen, Kim Høj; Rasmussen, Tonny Wederberg

2017-01-01

-sampled pulsewidth modulation and an analysis of converter generated voltage harmonics due to compensated dead-time. The decoupling capabilities of the proposed the SD harmonic model are verified through a power quality (PQ) assessment of a 3MW Type-IV wind turbine. The assessment shows that the magnitude and phase...... of low-order odd converter generated voltage harmonics are dependent on the converter operating point and the phase of the fundamental component of converter current respectively. The SD harmonic model can be used to make PQ assessments of Type-IV wind turbines or incorporated into harmonic load flows...... for computation of PQ in wind power plants....

Domain Adaptation of Translation Models for Multilingual Applications

Science.gov (United States)

2009-04-01

employed. In the past two years, domain adaptation for NLP tasks has become an active research area [3, 38, 25, 23]. New domain adaptation tasks have...and unlabeled data in the target domain and learn a mixture model to adapt from the source domain. Other NLP tasks where domain adaptation has been...evaluation forum, http://www.clef-campaign.org. [13] K. Darwish and D. Oard, CLIR experiments at maryland for TREC-2002: Evidence combination for arabic

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.

Synergistic linkage between remote sensing and biophysical models for estimating plant ecophysiological and ecosystem processes

International Nuclear Information System (INIS)

Inoue, Y.; Olioso, A.

2004-01-01

Abstract Information on the ecological and physiological status of crops is essential for growth diagnostics and yield prediction. Within-field or between-field spatial information is required, especially with the recent trend toward precision agriculture, which seeks the efficient use of agrochemicals, water, and energy. The study of carbon and nitrogen cycles as well as environmental management on local and regional scales requires assessment of the spatial variability of biophysical and ecophysiological variables, scaling up of which is also needed for scientific and decision-making purposes. Remote sensing has great potential for these applications because it enables wide-area non-destructive, and real-time acquisition of information about ecophysiological conditions of vegetation. With recent advances in sensor technology, a variety of electromagnetic signatures, such as hyperspectral reflectance, thermal-infrared temperature, and microwave backscattering coefficients, can be acquired for both plants and ecosystems using ground-based, airborne, and satellite platforms. Their spatial and temporal resolutions have both recently been improved. This article reviews the state of the art in the remote sensing of plant ecophysiological data, with special emphasis on the synergy between remote sensing signatures and biophysical and ecophysiological process models. Several case studies for the optical, thermal, and microwave domains have demonstrated the potential of this synergistic linkage. Remote sensing and process modeling methods complement each other when combined synergistically. Further research on this approach is needed f or a wide range of ecophysiological and ecosystem studies, as well as for practical crop management

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...

Analytical modeling of threshold voltage for Cylindrical Gate All Around (CGAA MOSFET using center potential

Directory of Open Access Journals (Sweden)

K.P. Pradhan

2015-12-01

Full Text Available In this paper, an analytical threshold voltage model is proposed for a cylindrical gate-all-around (CGAA MOSFET by solving the 2-D Poisson’s equation in the cylindrical coordinate system. A comparison is made for both the center and the surface potential model of CGAA MOSFET. This paper claims that the calculation of threshold voltage using center potential is more accurate rather than the calculation from surface potential. The effects of the device parameters like the drain bias (VDS, oxide thickness (tox, channel thickness (r, etc., on the threshold voltage are also studied in this paper. The model is verified with 3D numerical device simulator Sentaurus from Synopsys Inc.

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.

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.

Thickness dependence of voltage-driven magnetization switching in FeCo/PI/piezoelectric actuator heterostructures

Science.gov (United States)

Cui, B. S.; Guo, X. B.; Wu, K.; Li, D.; Zuo, Y. L.; Xi, L.

2016-03-01

Strain mediated magnetization switching of ferromagnetic/substrate/piezoelectric actuator heterostructures has become a hot issue due to the advantage of low-power consumption. In this work, Fe65Co35 thin films were deposited on a flexible polyamides (PI) substrate, which has quite low Young’s module (~4 GPa for PI as compared to ~180 GPa for Si) and benefits from complete transfer of the strain from the piezoelectric actuator to magnetic thin films. A complete 90° transition of the magnetic easy axis was realized in 50 nm thick FeCo films under the voltage of 70 V, while a less than 90° rotation angle of the magnetic easy axis direction was observed in other samples, which was ascribed to the distribution of the anisotropy field and/or the orthogonal misalignment between stress induced anisotropy and original uniaxial anisotropy. A model considering two uniaxial anisotropies with orthogonal arrangement was used to quantitatively understand the observed results and the linear-like voltage dependent anisotropy field, especially for 10 nm FeCo films, in which the switching mechanism along the easy axis direction can be explained by the domain wall depinning model. It indicates that the magnetic domain-wall movement velocity may be controlled by strain through tuning the energy barrier of the pinning in heterostructures. Moreover, voltage-driven 90° magnetization switching with low-power consumption was achieved in this work.

Thickness dependence of voltage-driven magnetization switching in FeCo/PI/piezoelectric actuator heterostructures

International Nuclear Information System (INIS)

Cui, B S; Guo, X B; Wu, K; Li, D; Zuo, Y L; Xi, L

2016-01-01

Strain mediated magnetization switching of ferromagnetic/substrate/piezoelectric actuator heterostructures has become a hot issue due to the advantage of low-power consumption. In this work, Fe 65 Co 35 thin films were deposited on a flexible polyamides (PI) substrate, which has quite low Young’s module (∼4 GPa for PI as compared to ∼180 GPa for Si) and benefits from complete transfer of the strain from the piezoelectric actuator to magnetic thin films. A complete 90° transition of the magnetic easy axis was realized in 50 nm thick FeCo films under the voltage of 70 V, while a less than 90° rotation angle of the magnetic easy axis direction was observed in other samples, which was ascribed to the distribution of the anisotropy field and/or the orthogonal misalignment between stress induced anisotropy and original uniaxial anisotropy. A model considering two uniaxial anisotropies with orthogonal arrangement was used to quantitatively understand the observed results and the linear-like voltage dependent anisotropy field, especially for 10 nm FeCo films, in which the switching mechanism along the easy axis direction can be explained by the domain wall depinning model. It indicates that the magnetic domain-wall movement velocity may be controlled by strain through tuning the energy barrier of the pinning in heterostructures. Moreover, voltage-driven 90° magnetization switching with low-power consumption was achieved in this work. (paper)

Time versus frequency domain measurements: layered model ...

African Journals Online (AJOL)

... their high frequency content while among TEM data sets with low frequency content, the averaging times for the FEM ellipticity were shorter than the TEM quality. Keywords: ellipticity, frequency domain, frequency electromagnetic method, model parameter, orientation error, time domain, transient electromagnetic method

Regional climate model sensitivity to domain size

Energy Technology Data Exchange (ETDEWEB)

Leduc, Martin [Universite du Quebec a Montreal, Canadian Regional Climate Modelling and Diagnostics (CRCMD) Network, ESCER Centre, Montreal (Canada); UQAM/Ouranos, Montreal, QC (Canada); Laprise, Rene [Universite du Quebec a Montreal, Canadian Regional Climate Modelling and Diagnostics (CRCMD) Network, ESCER Centre, Montreal (Canada)

2009-05-15

Regional climate models are increasingly used to add small-scale features that are not present in their lateral boundary conditions (LBC). It is well known that the limited area over which a model is integrated must be large enough to allow the full development of small-scale features. On the other hand, integrations on very large domains have shown important departures from the driving data, unless large scale nudging is applied. The issue of domain size is studied here by using the ''perfect model'' approach. This method consists first of generating a high-resolution climatic simulation, nicknamed big brother (BB), over a large domain of integration. The next step is to degrade this dataset with a low-pass filter emulating the usual coarse-resolution LBC. The filtered nesting data (FBB) are hence used to drive a set of four simulations (LBs for Little Brothers), with the same model, but on progressively smaller domain sizes. The LB statistics for a climate sample of four winter months are compared with BB over a common region. The time average (stationary) and transient-eddy standard deviation patterns of the LB atmospheric fields generally improve in terms of spatial correlation with the reference (BB) when domain gets smaller. The extraction of the small-scale features by using a spectral filter allows detecting important underestimations of the transient-eddy variability in the vicinity of the inflow boundary, which can penalize the use of small domains (less than 100 x 100 grid points). The permanent ''spatial spin-up'' corresponds to the characteristic distance that the large-scale flow needs to travel before developing small-scale features. The spin-up distance tends to grow in size at higher levels in the atmosphere. (orig.)

Aspects of a generic photovoltaic model examined under the German grid code for medium voltage

Energy Technology Data Exchange (ETDEWEB)

Theologitis, Ioannis-Thomas; Troester, Eckehard; Ackermann, Thomas [Energynautics GmbH, Langen (Germany)

2011-07-01

The increasing peneration of photovoltaic power systems into the power grid has attached attention to the issue of ensuring the smooth absorbance of the solar energy, while securing the normal and steady operation of the grid as well. Nowadays, the PV systems must meet a number of technical requirements to address this issue. This paper investigates a generic grid-connected photovoltaic model that was developed by DIgSILENT and is part of the library in the new version of PowerFactory v.14.1 software that is used in this study. The model has a nominal rated peak power of 0.5 MVA and a designed power factor cos{phi}0.95. The study focuses on the description of the model, its control system and its ability to reflect important requirements that a grid-connected PV system should have by January 2011 according to the German grid code for medium voltage. The model undergoes various simulations. Static voltage support, active power control and dynamic voltage support - Fault Ride Through (FRT) is examined. The results show that the generic model is capable for active power reduction under over-frequency occasions and FRT behavior in cases of voltage dips. The reactive power control that is added in the model improves the control system and makes the model capable for static voltage support in sudden active power injection changes at the point of common coupling. Beside the simplifications and shortcomings of this generic model, basic requirements of the modern PV systems can be addressed. Further improvements could make it more complete and applicable for more detailed studies. (orig.)

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)

Hydrological model performance and parameter estimation in the wavelet-domain

Directory of Open Access Journals (Sweden)

B. Schaefli

2009-10-01

Full Text Available This paper proposes a method for rainfall-runoff model calibration and performance analysis in the wavelet-domain by fitting the estimated wavelet-power spectrum (a representation of the time-varying frequency content of a time series of a simulated discharge series to the one of the corresponding observed time series. As discussed in this paper, calibrating hydrological models so as to reproduce the time-varying frequency content of the observed signal can lead to different results than parameter estimation in the time-domain. Therefore, wavelet-domain parameter estimation has the potential to give new insights into model performance and to reveal model structural deficiencies. We apply the proposed method to synthetic case studies and a real-world discharge modeling case study and discuss how model diagnosis can benefit from an analysis in the wavelet-domain. The results show that for the real-world case study of precipitation – runoff modeling for a high alpine catchment, the calibrated discharge simulation captures the dynamics of the observed time series better than the results obtained through calibration in the time-domain. In addition, the wavelet-domain performance assessment of this case study highlights the frequencies that are not well reproduced by the model, which gives specific indications about how to improve the model structure.

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.

Modeling, analysis, and design of stationary reference frame droop controlled parallel three-phase voltage source inverters

DEFF Research Database (Denmark)

Vasquez, Juan Carlos; Guerrero, Josep M.; Savaghebi, Mehdi

2011-01-01

and discussed. Experimental results are provided to validate the performance and robustness of the VSIs functionality during Islanded and grid-connected operations, allowing a seamless transition between these modes through control hierarchies by regulating frequency and voltage, main-grid interactivity......Power electronics based microgrids consist of a number of voltage source inverters (VSIs) operating in parallel. In this paper, the modeling, control design, and stability analysis of three-phase VSIs are derived. The proposed voltage and current inner control loops and the mathematical models...

Ferroelectric domain switching dynamics and memristive behaviors in BiFeO3-based magnetoelectric heterojunctions

Science.gov (United States)

Huang, Weichuan; Liu, Yukuai; Luo, Zhen; Hou, Chuangming; Zhao, Wenbo; Yin, Yuewei; Li, Xiaoguang

2018-06-01

The ferroelectric domain reversal dynamics and the corresponding resistance switching as well as the memristive behaviors in epitaxial BiFeO3 (BFO, ~150 nm) based multiferroic heterojunctions were systematically investigated. The ferroelectric domain reversal dynamics could be described by the nucleation-limited-switching model with the Lorentzian distribution of logarithmic domain-switching times. By engineering the domain states, multi and even continuously tunable resistances states, i.e. memristive states, could be non-volatilely achieved. The resistance switching speed can be as fast as 30 ns in the BFO-based multiferroic heterojunctions with a write voltage of ~20 V. By reducing the thickness of BFO, the La0.6Sr0.4MnO3/BFO (~5 nm)/La0.6Sr0.4MnO3 multiferroic tunnel junction (MFTJ) shows an even a quicker switching speed (20 ns) with a much lower operation voltage (~4 V). Importantly, the MFTJ exhibits a tunable interfacial magnetoelectric coupling related to the ferroelectric domain switching dynamics. These findings enrich the potential applications of multiferroic BFO based devices in high-speed, low-power, and high-density memories as well as future neuromorphic computational architectures.

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

Two ways to model voltage-current curves of adiabatic MgB2 wires

International Nuclear Information System (INIS)

Stenvall, A; Korpela, A; Lehtonen, J; Mikkonen, R

2007-01-01

Usually overheating of the sample destroys attempts to measure voltage-current curves of conduction cooled high critical current MgB 2 wires at low temperatures. Typically, when a quench occurs a wire burns out due to massive heat generation and negligible cooling. It has also been suggested that high n values measured with MgB 2 wires and coils are not an intrinsic property of the material but arise due to heating during the voltage-current measurement. In addition, quite recently low n values for MgB 2 wires have been reported. In order to find out the real properties of MgB 2 an efficient computational model is required to simulate the voltage-current measurement. In this paper we go back to basics and consider two models to couple electromagnetic and thermal phenomena. In the first model the magnetization losses are computed according to the critical state model and the flux creep losses are considered separately. In the second model the superconductor resistivity is described by the widely used power law. Then the coupled current diffusion and heat conduction equations are solved with the finite element method. In order to compare the models, example runs are carried out with an adiabatic slab. Both models produce a similar significant temperature rise near the critical current which leads to fictitiously high n values

Modelling chloride penetration in concrete using electrical voltage and current approaches

Directory of Open Access Journals (Sweden)

Juan Lizarazo-Marriaga

2011-03-01

Full Text Available This paper reports a research programme aimed at giving a better understanding of the phenomena involved in the chloride penetration in cement-based materials. The general approach used was to solve the Nernst-Planck equation numerically for two physical ideal states that define the possible conditions under which chlorides will move through concrete. These conditions are named in this paper as voltage control and current control. For each condition, experiments and simulations were carried out in order to establish the importance of electrical variables such as voltage and current in modelling chloride transport in concrete. The results of experiments and simulations showed that if those electrical variables are included as key parameters in the modelling of chloride penetration through concrete, a better understanding of this complex phenomenon can be obtained.

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.

Dynamic model based on voltage transfer curve for pattern formation in dielectric barrier glow discharge

Energy Technology Data Exchange (ETDEWEB)

Li, Ben; He, Feng; Ouyang, Jiting, E-mail: jtouyang@bit.edu.cn [School of Physics, Beijing Institute of Technology, Beijing 100081 (China); Duan, Xiaoxi [Research Center of Laser Fusion, CAEP, Mianyang 621900 (China)

2015-12-15

Simulation work is very important for understanding the formation of self-organized discharge patterns. Previous works have witnessed different models derived from other systems for simulation of discharge pattern, but most of these models are complicated and time-consuming. In this paper, we introduce a convenient phenomenological dynamic model based on the basic dynamic process of glow discharge and the voltage transfer curve (VTC) to study the dielectric barrier glow discharge (DBGD) pattern. VTC is an important characteristic of DBGD, which plots the change of wall voltage after a discharge as a function of the initial total gap voltage. In the modeling, the combined effect of the discharge conditions is included in VTC, and the activation-inhibition effect is expressed by a spatial interaction term. Besides, the model reduces the dimensionality of the system by just considering the integration effect of current flow. All these greatly facilitate the construction of this model. Numerical simulations turn out to be in good accordance with our previous fluid modeling and experimental result.

Nonlinear empirical model of gas humidity-related voltage dynamics of a polymer-electrolyte-membrane fuel cell stack

Science.gov (United States)

Meiler, M.; Andre, D.; Schmid, O.; Hofer, E. P.

Intelligent energy management is a cost-effective key path to realize efficient automotive drive trains [R. O'Hayre, S.W. Cha, W. Colella, F.B. Prinz. Fuel Cell Fundamentals, John Wiley & Sons, Hoboken, 2006]. To develop operating strategy in fuel cell drive trains, precise and computational efficient models of all system components, especially the fuel cell stack, are needed. Should these models further be used in diagnostic or control applications, then some major requirements must be fulfilled. First, the model must predict the mean fuel cell voltage very precisely in all possible operating conditions, even during transients. The model output should be as smooth as possible to support best efficient optimization strategies of the complete system. At least, the model must be computational efficient. For most applications, a difference between real fuel cell voltage and model output of less than 10 mV and 1000 calculations per second will be sufficient. In general, empirical models based on system identification offer a better accuracy and consume less calculation resources than detailed models derived from theoretical considerations [J. Larminie, A. Dicks. Fuel Cell Systems Explained, John Wiley & Sons, West Sussex, 2003]. In this contribution, the dynamic behaviour of the mean cell voltage of a polymer-electrolyte-membrane fuel cell (PEMFC) stack due to variations in humidity of cell's reactant gases is investigated. The validity of the overall model structure, a so-called general Hammerstein model (or Uryson model), was introduced recently in [M. Meiler, O. Schmid, M. Schudy, E.P. Hofer. Dynamic fuel cell stack model for real-time simulation based on system identification, J. Power Sources 176 (2007) 523-528]. Fuel cell mean voltage is calculated as the sum of a stationary and a dynamic voltage component. The stationary component of cell voltage is represented by a lookup-table and the dynamic voltage by a parallel placed, nonlinear transfer function. A

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

Directory of Open Access Journals (Sweden)

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.

Simple mechanical parameters identification of induction machine using voltage sensor only

International Nuclear Information System (INIS)

Horen, Yoram; Strajnikov, Pavel; Kuperman, Alon

2015-01-01

Highlights: • A simple low cost algorithm for induction motor mechanical parameters estimation is proposed. • Voltage sensing only is performed; speed sensor is not required. • The method is suitable for both wound rotor and squirrel cage motors. - Abstract: A simple low cost algorithm for induction motor mechanical parameters estimation without speed sensor is presented in this paper. Estimation is carried out by recording stator terminal voltage during natural braking and subsequent offline curve fitting. The algorithm allows accurately reconstructing mechanical time constant as well as loading torque speed dependency. Although the mathematical basis of the presented method is developed for wound rotor motors, it is shown to be suitable for squirrel cage motors as well. The algorithm is first tested by reconstruction of simulation model parameters and then by processing measurement results of several motors. Simulation and experimental results support the validity of the proposed algorithm

An ultra-low-voltage electronic implementation of inertial neuron model with nonmonotonous Liao's activation function.

Science.gov (United States)

Kant, Nasir Ali; Dar, Mohamad Rafiq; Khanday, Farooq Ahmad

2015-01-01

The output of every neuron in neural network is specified by the employed activation function (AF) and therefore forms the heart of neural networks. As far as the design of artificial neural networks (ANNs) is concerned, hardware approach is preferred over software one because it promises the full utilization of the application potential of ANNs. Therefore, besides some arithmetic blocks, designing AF in hardware is the most important for designing ANN. While attempting to design the AF in hardware, the designs should be compatible with the modern Very Large Scale Integration (VLSI) design techniques. In this regard, the implemented designs should: only be in Metal Oxide Semiconductor (MOS) technology in order to be compatible with the digital designs, provide electronic tunability feature, and be able to operate at ultra-low voltage. Companding is one of the promising circuit design techniques for achieving these goals. In this paper, 0.5 V design of Liao's AF using sinh-domain technique is introduced. Furthermore, the function is tested by implementing inertial neuron model. The performance of the AF and inertial neuron model have been evaluated through simulation results, using the PSPICE software with the MOS transistor models provided by the 0.18-μm Taiwan Semiconductor Manufacturer Complementary Metal Oxide Semiconductor (TSM CMOS) process.

A threshold-voltage model for small-scaled GaAs nMOSFET with stacked high-k gate dielectric

International Nuclear Information System (INIS)

Liu Chaowen; Xu Jingping; Liu Lu; Lu Hanhan; Huang Yuan

2016-01-01

A threshold-voltage model for a stacked high-k gate dielectric GaAs MOSFET is established by solving a two-dimensional Poisson's equation in channel and considering the short-channel, DIBL and quantum effects. The simulated results are in good agreement with the Silvaco TCAD data, confirming the correctness and validity of the model. Using the model, impacts of structural and physical parameters of the stack high-k gate dielectric on the threshold-voltage shift and the temperature characteristics of the threshold voltage are investigated. The results show that the stacked gate dielectric structure can effectively suppress the fringing-field and DIBL effects and improve the threshold and temperature characteristics, and on the other hand, the influence of temperature on the threshold voltage is overestimated if the quantum effect is ignored. (paper)

Technical Note: Procedure for the calibration and validation of kilo-voltage cone-beam CT models

Energy Technology Data Exchange (ETDEWEB)

Vilches-Freixas, Gloria; Létang, Jean Michel; Rit, Simon, E-mail: simon.rit@creatis.insa-lyon.fr [Université de Lyon, CREATIS, CNRS UMR5220, Inserm U1206, INSA-Lyon, Université Lyon 1, Centre Léon Bérard, Lyon 69373 Cedex 08 (France); Brousmiche, Sébastien [Ion Beam Application, Louvain-la-Neuve 1348 (Belgium); Romero, Edward; Vila Oliva, Marc [Université de Lyon, CREATIS, CNRS UMR5220, Inserm U1206, INSA-Lyon, Université Lyon 1, Centre Léon Bérard, Lyon 69373 Cedex 08, France and Ion Beam Application, Louvain-la-Neuve 1348 (Belgium); Kellner, Daniel; Deutschmann, Heinz; Keuschnigg, Peter; Steininger, Philipp [Institute for Research and Development on Advanced Radiation Technologies, Paracelsus Medical University, Salzburg 5020 (Austria)

2016-09-15

Purpose: The aim of this work is to propose a general and simple procedure for the calibration and validation of kilo-voltage cone-beam CT (kV CBCT) models against experimental data. Methods: The calibration and validation of the CT model is a two-step procedure: the source model then the detector model. The source is described by the direction dependent photon energy spectrum at each voltage while the detector is described by the pixel intensity value as a function of the direction and the energy of incident photons. The measurements for the source consist of a series of dose measurements in air performed at each voltage with varying filter thicknesses and materials in front of the x-ray tube. The measurements for the detector are acquisitions of projection images using the same filters and several tube voltages. The proposed procedure has been applied to calibrate and assess the accuracy of simple models of the source and the detector of three commercial kV CBCT units. If the CBCT system models had been calibrated differently, the current procedure would have been exclusively used to validate the models. Several high-purity attenuation filters of aluminum, copper, and silver combined with a dosimeter which is sensitive to the range of voltages of interest were used. A sensitivity analysis of the model has also been conducted for each parameter of the source and the detector models. Results: Average deviations between experimental and theoretical dose values are below 1.5% after calibration for the three x-ray sources. The predicted energy deposited in the detector agrees with experimental data within 4% for all imaging systems. Conclusions: The authors developed and applied an experimental procedure to calibrate and validate any model of the source and the detector of a CBCT unit. The present protocol has been successfully applied to three x-ray imaging systems. The minimum requirements in terms of material and equipment would make its implementation suitable in

A Probabilistic Graphical Model to Detect Chromosomal Domains

Science.gov (United States)

Heermann, Dieter; Hofmann, Andreas; Weber, Eva

To understand the nature of a cell, one needs to understand the structure of its genome. For this purpose, experimental techniques such as Hi-C detecting chromosomal contacts are used to probe the three-dimensional genomic structure. These experiments yield topological information, consistently showing a hierarchical subdivision of the genome into self-interacting domains across many organisms. Current methods for detecting these domains using the Hi-C contact matrix, i.e. a doubly-stochastic matrix, are mostly based on the assumption that the domains are distinct, thus non-overlapping. For overcoming this simplification and for being able to unravel a possible nested domain structure, we developed a probabilistic graphical model that makes no a priori assumptions on the domain structure. Within this approach, the Hi-C contact matrix is analyzed using an Ising like probabilistic graphical model whose coupling constant is proportional to each lattice point (entry in the contact matrix). The results show clear boundaries between identified domains and the background. These domain boundaries are dependent on the coupling constant, so that one matrix yields several clusters of different sizes, which show the self-interaction of the genome on different scales. This work was supported by a Grant from the International Human Frontier Science Program Organization (RGP0014/2014).

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.