Blockade of HERG human K+ channels and IKr of guinea-pig cardiomyocytes by the antipsychotic drug clozapine

PubMed Central

Lee, So-Young; Kim, Young-Jin; Kim, Kyong-Tai; Choe, Han; Jo, Su-Hyun

2006-01-01

Clozapine, a commonly used antipsychotic drug, can induce QT prolongation, which may lead to torsades de pointes and sudden death. To investigate the arrhythmogenic side effects of clozapine, we studied the impact of clozapine on human ether-a-go-go-related gene (HERG) channels expressed in Xenopus oocytes and HEK293 cells, and on the delayed rectifier K+ currents of guinea-pig cardiomyocytes. Clozapine dose-dependently decreased the amplitudes of the currents at the end of voltage steps, and the tail currents of HERG. The IC50 for the clozapine blockade of HERG currents in Xenopus oocytes progressively decreased relative to depolarization (39.9 μM at −40 mV, 28.3 μM at 0 mV and 22.9 μM at +40 mV), whereas the IC50 for the clozapine-induced blockade of HERG currents in HEK293 cells at 36°C was 2.5 μM at +20 mV. The clozapine-induced blockade of HERG currents was time dependent: the fractional current was 0.903 of the control at the beginning of the pulse, but declined to 0.412 after 4 s at a test potential of 0 mV. The clozapine-induced blockade of HERG currents was use-dependent, exhibiting more rapid onset and greater steady state blockade at higher frequencies of activation, with a partial relief of blockade observed when the frequency of activation was decreased. In guinea-pig ventricular myocytes held at 36°C, treatment with 1 and 5 μM clozapine blocked the rapidly activating delayed rectifier K+ current (IKr) by 24.7 and 79.6%, respectively, but did not significantly block the slowly activating delayed rectifier K+ current (IKs). Our findings collectively suggest that blockade of HERG currents and IKr, but not IKs, may contribute to the arrhythmogenic side effects of clozapine. PMID:16633353

Risperidone prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current.

PubMed

Drolet, Benoit; Yang, Tao; Daleau, Pascal; Roden, Dan M; Turgeon, Jacques

2003-06-01

Cases of QT prolongation and sudden death have been reported with risperidone, a neuroleptic agent increasingly prescribed worldwide. Although hypokalemia was present in some of these events, we hypothesized that risperidone may have unsuspected electrophysiologic effects predisposing patients to proarrhythmia. In six isolated guinea pig hearts, risperidone elicited prolongation of cardiac repolarization: action potential duration increased from a baseline value of 128 ms +/- 5 to 147 ms +/- 5 (15%) with risperidone 1 microM during pacing at 250-ms cycle length, whereas the increase was only 10%, from 101 ms +/- 2 to 111 ms +/- 4, with pacing at a cycle length of 150 ms. In human ether-a-go-go (HERG)-transfected Chinese hamster ovary cells (n = 16), risperidone caused concentration-dependent block of the rapid component (I(Kr)) of the delayed rectifier potassium current with an IC(50) for tail block of 261 nM. Risperidone did not block I(Ks). Risperidone exerts cardiac electrophysiologic effects similar to those of Class III antiarrhythmic drugs. These effects are observed at clinically relevant concentrations. Because risperidone is metabolized primarily by CYP2D6, these actions likely enhance risk for risperidone-related QT prolongation and proarrhythmia in specific patient subsets (e.g., poor metabolizers and those taking interacting drugs).

β1-adrenergic regulation of rapid component of delayed rectifier K+ currents in guinea-pig cardiac myocytes.

PubMed

Wang, Sen; Xu, Di; Wu, Ting-Ting; Guo, Yan; Chen, Yan-Hong; Zou, Jian-Gang

2014-05-01

Human ether-à-go-go-related gene (hERG) potassium channels conduct the rapid component of the delayed rectifier potassium current (IKr), which is crucial for repolarization of cardiac action potential. Patients with hERG‑associated long QT syndrome usually develop tachyarrhythmias during physical and/or emotional stress, both known to stimulate adrenergic receptors. The present study aimed to investigate a putative functional link between β1-adrenergic stimulation and IKr in guinea-pig left ventricular myocytes and to analyze how IKr is regulated following activation of the β1-adrenergic signaling pathway. The IKr current was measured using a whole-cell patch-clamp technique. A selective β1-adrenergic receptor agonist, xamoterol, at concentrations of 0.01-100 µM decreased IKr in a concentration-dependent manner. The 10 µM xamoterol-induced inhibition of IKr was attenuated by the protein kinase A (PKA) inhibitor KT5720, the protein kinase C (PKC) inhibitor chelerythrine, and the phospholipase (PLC) inhibitor U73122, indicating involvement of PKA, PKC and PLC in β1-adrenergic inhibition of IKr. The results of the present study indicate an association between IKr and the β1-adrenergic receptor in arrhythmogenesis, involving the activation of PKA, PKC and PLC.

Inhibitory effects of hesperetin on Kv1.5 potassium channels stably expressed in HEK 293 cells and ultra-rapid delayed rectifier K(+) current in human atrial myocytes.

PubMed

Wang, Huan; Wang, Hong-Fei; Wang, Chen; Chen, Yu-Fang; Ma, Rong; Xiang, Ji-Zhou; Du, Xin-Ling; Tang, Qiang

2016-10-15

In the present study, the inhibitory effects of hesperetin (HSP) on human cardiac Kv1.5 channels expressed in HEK 293 cells and the ultra-rapid delayed rectifier K(+) current (Ikur) in human atrial myocytes were examined by using the whole-cell configuration of the patch-clamp techniques. We found that hesperetin rapidly and reversibly suppressed human Kv1.5 current in a concentration dependent manner with a half-maximal inhibition (IC50) of 23.15 μΜ with a Hill coefficient of 0.89. The current was maximally diminished about 71.36% at a concentration of 300μM hesperetin. Hesperetin significantly positive shifted the steady-state activation curve of Kv1.5, while negative shifted the steady-state inactivation curve. Hesperetin also accelerated the inactivation and markedly slowed the recovery from the inactivation of Kv1.5 currents. Block of Kv1.5 currents by hesperetin was in a frequency dependent manner. However, inclusion of 30μM hesperetin in pipette solution produced no effect on Kv1.5 channel current, while the current were remarkable and reversibly inhibited by extracellular application of 30μM hesperetin. We also found that hesperetin potently and reversibly inhibited the ultra-repaid delayed K(+) current (Ikur) in human atrial myocytes, which is in consistent with the effects of hesperetin on Kv1.5 currents in HEK 293 cells. In conclusion, hesperetin is a potent inhibitor of Ikur (which is encoded by Kv1.5), with blockade probably due to blocking of both open state and inactivated state channels from outside of the cell. Copyright © 2016 Elsevier B.V. All rights reserved.

Quantitative analysis of the Ca2+ -dependent regulation of delayed rectifier K+ current IKs in rabbit ventricular myocytes.

PubMed

Bartos, Daniel C; Morotti, Stefano; Ginsburg, Kenneth S; Grandi, Eleonora; Bers, Donald M

2017-04-01

[Ca 2+ ] i enhanced rabbit ventricular slowly activating delayed rectifier K + current (I Ks ) by negatively shifting the voltage dependence of activation and slowing deactivation, similar to perfusion of isoproterenol. Rabbit ventricular rapidly activating delayed rectifier K + current (I Kr ) amplitude and voltage dependence were unaffected by high [Ca 2+ ] i . When measuring or simulating I Ks during an action potential, I Ks was not different during a physiological Ca 2+ transient or when [Ca 2+ ] i was buffered to 500 nm. The slowly activating delayed rectifier K + current (I Ks ) contributes to repolarization of the cardiac action potential (AP). Intracellular Ca 2+ ([Ca 2+ ] i ) and β-adrenergic receptor (β-AR) stimulation modulate I Ks amplitude and kinetics, but details of these important I Ks regulators and their interaction are limited. We assessed the [Ca 2+ ] i dependence of I Ks in steady-state conditions and with dynamically changing membrane potential and [Ca 2+ ] i during an AP. I Ks was recorded from freshly isolated rabbit ventricular myocytes using whole-cell patch clamp. With intracellular pipette solutions that controlled free [Ca 2+ ] i , we found that raising [Ca 2+ ] i from 100 to 600 nm produced similar increases in I Ks as did β-AR activation, and the effects appeared additive. Both β-AR activation and high [Ca 2+ ] i increased maximally activated tail I Ks , negatively shifted the voltage dependence of activation, and slowed deactivation kinetics. These data informed changes in our well-established mathematical model of the rabbit myocyte. In both AP-clamp experiments and simulations, I Ks recorded during a normal physiological Ca 2+ transient was similar to I Ks measured with [Ca 2+ ] i clamped at 500-600 nm. Thus, our study provides novel quantitative data as to how physiological [Ca 2+ ] i regulates I Ks amplitude and kinetics during the normal rabbit AP. Our results suggest that micromolar [Ca 2+ ] i , in the submembrane or junctional cleft space, is not required to maximize [Ca 2+ ] i -dependent I Ks activation during normal Ca 2+ transients. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Quantitative analysis of the Ca2+‐dependent regulation of delayed rectifier K+ current I Ks in rabbit ventricular myocytes

PubMed Central

Bartos, Daniel C.; Morotti, Stefano; Ginsburg, Kenneth S.; Grandi, Eleonora

2017-01-01

Key points [Ca2+]i enhanced rabbit ventricular slowly activating delayed rectifier K+ current (I Ks) by negatively shifting the voltage dependence of activation and slowing deactivation, similar to perfusion of isoproterenol.Rabbit ventricular rapidly activating delayed rectifier K+ current (I Kr) amplitude and voltage dependence were unaffected by high [Ca2+]i.When measuring or simulating I Ks during an action potential, I Ks was not different during a physiological Ca2+ transient or when [Ca2+]i was buffered to 500 nm. Abstract The slowly activating delayed rectifier K+ current (I Ks) contributes to repolarization of the cardiac action potential (AP). Intracellular Ca2+ ([Ca2+]i) and β‐adrenergic receptor (β‐AR) stimulation modulate I Ks amplitude and kinetics, but details of these important I Ks regulators and their interaction are limited. We assessed the [Ca2+]i dependence of I Ks in steady‐state conditions and with dynamically changing membrane potential and [Ca2+]i during an AP. I Ks was recorded from freshly isolated rabbit ventricular myocytes using whole‐cell patch clamp. With intracellular pipette solutions that controlled free [Ca2+]i, we found that raising [Ca2+]i from 100 to 600 nm produced similar increases in I Ks as did β‐AR activation, and the effects appeared additive. Both β‐AR activation and high [Ca2+]i increased maximally activated tail I Ks, negatively shifted the voltage dependence of activation, and slowed deactivation kinetics. These data informed changes in our well‐established mathematical model of the rabbit myocyte. In both AP‐clamp experiments and simulations, I Ks recorded during a normal physiological Ca2+ transient was similar to I Ks measured with [Ca2+]i clamped at 500–600 nm. Thus, our study provides novel quantitative data as to how physiological [Ca2+]i regulates I Ks amplitude and kinetics during the normal rabbit AP. Our results suggest that micromolar [Ca2+]i, in the submembrane or junctional cleft space, is not required to maximize [Ca2+]i‐dependent I Ks activation during normal Ca2+ transients. PMID:28008618

[Effects of allitridum on rapidly delayed rectifier potassium current in HEK293 cell line].

PubMed

Zhang, Jiancheng; Lin, Kun; Wei, Zhixiong; Chen, Qian; Liu, Li; Zhao, Xiaojing; Zhao, Ying; Xu, Bin; Chen, Xi; Li, Yang

2015-08-01

To study the effect of allitridum on rapidly delayed rectifier potassium current (IKr) in HEK293 cell line. HEK293 cells were transiently transfected with HERG channel cDNA plasmid pcDNA3.1 via Lipofectamine. Allitridum was added to the extracellular solution by partial perfusion after giga seal at the final concentration of 30 µmol/L. Whole-cell patch clamp technique was used to record the HERG currents and gating kinetics before and after allitridum exposure at room temperature. The amplitude and density of IHERG were both suppressed by allitridum in a voltage-dependent manner. In the presence of allitridum, the peak current of IHERG was reduced from 73.5∓4.3 pA/pF to 42.1∓3.6 pA/pF at the test potential of +50 mV (P<0.01). Allitridum also concentration-dependently decreased the density of the IHERG. The IC50 of allitridum was 34.74 µmol/L with a Hill coefficient of 1.01. Allitridum at 30 µmol/L caused a significant positive shift of the steady-state activation curve of IHERG and a markedly negative shift of the steady-state inactivation of IHERG, and significantly shortened the slow time constants of IHERG deactivation. Allitridum can potently block IHERG in HEK293 cells, which might be the electrophysiological basis for its anti-arrhythmic action.

Fast inactivation of delayed rectifier K conductance in squid giant axon and its cell bodies.

PubMed

Mathes, C; Rosenthal, J J; Armstrong, G M; Gilly, W F

1997-04-01

Inactivation of delayed rectifier K conductance (gk) was studied in squid giant axons and in the somata of giant fiber lobe (GFL) neurons. Axon measurements were made with an axial wire voltage clamp by pulsing to VK (approximately -10 mV in 50-70 mM external K) for a variable time and then assaying available gK with a strong, brief test pulse. GFL cells were studied with whole-cell patch clamp using the same prepulse procedure as well as with long depolarizations. Under our experimental conditions (12-18 degrees C, 4 mM internal MgATP) a large fraction of gK inactivates within 250 ms at -10 mV in both cell bodies and axons, although inactivation tends to be more complete in cell bodies. Inactivation in both preparations shows two kinetic components. The faster component is more temperature-sensitive and becomes very prominent above 12 degrees C. Contribution of the fast component to inactivation shows a similar voltage dependence to that of gK, suggesting a strong coupling of this inactivation path to the open state. Omission of internal MgATP or application of internal protease reduces the amount of fast inactivation. High external K decreases the amount of rapidly inactivating IK but does not greatly alter inactivation kinetics. Neither external nor internal tetraethylammonium has a marked effect on inactivation kinetics. Squid delayed rectifier K channels in GFL cell bodies and giant axons thus share complex fast inactivation properties that do not closely resemble those associated with either C-type or N-type inactivation of cloned Kvl channels studied in heterologous expression systems.

Fast Inactivation of Delayed Rectifier K Conductance in Squid Giant Axon and Its Cell Bodies

PubMed Central

Mathes, Chris; Rosenthal, Joshua J.C.; Armstrong, Clay M.; Gilly, William F.

1997-01-01

Inactivation of delayed rectifier K conductance (gK) was studied in squid giant axons and in the somata of giant fiber lobe (GFL) neurons. Axon measurements were made with an axial wire voltage clamp by pulsing to VK (∼−10 mV in 50–70 mM external K) for a variable time and then assaying available gK with a strong, brief test pulse. GFL cells were studied with whole-cell patch clamp using the same prepulse procedure as well as with long depolarizations. Under our experimental conditions (12–18°C, 4 mM internal MgATP) a large fraction of gK inactivates within 250 ms at −10 mV in both cell bodies and axons, although inactivation tends to be more complete in cell bodies. Inactivation in both preparations shows two kinetic components. The faster component is more temperature-sensitive and becomes very prominent above 12°C. Contribution of the fast component to inactivation shows a similar voltage dependence to that of gK, suggesting a strong coupling of this inactivation path to the open state. Omission of internal MgATP or application of internal protease reduces the amount of fast inactivation. High external K decreases the amount of rapidly inactivating IK but does not greatly alter inactivation kinetics. Neither external nor internal tetraethylammonium has a marked effect on inactivation kinetics. Squid delayed rectifier K channels in GFL cell bodies and giant axons thus share complex fast inactivation properties that do not closely resemble those associated with either C-type or N-type inactivation of cloned Kv1 channels studied in heterologous expression systems. PMID:9101403

Gating, modulation and subunit composition of voltage-gated K+ channels in dendritic inhibitory interneurones of rat hippocampus

PubMed Central

Lien, Cheng-Chang; Martina, Marco; Schultz, Jobst H; Ehmke, Heimo; Jonas, Peter

2002-01-01

GABAergic interneurones are diverse in their morphological and functional properties. Perisomatic inhibitory cells show fast spiking during sustained current injection, whereas dendritic inhibitory cells fire action potentials with lower frequency. We examined functional and molecular properties of K+ channels in interneurones with horizontal dendrites in stratum oriens-alveus (OA) of the hippocampal CA1 region, which mainly comprise somatostatin-positive dendritic inhibitory cells. Voltage-gated K+ currents in nucleated patches isolated from OA interneurones consisted of three major components: a fast delayed rectifier K+ current component that was highly sensitive to external 4-aminopyridine (4-AP) and tetraethylammonium (TEA) (half-maximal inhibitory concentrations < 0.1 mm for both blockers), a slow delayed rectifier K+ current component that was sensitive to high concentrations of TEA, but insensitive to 4-AP, and a rapidly inactivating A-type K+ current component that was blocked by high concentrations of 4-AP, but resistant to TEA. The relative contributions of these components to the macroscopic K+ current were estimated as 57 ± 5, 25 ± 6, and 19 ± 2 %, respectively. Dendrotoxin, a selective blocker of Kv1 channels had only minimal effects on K+ currents in nucleated patches. Coapplication of the membrane-permeant cAMP analogue 8-(4-chlorophenylthio)-adenosine 3′:5′-cyclic monophosphate (cpt-cAMP) and the phosphodiesterase blocker isobutyl-methylxanthine (IBMX) resulted in a selective inhibition of the fast delayed rectifier K+ current component. This inhibition was absent in the presence of the protein kinase A (PKA) inhibitor H-89, implying the involvement of PKA-mediated phosphorylation. Single-cell reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed a high abundance of Kv3.2 mRNA in OA interneurones, whereas the expression level of Kv3.1 mRNA was markedly lower. Similarly, RT-PCR analysis showed a high abundance of Kv4.3 mRNA, whereas Kv4.2 mRNA was undetectable. This suggests that the fast delayed rectifier K+ current and the A-type K+ current component are mediated predominantly by homomeric Kv3.2 and Kv4.3 channels. Selective modulation of Kv3.2 channels in OA interneurones by cAMP is likely to be an important factor regulating the activity of dendritic inhibitory cells in principal neurone-interneurone microcircuits. PMID:11790809

Voltage sensitivity of M2 muscarinic receptors underlies the delayed rectifier-like activation of ACh-gated K(+) current by choline in feline atrial myocytes.

PubMed

Navarro-Polanco, Ricardo A; Aréchiga-Figueroa, Iván A; Salazar-Fajardo, Pedro D; Benavides-Haro, Dora E; Rodríguez-Elías, Julio C; Sachse, Frank B; Tristani-Firouzi, Martin; Sánchez-Chapula, José A; Moreno-Galindo, Eloy G

2013-09-01

Choline (Ch) is a precursor and metabolite of the neurotransmitter acetylcholine (ACh). In canine and guinea pig atrial myocytes, Ch was shown to activate an outward K(+) current in a delayed rectifier fashion. This current has been suggested to modulate cardiac electrical activity and to play a role in atrial fibrillation pathophysiology. However, the exact nature and identity of this current has not been convincingly established. We recently described the unique ligand- and voltage-dependent properties of muscarinic activation of ACh-activated K(+) current (IKACh) and showed that, in contrast to ACh, pilocarpine induces a current with delayed rectifier-like properties with membrane depolarization. Here, we tested the hypothesis that Ch activates IKACh in feline atrial myocytes in a voltage-dependent manner similar to pilocarpine. Single-channel recordings, biophysical profiles, specific pharmacological inhibition and computational data indicate that the current activated by Ch is IKACh. Moreover, we show that membrane depolarization increases the potency and efficacy of IKACh activation by Ch and thus gives the appearance of a delayed rectifier activating K(+) current at depolarized potentials. Our findings support the emerging concept that IKACh modulation is both voltage- and ligand-specific and reinforce the importance of these properties in understanding cardiac physiology.

An Inductorless Self-Controlled Rectifier for Piezoelectric Energy Harvesting

PubMed Central

Lu, Shaohua; Boussaid, Farid

2015-01-01

This paper presents a high-efficiency inductorless self-controlled rectifier for piezoelectric energy harvesting. High efficiency is achieved by discharging the piezoelectric device (PD) capacitance each time the current produced by the PD changes polarity. This is achieved automatically without the use of delay lines, thereby making the proposed circuit compatible with any type of PD. In addition, the proposed rectifier alleviates the need for an inductor, making it suitable for on-chip integration. Reported experimental results show that the proposed rectifier can harvest up to 3.9 times more energy than a full wave bridge rectifier. PMID:26610492

An Inductorless Self-Controlled Rectifier for Piezoelectric Energy Harvesting.

PubMed

Lu, Shaohua; Boussaid, Farid

2015-11-19

This paper presents a high-efficiency inductorless self-controlled rectifier for piezoelectric energy harvesting. High efficiency is achieved by discharging the piezoelectric device (PD) capacitance each time the current produced by the PD changes polarity. This is achieved automatically without the use of delay lines, thereby making the proposed circuit compatible with any type of PD. In addition, the proposed rectifier alleviates the need for an inductor, making it suitable for on-chip integration. Reported experimental results show that the proposed rectifier can harvest up to 3.9 times more energy than a full wave bridge rectifier.

Sildenafil (Viagra) prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current.

PubMed

Geelen, P; Drolet, B; Rail, J; Bérubé, J; Daleau, P; Rousseau, G; Cardinal, R; O'Hara, G E; Turgeon, J

2000-07-18

BACKGROUND-Several cases of unexpected death have been reported with sildenafil in patients predisposed to ischemic cardiac events. Although acute episodes of ischemia could account for some of these deaths, we hypothesized that sildenafil may have unsuspected electrophysiological effects predisposing some patients to proarrhythmia. METHODS AND RESULTS-Studies were undertaken in 10 isolated guinea pig hearts that demonstrated prolongation of cardiac repolarization in a reverse use-dependent manner by sildenafil 30 mcmol/L. Action potential duration increased 15% from baseline 117+/-3 to 134+/-2 ms with sildenafil during pacing at 250 ms cycle length, whereas a 6% increase from 99+/-2 to 105+/-2 ms was seen with pacing at 150 ms cycle length. Experiments in human ether-a-go-go-related gene (HERG)-transfected HEK293 cells (n=30) demonstrated concentration-dependent block of the rapid component (I(Kr)) of the delayed rectifier potassium current: activating current was 50% decreased at 100 mcmol/L. This effect was confirmed using HERG-transfected Chinese hamster ovary (CHO) cells, which exhibit no endogenous I(K)-like current. CONCLUSIONS-Sildenafil possesses direct cardiac electrophysiological effects similar to class III antiarrhythmic drugs. These effects are observed at concentrations that may be found in conditions of impaired drug elimination such as renal or hepatic insufficiency, during coadministration of another CYP3A substrate/inhibitor, or after drug overdose and offer a new potential explanation for sudden death during sildenafil treatment.

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

PubMed Central

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

2009-01-01

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

Distinct gene-specific mechanisms of arrhythmia revealed by cardiac gene transfer of two long QT disease genes, HERG and KCNE1.

PubMed

Hoppe, U C; Marbán, E; Johns, D C

2001-04-24

The long QT syndrome (LQTS) is a heritable disorder that predisposes to sudden cardiac death. LQTS is caused by mutations in ion channel genes including HERG and KCNE1, but the precise mechanisms remain unclear. To clarify this situation we injected adenoviral vectors expressing wild-type or LQT mutants of HERG and KCNE1 into guinea pig myocardium. End points at 48-72 h included electrophysiology in isolated myocytes and electrocardiography in vivo. HERG increased the rapid component, I(Kr), of the delayed rectifier current, thereby accelerating repolarization, increasing refractoriness, and diminishing beat-to-beat action potential variability. Conversely, HERG-G628S suppressed I(Kr) without significantly delaying repolarization. Nevertheless, HERG-G628S abbreviated refractoriness and increased beat-to-beat variability, leading to early afterdepolarizations (EADs). KCNE1 increased the slow component of the delayed rectifier, I(Ks), without clear phenotypic sequelae. In contrast, KCNE1-D76N suppressed I(Ks) and markedly slowed repolarization, leading to frequent EADs and electrocardiographic QT prolongation. Thus, the two genes predispose to sudden death by distinct mechanisms: the KCNE1 mutant flagrantly undermines cardiac repolarization, and HERG-G628S subtly facilitates the genesis and propagation of premature beats. Our ability to produce electrocardiographic long QT in vivo with a clinical KCNE1 mutation demonstrates the utility of somatic gene transfer in creating genotype-specific disease models.

Electrophysiological characterization of 14-benzoyltalatisamine, a selective blocker of the delayed rectifier K+ channel found in virtual screening.

PubMed

Song, Ming-Ke; Liu, Hong; Jiang, Hua-Liang; Yue, Jian-Min; Hu, Guo-Yuan

2006-02-15

14-Benzoyltalatisamine is a potent and selective blocker of the delayed rectifier K+ channel found in a computational virtual screening study. The compound was found to block the K+ channel from the extracellular side. However, it is unclear whether 14-benzoyltalatisamine shares the same block mechanism with tetraethylammonium (TEA). In order to elucidate how the hit compound found by the virtual screening interacts with the outer vestibule of the K+ channel, the effects of 14-benzoyltalatisamine and TEA on the delayed rectifier K+ current of rat dissociated hippocampal neurons were compared using whole-cell voltage-clamp recording. External application of 14-benzoyltalatisamine and TEA reversibly inhibited the current with IC50 values of 10.1+/-2.2 microM and 1.05+/-0.21 mM, respectively. 14-Benzoyltalatisamine exerted voltage-dependent inhibition, markedly accelerated the decay of the current, and caused a significant hyperpolarizing shift of the steady-state activation curve, whereas TEA caused voltage-independent inhibition, without affecting the kinetic parameters of the current. The blockade by 14-benzoyltalatisamine, but not by TEA, was significantly diminished in a high K+ (60 mM) external solution. The potency of 14-benzoyltalatisamine was markedly reduced in the presence of 15 mM TEA. The results suggest that 14-benzoyltalatisamine bind to the external pore entry of the delayed rectifier K+ channel with partial insertion into the selectivity filter, which is in conformity with that predicted by the molecular docking model in the virtual screening.

Discovery of talatisamine as a novel specific blocker for the delayed rectifier K+ channels in rat hippocampal neurons.

PubMed

Song, M-K; Liu, H; Jiang, H-L; Yue, J-M; Hu, G-Y; Chen, H-Z

2008-08-13

Blocking specific K+ channels has been proposed as a promising strategy for the treatment of neurodegenerative diseases. Using a computational virtual screening approach and electrophysiological testing, we found four Aconitum alkaloids are potent blockers of the delayed rectifier K+ channel in rat hippocampal neurons. In the present study, we first tested the action of the four alkaloids on the voltage-gated K+, Na+ and Ca2+ currents in rat hippocampal neurons, and then identified that talatisamine is a specific blocker for the delayed rectifier K+ channel. External application of talatisamine reversibly inhibited the delayed rectifier K+ current (IK) with an IC50 value of 146.0+/-5.8 microM in a voltage-dependent manner, but exhibited very slight blocking effect on the voltage-gated Na+ and Ca2+ currents even at the high concentration of 1-3 mM. Moreover, talatisamine exerted a significant hyperpolarizing shift of the steady-state activation, but did not influence the steady state inactivation of IK and its recovery from inactivation, suggesting that talatisamine had no allosteric action on IK channel and was a pure blocker binding to the external pore entry of the channel. Our present study made the first discovery of potent and specific IK channel blocker from Aconitum alkaloids. It has been argued that suppressing K+ efflux by blocking IK channel may be favorable for Alzheimer's disease therapy. Talatisamine can therefore be considered as a leading compound worthy of further investigations.

Inhibitory Effects of Glycyrrhetinic Acid on the Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytes and HERG Channel

PubMed Central

Wu, Delin; Jiang, Linqing; Wu, Hongjin; Wang, Shengqi; Zheng, Sidao; Yang, Jiyuan; Liu, Yuna; Ren, Jianxun; Chen, Xianbing

2013-01-01

Background. Licorice has long been used to treat many ailments including cardiovascular disorders in China. Recent studies have shown that the cardiac actions of licorice can be attributed to its active component, glycyrrhetinic acid (GA). However, the mechanism of action remains poorly understood. Aim. The effects of GA on the delayed rectifier potassium current (I K), the rapidly activating (I Kr) and slowly activating (I Ks) components of I K, and the HERG K+ channel expressed in HEK-293 cells were investigated. Materials and Methods. Single ventricular myocytes were isolated from guinea pig myocardium using enzymolysis. The wild type HERG gene was stably expressed in HEK293 cells. Whole-cell patch clamping was used to record I K (I Kr, I Ks) and the HERG K+ current. Results. GA (1, 5, and 10 μM) inhibited I K (I Kr, I Ks) and the HERG K+ current in a concentration-dependent manner. Conclusion. GA significantly inhibited the potassium currents in a dose- and voltage-dependent manner, suggesting that it exerts its antiarrhythmic action through the prolongation of APD and ERP owing to the inhibition of I K (I Kr, I Ks) and HERG K+ channel. PMID:24069049

Inactivation properties of voltage-gated K+ channels altered by presence of beta-subunit.

PubMed

Rettig, J; Heinemann, S H; Wunder, F; Lorra, C; Parcej, D N; Dolly, J O; Pongs, O

1994-05-26

Structural and functional diversity of voltage-gated Kv1-type potassium channels in rat brain is enhanced by the association of two different types of subunits, the membrane-bound, poreforming alpha-subunits and a peripheral beta-subunit. We have cloned a beta-subunit (Kv beta 1) that is specifically expressed in the rat nervous system. Association of Kv beta 1 with alpha-subunits confers rapid A-type inactivation on non-inactivating Kv1 channels (delayed rectifiers) in expression systems in vitro. This effect is mediated by an inactivating ball domain in the Kv beta 1 amino terminus.

Photoperiod Modulates Fast Delayed Rectifier Potassium Currents in the Mammalian Circadian Clock.

PubMed

Farajnia, Sahar; Meijer, Johanna H; Michel, Stephan

2016-10-01

One feature of the mammalian circadian clock, situated in the suprachiasmatic nucleus (SCN), is its ability to measure day length and thereby contribute to the seasonal adaptation of physiology and behavior. The timing signal from the SCN, namely the 24 hr pattern of electrical activity, is adjusted according to the photoperiod being broader in long days and narrower in short days. Vasoactive intestinal peptide and gamma-aminobutyric acid play a crucial role in intercellular communication within the SCN and contribute to the seasonal changes in phase distribution. However, little is known about the underlying ionic mechanisms of synchronization. The present study was aimed to identify cellular mechanisms involved in seasonal encoding by the SCN. Mice were adapted to long-day (light-dark 16:8) and short-day (light-dark 8:16) photoperiods and membrane properties as well as K + currents activity of SCN neurons were measured using patch-clamp recordings in acute slices. Remarkably, we found evidence for a photoperiodic effect on the fast delayed rectifier K + current, that is, the circadian modulation of this ion channel's activation reversed in long days resulting in 50% higher peak values during the night compared with the unaltered day values. Consistent with fast delayed rectifier enhancement, duration of action potentials during the night was shortened and afterhyperpolarization potentials increased in amplitude and duration. The slow delayed rectifier, transient K + currents, and membrane excitability were not affected by photoperiod. We conclude that photoperiod can change intrinsic ion channel properties of the SCN neurons, which may influence cellular communication and contribute to photoperiodic phase adjustment. © The Author(s) 2016.

Delayed rectifier and A-type potassium channels associated with Kv 2.1 and Kv 4.3 expression in embryonic rat neural progenitor cells.

PubMed

Smith, Dean O; Rosenheimer, Julie L; Kalil, Ronald E

2008-02-13

Because of the importance of voltage-activated K(+) channels during embryonic development and in cell proliferation, we present here the first description of these channels in E15 rat embryonic neural progenitor cells derived from the subventricular zone (SVZ). Activation, inactivation, and single-channel conductance properties of recorded progenitor cells were compared with those obtained by others when these Kv gene products were expressed in oocytes. Neural progenitor cells derived from the subventricular zone of E15 embryonic rats were cultured under conditions that did not promote differentiation. Immunocytochemical and Western blot assays for nestin expression indicated that almost all of the cells available for recording expressed this intermediate filament protein, which is generally accepted as a marker for uncommitted embryonic neural progenitor cells. However, a very small numbers of the cells expressed GFAP, a marker for astrocytes, O4, a marker for immature oligodendrocytes, and betaIII-tubulin, a marker for neurons. Using immunocytochemistry and Western blots, we detected consistently the expression of Kv2.1, and 4.3. In whole-cell mode, we recorded two outward currents, a delayed rectifier and an A-type current. We conclude that Kv2.1, and 4.3 are expressed in E15 SVZ neural progenitor cells, and we propose that they may be associated with the delayed-rectifier and the A-type currents, respectively, that we recorded. These results demonstrate the early expression of delayed rectifier and A-type K(+) currents and channels in embryonic neural progenitor cells prior to the differentiation of these cells.

Differential regulation of the slow and rapid components of guinea-pig cardiac delayed rectifier K+ channels by hypoxia

PubMed Central

Hool, Livia C

2004-01-01

The aim of this study was to examine the effects of acute hypoxia on the slow (IKs) and rapid (IKr) components of the native delayed rectifier K+ channel in the absence and presence of the β-adrenergic receptor agonist isoproterenol (isoprenaline; Iso) using the whole-cell configuration of the patch-clamp technique. Hypoxia reversibly inhibited basal IKs. The effect could be mimicked by exposing the cells to the thiol-specific reducing agent dithiothreitol (DTT) and attenuated upon exposure of cells to the membrane-impermeant thiol-specific oxidizing compound 5,5′-dithio-bis[2-nitrobenzoic acid] (DTNB). In the presence of hypoxia, the K0.5 for activation of IKs by Iso was significantly decreased from 18.3 to 1.9 nm. DTT mimicked the effect of hypoxia on the sensitivity of IKs to Iso while DTNB had no effect. Hypoxia increased the sensitivity of IKs to histamine and forskolin suggesting that the effect of hypoxia is not occurring at the β-adrenergic receptor. The increase in sensitivity of IKs to Iso could be attenuated with addition of PKCβ peptide to the pipette solution. While hypoxia and DTT inhibited basal IKs they were without effect on IKr. In addition, Iso did not appear to alter the magnitude of IKr in the absence or presence of hypoxia. These data suggest that hypoxia regulates native IKs through two distinct mechanisms: direct inhibition of basal IKs and an increase in sensitivity to Iso that occurs downstream from the β-adrenergic receptor. Both mechanisms appear to involve redox modification of thiol groups. In contrast native IKr does not appear to be regulated by Iso, hypoxia or redox state. PMID:14634203

Different protein kinase C isoenzymes mediate inhibition of cardiac rapidly activating delayed rectifier K+ current by different G-protein coupled receptors.

PubMed

Liu, Xueli; Wang, Yuhong; Zhang, Hua; Shen, Li; Xu, Yanfang

2017-12-01

Elevated angiotensin II (Ang II) and sympathetic activity contributes to a high risk of ventricular arrhythmias in heart disease. The rapidly activating delayed rectifier K + current (I Kr ) carried by the hERG channels plays a critical role in cardiac repolarization, and decreased I Kr is involved in increased cardiac arrhythmogenicity. Stimulation of α 1A -adrenoreceptors or angiotensin II AT 1 receptors is known to inhibit I Kr via PKC. Here, we have identified the PKC isoenzymes mediating the inhibition of I Kr by activation of these two different GPCRs. The whole-cell patch-clamp technique was used to record I Kr in guinea pig cardiomyocytes and HEK293 cells co-transfected with hERG and α 1A -adrenoreceptor or AT 1 receptor genes. A broad spectrum PKC inhibitor Gö6983 (not inhibiting PKCε), a selective cPKC inhibitor Gö6976 and a PKCα-specific inhibitor peptide, blocked the inhibition of I Kr by the α 1A -adrenoreceptor agonist A61603. However, these inhibitors did not affect the reduction of I Kr by activation of AT 1 receptors, whereas the PKCε-selective inhibitor peptide did block the effect. The effects of angiotensin II and the PKCε activator peptide were inhibited in mutant hERG channels in which 17 of the 18 PKC phosphorylation sites were deleted, whereas a deletion of the N-terminus of the hERG channels selectively prevented the inhibition elicited by A61603 and the cPKC activator peptide. Our results indicated that inhibition of I Kr by activation of α 1A -adrenoreceptors or AT 1 receptors were mediated by PKCα and PKCε isoforms respectively, through different molecular mechanisms. © 2017 The British Pharmacological Society.

Attenuation of ischemia/reperfusion-induced inhibition of the rapid component of delayed rectifier potassium current by Isosteviol through scavenging reactive oxygen species.

PubMed

Yin, Chunxia; Chen, Yaoxu; Wu, Huanlin; Xu, Danping; Tan, Wen

2017-12-01

Isosteviol has been demonstrated to play a protective role during ischemia reperfusion (I/R) myocardial infarction. However, the underlying electrophysiological mechanisms of isosteviol are still unknown. Our previous study showed that the rapid component of the delayed rectifier potassium channel (I Kr ) plays an important role in the prolongation of I/R-induced QT interval-related arrhythmia. This study aimed to investigate whether isosteviol could attenuate I/R-induced prolongation of the action potential duration (APD) along with inhibition of I Kr , and we aimed to clarify the electrophysiological mechanism of isosteviol to determine its cardioprotective effects in guinea pigs. We observed that the APD 90 were 298.5±41.6ms in control, 528.6±56.7ms during I/R, and reduced to 327.8±40.5ms after 10μmol/L of isosteviol treatment. The I Kr currents were 1.44±0.06 pA·pF -1 in the control group, 0.50±0.07pA·pF -1 during I/R, and recovered to 1.20±0.12pA·pF -1 after 10μmol/L of isoteviol treatment. Moreover, isosteviol reduced the over-production of reactive oxygen species (ROS) during I/R. Importantly, isosteviol does not affect the I Kr and human ether-a-go-go-related gene currents of normal cardiomyocytes. It attenuated the I/R-induced inhibition of I Kr due to reduced over-production of ROS. Furthermore, isosteviol is safe and has no cardiotoxicity, and it might be beneficial for coronary reperfusion therapy. Copyright © 2017. Published by Elsevier B.V.

Delayed Rectifier and A-Type Potassium Channels Associated with Kv 2.1 and Kv 4.3 Expression in Embryonic Rat Neural Progenitor Cells

PubMed Central

Smith, Dean O.; Rosenheimer, Julie L.; Kalil, Ronald E.

2008-01-01

Background Because of the importance of voltage-activated K+ channels during embryonic development and in cell proliferation, we present here the first description of these channels in E15 rat embryonic neural progenitor cells derived from the subventricular zone (SVZ). Activation, inactivation, and single-channel conductance properties of recorded progenitor cells were compared with those obtained by others when these Kv gene products were expressed in oocytes. Methodology/Principal Findings Neural progenitor cells derived from the subventricular zone of E15 embryonic rats were cultured under conditions that did not promote differentiation. Immunocytochemical and Western blot assays for nestin expression indicated that almost all of the cells available for recording expressed this intermediate filament protein, which is generally accepted as a marker for uncommitted embryonic neural progenitor cells. However, a very small numbers of the cells expressed GFAP, a marker for astrocytes, O4, a marker for immature oligodendrocytes, and βIII-tubulin, a marker for neurons. Using immunocytochemistry and Western blots, we detected consistently the expression of Kv2.1, and 4.3. In whole-cell mode, we recorded two outward currents, a delayed rectifier and an A-type current. Conclusions/Significance We conclude that Kv2.1, and 4.3 are expressed in E15 SVZ neural progenitor cells, and we propose that they may be associated with the delayed-rectifier and the A-type currents, respectively, that we recorded. These results demonstrate the early expression of delayed rectifier and A-type K+ currents and channels in embryonic neural progenitor cells prior to the differentiation of these cells. PMID:18270591

Molecular basis and function of voltage-gated K+ channels in pulmonary arterial smooth muscle cells.

PubMed

Yuan, X J; Wang, J; Juhaszova, M; Golovina, V A; Rubin, L J

1998-04-01

K(+)-channel activity-mediated alteration of the membrane potential and cytoplasmic free Ca2+ concentration ([Ca2+]cyt) is a pivotal mechanism in controlling pulmonary vasomotor tone. By using combined approaches of patch clamp, imaging fluorescent microscopy, and molecular biology, we examined the electrophysiological properties of K+ channels and the role of different K+ currents in regulating [Ca2+]cyt and explored the molecular identification of voltage-gated K+ (KV)- and Ca(2+)-activated K+ (KCa)-channel genes expressed in pulmonary arterial smooth muscle cells (PASMC). Two kinetically distinct KV currents [IK(V)], a rapidly inactivating (A-type) and a noninactivating delayed rectifier, as well as a slowly activated KCa current [IK(Ca)] were identified. IK(V) was reversibly inhibited by 4-aminopyridine (5 mM), whereas IK(Ca) was significantly inhibited by charybdotoxin (10-20 nM). K+ channels are composed of pore-forming alpha-subunits and auxiliary beta-subunits. Five KV-channel alpha-subunit genes from the Shaker subfamily (KV1.1, KV1.2, KV1.4, KV1.5, and KV1.6), a KV-channel alpha-subunit gene from the Shab subfamily (KV2.1), a KV-channel modulatory alpha-subunit (KV9.3), and a KCa-channel alpha-subunit gene (rSlo), as well as three KV-channel beta-subunit genes (KV beta 1.1, KV beta 2, and KV beta 3) are expressed in PASMC. The data suggest that 1) native K+ channels in PASMC are encoded by multiple genes; 2) the delayed rectifier IK(V) may be generated by the KV1.1, KV1.2, KV1.5, KV1.6, KV2.1, and/or KV2.1/KV9.3 channels; 3) the A-type IK(V) may be generated by the KV1.4 channel and/or the delayed rectifier KV channels (KV1 subfamily) associated with beta-subunits; and 4) the IK(Ca) may be generated by the rSlo gene product. The function of the KV channels plays an important role in the regulation of membrane potential and [Ca2+]cyt in PASMC.

Block of the delayed rectifier current (IK) by the 5-HT3 antagonists ondansetron and granisetron in feline ventricular myocytes.

PubMed Central

de Lorenzi, F G; Bridal, T R; Spinelli, W

1994-01-01

1. We investigated the effects of two 5-HT3 antagonists, ondansetron and granisetron, on the action potential duration (APD) and the delayed rectifier current (IK) of feline isolated ventricular myocytes. Whole-cell current and action potential recordings were performed at 37 degrees C with the patch clamp technique. 2. Ondansetron and granisetron blocked IK with a KD of 1.7 +/- 1.0 and 4.3 +/- 1.7 microM, respectively. At a higher concentration (30 microM), both drugs blocked the inward rectifier (IKl). 3. The block of IK was dependent on channel activation. Both drugs slowed the decay of IK tail currents and produced a crossover with the pre-drug current trace. These results are consistent with block and unblock from the open state of the channel. 4. Granisetron showed an intrinsic voltage-dependence as the block increased with depolarization. The equivalent voltage-dependency of block (delta) was 0.10 +/- 0.04, suggesting that granisetron blocks from the intracellular side at a binding site located 10% across the transmembrane electrical field. 5. Ondansetron (1 microM) and granisetron (3 microM) prolonged APD by about 30% at 0.5 Hz. The prolongation of APD by ondansetron was abolished at faster frequencies (3 Hz) showing reverse rate dependence. 6. In conclusion, the 5-HT3 antagonists, ondansetron and granisetron, are open state blockers of the ventricular delayed rectifier and show a clear class III action. PMID:7834204

Inward Rectifier Potassium Channels Control Rotor Frequency in Ventricular Fibrillation

PubMed Central

Jalife, José

2009-01-01

Summary Ventricular fibrillation (VF) is the most important cause of sudden cardiac death. While traditionally thought to result from random activation of the ventricles by multiple independent wavelets, recent evidence suggests that VF may be determined by the sustained activation of a relatively small number of reentrant sources. In addition, recent experimental data in various species as well as computer simulations have provided important clues about its ionic and molecular mechanisms, particularly in regards to the role of potassium currents in such mechanisms. The results strongly argue that the inward rectifier current, Ik1, is an important current during functional reentry because it mediates the electrotonic interactions between the unexcited core and its immediate surroundings. In addition, IK1 is a stabilizer of reentry due to its ability to shorten action potential duration and reducing conduction velocity near the center of rotation. Increased I K1 prevents wavefront-wavetail interactions and thus averts rotor destabilization and breakup. Other studies have shown that while the slow component of the delayed rectifier potassium current, IKs, does not significantly modify rotor frequency or stability, it plays a major role in post-repolarization refractoriness and wavebreak formation. Therefore, the interplay between IK1 and the rapid sodium inward current (INa) is a major factor in the control of cardiac excitability and therefore the stability and frequency of reentry while IKs is an important determinant of fibrillatory conduction. PMID:19880073

Update on the slow delayed rectifier potassium current (I(Ks)): role in modulating cardiac function.

PubMed

Liu, Zhenzhen; Du, Lupei; Li, Minyong

2012-01-01

The slow delayed rectifier current (I(Ks)) is the slow component of cardiac delayed rectifier current and is critical for the late phase repolarization of cardiac action potential. This current is also an important target for Sympathetic Nervous System (SNS) to regulate the cardiac electivity to accommodate to heart rate alterations in response to exercise or emotional stress and can be up-regulated by β- adrenergic or other signal molecules. I(Ks) channel is originated by the co-assembly of pore-forming KCNQ1 α-subunit and accessory KCNE1 β-subunit. Mutations in any subunit can bring about severe long QT syndrome (LQT-1, LQT-5) as characterized by deliquium, seizures and sudden death. This review summarizes the normal physiological functions and molecular basis of I(Ks) channels, as well as illustrates up-to-date development on its blockers and activators. Therefore, the current extensive survey should generate fundamental understanding of the role of I(Ks) channel in modulating cardiac function and donate some instructions to the progression of I(Ks) blockers and activators as potential antiarrhythmic agents or pharmacological tools to determine the physiological and pathological function of I(Ks).

Role of voltage-gated K(+) channels in regulating Ca(2+) entry in rat cortical astrocytes.

PubMed

Wu, King-Chuen; Kuo, Chang-Shin; Chao, Chia-Chia; Huang, Chieh-Chen; Tu, Yuan-Kun; Chan, Paul; Leung, Yuk-Man

2015-03-01

Astrocytes have multiple functions such as provision of nourishment and mechanical support to the nervous system, helping to clear extracellular metabolites of neurons and modulating synaptic transmission by releasing gliotransmitters. In excitable cells, voltage-gated K(+) (Kv) channels serve to repolarize during action potentials. Astrocytes are considered non-excitable cells since they are not able to generate action potentials. There is an abundant expression of various Kv channels in astrocytes but the functions of these Kv channels remain unclear. We examined whether these astrocyte Kv channels regulate astrocyte "excitability" in the form of cytosolic Ca(2+) signaling. Electrophysiological examination revealed that neonatal rat cortical astrocytes possessed both delayed rectifier type and A-type Kv channels. Pharmacological blockade of both delayed rectifier Kv channels by TEA and A-type Kv channels by quinidine significantly suppressed store-operated Ca(2+) influx; however, TEA alone or quinidine alone did not suffice to cause such suppression. TEA and quinidine together dramatically enhanced current injection-triggered membrane potential overshoot (depolarization); either drug alone caused much smaller enhancements. Taken together, the results suggest both delayed rectifier and A-type Kv channels regulate astrocyte Ca(2+) signaling via controlling membrane potential.

Utility of multi-channel surface electromyography in assessment of focal hand dystonia.

PubMed

Sivadasan, Ajith; Sanjay, M; Alexander, Mathew; Devasahayam, Suresh R; Srinivasa, Babu K

2013-09-01

Surface electromyography (SEMG) allows objective assessment and guides selection of appropriate treatment in focal hand dystonia (FHD). Sixteen-channel SEMG obtained during different phases of a writing task was used to study timing, activation patterns, and spread of muscle contractions in FHD compared with normal controls. Customized software was developed to acquire and analyze EMG signals. SEMG of FHD subjects (20) showed "early onset" during motor imagery, rapid proximal muscle recruitment, agonist-antagonist co-contraction involving proximal muscle groups, "delayed offset" after stopping writing, higher rectified mean amplitudes, and mirror activity in contralateral limb compared with controls (16). Muscle activation latencies were heterogenous in FHD. Anticipation, delayed relaxation, and mirror EMG activation were noted in FHD. A clear pattern of muscle activation cannot be ascertained. Multi-channel SEMG can aid in objective assessment of temporal-spatial distribution of activity and can refine targeted therapies like chemodenervation and biofeedback. Copyright © 2013 Wiley Periodicals, Inc.

An Integrated Power-Efficient Active Rectifier With Offset-Controlled High Speed Comparators for Inductively Powered Applications

PubMed Central

Lee, Hyung-Min; Ghovanloo, Maysam

2011-01-01

We present an active full-wave rectifier with offset-controlled high speed comparators in standard CMOS that provides high power conversion efficiency (PCE) in high frequency (HF) range for inductively powered devices. This rectifier provides much lower dropout voltage and far better PCE compared to the passive on-chip or off-chip rectifiers. The built-in offset-control functions in the comparators compensate for both turn-on and turn-off delays in the main rectifying switches, thus maximizing the forward current delivered to the load and minimizing the back current to improve the PCE. We have fabricated this active rectifier in a 0.5-μm 3M2P standard CMOS process, occupying 0.18 mm2 of chip area. With 3.8 V peak ac input at 13.56 MHz, the rectifier provides 3.12 V dc output to a 500 Ω load, resulting in the PCE of 80.2%, which is the highest measured at this frequency. In addition, overvoltage protection (OVP) as safety measure and built-in back telemetry capabilities have been incorporated in our design using detuning and load shift keying (LSK) techniques, respectively, and tested. PMID:22174666

Arrhythmic hazard map for a 3D whole-ventricles model under multiple ion channel block.

PubMed

Okada, Jun-Ichi; Yoshinaga, Takashi; Kurokawa, Junko; Washio, Takumi; Furukawa, Tetsushi; Sawada, Kohei; Sugiura, Seiryo; Hisada, Toshiaki

2018-05-10

To date, proposed in silico models for preclinical cardiac safety testing are limited in their predictability and usability. We previously reported a multi-scale heart simulation that accurately predicts arrhythmogenic risk for benchmark drugs. We extend this approach and report the first comprehensive hazard map of drug-induced arrhythmia based on the exhaustive in silico electrocardiogram (ECG) database of drug effects, developed using a petaflop computer. A total of 9075 electrocardiograms constitute the five-dimensional hazard map, with coordinates representing the extent of the block of each of the five ionic currents (rapid delayed rectifier potassium current (IKr), fast (INa) and late (INa,L) components of the sodium current, L-type calcium current (ICa,L) and slow delayed rectifier current (IKs)), involved in arrhythmogenesis. Results of the evaluation of arrhythmogenic risk based on this hazard map agreed well with the risk assessments reported in three references. ECG database also suggested that the interval between the J-point and the T-wave peak is a superior index of arrhythmogenicity compared to other ECG biomarkers including the QT interval. Because concentration-dependent effects on electrocardiograms of any drug can be traced on this map based on in vitro current assay data, its arrhythmogenic risk can be evaluated without performing costly and potentially risky human electrophysiological assays. Hence, the map serves as a novel tool for use in pharmaceutical research and development. This article is protected by copyright. All rights reserved.

Effects of nerve growth factor on the action potential duration and repolarizing currents in a rabbit model of myocardial infarction

PubMed Central

Lan, Yun-Feng; Zhang, Jian-Cheng; Gao, Jin-Lao; Wang, Xue-Ping; Fang, Zhou; Fu, Yi-Cheng; Chen, Mei-Yan; Lin, Min; Xue, Qiao; Li, Yang

2013-01-01

Objectives To investigate the effect of nerve growth factor (NGF) on the action potential and potassium currents of non-infarcted myocardium in the myocardial infarcted rabbit model. Methods Rabbits with occlusion of the left anterior descending coronary artery were prepared and allowed to recover for eight weeks (healed myocardial infarction, HMI). During ligation surgery of the left coronary artery, a polyethylene tube was placed near the left stellate ganglion in the subcutis of the neck for the purpose of administering NGF 400 U/d for eight weeks (HMI + NGF group). Cardiomyocytes were isolated from regions of the non-infarcted left ventricular wall and the action potentials and ion currents in these cells were recorded using whole-cell patch clamps. Results Compared with HMI and control cardiomyocytes, significant prolongation of APD50 or APD90 (Action potential duration (APD) measured at 50% and 90% of repolarization) in HMI + NGF cardiomyocytes was found. The results showed that the 4-aminopyridine sensitive transient outward potassium current (Ito), the rapidly activated omponent of delayed rectifier potassium current (IKr), the slowly activated component of delayed rectifier potassium current (IKs), and the L-type calcium current (ICaL) were significantly altered in NGF + HMI cardiomyocytes compared with HMI and control cells. Conclusions Our results suggest that NGF treatment significantly prolongs APD in HMI cardiomyocytes and that a decrease in outward potassium currents and an increase of inward Ca2+ current are likely the underlying mechanism of action. PMID:23610573

Effects of nerve growth factor on the action potential duration and repolarizing currents in a rabbit model of myocardial infarction.

PubMed

Lan, Yun-Feng; Zhang, Jian-Cheng; Gao, Jin-Lao; Wang, Xue-Ping; Fang, Zhou; Fu, Yi-Cheng; Chen, Mei-Yan; Lin, Min; Xue, Qiao; Li, Yang

2013-03-01

To investigate the effect of nerve growth factor (NGF) on the action potential and potassium currents of non-infarcted myocardium in the myocardial infarcted rabbit model. Rabbits with occlusion of the left anterior descending coronary artery were prepared and allowed to recover for eight weeks (healed myocardial infarction, HMI). During ligation surgery of the left coronary artery, a polyethylene tube was placed near the left stellate ganglion in the subcutis of the neck for the purpose of administering NGF 400 U/d for eight weeks (HMI + NGF group). Cardiomyocytes were isolated from regions of the non-infarcted left ventricular wall and the action potentials and ion currents in these cells were recorded using whole-cell patch clamps. Compared with HMI and control cardiomyocytes, significant prolongation of APD50 or APD90 (Action potential duration (APD) measured at 50% and 90% of repolarization) in HMI + NGF cardiomyocytes was found. The results showed that the 4-aminopyridine sensitive transient outward potassium current (I to), the rapidly activated omponent of delayed rectifier potassium current (I Kr), the slowly activated component of delayed rectifier potassium current (I Ks), and the L-type calcium current (I CaL) were significantly altered in NGF + HMI cardiomyocytes compared with HMI and control cells. Our results suggest that NGF treatment significantly prolongs APD in HMI cardiomyocytes and that a decrease in outward potassium currents and an increase of inward Ca(2+) current are likely the underlying mechanism of action.

Inward rectifier potassium channels control rotor frequency in ventricular fibrillation.

PubMed

Jalife, José

2009-11-01

Ventricular fibrillation (VF) is the most important cause of sudden cardiac death. While traditionally thought to result from random activation of the ventricles by multiple independent wavelets, recent evidence suggests that VF may be determined by the sustained activation of a relatively small number of reentrant sources. In addition, recent experimental data in various species as well as computer simulations have provided important clues about its ionic and molecular mechanisms, particularly in regards to the role of potassium currents in such mechanisms. The results strongly argue that the inward rectifier current, I(K1,) is an important current during functional reentry because it mediates the electrotonic interactions between the unexcited core and its immediate surroundings. In addition, I(K1) is a stabilizer of reentry due to its ability to shorten action potential duration and reduce conduction velocity near the center of rotation. Increased I(K1) prevents wave front-wave tail interactions and thus averts rotor destabilization and breakup. Other studies have shown that while the slow component of the delayed rectifier potassium current I(Ks) does not significantly modify rotor frequency or stability, it plays a major role in postrepolarization refractoriness and wave break formation. Therefore, the interplay between I(K1) and the rapid sodium inward current (I(Na)) is a major factor in the control of cardiac excitability and thus the stability and frequency of reentry, while I(Ks) is an important determinant of fibrillatory conduction.

Atrial-selective K+ channel blockers: potential antiarrhythmic drugs in atrial fibrillation?

PubMed

Ravens, Ursula

2017-11-01

In the wake of demographic change in Western countries, atrial fibrillation has reached an epidemiological scale, yet current strategies for drug treatment of the arrhythmia lack sufficient efficacy and safety. In search of novel medications, atrial-selective drugs that specifically target atrial over other cardiac functions have been developed. Here, I will address drugs acting on potassium (K + ) channels that are either predominantly expressed in atria or possess electrophysiological properties distinct in atria from ventricles. These channels include the ultra-rapidly activating, delayed outward-rectifying Kv1.5 channel conducting I Kur , the acetylcholine-activated inward-rectifying Kir3.1/Kir3.4 channel conducting I K,ACh , the Ca 2+ -activated K + channels of small conductance (SK) conducting I SK , and the two-pore domain K + (K2P) channels (tandem of P domains, weak inward-rectifying K + channels (TWIK-1), TWIK-related acid-sensitive K + channels (TASK-1 and TASK-3)) that are responsible for voltage-independent background currents I TWIK-1 , I TASK-1 , and I TASK-3 . Direct drug effects on these channels are described and their putative value in treatment of atrial fibrillation is discussed. Although many potential drug targets have emerged in the process of unravelling details of the pathophysiological mechanisms responsible for atrial fibrillation, we do not know whether novel antiarrhythmic drugs will be more successful when modulating many targets or a single specific one. The answer to this riddle can only be solved in a clinical context.

Histamine H1-receptor-mediated modulation of the delayed rectifier K+ current in guinea-pig atrial cells: opposite effects on IKs and IKr

PubMed Central

Matsumoto, Yasunori; Ogura, Takehiko; Uemura, Hiroko; Saito, Toshihiro; Masuda, Yoshiaki; Nakaya, Haruaki

1999-01-01

Histamine receptor-mediated modulation of the rapid and slow components of the delayed rectifier K+ current (IK) was investigated in enzymatically-dissociated atrial cells of guinea-pigs using the whole cell configuration of the patch clamp technique.Histamine at a concentration of 10 μM enhanced IK recorded during strong depolarization to potentials ranging from +20 to +40 mV and inhibited IK recorded during mild depolarization to potentials ranging from −20 to −10 mV. The increase of IK was more prominent with longer depolarizing pulses, whereas the inhibition of IK was more marked with shorter depolarizing pulses, suggesting that histamine enhances IKs (the slow component of IK) and inhibits IKr (the rapid component of IK).The histamine-induced enhancement of IKs and inhibition of IKr were abolished by 3 μM chlorpheniramine but not by 10 μM cimetidine, suggesting that these opposite effects of histamine on IKr and IKs are mediated by H1-receptors.In the presence of 5 μM E-4031, an IKr blocker, histamine hardly affected IK during mild depolarization although it enhanced IK during strong depolarization in a concentration-dependent manner. Histamine increased IKs with EC50 value of 0.7 μM. In the presence of 300 μM indapamide, an IKs blocker, histamine hardly affected IKs but inhibited IKr in a concentration-dependent manner. Histamine decreased IKr with IC50 value of 0.3 μM.Pretreatment with 100 nM calphostin C or 30 nM staurosporine, protein kinase C inhibitors, abolished the histamine-induced enhancement of IKs, but failed to affect the histamine-induced inhibition of IKr.We conclude that in guinea-pig atrial cells H1-receptor stimulation enhances IKs and inhibits IKr through different intracellular mechanisms. PMID:10602335

Genistein and tyrphostin AG556 decrease ultra-rapidly activating delayed rectifier K+ current of human atria by inhibiting EGF receptor tyrosine kinase.

PubMed

Xiao, Guo-Sheng; Zhang, Yan-Hui; Wu, Wei; Sun, Hai-Ying; Wang, Yan; Li, Gui-Rong

2017-03-01

The ultra-rapidly activating delayed rectifier K + current I Kur (encoded by K v 1.5 or KCNA5) plays an important role in human atrial repolarization. The present study investigates the regulation of this current by protein tyrosine kinases (PTKs). Whole-cell patch voltage clamp technique and immunoprecipitation and Western blotting analysis were used to investigate whether the PTK inhibitors genistein, tyrphostin AG556 (AG556) and PP2 regulate human atrial I Kur and hKv1.5 channels stably expressed in HEK 293 cells. Human atrial I Kur was decreased by genistein (a broad-spectrum PTK inhibitor) and AG556 (a highly selective EGFR TK inhibitor) in a concentration-dependent manner. Inhibition of I Kur induced by 30 μM genistein or 10 μM AG556 was significantly reversed by 1 mM orthovanadate (a protein tyrosine phosphatase inhibitor). Similar results were observed in HEK 293 cells stably expressing hK v 1.5 channels. On the other hand, the Src family kinase inhibitor PP2 (1 μM) slightly enhanced I Kur and hK v 1.5 current, and the current increase was also reversed by orthovanadate. Immunoprecipitation and Western blotting analysis showed that genistein, AG556, and PP2 decreased tyrosine phosphorylation of hK v 1.5 channels and that the decrease was countered by orthovanadate. The PTK inhibitors genistein and AG556 decrease human atrial I Kur and cloned hK v 1.5 channels by inhibiting EGFR TK, whereas the Src kinase inhibitor PP2 increases I Kur and hK v 1.5 current. These results imply that EGFR TK and the soluble Src kinases may have opposite effects on human atrial I Kur . © 2017 The British Pharmacological Society.

The actions of mdivi-1, an inhibitor of mitochondrial fission, on rapidly activating delayed-rectifier K⁺ current and membrane potential in HL-1 murine atrial cardiomyocytes.

PubMed

So, Edmund Cheung; Hsing, Chung-Hsi; Liang, Chia-Hua; Wu, Sheng-Nan

2012-05-15

Mdivi-1 is an inhibitor of dynamin related protein 1- (drp1)-mediated mitochondrial fission. However, the mechanisms through which this compound interacts directly with ion currents in heart cells remain unknown. In this study, its effects on ion currents and membrane potential in murine HL-1 cardiomyocytes were investigated. In whole-cell recordings, the addition of mdivi-1 decreased the amplitude of tail current (I(tail)) for the rapidly activating delayed-rectifier K⁺ current (I(Kr)) in a concentration-dependent manner with an IC₅₀ value at 11.6 μM, a value that resembles the inhibition requirement for mitochondrial division. It shifted the activation curve of I(tail) to depolarized voltages with no change in the gating charge. However, mdivi-1 did not alter the rate of recovery from current inactivation. In cell-attached configuration, mdivi-1 inside the pipette suppressed the activity of acetylcholine-activated K⁺ channels without modifying the single-channel conductance. Mdivi-1 (30 μM) slightly depressed the peak amplitude of Na⁺ current with no change in the overall current-voltage relationship. Under current-clamp recordings, addition of mdivi-1 resulted in prolongation for the duration of action potentials (APs) and to increase the firing of spontaneous APs in HL-1 cells. Similarly, in pituitary GH₃ cells, mdivi-1 was effective in directly suppressing the amplitude of ether-à-go-go-related gene-mediated K⁺ current. Therefore, the lengthening of AP duration and increased firing of APs caused by mdivi-1 can be primarily explained by its inhibition of these K⁺ channels enriched in heart cells. The observed effects of mdivi-1 on ion currents were direct and not associated with its inhibition of mitochondrial division. Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of itopride hydrochloride on the delayed rectifier K+ and L-type CA2+ currents in guinea-pig ventricular myocytes.

PubMed

Morisawa, T; Hasegawa, J; Hama, R; Kitano, M; Kishimoto, Y; Kawasaki, H

1999-01-01

The effects of itopride hydrochloride, a new drug used to regulate motility in the gastrointestinal tract, on the delayed rectifier K+ current (I(K)) and the L-type Ca2+ current (I(Ca)) were evaluated in guinea-pig ventricular myocytes at concentrations of 1, 10 and 100 microM to determine whether the drug has a proarrhythmic effect through blockade of I(K). Itopride did not affect I(K) at concentrations of 100 microM or less, and no significant effects of 1, 10 or 100 microM itopride were observed on the inward rectifier K+ current (I(K1)) responsible for the resting potential and final repolarization phase of the action potential. We next investigated the effects of itopride on L-type Ca2+ current (I(Ca)). Significant inhibition of I(Ca) was observed at itopride concentrations greater than 10 microM. These results suggested that itopride hydrochloride has an inhibitory effect on I(Ca) at concentrations much higher than those in clinical use.

Voltage-dependent ion channels in the mouse RPE: comparison with Norrie disease mice.

PubMed

Wollmann, Guido; Lenzner, Steffen; Berger, Wolfgang; Rosenthal, Rita; Karl, Mike O; Strauss, Olaf

2006-03-01

We studied electrophysiological properties of cultured retinal pigment epithelial (RPE) cells from mouse and a mouse model for Norrie disease. Wild-type RPE cells revealed the expression of ion channels known from other species: delayed-rectifier K(+) channels composed of Kv1.3 subunits, inward rectifier K(+) channels, Ca(V)1.3 L-type Ca(2+) channels and outwardly rectifying Cl(-) channels. Expression pattern and the ion channel characteristics current density, blocker sensitivity, kinetics and voltage-dependence were compared in cells from wild-type and Norrie mice. Although no significant differences were observed, our study provides a base for future studies on ion channel function and dysfunction in transgenic mouse models.

VEGF attenuated increase of outward delayed-rectifier potassium currents in hippocampal neurons induced by focal ischemia via PI3-K pathway.

PubMed

Wu, K W; Yang, P; Li, S S; Liu, C W; Sun, F Y

2015-07-09

We recently indicated that the vascular endothelial growth factor (VEGF) protects neurons against hypoxic death via enhancement of tyrosine phosphorylation of Kv1.2, an isoform of the delayed-rectifier potassium channels through activation of the phosphatidylinositol 3-kinase (PI3-K) signaling pathway. The present study investigated whether VEGF could attenuate ischemia-induced increase of the potassium currents in the hippocampal pyramidal neurons of rats after ischemic injury. Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion (MCAO) to induce brain ischemia. The whole-cell patch-clamp technique was used to record the potassium currents of hippocampal neurons in brain slices from the ischemically injured brains of the rats 24h after MCAO. We detected that transient MCAO caused a significant increase of voltage-gated potassium currents (Kv) and outward delayed-rectifier potassium currents (IK), but not outward transient potassium currents (IA), in the ipsilateral hippocampus compared with the sham. Moreover, we found that VEGF could acutely, reversibly and voltage-dependently inhibit the ischemia-induced IK increase. This inhibitory effect of VEGF could be completely abolished by wortmannin, an inhibitor of PI3-K. Our data indicate that VEGF attenuates the ischemia-induced increase of IK via activation of the PI3-K signaling pathway. Published by Elsevier Ltd.

Delayed Maturation of Fast-Spiking Interneurons Is Rectified by Activation of the TrkB Receptor in the Mouse Model of Fragile X Syndrome

PubMed Central

Nomura, Toshihiro; Zhu, Yiwen; Remmers, Christine L.; Xu, Jian; Nicholson, Daniel A.

2017-01-01

Fragile X syndrome (FXS) is a neurodevelopmental disorder that is a leading cause of inherited intellectual disability, and the most common known cause of autism spectrum disorder. FXS is broadly characterized by sensory hypersensitivity and several developmental alterations in synaptic and circuit function have been uncovered in the sensory cortex of the mouse model of FXS (Fmr1 KO). GABA-mediated neurotransmission and fast-spiking (FS) GABAergic interneurons are central to cortical circuit development in the neonate. Here we demonstrate that there is a delay in the maturation of the intrinsic properties of FS interneurons in the sensory cortex, and a deficit in the formation of excitatory synaptic inputs on to these neurons in neonatal Fmr1 KO mice. Both these delays in neuronal and synaptic maturation were rectified by chronic administration of a TrkB receptor agonist. These results demonstrate that the maturation of the GABAergic circuit in the sensory cortex is altered during a critical developmental period due in part to a perturbation in BDNF-TrkB signaling, and could contribute to the alterations in cortical development underlying the sensory pathophysiology of FXS. SIGNIFICANCE STATEMENT Fragile X (FXS) individuals have a range of sensory related phenotypes, and there is growing evidence of alterations in neuronal circuits in the sensory cortex of the mouse model of FXS (Fmr1 KO). GABAergic interneurons are central to the correct formation of circuits during cortical critical periods. Here we demonstrate a delay in the maturation of the properties and synaptic connectivity of interneurons in Fmr1 KO mice during a critical period of cortical development. The delays both in cellular and synaptic maturation were rectified by administration of a TrkB receptor agonist, suggesting reduced BDNF-TrkB signaling as a contributing factor. These results provide evidence that the function of fast-spiking interneurons is disrupted due to a deficiency in neurotrophin signaling during early development in FXS. PMID:29038238

Input Power Characteristics of a Three-Phase Thyristor Converter

DOT National Transportation Integrated Search

1973-10-01

A phase delay rectifier operating into a passive resistive load was instrumented in the laboratory. Techniques for accurate measurement of power, displacement reactive power, harmonic components, and distortion reactive power are presented. The chara...

Atrial fibrillation: Therapeutic potential of atrial K+ channel blockers.

PubMed

Ravens, Ursula; Odening, Katja E

2017-08-01

Despite the epidemiological scale of atrial fibrillation, current treatment strategies are of limited efficacy and safety. Ideally, novel drugs should specifically correct the pathophysiological mechanisms responsible for atrial fibrillation with no other cardiac or extracardiac actions. Atrial-selective drugs are directed toward cellular targets with sufficiently different characteristics in atria and ventricles to modify only atrial function. Several potassium (K + ) channels with either predominant expression in atria or distinct electrophysiological properties in atria and ventricles can serve as atrial-selective drug targets. These channels include the ultra-rapidly activating, delayed outward-rectifying Kv1.5 channel conducting I Kur , the acetylcholine-activated inward-rectifying Kir3.1/Kir3.4 channel conducting I K,ACh , the Ca 2+ -activated K + channels of small conductance (SK) conducting I SK , and the two pore domain K + (K2P) channels TWIK-1, TASK-1 and TASK-3 that are responsible for voltage-independent background currents I TWIK-1 , I TASK-1 , and I TASK-3 . Here, we briefly review the characteristics of these K + channels and their roles in atrial fibrillation. The antiarrhythmic potential of drugs targeting the described channels is discussed as well as their putative value in treatment of atrial fibrillation. Copyright © 2016 Elsevier Inc. All rights reserved.

Seasonal acclimatization of the cardiac action potential in the Arctic navaga cod (Eleginus navaga, Gadidae).

PubMed

Hassinen, Minna; Abramochkin, Denis V; Vornanen, Matti

2014-04-01

Freshwater fishes of north-temperate latitudes adjust electrical excitability of the heart to seasonal temperature changes by changing expression levels of ion channel isoforms. However, little is known about thermal responses of action potential (AP) in the hearts of marine polar fishes. To this end, we examined cardiac AP in the atrial myocardium of the Arctic navaga cod (Eleginus navaga) from the White Sea (Russia) acclimatized to winter (March) and summer (September) seasons. Acute increases in temperature from 4 to 10 °C were associated with increases in heart rate, maximum velocity of AP upstroke and negative resting membrane potential, while duration of AP was shortened in both winter-acclimatized and summer-acclimatized navaga hearts. In winter, there was a compensatory shortening (41.1%) of atrial AP duration and this was associated with a strong increase in transcript expression of Erg K(+) channels, known to produce the rapid component of the delayed rectifier K(+) current, I(Kr). Smaller increases were found in the expression of Kir2.1 channels that produce the inward rectifier K(+) current, I(K1). These findings indicate that the heart of navaga cod has a good acclimatory capacity in electrical excitation of cardiac myocytes, which enables cardiac function in the cold-eurythermal waters of the subarctic White Sea.

The human ether-a-go-go-related gene (hERG) current inhibition selectively prolongs action potential of midmyocardial cells to augment transmural dispersion.

PubMed

Yasuda, C; Yasuda, S; Yamashita, H; Okada, J; Hisada, T; Sugiura, S

2015-08-01

The majority of drug induced arrhythmias are related to the prolongation of action potential duration following inhibition of rapidly activating delayed rectifier potassium current (I(Kr)) mediated by the hERG channel. However, for arrhythmias to develop and be sustained, not only the prolongation of action potential duration but also its transmural dispersion are required. Herein, we evaluated the effect of hERG inhibition on transmural dispersion of action potential duration using the action potential clamp technique that combined an in silico myocyte model with the actual I(Kr) measurement. Whole cell I(Kr) current was measured in Chinese hamster ovary cells stably expressing the hERG channel. The measured current was coupled with models of ventricular endocardial, M-, and epicardial cells to calculate the action potentials. Action potentials were evaluated under control condition and in the presence of 1, 10, or 100 μM disopyramide, an hERG inhibitor. Disopyramide dose-dependently increased the action potential durations of the three cell types. However, action potential duration of M-cells increased disproportionately at higher doses, and was significantly different from that of epicardial and endocardial cells (dispersion of repolarization). By contrast, the effects of disopyramide on peak I(Kr) and instantaneous current-voltage relation were similar in all cell types. Simulation study suggested that the reduced repolarization reserve of M-cell with smaller amount of slowly activating delayed rectifier potassium current levels off at longer action potential duration to make such differences. The action potential clamp technique is useful for studying the mechanism of arrhythmogenesis by hERG inhibition through the transmural dispersion of repolarization.

New in vitro model for proarrhythmia safety screening: IKs inhibition potentiates the QTc prolonging effect of IKr inhibitors in isolated guinea pig hearts.

PubMed

Kui, Péter; Orosz, Szabolcs; Takács, Hedvig; Sarusi, Annamária; Csík, Norbert; Rárosi, Ferenc; Csekő, Csongor; Varró, András; Papp, Julius Gy; Forster, Tamás; Farkas, Attila S; Farkas, András

2016-01-01

Preclinical in vivo QT measurement as a proarrhythmia essay is expensive and not reliable enough. The aim of the present study was to develop a sensitive, cost-effective, Langendorff perfused guinea pig heart model for proarrhythmia safety screening. Low concentrations of dofetilide and cisapride (inhibitors of the rapid delayed rectifier potassium current, IKr) were tested alone and co-perfused with HMR-1556 (inhibitor of the slow delayed rectifier potassium current, IKs) in Langendorff perfused guinea pig hearts. The electrocardiographic rate corrected QT (QTc) interval, the Tpeak-Tend interval and the beat-to-beat variability and instability (BVI) of the QT interval were determined in sinus rhythm. Dofetilide and HMR-1556 alone or co-perfused, prolonged the QTc interval by 20±2%, 10±1% and 55±10%, respectively. Similarly, cisapride and HMR-1556 alone or co-perfused, prolonged the QTc interval by 11±3%, 11±4% and 38±6%, respectively. Catecholamine-induced fast heart rate abolished the QTc prolonging effects of the IKr inhibitors, but augmented the QTc prolongation during IKs inhibition. None of the drug perfusions increased significantly the Tpeak-Tend interval and the sinus BVI of the QT interval. IKs inhibition increased the QTc prolonging effect of IKr inhibitors in a super-additive (synergistic) manner, and the QTc interval was superior to other proarrhythmia biomarkers measured in sinus rhythm in isolated guinea pig hearts. The effect of catecholamines on the QTc facilitated differentiation between IKr and IKs inhibitors. Thus, QTc measurement in Langendorff perfused guinea pig hearts with pharmacologically attenuated repolarization reserve and periodic catecholamine perfusion seems to be suitable for preclinical proarrhythmia screening. Copyright © 2016 Elsevier Inc. All rights reserved.

[Effect of down-regulation of IKs repolarization-reserve on ventricular arrhythmogenesis in a guinea pig model of cardiac hypertrophy].

PubMed

Wang, Hegui; Huang, Ting; Wang, Zheng; Ge, Nannan; Ke, Yongsheng

2018-04-28

To observe the changes of rapidly activated delayed rectifier potassium channel (IKr) and slowly activated delayed rectifier potassium channel (IKs) in cardiac hypertrophy and to evaluate the effects of IKr and IKs blocker on the incidence of ventricular arrhythmias in guinea pigs with left ventricular hypertrophy (LVH).
 Methods: Guinea pigs were divided into a sham operation group and a left ventricular hypertrophy (LVH) group. LVH model was prepared. Whole cell patch-clamp technique was used to record IKr and IKs tail currents in a guinea pig model with LVH. The changes of QTc and the incidence rate of ventricular arrhythmias in LVH guinea pigs were observed by using the IKr and IKs blockers.
 Results: Compared with cardiac cells in the control group, the interventricular septal thickness at end systole (IVSs), left ventricular posterior wall thickness at end systole (LVPWs), QTc interval and cell capacitance in guinea pigs with LVH were significantly increased (P<0.05); while IKs densities were significantly reduced [+60 mV: (0.36±0.03) pA/pF vs (0.58±0.05) pA/pF, P<0.01]. However, LVH exerted no significant effect on IKr densities. IKr blocker markedly prolonged the QTc interval (P<0.01) and increased the incidence of ventricular arrhythmias in guinea pigs with LVH compared with the control guinea pigs. In contrast, IKs blocker produced modest increase in QTc interval in guinea pigs of control group with no increase in LVH animals. IKs blocker did not induce ventricular arrhythmias incidence in either control or LVH animals.
 Conclusion: The cardiac hypertrophy-induced arrhythmogenesis is due to the down-regulation 
of IKs.

Molecular basis and drug sensitivity of the delayed rectifier (IKr) in the fish heart.

PubMed

Hassinen, Minna; Haverinen, Jaakko; Vornanen, Matti

2015-01-01

Fishes are increasingly used as models for human cardiac diseases, creating a need for a better understanding of the molecular basis of fish cardiac ion currents. To this end we cloned KCNH6 channel of the crucian carp (Carassius carassius) that produces the rapid component of the delayed rectifier K(+) current (IKr), the main repolarising current of the fish heart. KCNH6 (ccErg2) was the main isoform of the Kv11 potassium channel family with relative transcript levels of 98.9% and 99.6% in crucian carp atrium and ventricle, respectively. KCNH2 (ccErg1), an orthologue to human cardiac Erg (Herg) channel, was only slightly expressed in the crucian carp heart. The native atrial IKr and the cloned ccErg2 were inhibited by similar concentrations of verapamil, terfenadine and KB-R7943 (P>0.05), while the atrial IKr was about an order of magnitude more sensitive to E-4031 than ccErg2 (P<0.05) suggesting that some accessory β-subunits may be involved. Sensitivity of the crucian carp atrial IKr to E-4031, terfenadine and KB-R7943 was similar to what has been reported for the Herg channel. In contrast, the sensitivity of the crucian carp IKr to verapamil was approximately 30 times higher than the previously reported values for the Herg current. In conclusion, the cardiac IKr is produced by non-orthologous gene products in fish (Erg2) and mammalian hearts (Erg1) and some marked differences exist in drug sensitivity between fish and mammalian Erg1/2 which need to be taken into account when using fish heart as a model for human heart. Copyright © 2015 Elsevier Inc. All rights reserved.

Chronic Ca2+ influx through voltage-dependent Ca2+ channels enhance delayed rectifier K+ currents via activating Src family tyrosine kinase in rat hippocampal neurons.

PubMed

Yang, Yoon-Sil; Jeon, Sang-Chan; Kim, Dong-Kwan; Eun, Su-Yong; Jung, Sung-Cherl

2017-03-01

Excessive influx and the subsequent rapid cytosolic elevation of Ca 2+ in neurons is the major cause to induce hyperexcitability and irreversible cell damage although it is an essential ion for cellular signalings. Therefore, most neurons exhibit several cellular mechanisms to homeostatically regulate cytosolic Ca 2+ level in normal as well as pathological conditions. Delayed rectifier K + channels (I DR channels) play a role to suppress membrane excitability by inducing K + outflow in various conditions, indicating their potential role in preventing pathogenic conditions and cell damage under Ca 2+ -mediated excitotoxic conditions. In the present study, we electrophysiologically evaluated the response of I DR channels to hyperexcitable conditions induced by high Ca 2+ pretreatment (3.6 mM, for 24 hours) in cultured hippocampal neurons. In results, high Ca 2+ -treatment significantly increased the amplitude of I DR without changes of gating kinetics. Nimodipine but not APV blocked Ca 2+ -induced I DR enhancement, confirming that the change of I DR might be targeted by Ca 2+ influx through voltage-dependent Ca 2+ channels (VDCCs) rather than NMDA receptors (NMDARs). The VDCC-mediated I DR enhancement was not affected by either Ca 2+ -induced Ca 2+ release (CICR) or small conductance Ca 2+ -activated K + channels (SK channels). Furthermore, PP2 but not H89 completely abolished I DR enhancement under high Ca 2+ condition, indicating that the activation of Src family tyrosine kinases (SFKs) is required for Ca 2+ -mediated I DR enhancement. Thus, SFKs may be sensitive to excessive Ca 2+ influx through VDCCs and enhance I DR to activate a neuroprotective mechanism against Ca 2+ -mediated hyperexcitability in neurons.

Bepridil differentially inhibits two delayed rectifier K+ currents, IKr and IKs, in guinea-pig ventricular myocytes

PubMed Central

Wang, Jin-Cheng; Kiyosue, Tatsuto; Kiriyama, Kuninori; Arita, Makoto

1999-01-01

We investigated the effects of bepridil on the two components of the delayed rectifier K+ current, i.e., the rapidly activating (IKr) and the slowly activating (IKs) currents using tight-seal whole-cell patch-clamp techniques in guinea-pig ventricular myocytes, under blockade of L-type Ca2+ current with nitrendipine (5 μM) or D600 (1 μM).Bepridil decreased IKs under blockade of IKr with E4031 (5 μM), in a concentration-dependent manner. The concentration-dependent inhibition of IKs by bepridil was fitted by a curve, assuming one-to-one interactions between the channel and the drug molecule. The concentration of half-maximal inhibition (IC50) was found to be 6.2 μM.The effect of bepridil on IKr was assessed using an envelope-of-tails test. In the control condition, a ratio of the tail current to the time-dependent current measured during depolarization was large (>1) at shorter pulses (<200 ms), and it decreased to a steady state value of ∼0.4 with increases in the pulse duration. Bepridil at a concentration of 2 μM did not decrease this ratio at shorter pulses.In a short-pulse (duration=50 ms) experiment that largely activates IKr, the drug was found to block IKr in a cooperative manner (Hill coefficient=3.03) and the IC50 was 13.2 μM.These results suggest that bepridil at a clinical therapeutic concentration (∼2 μM) selectively blocks IKs but does not inhibit IKr. This may relate to the characteristic frequency-dependent effects of bepridil on the action potential duration (APD), e.g., the non-reverse use-dependent prolongation of APD. PMID:10588929

Molecular determinants of Kv7.1/KCNE1 channel inhibition by amitriptyline.

PubMed

Villatoro-Gómez, Kathya; Pacheco-Rojas, David O; Moreno-Galindo, Eloy G; Navarro-Polanco, Ricardo A; Tristani-Firouzi, Martin; Gazgalis, Dimitris; Cui, Meng; Sánchez-Chapula, José A; Ferrer, Tania

2018-06-01

Amitriptyline (AMIT) is a compound widely prescribed for psychiatric and non-psychiatric conditions including depression, migraine, chronic pain, and anorexia. However, AMIT has been associated with risks of cardiac arrhythmia and sudden death since it can induce prolongation of the QT interval on the surface electrocardiogram and torsade de pointes ventricular arrhythmia. These complications have been attributed to the inhibition of the rapid delayed rectifier potassium current (I Kr ). The slow delayed rectifier potassium current (I Ks ) is the main repolarizing cardiac current when I Kr is compromised and it has an important role in cardiac repolarization at fast heart rates induced by an elevated sympathetic tone. Therefore, we sought to characterize the effects of AMIT on Kv7.1/KCNE1 and homomeric Kv7.1 channels expressed in HEK-293H cells. Homomeric Kv7.1 and Kv7.1/KCNE1 channels were inhibited by AMIT in a concentration-dependent manner with IC50 values of 8.8 ± 2.1 μM and 2.5 ± 0.8 μM, respectively. This effect was voltage-independent for both homomeric Kv7.1 and Kv7.1/KCNE1 channels. Moreover, mutation of residues located on the P-loop and S6 domain along with molecular docking, suggest that T312, I337 and F340 are the most important molecular determinants for AMIT-Kv7.1 channel interaction. Our experimental findings and modeling suggest that AMIT preferentially blocks the open state of Kv7.1/KCNE1 channels by interacting with specific residues that were previously reported to be important for binding of other compounds, such as chromanol 293B and the benzodiazepine L7. Copyright © 2018 Elsevier Inc. All rights reserved.

A 13.56 MHz CMOS Active Rectifier With Switched-Offset and Compensated Biasing for Biomedical Wireless Power Transfer Systems.

PubMed

Yan Lu; Wing-Hung Ki

2014-06-01

A full-wave active rectifier switching at 13.56 MHz with compensated bias current for a wide input range for wirelessly powered high-current biomedical implants is presented. The four diodes of a conventional passive rectifier are replaced by two cross-coupled PMOS transistors and two comparator- controlled NMOS switches to eliminate diode voltage drops such that high voltage conversion ratio and power conversion efficiency could be achieved even at low AC input amplitude |VAC|. The comparators are implemented with switched-offset biasing to compensate for the delays of active diodes and to eliminate multiple pulsing and reverse current. The proposed rectifier uses a modified CMOS peaking current source with bias current that is quasi-inversely proportional to the supply voltage to better control the reverse current over a wide AC input range (1.5 to 4 V). The rectifier was fabricated in a standard 0.35 μm CMOS N-well process with active area of 0.0651 mm(2). For the proposed rectifier measured at |VAC| = 3.0 V, the voltage conversion ratios are 0.89 and 0.93 for RL=500 Ω and 5 kΩ, respectively, and the measured power conversion efficiencies are 82.2% to 90.1% with |VAC| ranges from 1.5 to 4 V for RL=500 Ω.

Pseudomonas fluorescens lipopolysaccharide inhibits both delayed rectifier and transient A-type K+ channels of cultured rat cerebellar granule neurons.

PubMed

Mezghani-Abdelmoula, Sana; Chevalier, Sylvie; Lesouhaitier, Olivier; Orange, Nicole; Feuilloley, Marc G J; Cazin, Lionel

2003-09-05

Pseudomonas fluorescens is a Gram-negative bacillus closely related to the pathogen P. aeruginosa known to provoke infectious disorders in the central nervous system (CNS). The endotoxin lipopolysaccharide (LPS) expressed by the bacteria is the first infectious factor that can interact with the plasma membrane of host cells. In the present study, LPS extracted from P. fluorescens MF37 was examined for its actions on delayed rectifier and A-type K(+) channels, two of the main types of voltage-activated K(+) channels involved in the action potential firing. Current recordings were performed in cultured rat cerebellar granule neurons at days 7 or 8, using the whole-cell patch-clamp technique. A 3-h incubation with LPS (200 ng/ml) markedly depressed both the delayed rectifier (I(KV)) and transient A-type (I(A)) K(+) currents evoked by depolarizations above 0 and -40 mV, respectively. The percent decrease of I(KV) and I(A) ( approximately 30%) did not vary with membrane potential, suggesting that inhibition of both types of K(+) channels by LPS was voltage-insensitive. The endotoxin did neither modify the steady-state voltage-dependent activation properties of I(KV) and I(A) nor the steady-state inactivation of I(A). The present results suggest that, by inhibiting I(KV) and I(A), LPS applied extracellulary increases the action potential firing in cerebellar granule neurons. It is concluded that P. fluorescens MF37 may provoke in the CNS disorders associated with sever alterations of membrane ionic channel functions.

Automated and manual patch clamp data of human induced pluripotent stem cell-derived dopaminergic neurons.

PubMed

Franz, Denise; Olsen, Hervør Lykke; Klink, Oliver; Gimsa, Jan

2017-04-25

Human induced pluripotent stem cells can be differentiated into dopaminergic neurons (Dopa.4U). Dopa.4U neurons expressed voltage-gated Na V and K V channels and showed neuron-like spontaneous electrical activity. In automated patch clamp measurements with suspended Dopa.4U neurons, delayed rectifier K + current (delayed K V ) and rapidly inactivating A-type K + current (fast K V ) were identified. Examination of the fast K V current with inhibitors yielded IC 50 values of 0.4 mM (4-aminopyridine) and 0.1 mM (tetraethylammonium). In manual patch clamp measurements with adherent Dopa.4U neurons, fast K V current could not be detected, while the delayed K V current showed an IC 50 of 2 mM for 4-aminopyridine. The Na V channels in adherent and suspended Dopa.4U neurons showed IC 50 values for tetrodotoxin of 27 and 2.9 nM, respectively. GABA-induced currents that could be observed in adherent Dopa.4U neurons could not be detected in suspended cells. Application of current pulses induced action potentials in approx. 70 % of the cells. Our results proved the feasibility of automated electrophysiological characterization of neuronal cells.

Effects of pioglitazone on cardiac ion currents and action potential morphology in canine ventricular myocytes.

PubMed

Kistamás, Kornél; Szentandrássy, Norbert; Hegyi, Bence; Ruzsnavszky, Ferenc; Váczi, Krisztina; Bárándi, László; Horváth, Balázs; Szebeni, Andrea; Magyar, János; Bányász, Tamás; Kecskeméti, Valéria; Nánási, Péter P

2013-06-15

Despite its widespread therapeutical use there is little information on the cellular cardiac effects of the antidiabetic drug pioglitazone in larger mammals. In the present study, therefore, the concentration-dependent effects of pioglitazone on ion currents and action potential configuration were studied in isolated canine ventricular myocytes using standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques. Pioglitazone decreased the maximum velocity of depolarization and the amplitude of phase-1 repolarization at concentrations ≥3 μM. Action potentials were shortened by pioglitazone at concentrations ≥10 μM, which effect was accompanied with significant reduction of beat-to-beat variability of action potential duration. Several transmembrane ion currents, including the transient outward K(+) current (Ito), the L-type Ca(2+) current (ICa), the rapid and slow components of the delayed rectifier K(+) current (IKr and IKs, respectively), and the inward rectifier K(+) current (IK1) were inhibited by pioglitazone under conventional voltage clamp conditions. Ito was blocked significantly at concentrations ≥3 μM, ICa, IKr, IKs at concentrations ≥10 μM, while IK1 at concentrations ≥30 μM. Suppression of Ito, ICa, IKr, and IK1 has been confirmed also under action potential voltage clamp conditions. ATP-sensitive K(+) current, when activated by lemakalim, was effectively blocked by pioglitazone. Accordingly, action potentials were prolonged by 10 μM pioglitazone when the drug was applied in the presence of lemakalim. All these effects developed rapidly and were readily reversible upon washout. In conclusion, pioglitazone seems to be a harmless agent at usual therapeutic concentrations. Copyright © 2013 Elsevier B.V. All rights reserved.

Regulation of the instantaneous inward rectifier and the delayed outward rectifier potassium channels by Captopril and Angiotensin II via the Phosphoinositide-3 kinase pathway in volume-overload-induced hypertrophied cardiac myocytes.

PubMed

Alvin, Zikiar V; Laurence, Graham G; Coleman, Bernell R; Zhao, Aiqiu; Hajj-Moussa, Majd; Haddad, Georges E

2011-07-01

Early development of cardiac hypertrophy may be beneficial but sustained hypertrophic activation leads to myocardial dysfunction. Regulation of the repolarizing currents can be modulated by the activation of humoral factors, such as angiotensin II (ANG II) through protein kinases. The aim of this work is to assess the regulation of IK and IK1 by ANG II through the PI3-K pathway in hypertrophied ventricular myocytes. Cardiac eccentric hypertrophy was induced through volume-overload in adult male rats by aorto-caval shunt (3 weeks). After one week half of the rats were given captopril (2 weeks; 0.5 g/l/day) and the other half served as control. The voltage-clamp and western blot techniques were used to measure the delayed outward rectifier potassium current (IK) and the instantaneous inward rectifier potassium current (IK1) and Akt activity, respectively. Hypertrophied cardiomyocytes showed reduction in IK and IK1. Treatment with captopril alleviated this difference seen between sham and shunt cardiomyocytes. Acute administration of ANG II (10-6M) to cardiocytes treated with captopril reduced IK and IK1 in shunts, but not in sham. Captopril treatment reversed ANG II effects on IK and IK1 in a PI3-K-independent manner. However in the absence of angiotensin converting enzyme inhibition, ANG II increased both IK and IK1 in a PI3-K-dependent manner in hypertrophied cardiomyocytes. Thus, captopril treatment reveals a negative effect of ANG II on IK and IK1, which is PI3-K independent, whereas in the absence of angiotensin converting enzyme inhibition IK and IK1 regulation is dependent upon PI3-K.

Delayed Maturation of Fast-Spiking Interneurons Is Rectified by Activation of the TrkB Receptor in the Mouse Model of Fragile X Syndrome.

PubMed

Nomura, Toshihiro; Musial, Timothy F; Marshall, John J; Zhu, Yiwen; Remmers, Christine L; Xu, Jian; Nicholson, Daniel A; Contractor, Anis

2017-11-22

Fragile X syndrome (FXS) is a neurodevelopmental disorder that is a leading cause of inherited intellectual disability, and the most common known cause of autism spectrum disorder. FXS is broadly characterized by sensory hypersensitivity and several developmental alterations in synaptic and circuit function have been uncovered in the sensory cortex of the mouse model of FXS ( Fmr1 KO). GABA-mediated neurotransmission and fast-spiking (FS) GABAergic interneurons are central to cortical circuit development in the neonate. Here we demonstrate that there is a delay in the maturation of the intrinsic properties of FS interneurons in the sensory cortex, and a deficit in the formation of excitatory synaptic inputs on to these neurons in neonatal Fmr1 KO mice. Both these delays in neuronal and synaptic maturation were rectified by chronic administration of a TrkB receptor agonist. These results demonstrate that the maturation of the GABAergic circuit in the sensory cortex is altered during a critical developmental period due in part to a perturbation in BDNF-TrkB signaling, and could contribute to the alterations in cortical development underlying the sensory pathophysiology of FXS. SIGNIFICANCE STATEMENT Fragile X (FXS) individuals have a range of sensory related phenotypes, and there is growing evidence of alterations in neuronal circuits in the sensory cortex of the mouse model of FXS ( Fmr1 KO). GABAergic interneurons are central to the correct formation of circuits during cortical critical periods. Here we demonstrate a delay in the maturation of the properties and synaptic connectivity of interneurons in Fmr1 KO mice during a critical period of cortical development. The delays both in cellular and synaptic maturation were rectified by administration of a TrkB receptor agonist, suggesting reduced BDNF-TrkB signaling as a contributing factor. These results provide evidence that the function of fast-spiking interneurons is disrupted due to a deficiency in neurotrophin signaling during early development in FXS. Copyright © 2017 the authors 0270-6474/17/3711298-13$15.00/0.

K(+) channels of squid giant axons open by an osmotic stress in hypertonic solutions containing nonelectrolytes.

PubMed

Kukita, Fumio

2011-08-01

In hypertonic solutions made by adding nonelectrolytes, K(+) channels of squid giant axons opened at usual asymmetrical K(+) concentrations in two different time courses; an initial instantaneous activation (I (IN)) and a sigmoidal activation typical of a delayed rectifier K(+) channel (I (D)). The current-voltage relation curve for I (IN) was fitted well with Goldman equation described with a periaxonal K(+) concentration at the membrane potential above -10 mV. Using the activation-voltage curve obtained from tail currents, K(+) channels for I (IN) are confirmed to activate at the membrane potential that is lower by 50 mV than those for I (D). Both I (IN) and I (D) closed similarly at the holding potential below -100 mV. The logarithm of I (IN)/I (D) was linearly related with the osmolarity for various nonelectrolytes. Solute inaccessible volumes obtained from the slope increased with the nonelectrolyte size from 15 to 85 water molecules. K(+) channels representing I (D) were blocked by open channel blocker tetra-butyl ammonium (TBA) more efficiently than in the absence of I (IN), which was explained by the mechanism that K(+) channels for I (D) were first converted to those for I (IN) by the osmotic pressure and then blocked. So K(+) channels for I (IN) were suggested to be derived from the delayed rectifier K(+) channels. Therefore, the osmotic pressure is suggested to exert delayed-rectifier K(+) channels to open in shrinking rather hydrophilic flexible parts outside the pore than the pore itself, which is compatible with the recent structure of open K(+) channel pore.

Inhibitory effects of pimozide on cloned and native voltage-gated potassium channels.

PubMed

Zhang, Zhi-Hao; Lee, Yan T; Rhodes, Kenneth; Wang, Kewei; Argentieri, Thomas M; Wang, Qiang

2003-07-04

The primary goal of this study was to use the cloned neuronal Kv channels to test if pimozide (PMZD), an antipsychotic drug, modulates the activity of Kv channels. In CHO cells, PMZD blocked Kv2.1, a major neuronal delayed rectifier, in a manner that depends upon time and concentration. The estimated IC50 was 4.2 microM at +50 mV. Tail current analysis shows that PMZD reduced the amplitude of the currents, with no effect on the steady-state activation curve (V(1/2) from 14.1 to 11.1 mV) or the slope (16.7 vs. 14.0 mV). From -120 to -20 mV, PMZD did not impact the deactivation kinetics of Kv2.1. PMZD also blocked Kv1.1, another neuronal delayed rectifier, with 16.1 microM of IC50. When Kv1.1 was co-expressed with Kvbeta1, approximately 50% of the Kv1.1 were converted into an inactivating A-type current and the Kv1.1/Kvbeta1 A-type currents were insensitive to PMZD. PMZD (10 microM) had minimal effect on Kv1.4, and had no effect on the M-current candidates, KCNQ2 and KCNQ3 when co-expressed in Xenopus oocytes. In hippocampal neurons, PMZD inhibited the delayed rectifiers by approximately 60%, and A-type currents were insensitive to PMZD. The results suggest that PMZD inhibits certain neuronal Kv channels in heterologous expression systems and in hippocampal neurons. PMZD was less effective on A-type currents, presumably because its ability to block requires a prolonged opening of the K channels. It is thus conceivable that the time-dependent and/or subunit-specific inhibition of Kv channels may increase the release of neurotransmitters such as serotonin and glutamate.

The Electrophysiological Effects of Qiliqiangxin on Cardiac Ventricular Myocytes of Rats

PubMed Central

Wei, Yidong; Liu, Xiaoyu; Wei, Haidong; Hou, Lei; Che, Wenliang; The, Erlinda; Li, Gang; Jhummon, Muktanand Vikash; Wei, Wanlin

2013-01-01

Qiliqiangxin, a Chinese herb, represents the affection in Ca channel function of cardiac myocytes. It is unknown whether Qiliqiangxin has an effect on Na current and K current because the pharmacological actions of this herb's compound are very complex. We investigated the rational usage of Qiliqiangxin on cardiac ventricular myocytes of rats. Ventricular myocytes were exposed acutely to 1, 10, and 50 mg/L Qiliqiangxin, and whole cell patch-clamp technique was used to study the acute effects of Qiliqiangxin on Sodium current (I Na), outward currents delayed rectifier outward K+ current (I K), slowly activating delayed rectifier outward K+ current (I Ks), transient outward K+ current (I to), and inward rectifier K+ current (I K1). Qiliqiangxin can decrease I Na by 28.53% ± 5.98%, and its IC50 was 9.2 mg/L. 10 and 50 mg/L Qiliqiangxin decreased by 37.2% ± 6.4% and 55.9% ± 5.5% summit current density of I to. 10 and 50 mg/L Qiliqiangxin decreased I Ks by 15.51% ± 4.03% and 21.6% ± 5.6%. Qiliqiangxin represented a multifaceted pharmacological profile. The effects of Qiliqiangxin on Na and K currents of ventricular myocytes were more profitable in antiarrhythmic therapy in the clinic. We concluded that the relative efficacy of Qiliqiangxin was another choice for the existing antiarrhythmic therapy. PMID:24250713

Combinational logic for generating gate drive signals for phase control rectifiers

NASA Technical Reports Server (NTRS)

Dolland, C. R.; Trimble, D. W. (Inventor)

1982-01-01

Control signals for phase-delay rectifiers, which require a variable firing angle that ranges from 0 deg to 180 deg, are derived from line-to-line 3-phase signals and both positive and negative firing angle control signals which are generated by comparing current command and actual current. Line-to-line phases are transformed into line-to-neutral phases and integrated to produce 90 deg phase delayed signals that are inverted to produce three cosine signals, such that for each its maximum occurs at the intersection of positive half cycles of the other two phases which are inputs to other inverters. At the same time, both positive and negative (inverted) phase sync signals are generated for each phase by comparing each with the next and producing a square wave when it is greater. Ramp, sync and firing angle controls signals are than used in combinational logic to generate the gate firing control signals SCR gate drives which fire SCR devices in a bridge circuit.

Delayed rectifier K channels contribute to contrast adaptation in mammalian retinal ganglion cells

PubMed Central

Weick, Michael; Demb, Jonathan B.

2011-01-01

SUMMARY Retinal ganglion cells adapt by reducing their sensitivity during periods of high contrast. Contrast adaptation in the firing response depends on both presynaptic and intrinsic mechanisms. Here, we investigated intrinsic mechanisms for contrast adaptation in OFF Alpha ganglion cells in the in vitro guinea pig retina. Using either visual stimulation or current injection, we show that brief depolarization evoked spiking and suppressed firing during subsequent depolarization. The suppression could be explained by Na channel inactivation, as shown in salamander cells. However, brief hyperpolarization in the physiological range (5–10 mV) also suppressed firing during subsequent depolarization. This suppression was sensitive selectively to blockers of delayed-rectifier K channels (KDR). Somatic membrane patches showed TEA-sensitive KDR currents with activation near −25 mV and removal of inactivation at voltages negative to Vrest. Brief periods of hyperpolarization apparently remove KDR inactivation and thereby increase the channel pool available to suppress excitability during subsequent depolarization. PMID:21745646

Delayed-rectifier K channels contribute to contrast adaptation in mammalian retinal ganglion cells.

PubMed

Weick, Michael; Demb, Jonathan B

2011-07-14

Retinal ganglion cells adapt by reducing their sensitivity during periods of high contrast. Contrast adaptation in the firing response depends on both presynaptic and intrinsic mechanisms. Here, we investigated intrinsic mechanisms for contrast adaptation in OFF Alpha ganglion cells in the in vitro guinea pig retina. Using either visual stimulation or current injection, we show that brief depolarization evoked spiking and suppressed firing during subsequent depolarization. The suppression could be explained by Na channel inactivation, as shown in salamander cells. However, brief hyperpolarization in the physiological range (5-10 mV) also suppressed firing during subsequent depolarization. This suppression was selectively sensitive to blockers of delayed-rectifier K channels (K(DR)). In somatic membrane patches, we observed tetraethylammonium-sensitive K(DR) currents that activated near -25 mV. Recovery from inactivation occurred at potentials hyperpolarized to V(rest). Brief periods of hyperpolarization apparently remove K(DR) inactivation and thereby increase the channel pool available to suppress excitability during subsequent depolarization. Copyright © 2011 Elsevier Inc. All rights reserved.

Rhynchophylline from Uncaria rhynchophylla functionally turns delayed rectifiers into A-Type K+ channels.

PubMed

Chou, Chun-Hsiao; Gong, Chi-Li; Chao, Chia-Chia; Lin, Chia-Huei; Kwan, Chiu-Yin; Hsieh, Ching-Liang; Leung, Yuk-Man

2009-05-22

Rhynchophylline (1), a neuroprotective agent isolated from the traditional Chinese medicinal herb Uncaria rhynchophylla, was shown to affect voltage-gated K(+) (Kv) channel slow inactivation in mouse neuroblastoma N2A cells. Extracellular 1 (30 microM) accelerated the slow decay of Kv currents and shifted the steady-state inactivation curve to the left. Intracellular dialysis of 1 did not accelerate the slow current decay, suggesting that this compound acts extracellularly. In addition, the percent blockage of Kv currents by this substance was independent of the degree of depolarization and the intracellular K(+) concentration. Therefore, 1 did not appear to directly block the outer channel pore, with the results obtained suggesting that it drastically accelerated Kv channel slow inactivation. Interestingly, 1 also shifted the activation curve to the left. This alkaloid also strongly accelerated slow inactivation and caused a left shift of the activation curve of Kv1.2 channels heterologously expressed in HEK293 cells. Thus, this compound functionally turned delayed rectifiers into A-type K(+) channels.

Inhibition of the cardiac inward rectifier potassium currents by KB-R7943.

PubMed

Abramochkin, Denis V; Alekseeva, Eugenia I; Vornanen, Matti

2013-09-01

KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea) was developed as a specific inhibitor of the sarcolemmal sodium-calcium exchanger (NCX) with potential experimental and therapeutic use. However, KB-R7943 is shown to be a potent blocker of several ion currents including inward and delayed rectifier K(+) currents of cardiomyocytes. To further characterize KB-R7943 as a blocker of the cardiac inward rectifiers we compared KB-R7943 sensitivity of the background inward rectifier (IK1) and the carbacholine-induced inward rectifier (IKACh) currents in mammalian (Rattus norvegicus; rat) and fish (Carassius carassius; crucian carp) cardiac myocytes. The basal IK1 of ventricular myocytes was blocked with apparent IC50-values of 4.6×10(-6) M and 3.5×10(-6) M for rat and fish, respectively. IKACh was almost an order of magnitude more sensitive to KB-R7943 than IK1 with IC50-values of 6.2×10(-7) M for rat and 2.5×10(-7) M for fish. The fish cardiac NCX current was half-maximally blocked at the concentration of 1.9-3×10(-6) M in both forward and reversed mode of operation. Thus, the sensitivity of three cardiac currents to KB-R7943 block increases in the order IK1~INCX

Safety and efficacy of vernakalant for acute cardioversion of atrial fibrillation: an update

PubMed Central

Tsuji, Yukiomi; Dobrev, Dobromir

2013-01-01

Intravenous vernakalant has recently been approved in Europe as an atrial-selective antiarrhythmic drug for the conversion of recent-onset atrial fibrillation (AF). It inhibits atrial-selective K+ currents (IK,ACh and IKur) and causes rate-dependent atrial-predominant Na+ channel block, with only a small inhibitory effect on the rapid delayed rectifier K+ current (IKr) in the ventricle. Due to its atrial-selective properties, vernakalant prolongs the effective refractory period of the atria with minimal effects on the ventricles, being associated with a low proarrhythmic risk for torsades de pointes arrhythmias. Five pivotal clinical trials consistently demonstrated that vernakalant rapidly terminates AF with stable maintenance of sinus rhythm for up to 24 hours. A head-to-head comparative trial showed that the 90-minute conversion rate of vernakalant was substantially higher than that of amiodarone. Initially, a longer-acting oral formulation of vernakalant was shown to be effective and safe in preventing AF recurrence after cardioversion in a Phase IIb study. However, the clinical studies testing oral vernakalant for maintenance of sinus rhythm after AF cardioversion were prematurely halted for undisclosed reasons. This review article provides an update on the safety and efficacy of intravenous vernakalant for the rapid cardioversion of AF. PMID:23637539

Hyperventilation assists proarrhythmia development during delayed repolarization in clofilium-treated, anaesthetized, mechanically ventilated rabbits.

PubMed

Papp, H; Sarusi, A; Farkas, A S; Takacs, H; Kui, P; Vincze, D; Ivany, E; Varro, A; Papp, J G; Forster, T; Farkas, A

2016-10-01

Hyperventilation reduces partial pressure of CO 2 (PCO 2 ) in the blood, which results in hypokalaemia. Hypokalaemia helps the development of the life-threatening torsades de pointes type ventricular arrhythmia (TdP) evoked by repolarization delaying drugs. This implies that hyperventilation may assist the development of proarrhythmic events. Therefore, this study experimentally investigated the effect of hyperventilation on proarrhythmia development during delayed repolarization. Phenylephrine (an α 1 -adrenoceptor agonist) and clofilium (as a representative repolarization delaying agent inhibiting the rapid component of the delayed rectifier potassium current, I Kr ) were administered intravenously to pentobarbital-anaesthetized, mechanically ventilated, open chest rabbits. ECG was recorded, and the onset times and incidences of the arrhythmias were determined. Serum K + , pH and PCO 2 were measured in arterial blood samples. Clofilium prolonged the rate corrected QT interval. TdP occurred in 15 animals (TdP+ group), and did not occur in 14 animals (TdP- group). We found a strong, positive, linear correlation between serum K + and PCO 2 . There was no relationship between the occurrence of TdP and the baseline K + and PCO 2 values. However, a positive, linear correlation was found between the onset time of the first arrhythmias and the K + and PCO 2 values. The regression lines describing the relationship between PCO 2 and onset time of first arrhythmias were parallel in the TdP+ and TdP- groups, but the same PCO 2 resulted in earlier arrhythmia onset in the TdP+ group than in the TdP- group. We conclude that hyperventilation and hypocapnia with the resultant hypokalaemia assist the multifactorial process of proarrhythmia development during delayed repolarization. This implies that PCO 2 and serum K + should be controlled tightly during mechanical ventilation in experimental investigations and clinical settings when repolarization-delaying drugs are applied.

Involvement of Potassium and Cation Channels in Hippocampal Abnormalities of Embryonic Ts65Dn and Tc1 Trisomic Mice

PubMed Central

Stern, Shani; Segal, Menahem; Moses, Elisha

2015-01-01

Down syndrome (DS) mouse models exhibit cognitive deficits, and are used for studying the neuronal basis of DS pathology. To understand the differences in the physiology of DS model neurons, we used dissociated neuronal cultures from the hippocampi of Ts65Dn and Tc1 DS mice. Imaging of [Ca2+]i and whole cell patch clamp recordings were used to analyze network activity and single neuron properties, respectively. We found a decrease of ~ 30% in both fast (A-type) and slow (delayed rectifier) outward potassium currents. Depolarization of Ts65Dn and Tc1 cells produced fewer spikes than diploid cells. Their network bursts were smaller and slower than diploids, displaying a 40% reduction in Δf / f0 of the calcium signals, and a 30% reduction in propagation velocity. Additionally, Ts65Dn and Tc1 neurons exhibited changes in the action potential shape compared to diploid neurons, with an increase in the amplitude of the action potential, a lower threshold for spiking, and a sharp decrease of about 65% in the after-hyperpolarization amplitude. Numerical simulations reproduced the DS measured phenotype by variations in the conductance of the delayed rectifier and A-type, but necessitated also changes in inward rectifying and M-type potassium channels and in the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. We therefore conducted whole cell patch clamp measurements of M-type potassium currents, which showed a ~ 90% decrease in Ts65Dn neurons, while HCN measurements displayed an increase of ~ 65% in Ts65Dn cells. Quantitative real-time PCR analysis indicates overexpression of 40% of KCNJ15, an inward rectifying potassium channel, contributing to the increased inhibition. We thus find that changes in several types of potassium channels dominate the observed DS model phenotype. PMID:26501103

Efficient Hybrid Actuation Using Solid-State Actuators

NASA Technical Reports Server (NTRS)

Leo, Donald J.; Cudney, Harley H.; Horner, Garnett (Technical Monitor)

2001-01-01

Piezohydraulic actuation is the use of fluid to rectify the motion of a piezoelectric actuator for the purpose of overcoming the small stroke limitations of the material. In this work we study a closed piezohydraulic circuit that utilizes active valves to rectify the motion of a hydraulic end affector. A linear, lumped parameter model of the system is developed and correlated with experiments. Results demonstrate that the model accurately predicts the filtering of the piezoelectric motion caused by hydraulic compliance. Accurate results are also obtained for predicting the unidirectional motion of the cylinder when the active valves are phased with respect to the piezoelectric actuator. A time delay associated with the mechanical response of the valves is incorporated into the model to reflect the finite time required to open or close the valves. This time delay is found to be the primary limiting factor in achieving higher speed and greater power from the piezohydraulic unit. Experiments on the piezohydraulic unit demonstrate that blocked forces on the order of 100 N and unloaded velocities of 180 micrometers/sec are achieved.

Testosterone-mediated upregulation of delayed rectifier potassium channel in cardiomyocytes causes abbreviation of QT intervals in rats.

PubMed

Masuda, Kimiko; Takanari, Hiroki; Morishima, Masaki; Ma, FangFang; Wang, Yan; Takahashi, Naohiko; Ono, Katsushige

2018-01-13

Men have shorter rate-corrected QT intervals (QTc) than women, especially at the period of adolescence or later. The aim of this study was to elucidate the long-term effects of testosterone on cardiac excitability parameters including electrocardiogram (ECG) and potassium channel current. Testosterone shortened QT intervals in ECG in castrated male rats, not immediately after, but on day 2 or later. Expression of Kv7.1 (KCNQ1) mRNA was significantly upregulated by testosterone in cardiomyocytes of male and female rats. Short-term application of testosterone was without effect on delayed rectifier potassium channel current (I Ks ), whereas I Ks was significantly increased in cardiomyocytes treated with dihydrotestosterone for 24 h, which was mimicked by isoproterenol (24 h). Gene-selective inhibitors of a transcription factor SP1, mithramycin, abolished the effects of testosterone on Kv7.1. Testosterone increases Kv7.1-I Ks possibly through a pathway related to a transcription factor SP1, suggesting a genomic effect of testosterone as an active factor for cardiac excitability.

Delayed Repolarization Underlies Ventricular Arrhythmias in Rats With Heart Failure and Preserved Ejection Fraction.

PubMed

Cho, Jae Hyung; Zhang, Rui; Kilfoil, Peter J; Gallet, Romain; de Couto, Geoffrey; Bresee, Catherine; Goldhaber, Joshua I; Marbán, Eduardo; Cingolani, Eugenio

2017-11-21

Heart failure with preserved ejection fraction (HFpEF) represents approximately half of heart failure, and its incidence continues to increase. The leading cause of mortality in HFpEF is sudden death, but little is known about the underlying mechanisms. Dahl salt-sensitive rats were fed a high-salt diet (8% NaCl) from 7 weeks of age to induce HFpEF (n=38). Rats fed a normal-salt diet (0.3% NaCl) served as controls (n=13). Echocardiograms were performed to assess systolic and diastolic function from 14 weeks of age. HFpEF-verified and control rats underwent programmed electrical stimulation. Corrected QT interval was measured by surface ECG. The mechanisms of ventricular arrhythmias (VA) were probed by optical mapping, whole-cell patch clamp to measure action potential duration and ionic currents, and quantitative polymerase chain reaction and Western blotting to investigate changes in ion channel expression. After 7 weeks of a high-salt diet, 31 of 38 rats showed diastolic dysfunction and preserved ejection fraction along with signs of heart failure and hence were diagnosed with HFpEF. Programmed electric stimulation demonstrated increased susceptibility to VA in HFpEF rats ( P <0.001 versus controls). The arrhythmogenicity index was increased ( P <0.001) and the corrected QT interval on ECG was prolonged ( P <0.001) in HFpEF rats. Optical mapping of HFpEF hearts demonstrated prolonged action potentials ( P <0.05) and multiple reentry circuits during induced VA. Single-cell recordings of cardiomyocytes isolated from HFpEF rats confirmed a delay of repolarization ( P =0.001) and revealed downregulation of transient outward potassium current ( I to ; P <0.05). The rapid components of the delayed rectifier potassium current ( I Kr ) and the inward rectifier potassium current ( I K1 ) were also downregulated ( P <0.05), but the current densities were much lower than for I to . In accordance with the reduction of I to , both Kcnd3 transcript and Kv4.3 protein levels were decreased in HFpEF rat hearts. Susceptibility to VA was markedly increased in rats with HFpEF. Underlying abnormalities include QT prolongation, delayed repolarization from downregulation of potassium currents, and multiple reentry circuits during VA. Our findings are consistent with the hypothesis that potassium current downregulation leads to abnormal repolarization in HFpEF, which in turn predisposes to VA and sudden cardiac death. © 2017 American Heart Association, Inc.

Thermal adaptation of the crucian carp (Carassius carassius) cardiac delayed rectifier current, IKs, by homomeric assembly of Kv7.1 subunits without MinK.

PubMed

Hassinen, Minna; Laulaja, Salla; Paajanen, Vesa; Haverinen, Jaakko; Vornanen, Matti

2011-07-01

Ectothermic vertebrates experience acute and chronic temperature changes which affect cardiac excitability and may threaten electrical stability of the heart. Nevertheless, ectothermic hearts function over wide range of temperatures without cardiac arrhythmias, probably due to special molecular adaptations. We examine function and molecular basis of the slow delayed rectifier K(+) current (I(Ks)) in cardiac myocytes of a eurythermic fish (Carassius carassius L.). I(Ks) is an important repolarizing current that prevents excessive prolongation of cardiac action potential, but it is extremely slowly activating when expressed in typical molecular composition of the endothermic animals. Comparison of the I(Ks) of the crucian carp atrial myocytes with the currents produced by homomeric K(v)7.1 and heteromeric K(v)7.1/MinK channels in Chinese hamster ovary cells indicates that activation kinetics and pharmacological properties of the I(Ks) are similar to those of the homomeric K(v)7.1 channels. Consistently with electrophysiological properties and homomeric K(v)7.1 channel composition, atrial transcript expression of the MinK subunit is only 1.6-1.9% of the expression level of the K(v)7.1 subunit. Since activation kinetics of the homomeric K(v)7.1 channels is much faster than activation of the heteromeric K(v)7.1/MinK channels, the homomeric K(v)7.1 composition of the crucian carp cardiac I(Ks) is thermally adaptive: the slow delayed rectifier channels can open despite low body temperatures and curtail the duration of cardiac action potential in ectothermic crucian carp. We suggest that the homomeric K(v)7.1 channel assembly is an evolutionary thermal adaptation of ectothermic hearts and the heteromeric K(v)7.1/MinK channels evolved later to adapt I(Ks) to high body temperature of endotherms.

Deletion of the Kv2.1 delayed rectifier potassium channel leads to neuronal and behavioral hyperexcitability

PubMed Central

Speca, David J.; Ogata, Genki; Mandikian, Danielle; Bishop, Hannah I.; Wiler, Steve W.; Eum, Kenneth; Wenzel, H. Jürgen; Doisy, Emily T.; Matt, Lucas; Campi, Katharine L.; Golub, Mari S.; Nerbonne, Jeanne M.; Hell, Johannes W.; Trainor, Brian C.; Sack, Jon T.; Schwartzkroin, Philip A.; Trimmer, James S.

2014-01-01

The Kv2.1 delayed rectifier potassium channel exhibits high-level expression in both principal and inhibitory neurons throughout the central nervous system, including prominent expression in hippocampal neurons. Studies of in vitro preparations suggest that Kv2.1 is a key yet conditional regulator of intrinsic neuronal excitability, mediated by changes in Kv2.1 expression, localization and function via activity-dependent regulation of Kv2.1 phosphorylation. Here we identify neurological and behavioral deficits in mutant (Kv2.1−/−) mice lacking this channel. Kv2.1−/− mice have grossly normal characteristics. No impairment in vision or motor coordination was apparent, although Kv2.1−/− mice exhibit reduced body weight. The anatomic structure and expression of related Kv channels in the brains of Kv2.1−/− mice appears unchanged. Delayed rectifier potassium current is diminished in hippocampal neurons cultured from Kv2.1−/− animals. Field recordings from hippocampal slices of Kv2.1−/− mice reveal hyperexcitability in response to the convulsant bicuculline, and epileptiform activity in response to stimulation. In Kv2.1−/− mice, long-term potentiation at the Schaffer collateral – CA1 synapse is decreased. Kv2.1−/− mice are strikingly hyperactive, and exhibit defects in spatial learning, failing to improve performance in a Morris Water Maze task. Kv2.1−/− mice are hypersensitive to the effects of the convulsants flurothyl and pilocarpine, consistent with a role for Kv2.1 as a conditional suppressor of neuronal activity. Although not prone to spontaneous seizures, Kv2.1−/− mice exhibit accelerated seizure progression. Together, these findings suggest homeostatic suppression of elevated neuronal activity by Kv2.1 plays a central role in regulating neuronal network function. PMID:24494598

Inactivation gating determines nicotine blockade of human HERG channels.

PubMed

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

1999-09-01

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

Rapid disinhibition by adjustment of PV intrinsic excitability during whisker map plasticity in mouse S1.

PubMed

Gainey, Melanie A; Aman, Joseph W; Feldman, Daniel E

2018-04-20

Rapid plasticity of layer (L) 2/3 inhibitory circuits is an early step in sensory cortical map plasticity, but its cellular basis is unclear. We show that, in mice of either sex, 1 day whisker deprivation drives rapid loss of L4-evoked feedforward inhibition and more modest loss of feedforward excitation in L2/3 pyramidal (PYR) cells, increasing E-I conductance ratio. Rapid disinhibition was due to reduced L4-evoked spiking by L2/3 parvalbumin (PV) interneurons, caused by reduced PV intrinsic excitability. This included elevated PV spike threshold, associated with an increase in low-threshold, voltage activated delayed rectifier (presumed Kv1) and A-type potassium currents. Excitatory synaptic input and unitary inhibitory output of PV cells were unaffected. Functionally, the loss of feedforward inhibition and excitation were precisely coordinated in L2/3 PYR cells, so that peak feedforward synaptic depolarization remained stable. Thus, rapid plasticity of PV intrinsic excitability offsets early weakening of excitatory circuits to homeostatically stabilize synaptic potentials in PYR cells of sensory cortex. SIGNIFICANCE STATEMENT Inhibitory circuits in cerebral cortex are highly plastic, but the cellular mechanisms and functional importance of this plasticity are incompletely understood. We show that brief (1-day) sensory deprivation rapidly weakens parvalbumin (PV) inhibitory circuits by reducing the intrinsic excitability of PV neurons. This involved a rapid increase in voltage-gated potassium conductances that control near-threshold spiking excitability. Functionally, the loss of PV-mediated feedforward inhibition in L2/3 pyramidal cells was precisely balanced with the separate loss of feedforward excitation, resulting in a net homeostatic stabilization of synaptic potentials. Thus, rapid plasticity of PV intrinsic excitability implements network-level homeostasis to stabilize synaptic potentials in sensory cortex. Copyright © 2018 the authors.

Control of resting membrane potential by delayed rectifier potassium currents in ferret airway smooth muscle cells.

PubMed Central

Fleischmann, B K; Washabau, R J; Kotlikoff, M I

1993-01-01

1. In order to determine the physiological role of specific potassium currents in airway smooth muscle, potassium currents were measured in freshly dissociated ferret trachealis cells using the nystatin-permeabilized, whole-cell method, at 35 degrees C. 2. The magnitude of the outward currents was markedly increased as bath temperature was increased from 22 to 35 degrees C. This increase was primarily due to the increase in maximum potassium conductance (gK,max), although there was also a small leftward shift in the relationship between gK and voltage at higher temperatures. The maximum conductance and the kinetics of current activation and inactivation were also temperature dependent. At 35 degrees C, gating of the current was steeply voltage dependent between -40 and 0 mV. Current activation was well fitted by fourth-order kinetics; the mean time constants of activation (30 mV clamp step) were 1.09 +/- 0.17 and 1.96 +/- 0.27 ms at 35 and 22 degrees C, respectively. 3. Outward currents using the nystatin method were qualitatively similar to delayed rectifier currents recorded in dialysed cells with high calcium buffering capacity solutions. 4-Aminopyridine (4-AP; 2 mM), a specific blocker of delayed rectifier potassium channels in this tissue, inhibited over 80% of the outward current evoked by voltage-clamp steps to between -10 and +20 mV (n = 6). Less than 5% of the outward current was blocked over the same voltage range by charybdotoxin (100 nM; n = 15), a specific antagonist of large-conductance, calcium-activated potassium channels in this tissue. 4. The degree to which delayed rectifier and calcium-activated potassium conductances control resting membrane potential was examined in current-clamp experiments. The resting membrane potential of current clamped cells was -33.6 +/- 1.0 mV (n = 62). Application of 4-AP (2 mM) resulted in a 14.4 +/- 1.0 mV depolarization (n = 8) and an increase in input resistance. Charybdotoxin (100 nM) had no effect on resting membrane potential (n = 6). 5. Force measurements were made in isolated strips of trachealis muscle to determine the effect of pharmacological blockade of individual potassium conductances on resting tone. In the presence of tetrodotoxin (1 microM) and atropine (1 microM), 4-AP increased baseline tension in a dose-dependent manner, with an EC50 of 1.8 mM (n = 13); application of 5 mM 4-AP increased tone to 86.8 +/- 8.1% of that produced by 1 microM methacholine, and this tone was almost completely inhibited by nifedipine (1 microM).(ABSTRACT TRUNCATED AT 400 WORDS) PMID:8271220

K+ channels of Müller glial cells in retinal disorders.

PubMed

Gao, Feng; Xu, Linjie; Zhao, Yuan; Sun, Xinghuai; Wang, Zhongfeng

2018-02-01

Müller cell is the major type glial cell in the vertebrate retina. Müller cells express various types of K+ channels, such as inwardly rectifying K+ (Kir) channels, big conductance Ca2+-activated K+ (BKCa) channels, delayed rectifier K+ channels (KDR), and transient A-type K+ channels. These K+ channels play important roles in maintaining physiological functions of Müller cells. Under some retinal pathological conditions, the changed expression and functions of K+ channels may contribute to retinal pathogenesis. In this article, we reviewed the physiological properties of K+ channels in retinal Müller cells and the functional changes of these channels in retinal disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Adaptive control system for line-commutated inverters

NASA Technical Reports Server (NTRS)

Dolland, C. R.; Bailey, D. A. (Inventor)

1983-01-01

A control system for a permanent magnet motor driven by a multiphase line commutated inverter is provided with integration for integrating the back EMF of each phase of the motor. This is used in generating system control signals for an inverter gate logic using a sync and firing angle (alpha) control generator connected to the outputs of the integrators. A precision full wave rectifier provides a speed control feedback signal to a phase delay rectifier via a gain and loop compensation circuit and to the integrators for adaptive control of the attenuation of low frequencies by the integrators as a function of motor speed. As the motor speed increases, the attenuation of low frequency components by the integrators is increased to offset the gain of the integrators to spurious low frequencies.

Taurine activates delayed rectifier KV channels via a metabotropic pathway in retinal neurons

PubMed Central

Bulley, Simon; Liu, Yufei; Ripps, Harris; Shen, Wen

2013-01-01

Taurine is one of the most abundant amino acids in the retina, throughout the CNS, and in heart and muscle cells. In keeping with its broad tissue distribution, taurine serves as a modulator of numerous basic processes, such as enzyme activity, cell development, myocardial function and cytoprotection. Despite this multitude of functional roles, the precise mechanism underlying taurine's actions has not yet been identified. In this study we report findings that indicate a novel role for taurine in the regulation of voltage-gated delayed rectifier potassium (KV) channels in retinal neurons by means of a metabotropic receptor pathway. The metabotropic taurine response was insensitive to the Cl− channel blockers, picrotoxin and strychnine, but it was inhibited by a specific serotonin 5-HT2A receptor antagonist, MDL11939. Moreover, we found that taurine enhanced KV channels via intracellular protein kinase C-mediated pathways. When 5-HT2A receptors were expressed in human embryonic kidney cells, taurine and AL34662, a non-specific 5-HT2 receptor activator, produced a similar regulation of KIR channels. In sum, this study provides new evidence that taurine activates a serotonin system, apparently via 5-HT2A receptors and related intracellular pathways. PMID:23045337

Kv channel subunits that contribute to voltage-gated K+ current in renal vascular smooth muscle.

PubMed

Fergus, Daniel J; Martens, Jeffrey R; England, Sarah K

2003-03-01

The rat renal arterial vasculature displays differences in K(+) channel current phenotypes along its length. Small arcuate to cortical radial arteries express a delayed rectifier phenotype, while the predominant Kv current in larger arcuate and interlobar arteries is composed of both transient and sustained components. We sought to determine whether Kvalpha subunits in the rat renal interlobar and arcuate arteries form heterotetramers, which may account for the unique currents, and whether modulatory Kvbeta subunits are present in renal vascular smooth muscle cells. RT-PCR indicated the presence of several different Kvalpha subunit isoform transcripts. Co-immunoprecipitation with immunoblotting and immunohistochemical evidence suggests that a portion of the K(+) current phenotype is a heteromultimer containing delayed-rectifier Kv1.2 and A-type Kv1.4 channel subunits. RT-PCR and immunoblot analyses also demonstrated the presence of both Kvbeta1.2 and Kvbeta1.3 in renal arteries. These results suggest that heteromultimeric formation of Kvalpha subunits and the presence of modulatory Kvbeta subunits are important factors in mediating Kv currents in the renal microvasculature and suggest a potentially critical role for these channel subunits in blood pressure regulation.

Down-regulation of delayed rectifier K+ channels in the hippocampus of seizure sensitive gerbils.

PubMed

Lee, Sang-Moo; Kim, Ji-Eun; Sohn, Jong-Hee; Choi, Hui-Chul; Lee, Ju-Sang; Kim, Sung-Hun; Kim, Min-Ju; Choi, Ihn-Geun; Kang, Tae-Cheon

2009-12-16

In order to confirm the species-specific distribution of voltage-gated K(+) (Kv) channels and the definitive relationship between their immunoreactivities and seizure activity, we investigated Kv2.x, Kv3.x and Kv4.x channel immunoreactivities in the hippocampi of seizure-resistant (SR) and seizure-sensitive (SS) gerbils. There was no difference in Kv2.1, Kv3.4, Kv4.2 and Kv4.3 immunoreactivity in the hippocampus between SR and SS gerbils. In comparison to SR gerbils, Kv3.1b immunoreactivity in neurons was significantly lower in SS gerbils instead Kv3.1b-immunoreactive astrocytes were clearly observed in SS gerbils (p<0.05). Kv3.2 immunoreactivity was also significantly lower in neurons of SS gerbils than in those of SR gerbils (p<0.05). Considering the findings of our previous study, these findings suggest that delayed rectifier K(+) channels (Kv1.1, Kv1.2, Kv1.5, Kv1.6, Kv2.1 and Kv3.1-2), not A-type K(+) channels (Kv1.4, Kv3.4 and Kv4.x), may be down-regulated in the SS gerbil hippocampus, as compared to SR gerbils.

Impact of ionic current variability on human ventricular cellular electrophysiology.

PubMed

Romero, Lucía; Pueyo, Esther; Fink, Martin; Rodríguez, Blanca

2009-10-01

Abnormalities in repolarization and its rate dependence are known to be related to increased proarrhythmic risk. A number of repolarization-related electrophysiological properties are commonly used as preclinical biomarkers of arrhythmic risk. However, the variability and complexity of repolarization mechanisms make the use of cellular biomarkers to predict arrhythmic risk preclinically challenging. Our goal is to investigate the role of ionic current properties and their variability in modulating cellular biomarkers of arrhythmic risk to improve risk stratification and identification in humans. A systematic investigation into the sensitivity of the main preclinical biomarkers of arrhythmic risk to changes in ionic current conductances and kinetics was performed using computer simulations. Four stimulation protocols were applied to the ten Tusscher and Panfilov human ventricular model to quantify the impact of +/-15 and +/-30% variations in key model parameters on action potential (AP) properties, Ca(2+) and Na(+) dynamics, and their rate dependence. Simulations show that, in humans, AP duration is moderately sensitive to changes in all repolarization current conductances and in L-type Ca(2+) current (I(CaL)) and slow component of the delayed rectifier current (I(Ks)) inactivation kinetics. AP triangulation, however, is strongly dependent only on inward rectifier K(+) current (I(K1)) and delayed rectifier current (I(Kr)) conductances. Furthermore, AP rate dependence (i.e., AP duration rate adaptation and restitution properties) and intracellular Ca(2+) and Na(+) levels are highly sensitive to both I(CaL) and Na(+)/K(+) pump current (I(NaK)) properties. This study provides quantitative insights into the sensitivity of preclinical biomarkers of arrhythmic risk to variations in ionic current properties in humans. The results show the importance of sensitivity analysis as a powerful method for the in-depth validation of mathematical models in cardiac electrophysiology.

Crataegus extract blocks potassium currents in guinea pig ventricular cardiac myocytes.

PubMed

Müller, A; Linke, W; Klaus, W

1999-05-01

Crataegus extract is used in cardiology for the treatment of mild to moderate heart failure (NYHA II) in Germany. However, little is known about the electrophysiological actions of Crataegus extract in the heart. Recently, it was shown that Crataegus extract prolongs the refractory period in isolated perfused hearts and increases action potential duration in guinea pig papillary muscle. It was the aim of this study to find out the mechanism of the increase in action potential duration caused by Crataegus extract. Using the patch-clamp technique, we measured the effects of Crataegus extract (10 mg/l; flavonoid content: 2.25%, total procyanidin content: 11.3 +/- 0.4%) on the inward rectifier and the delayed rectifier potassium current in isolated guinea pig ventricular myocytes. To get some insight into the mechanism underlying the positive inotropic effect of Crataegus extract, we also looked for effects on the L-type calcium current. Crataegus extract slightly blocked both the delayed and the inward rectifier potassium current. The inhibition amounted to 25% and about 15%, respectively. This amount of inhibition of these repolarising currents is sufficient to explain the prolongation of action potential duration caused by Crataegus extract. To our surprise we could not detect any influence of Crataegus extract on the L-type calcium current. In summary, our results show that Crataegus extract blocks repolarising potassium currents in ventricular myocytes. This effect is similar to the action of class III antiarrhythmic drugs and might be the basis of the antiarrhythmic effects described for Crataegus extract. Our measurements of the L-type calcium current indicate that Crataegus extract's positive inotropic effect is not caused by phosphodiesterase inhibition or a beta-sympathomimetic effect.

Human-induced pluripotent stem cell-derived cardiomyocytes from cardiac progenitor cells: effects of selective ion channel blockade.

PubMed

Altomare, Claudia; Pianezzi, Enea; Cervio, Elisabetta; Bolis, Sara; Biemmi, Vanessa; Benzoni, Patrizia; Camici, Giovanni G; Moccetti, Tiziano; Barile, Lucio; Vassalli, Giuseppe

2016-12-01

Human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes are likely to revolutionize electrophysiological approaches to arrhythmias. Recent evidence suggests the somatic cell origin of hiPSCs may influence their differentiation potential. Owing to their cardiomyogenic potential, cardiac-stromal progenitor cells (CPCs) are an interesting cellular source for generation of hiPSC-derived cardiomyocytes. The effect of ionic current blockade in hiPSC-derived cardiomyocytes generated from CPCs has not been characterized yet. Human-induced pluripotent stem cell-derived cardiomyocytes were generated from adult CPCs and skin fibroblasts from the same individuals. The effect of selective ionic current blockade on spontaneously beating hiPSC-derived cardiomyocytes was assessed using multi-electrode arrays. Cardiac-stromal progenitor cells could be reprogrammed into hiPSCs, then differentiated into hiPSC-derived cardiomyocytes. Human-induced pluripotent stem cell-derived cardiomyocytes of cardiac origin showed higher upregulation of cardiac-specific genes compared with those of fibroblastic origin. Human-induced pluripotent stem cell-derived cardiomyocytes of both somatic cell origins exhibited sensitivity to tetrodotoxin, a blocker of Na +  current (I Na ), nifedipine, a blocker of L-type Ca 2+  current (I CaL ), and E4031, a blocker of the rapid component of delayed rectifier K +  current (I Kr ). Human-induced pluripotent stem cell-derived cardiomyocytes of cardiac origin exhibited sensitivity to JNJ303, a blocker of the slow component of delayed rectifier K +  current (I Ks ). In hiPSC-derived cardiomyocytes of cardiac origin, I Na , I CaL , I Kr , and I Ks were present as tetrodotoxin-, nifedipine-, E4031-, and JNJ303-sensitive currents, respectively. Although cardiac differentiation efficiency was improved in hiPSCs of cardiac vs. non-cardiac origin, no major functional differences were observed between hiPSC-derived cardiomyocytes of different somatic cell origins. Further studies are warranted to characterize electrophysiological properties of hiPSC-derived cardiomyocytes generated from CPCs. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.

Elimination of fast inactivation in Kv4 A-type potassium channels by an auxiliary subunit domain.

PubMed

Holmqvist, Mats H; Cao, Jie; Hernandez-Pineda, Ricardo; Jacobson, Michael D; Carroll, Karen I; Sung, M Amy; Betty, Maria; Ge, Pei; Gilbride, Kevin J; Brown, Melissa E; Jurman, Mark E; Lawson, Deborah; Silos-Santiago, Inmaculada; Xie, Yu; Covarrubias, Manuel; Rhodes, Kenneth J; Distefano, Peter S; An, W Frank

2002-01-22

The Kv4 A-type potassium currents contribute to controlling the frequency of slow repetitive firing and back-propagation of action potentials in neurons and shape the action potential in heart. Kv4 currents exhibit rapid activation and inactivation and are specifically modulated by K-channel interacting proteins (KChIPs). Here we report the discovery and functional characterization of a modular K-channel inactivation suppressor (KIS) domain located in the first 34 aa of an additional KChIP (KChIP4a). Coexpression of KChIP4a with Kv4 alpha-subunits abolishes fast inactivation of the Kv4 currents in various cell types, including cerebellar granule neurons. Kinetic analysis shows that the KIS domain delays Kv4.3 opening, but once the channel is open, it disrupts rapid inactivation and slows Kv4.3 closing. Accordingly, KChIP4a increases the open probability of single Kv4.3 channels. The net effects of KChIP4a and KChIP1-3 on Kv4 gating are quite different. When both KChIP4a and KChIP1 are present, the Kv4.3 current shows mixed inactivation profiles dependent on KChIP4a/KChIP1 ratios. The KIS domain effectively converts the A-type Kv4 current to a slowly inactivating delayed rectifier-type potassium current. This conversion is opposite to that mediated by the Kv1-specific "ball" domain of the Kv beta 1 subunit. Together, these results demonstrate that specific auxiliary subunits with distinct functions actively modulate gating of potassium channels that govern membrane excitability.

Fine Output Voltage Control Method considering Time-Delay of Digital Inverter System for X-ray Computed Tomography

NASA Astrophysics Data System (ADS)

Shibata, Junji; Kaneko, Kazuhide; Ohishi, Kiyoshi; Ando, Itaru; Ogawa, Mina; Takano, Hiroshi

This paper proposes a new output voltage control for an inverter system, which has time-delay and nonlinear load. In the next generation X-ray computed tomography of a medical device (X-ray CT) that uses the contactless power transfer method, the feedback signal often contains time-delay due to AD/DA conversion and error detection/correction time. When the PID controller of the inverter system is received the adverse effects of the time-delay, the controller often has an overshoot and a oscillated response. In order to overcome this problem, this paper proposes a compensation method based on the Smith predictor for an inverter system having a time-delay and the nonlinear loads which are the diode bridge rectifier and X-ray tube. The proposed compensation method consists of the hybrid Smith predictor system based on an equivalent analog circuit and DSP. The experimental results confirm the validity of the proposed system.

APOEε4 increases trauma induced early apoptosis via reducing delayed rectifier K(+) currents in neuronal/glial co-cultures model.

PubMed

Chen, Ligang; Sun, Xiaochuan; Jiang, Yong; Kuai, Li

2015-06-10

Traumatic brain injury (TBI) is a commonly encountered emergency and severe neurosurgical injury. Previous studies have shown that the presence of the apolipoprotein E (APOE) ε4 allele has adverse outcomes across the spectrum of TBI severity. Our objective was to evaluate the effects of APOE alleles on trauma induced early apoptosis via modification of delayed rectifier K(+) current (Ik(DR)) in neuronal/glial co-cultures model. An ex vivo neuronal/glial co-cultures model carrying individual APOE alleles (ε2, ε3, ε4) of mechanical injury was developed. Flow cytometry and patch clamp recording were performed to analyze the correlations among APOE genotypes, early apoptosis and Ik(DR). We found that APOEε4 increased early apoptosis at 24h (p<0.05) compared to the ones transfected with APOEε3 and APOEε2. Noticeably, APOEε4 significantly reduced the amplitude of the Ik(DR) at 24h compared to the APOEε3 and APOEε2 (p<0.05) which exacerbate Ca(2+) influx. This indicates a possible effect of APOEε4 on early apoptosis via inhibiting Ik(DR) following injury which may adversely affect the outcome of TBI. Copyright © 2015 Elsevier Inc. All rights reserved.

Suppressive effects of diltiazem and verapamil on delayed rectifier K(+)-channel currents in murine thymocytes.

PubMed

Baba, Asuka; Tachi, Masahiro; Maruyama, Yoshio; Kazama, Itsuro

2015-10-01

Lymphocytes predominantly express delayed rectifier K(+)-channels (Kv1.3) in their plasma membranes, and these channels play crucial roles in the lymphocyte activation and proliferation. Since diltiazem and verapamil, which are highly lipophilic Ca(2+) channel blockers (CCBs), exert relatively stronger immunomodulatory effects than the other types of CCBs, they would affect the Kv1.3-channel currents in lymphocytes. Employing the standard patch-clamp whole-cell recording technique in murine thymocytes, we examined the effects of these drugs on the channel currents and the membrane capacitance. Both diltiazem and verapamil significantly suppressed the peak and the pulse-end currents of the channels, although the effects of verapamil were more marked than those of diltiazem. Both drugs significantly lowered the membrane capacitance, indicating the interactions between the drugs and the plasma membranes. This study demonstrated for the first time that CCBs, such as diltiazem and verapamil, exert inhibitory effects on Kv1.3-channels expressed in lymphocytes. The effects of these drugs may be associated with the mechanisms of immunomodulation by which they decrease the production of inflammatory cytokines. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Enhanced basal late sodium current appears to underlie the age-related prolongation of action potential duration in guinea pig ventricular myocytes.

PubMed

Song, Yejia; Belardinelli, Luiz

2017-12-14

Aging hearts have prolonged QT interval and are vulnerable to oxidative stress. Because the QT interval indirectly reflects the action potential duration (APD), we examined the hypotheses that 1) the APD of ventricular myocytes increases with age; 2) the age-related prolongation of APD is due to an enhancement of basal late Na + current (I NaL ); 3) inhibition of I NaL may protect aging hearts from arrhythmogenic effects of hydrogen peroxide (H 2 O 2 ). Experiments were performed on ventricular myocytes isolated from one-month (young) and one-year (old) guinea pigs (GPs). The APD of myocytes from old GPs was significantly longer than that from young GPs and was shortened by the I NaL inhibitors GS967 and tetrodotoxin. The magnitude of I NaL was significantly larger in myocytes from old than from young GPs. The CaMKII inhibitors KN-93 and AIP and the Na V 1.5-channel blocker MTSEA blocked the I NaL . There were no significant differences between myocytes from young and old GPs in L-type Ca 2+ current and the rapidly- and slowly-activating delayed rectifier K + currents, although the inward rectifier K + current was slightly decreased in myocytes from old GPs. H 2 O 2 induced more early afterdepolarizations in myocytes from old than from young GPs. The effect of H 2 O 2 was attenuated by GS967. The results suggest that 1) the APD of myocytes from old GPs is prolonged, 2) a CaMKII-mediated increase in Na V 1.5-channel I NaL is responsible for the prolongation of APD, and 3) Inhibition of I NaL may be beneficial for maintaining electrical stability under oxidative stress in myocytes of old GPs.

Population of computational rabbit-specific ventricular action potential models for investigating sources of variability in cellular repolarisation.

PubMed

Gemmell, Philip; Burrage, Kevin; Rodriguez, Blanca; Quinn, T Alexander

2014-01-01

Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration) and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K(+), inward rectifying K(+), L-type Ca(2+), and Na(+)/K(+) pump currents) in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al.) at multiple cycle lengths (400, 600, 1,000 ms) was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in experimentally observed intercellular variability of rabbit ventricular action potential repolarisation.

Population of Computational Rabbit-Specific Ventricular Action Potential Models for Investigating Sources of Variability in Cellular Repolarisation

PubMed Central

Gemmell, Philip; Burrage, Kevin; Rodriguez, Blanca; Quinn, T. Alexander

2014-01-01

Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration) and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K+, inward rectifying K+, L-type Ca2+, and Na+/K+ pump currents) in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al.) at multiple cycle lengths (400, 600, 1,000 ms) was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in experimentally observed intercellular variability of rabbit ventricular action potential repolarisation. PMID:24587229

Dronedarone: an amiodarone analogue.

PubMed

Doggrell, Sheila A; Hancox, Jules C

2004-04-01

Of the antiarrhythmic drugs in current use, amiodarone is one of the most effective and is associated with a comparatively low risk of drug-induced pro-arrhythmia, probably due to its multiple pharmacological actions on cardiac ion channels and receptors. However, amiodarone is associated with significant extra-cardiac side effects and this has driven development of amiodarone analogues. These analogues include short acting analogues (e.g., AT-2001) with similar acute effects to amiodarone, the thyroid receptor antagonist KB-130015 and dronedarone. Dronedarone, (SR-33589; Sanofi-Synthelabo), is a non-iodinated amiodarone derivative that inhibits Na +, K + and Ca 2+ currents. It is a potent inhibitor of the acetylcholine-activated K + current from atrial and sinoatrial nodal tissue, and inhibits the rapid delayed rectifier more potently than slow and inward rectifier K + currents and inhibits L-type calcium current. Dronedarone is an antagonist at alpha- and beta-adrenoceptors and unlike amiodarone, has little effect at thyroid receptors. Dronedarone is more potent than amiodarone in inhibiting arrhythmias and death in animal models of ischaemia- and reperfusion-induced arrhythmias. In the Dronedarone Atrial Fibrillation Study After Electrical Cardioversion (DAFNE) clinical trial, dronedarone 800 mg/day appeared to be effective and safe for the prevention of atrial fibrillation relapses after cardioversion. The Antiarrhythmic Trial with Dronedarone in Moderate-to-Severe Congestive Heart Failure Evaluating Morbidity Decrease (ANDROMEDA) trial was stopped due to a potential increased risk of death in the dronedarone group. Trials of dronedarone in the maintenance of sinus rhythm in patients with atrial fibrillation and a safety and tolerability study in patients with an implantable cardioverter defibrillator are ongoing. Further experimental and clinical studies are required before we have a definitive answer to whether dronedarone has advantages over amiodarone and other amiodarone analogues.

Aldosterone down-regulates the slowly activated delayed rectifier potassium current in adult guinea pig cardiomyocytes.

PubMed

Lv, Yankun; Bai, Song; Zhang, Hua; Zhang, Hongxue; Meng, Jing; Li, Li; Xu, Yanfang

2015-12-01

There is emerging evidence that the mineralocorticoid hormone aldosterone is associated with arrhythmias in cardiovascular disease. However, the effect of aldosterone on the slowly activated delayed rectifier potassium current (IK s ) remains poorly understood. The present study was designed to investigate the modulation of IK s by aldosterone. Adult guinea pigs were treated with aldosterone for 28 days via osmotic pumps. Standard glass microelectrode recordings and whole-cell patch-clamp techniques were used to record action potentials in papillary muscles and IK s in ventricular cardiomyocytes. The aldosterone-treated animals exhibited a prolongation of the QT interval and action potential duration with a higher incidence of early afterdepolarizations. Patch-clamp recordings showed a significant down-regulation of IK s density in the ventricular myocytes of these treated animals. These aldosterone-induced electrophysiological changes were fully prevented by a combined treatment with spironolactone, a mineralocorticoid receptor (MR) antagonist. In addition, in in vitro cultured ventricular cardiomyocytes, treatment with aldosterone (sustained exposure for 24 h) decreased the IK s density in a concentration-dependent manner. Furthermore, a significant corresponding reduction in the mRNA/protein expression of IKs channel pore and auxiliary subunits, KCNQ1 and KCNE1 was detected in ventricular tissue from the aldosterone-treated animals. Aldosterone down-regulates IK s by inhibiting the expression of KCNQ1 and KCNE1, thus delaying the ventricular repolarization. These results provide new insights into the mechanism underlying K(+) channel remodelling in heart disease and may explain the highly beneficial effects of MR antagonists in HF. © 2015 The British Pharmacological Society.

Cardiac ion channel modulation by the hypoglycaemic agent rosiglitazone.

PubMed

Hancox, J C

2011-06-01

The hypoglycaemic thiazolidinedione rosiglitazone is used clinically in the treatment of type 2 diabetes. However, in 2010, information relating to rosiglitazone-associated increased cardiovascular risk led the European Medicines Agency to recommend suspension of marketing authorizations for rosiglitazone-containing anti-diabetes drugs, while the US Food and Drug Administration recommended significant restriction on the agent's use. Two timely studies in this issue of the British Journal of Phrarmacology provide new information regarding modification of cardiac cellular electrophysiology by rosiglitazone. Szentandrássy et al. demonstrate canine ventricular action potential modification and concentration-dependent suppression of L-type Ca current and of transient outward and rapid delayed rectifier K currents. Jeong et al. demonstrate concentration-dependent inhibition of recombinant K(v) 4.3 channels, providing mechanistic insight into the likely molecular basis of transient outward K current inhibition by the compound. Further studies using diabetic models would be of value to determine whether, in a diabetic setting, rosiglitazone modification of these channels could affect the risk of arrhythmia at clinically relevant drug concentrations. © 2011 The Author. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Selenium protects reproductive system and foetus development in a rat model of gestational lead exposure.

PubMed

Shen, W; Chen, J; Yin, J; Wang, S-L

2016-01-01

Lead is a common environmental contaminant. Lead accumulation in the body is especially dangerous for pregnant women and newborns. Selenium is a trace element which may rectify the damaging effects of lead. Here we tested potential protective effects of selenium against gestational lead exposure. Pregnant SD rats were exposed to 200 mg/L of lead acetate (given with water), with or without sodium selenite supplementation (2-8 mg/kg/day via intragastric administration). Pregnant rats not exposed to lead or selenium served as control animals. The outcomes in pregnant rats were serum lead and selenium levels, reproductive hormone (follicle-stimulating hormone, luteinizing hormone, prolactin, oestradiol, progesterone) levels, and uterine and ovarian morphological changes. The outcomes in the offspring were sex differentiation, survival rates (day 21 after birth), weight (days 0-35 after birth), weight of reproductive organs, and puberty onset (foreskin separation or vaginal opening). Selenium supplementation dose-dependently decreased serum lead levels, rectified reproductive hormone levels, and attenuated reproductive morphological changes caused by lead exposure. Lead exposure did not affect sex differentiation, but significantly (p < 0.05 vs. control animals) decreased the offspring weight on days 0-28 and the weight of their reproductive organs. Furthermore, lead exposure delayed the onset of puberty. These pathological changes were dose-dependently rectified or attenuated by selenium supplementation. Gestational lead exposure causes damages to the reproductive system of pregnant rats, and negatively modulates growth and reproductive system development of the offspring. These adverse effects are rectified or attenuated by selenium supplementation.

Critical period inhibition of NKCC1 rectifies synapse plasticity in the somatosensory cortex and restores adult tactile response maps in fragile X mice.

PubMed

He, Qionger; Arroyo, Erica D; Smukowski, Samuel N; Xu, Jian; Piochon, Claire; Savas, Jeffrey N; Portera-Cailliau, Carlos; Contractor, Anis

2018-04-27

Sensory perturbations in visual, auditory and tactile perception are core problems in fragile X syndrome (FXS). In the Fmr1 knockout mouse model of FXS, the maturation of synapses and circuits during critical period (CP) development in the somatosensory cortex is delayed, but it is unclear how this contributes to altered tactile sensory processing in the mature CNS. Here we demonstrate that inhibiting the juvenile chloride co-transporter NKCC1, which contributes to altered chloride homeostasis in developing cortical neurons of FXS mice, rectifies the chloride imbalance in layer IV somatosensory cortex neurons and corrects the development of thalamocortical excitatory synapses during the CP. Comparison of protein abundances demonstrated that NKCC1 inhibition during early development caused a broad remodeling of the proteome in the barrel cortex. In addition, the abnormally large size of whisker-evoked cortical maps in adult Fmr1 knockout mice was corrected by rectifying the chloride imbalance during the early CP. These data demonstrate that correcting the disrupted driving force through GABA A receptors during the CP in cortical neurons restores their synaptic development, has an unexpectedly large effect on differentially expressed proteins, and produces a long-lasting correction of somatosensory circuit function in FXS mice.

Role of an inward rectifier K+ current and of hyperpolarization in human myoblast fusion

PubMed Central

Liu, J-H; Bijlenga, P; Fischer-Lougheed, J; Occhiodoro, T; Kaelin, A; Bader, C R; Bernheim, L

1998-01-01

The role of K+ channels and membrane potential in myoblast fusion was evaluated by examining resting membrane potential and timing of expression of K+ currents at three stages of differentiation of human myogenic cells: undifferentiated myoblasts, fusion-competent myoblasts (FCMBs), and freshly formed myotubes. Two K+ currents contribute to a hyperpolarization of myoblasts prior to fusion: IK(NI), a non-inactivating delayed rectifier, and IK(IR), an inward rectifier. IK(NI) density is low in undifferentiated myoblasts, increases in FCMBs and declines in myotubes. On the other hand, IK(IR) is expressed in 28 % of the FCMBs and in all myotubes. IK(IR) is reversibly blocked by Ba2+ or Cs+. Cells expressing IK(IR) have resting membrane potentials of −65 mV. A block by Ba2+ or Cs+ induces a depolarization to a voltage determined by IK(NI) (−32 mV). Cs+ and Ba2+ ions reduce myoblast fusion. It is hypothesized that the IK(IR)-mediated hyperpolarization allows FCMBs to recruit Na+, K+ and T-type Ca2+ channels which are present in these cells and would otherwise be inactivated. FCMBs, rendered thereby capable of firing action potentials, could amplify depolarizing signals and may accelerate fusion. PMID:9705997

Physiological and molecular characterization of an IRK-type inward rectifier K+ channel in a tumour mast cell line.

PubMed

Wischmeyer, E; Lentes, K U; Karschin, A

1995-04-01

The basophilic leucaemia cell line RBL-2H3 exhibits a robust inwardly rectifying potassium current, IKIR, which is likely to be modulated by G proteins. We examined the physiological and molecular properties of this KIR conductance to define the nature of the underlying channel species. The macroscopic conductance revealed characteristics typical of classical K+ inward rectifiers of the IRK type. Channel gating was rapid, first order (tau approximately 1 ms at -100 mV) and steeply voltage dependent. Both activation potential and slope conductance were dependent on extracellular K+ concentration ([K+]o) and inward rectification persisted in the absence of internal Mg2+. The current was susceptible to a concentration- and voltage-dependent block by extracellular Na+, Cs+ and Ba2+. Initial IKIR whole-cell amplitudes as well as current rundown were dependent on the presence of 1 mM internal ATP. Perfusion of intracellular guanosine 5'-Q-(3-thiotriphosphate) (GTP[gamma S]) suppressed IKIR with an average half-time of decline of approximately 400 s. It was demonstrated that the dominant IRK-type 25 pS conductance channel was indeed suppressed by 100 microM preloaded GTP[gamma S]. Reverse transcriptase-polymerase chain reactions (RT-PCR) with RBL cell poly(A)+ RNA identified a full length K+ inward rectifier with 94% base pair homology to the recently cloned mouse IRK1 channel. It is concluded that RBL cells express a classical voltage-dependent IRK-type K+ inward rectifier RBL-IRK1 which is negatively controlled by G proteins.

High-risk long QT syndrome mutations in the Kv7.1 (KCNQ1) pore disrupt the molecular basis for rapid K(+) permeation.

PubMed

Burgess, Don E; Bartos, Daniel C; Reloj, Allison R; Campbell, Kenneth S; Johnson, Jonathan N; Tester, David J; Ackerman, Michael J; Fressart, Véronique; Denjoy, Isabelle; Guicheney, Pascale; Moss, Arthur J; Ohno, Seiko; Horie, Minoru; Delisle, Brian P

2012-11-13

Type 1 long QT syndrome (LQT1) is caused by loss-of-function mutations in the KCNQ1 gene, which encodes the K(+) channel (Kv7.1) that underlies the slowly activating delayed rectifier K(+) current in the heart. Intragenic risk stratification suggests LQT1 mutations that disrupt conserved amino acid residues in the pore are an independent risk factor for LQT1-related cardiac events. The purpose of this study is to determine possible molecular mechanisms that underlie the loss of function for these high-risk mutations. Extensive genotype-phenotype analyses of LQT1 patients showed that T322M-, T322A-, or G325R-Kv7.1 confers a high risk for LQT1-related cardiac events. Heterologous expression of these mutations with KCNE1 revealed they generated nonfunctional channels and caused dominant negative suppression of WT-Kv7.1 current. Molecular dynamics simulations of analogous mutations in KcsA (T85M-, T85A-, and G88R-KcsA) demonstrated that they disrupted the symmetrical distribution of the carbonyl oxygen atoms in the selectivity filter, which upset the balance between the strong attractive and K(+)-K(+) repulsive forces required for rapid K(+) permeation. We conclude high-risk LQT1 mutations in the pore likely disrupt the architectural and physical properties of the K(+) channel selectivity filter.

Internal combustion engine control for series hybrid electric vehicles by parallel and distributed genetic programming/multiobjective genetic algorithms

NASA Astrophysics Data System (ADS)

Gladwin, D.; Stewart, P.; Stewart, J.

2011-02-01

This article addresses the problem of maintaining a stable rectified DC output from the three-phase AC generator in a series-hybrid vehicle powertrain. The series-hybrid prime power source generally comprises an internal combustion (IC) engine driving a three-phase permanent magnet generator whose output is rectified to DC. A recent development has been to control the engine/generator combination by an electronically actuated throttle. This system can be represented as a nonlinear system with significant time delay. Previously, voltage control of the generator output has been achieved by model predictive methods such as the Smith Predictor. These methods rely on the incorporation of an accurate system model and time delay into the control algorithm, with a consequent increase in computational complexity in the real-time controller, and as a necessity relies to some extent on the accuracy of the models. Two complementary performance objectives exist for the control system. Firstly, to maintain the IC engine at its optimal operating point, and secondly, to supply a stable DC supply to the traction drive inverters. Achievement of these goals minimises the transient energy storage requirements at the DC link, with a consequent reduction in both weight and cost. These objectives imply constant velocity operation of the IC engine under external load disturbances and changes in both operating conditions and vehicle speed set-points. In order to achieve these objectives, and reduce the complexity of implementation, in this article a controller is designed by the use of Genetic Programming methods in the Simulink modelling environment, with the aim of obtaining a relatively simple controller for the time-delay system which does not rely on the implementation of real time system models or time delay approximations in the controller. A methodology is presented to utilise the miriad of existing control blocks in the Simulink libraries to automatically evolve optimal control structures.

Substance P provides neuroprotection in cerebellar granule cells through Akt and MAPK/Erk activation: evidence for the involvement of the delayed rectifier potassium current.

PubMed

Amadoro, G; Pieri, M; Ciotti, M T; Carunchio, I; Canu, N; Calissano, P; Zona, C; Severini, C

2007-05-01

In the current study, we have evaluated the ability of substance P (SP) and other neurokinin 1 receptor (NK1) agonists to protect, in a dose- and time-dependent manner, primary cultures of rat cerebellar granule cells (CGCs) from serum and potassium deprivation-induced cell death (S-K5). We also established the presence of SP high affinity NK1 transcripts and the NK1 protein localization in the membrane of a sub-population of CGCs. Moreover, SP significantly and dose-dependently reduced the Akt 1/2 and Erk1/2 dephosphorylation induced by S-K5 conditions, as demonstrated by Western blot analysis. Surprisingly, in SP-treated CGCs caspase-3 activity was not inhibited, while the calpain-1 activity was moderately reduced. Corroborating this result, SP blocked calpain-mediated cleavage of tau protein, as demonstrated by the reduced appearance of a diagnostic fragment of 17 kDa by Western blot analysis. In addition, SP induced a significant reduction of the delayed rectifier K+ currents (Ik) in about 42% of the patched neurons, when these were evoked with depolarizing potential steps. Taken together, the present results demonstrate that the activation of NK1 receptors expressed in CGCs promote the neuronal survival via pathways involving Akt and Erk activation and by inhibition of Ik which can contribute to the neuroprotective effect of the peptide.

Delayed Rapid Response Team Activation Is Associated With Increased Hospital Mortality, Morbidity, and Length of Stay in a Tertiary Care Institution.

PubMed

Barwise, Amelia; Thongprayoon, Charat; Gajic, Ognjen; Jensen, Jeffrey; Herasevich, Vitaly; Pickering, Brian W

2016-01-01

To identify whether delays in rapid response team activation contributed to worse patient outcomes (mortality and morbidity). Retrospective observational cohort study including all rapid response team activations in 2012. Tertiary academic medical center. All those 18 years old or older who had a rapid response team call activated. Vital sign data were abstracted from individual patient electronic medical records for the 24 hours before the rapid response team activation took place. Patients were considered to have a delayed rapid response team activation if more than 1 hour passed between the first appearance in the record of an abnormal vital sign meeting rapid response team criteria and the activation of an rapid response team. None. A total of 1,725 patients were included in the analysis. Data were compared between those who had a delayed rapid response team activation and those who did not. Fifty seven percent patients met the definition of delayed rapid response team activation. Patients in high-frequency physiologic monitored environments were more likely to experience delay than their floor counterparts. In the no-delay group, the most common reasons for rapid response team activation were tachycardia/bradycardia at 29% (217/748), respiratory distress/low SpO2 at 28% (213/748), and altered level of consciousness at 23% (170/748) compared with respiratory distress/low SpO2 at 43% (423/977), tachycardia/bradycardia at 33% (327/977), and hypotension at 27% (261/977) in the delayed group. The group with no delay had a higher proportion of rapid response team calls between 8:00 and 16:00, whereas those with delay had a higher proportion of calls between midnight and 08:00. The delayed group had higher hospital mortality (15% vs 8%; adjusted odds ratio, 1.6; p = 0.005); 30-day mortality (20% vs 13%; adjusted odds ratio, 1.4; p = 0.02); and hospital length of stay (7 vs 6 d; relative prolongation, 1.10; p = 0.02) compared with the no-delay group. Delays in rapid response team activation occur frequently and are independently associated with worse patient mortality and morbidity outcomes.

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

PubMed

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.

Inhibitory Effects of Honokiol on the Voltage-Gated Potassium Channels in Freshly Isolated Mouse Dorsal Root Ganglion Neurons.

PubMed

Sheng, Anqi; Zhang, Yan; Li, Guang; Zhang, Guangqin

2018-02-01

Voltage-gated potassium (K V ) currents, subdivided into rapidly inactivating A-type currents (I A ) and slowly inactivating delayed rectifier currents (I K ), play a fundamental role in modulating pain by controlling neuronal excitability. The effects of Honokiol (Hon), a natural biphenolic compound derived from Magnolia officinalis, on K V currents were investigated in freshly isolated mouse dorsal root ganglion neurons using the whole-cell patch clamp technique. Results showed that Hon inhibited I A and I K in concentration-dependent manner. The IC 50 values for block of I A and I K were 30.5 and 25.7 µM, respectively. Hon (30 µM) shifted the steady-state activation curves of I A and I K to positive potentials by 17.6 and 16.7 mV, whereas inactivation and recovery from the inactivated state of I A were unaffected. These results suggest that Hon preferentially interacts with the active states of the I A and I K channels, and has no effect on the resting state and inactivated state of the I A channel. Blockade on K + channels by Hon may contribute to its antinociceptive effect, especially anti-inflammatory pain.

The delayed rectifier, IKI, is the major conductance in type I vestibular hair cells across vestibular end organs

NASA Technical Reports Server (NTRS)

Ricci, A. J.; Rennie, K. J.; Correia, M. J.

1996-01-01

Hair cells were dissociated from the semicircular canal, utricle, lagena and saccule of white king pigeons. Type I hair cells were identified morphologically based on the ratios of neck width to cuticular plate width (NPR < 0.72) as well as neck width to cell body width (NBR < 0.64). The perforated patch variant of the whole-cell recording technique was used to measure electrical properties from type I hair cells. In voltage-clamp, the membrane properties of all identified type I cells were dominated by a predominantly outward potassium current, previously characterized in semicircular canal as IKI. Zero-current potential, activation, deactivation, slope conductance, pharmacologic and steady-state properties of the complex currents were not statistically different between type I hair cells of different vestibular end organs. The voltage dependence causes a significant proportion of this conductance to be active about the cell's zero-current potential. The first report of the whole-cell activation kinetics of the conductance is presented, showing a voltage dependence that could be best fit by an equation for a single exponential. Results presented here are the first data from pigeon dissociated type I hair cells from utricle, saccule and lagena suggesting that the basolateral conductances of a morphologically identified population of type I hair cells are conserved between functionally different vestibular end organs; the major conductance being a delayed rectifier characterized previously in semicircular canal hair cells as IKI.

Practical solution for control of the pre-analytical phase in decentralized clinical laboratories for meeting the requirements of the medical laboratory accreditation standard DIN EN ISO 15189.

PubMed

Vacata, Vladimir; Jahns-Streubel, Gerlinde; Baldus, Mirjana; Wood, William Graham

2007-01-01

This report was written in response to the article by Wood published recently in this journal. It describes a practical solution to the problems of controlling the pre-analytical phase in the clinical diagnostic laboratory. As an indicator of quality in the pre-analytical phase of sample processing, a target analyte was chosen which is sensitive to delay in centrifugation and/or analysis. The results of analyses of the samples sent by satellite medical practitioners were compared with those from an on-site hospital laboratory with a controllable optimized pre-analytical phase. The aim of the comparison was: (a) to identify those medical practices whose mean/median sample values significantly deviate from those of the control situation in the hospital laboratory due to the possible problems in the pre-analytical phase; (b) to aid these laboratories in the process of rectifying these problems. A Microsoft Excel-based Pre-Analytical Survey tool (PAS tool) has been developed which addresses the above mentioned problems. It has been tested on serum potassium which is known to be sensitive to delay and/or irregularities in sample treatment. The PAS tool has been shown to be one possibility for improving the quality of the analyses by identifying the sources of problems within the pre-analytical phase, thus allowing them to be rectified. Additionally, the PAS tool has an educational value and can also be adopted for use in other decentralized laboratories.

Synergistic Inhibition of Delayed Rectifier K+ and Voltage-Gated Na+ Currents by Artemisinin in Pituitary Tumor (GH3) Cells.

PubMed

So, Edmund Cheung; Wu, Sheng-Nan; Wu, Ping-Ching; Chen, Hui-Zhen; Yang, Chia-Jung

2017-01-01

Artemisinin (ART) is an anti-malarial agent reported to influence endocrine function. Effects of ART on ionic currents and action potentials (APs) in pituitary tumor (GH3) cells were evaluated by patch clamp techniques. ART inhibited the amplitude of delayed-rectifier K+ current (IK(DR)) in response to membrane depolarization and accelerated the process of current inactivation. It exerted an inhibitory effect on IK(DR) with an IC50 value of 11.2 µM and enhanced IK(DR) inactivation with a KD value of 14.7 µM. The steady-state inactivation curve of IK(DR) was shifted to hyperpolarization by 10 mV. Pretreatment of chlorotoxin (1 µM) or iloprost (100 nM) did not alter the magnitude of ART-induced inhibition of IK(DR) in GH3 cells. ART also decreased the peak amplitude of voltage-gated Na+ current (INa) with a concentration-dependent slowing in inactivation rate. Application of KMUP-1, an inhibitor of late INa, was effective at reversing ART-induced prolongation in inactivation time constant of INa. Under current-clamp recordings, ART alone reduced the amplitude of APs and prolonged the duration of APs. Under ART exposure, the inhibitory actions on both IK(DR) and INa could be a potential mechanisms through which this drug influences membrane excitability of endocrine or neuroendocrine cells appearing in vivo. © 2017 The Author(s). Published by S. Karger AG, Basel.

Forskolin suppresses delayed-rectifier K+ currents and enhances spike frequency-dependent adaptation of sympathetic neurons.

PubMed

Angel-Chavez, Luis I; Acosta-Gómez, Eduardo I; Morales-Avalos, Mario; Castro, Elena; Cruzblanca, Humberto

2015-01-01

In signal transduction research natural or synthetic molecules are commonly used to target a great variety of signaling proteins. For instance, forskolin, a diterpene activator of adenylate cyclase, has been widely used in cellular preparations to increase the intracellular cAMP level. However, it has been shown that forskolin directly inhibits some cloned K+ channels, which in excitable cells set up the resting membrane potential, the shape of action potential and regulate repetitive firing. Despite the growing evidence indicating that K+ channels are blocked by forskolin, there are no studies yet assessing the impact of this mechanism of action on neuron excitability and firing patterns. In sympathetic neurons, we find that forskolin and its derivative 1,9-Dideoxyforskolin, reversibly suppress the delayed rectifier K+ current (IKV). Besides, forskolin reduced the spike afterhyperpolarization and enhanced the spike frequency-dependent adaptation. Given that IKV is mostly generated by Kv2.1 channels, HEK-293 cells were transfected with cDNA encoding for the Kv2.1 α subunit, to characterize the mechanism of forskolin action. Both drugs reversible suppressed the Kv2.1-mediated K+ currents. Forskolin inhibited Kv2.1 currents and IKV with an IC50 of ~32 μM and ~24 µM, respectively. Besides, the drug induced an apparent current inactivation and slowed-down current deactivation. We suggest that forskolin reduces the excitability of sympathetic neurons by enhancing the spike frequency-dependent adaptation, partially through a direct block of their native Kv2.1 channels.

Aldosterone downregulates delayed rectifier potassium currents through an angiotensin type 1 receptor-dependent mechanism.

PubMed

Lv, Yankun; Wang, Yanjun; Zhu, Xiaoran; Zhang, Hua

2018-01-01

We have previously shown that aldosterone downregulates delayed rectifier potassium currents (I Ks ) via activation of the mineralocorticoid receptor (MR) in adult guinea pig cardiomyocytes. Here, we investigate whether angiotensin II/angiotensin type 1 receptor (AngII/AT1R) and intracellular calcium also play a role in these effects. Ventricular cardiomyocytes were isolated from adult guinea pigs and incubated with aldosterone (1 μmol·L -1 ) either alone or in combination with enalapril (1 μmol·L -1 ), losartan (1 μmol·L -1 ), nimodipine (1 μmol·L -1 ), or BAPTA-AM (2.5 μmol·L -1 ) for 24 h. We used the conventional whole cell patch-clamp technique to record the I Ks component. In addition, we evaluated expression of the I Ks subunits KCNQ1 and KCNE1 using Western blotting. Our results showed that both enalapril and losartan, but not nimodipine or BAPTA-AM, completely reversed the aldosterone-induced inhibition of I Ks and its effects on KCNQ1/KCNE1 protein levels. Furthermore, we found that AngII/AT1R mediates the inhibitory effects of aldosterone on I Ks . Finally, the downregulation of I Ks induced by aldosterone did not occur secondarily to a change in intracellular calcium concentrations. Taken together, our findings demonstrate that crosstalk between MR and AT1R underlies the effects of aldosterone, and provide new insights into the mechanism underlying potassium channels.

Docetaxel modulates the delayed rectifier potassium current (IK) and ATP-sensitive potassium current (IKATP) in human breast cancer cells.

PubMed

Sun, Tao; Song, Zhi-Guo; Jiang, Da-Qing; Nie, Hong-Guang; Han, Dong-Yun

2015-04-01

Ion channel expression and activity may be affected during tumor development and cancer growth. Activation of potassium (K(+)) channels in human breast cancer cells is reported to be involved in cell cycle progression. In this study, we investigated the effects of docetaxel on the delayed rectifier potassium current (I K) and the ATP-sensitive potassium current (I KATP) in two human breast cancer cell lines, MCF-7 and MDA-MB-435S, using the whole-cell patch-clamp technique. Our results show that docetaxel inhibited the I K and I KATP in both cell lines in a dose-dependent manner. Compared with the control at a potential of +60 mV, treatment with docetaxel at doses of 0.1, 1, 5, and 10 µM significantly decreased the I K in MCF-7 cells by 16.1 ± 3.5, 30.2 ± 5.2, 42.5 ± 4.3, and 46.4 ± 9% (n = 5, P < 0.05), respectively and also decreased the I KATP at +50 mV. Similar results were observed in MDA-MB-435S cells. The G-V curves showed no significant changes after treatment of either MCF-7 or MDA-MB-435S cells with 10 μM docetaxel. The datas indicate that the possible mechanisms of I K and I KATP inhibition by docetaxel may be responsible for its effect on the proliferation of human breast cancer cells.

Getting to the heart of hERG K(+) channel gating.

PubMed

Perry, Matthew D; Ng, Chai-Ann; Mann, Stefan A; Sadrieh, Arash; Imtiaz, Mohammad; Hill, Adam P; Vandenberg, Jamie I

2015-06-15

Potassium ion channels encoded by the human ether-a-go-go related gene (hERG) form the ion-conducting subunit of the rapid delayed rectifier potassium current (IKr ). Although hERG channels exhibit a widespread tissue distribution they play a particularly important role in the heart. There has been considerable interest in hERG K(+) channels for three main reasons. First, they have very unusual gating kinetics, most notably rapid and voltage-dependent inactivation coupled to slow deactivation, which has led to the suggestion that they may play a specific role in the suppression of arrhythmias. Second, mutations in hERG are the cause of 30-40% of cases of congenital long QT syndrome (LQTS), the commonest inherited primary arrhythmia syndrome. Third, hERG is the molecular target for the vast majority of drugs that cause drug-induced LQTS, the commonest cause of drug-induced arrhythmias and cardiac death. Drug-induced LQTS has now been reported for a large range of both cardiac and non-cardiac drugs, in which this side effect is entirely undesired. In recent years there have been comprehensive reviews published on hERG K(+) channels (Vandenberg et al. 2012) and we will not re-cover this ground. Rather, we focus on more recent work on the structural basis and dynamics of hERG gating with an emphasis on how the latest developments may facilitate translational research in the area of stratifying risk of arrhythmias. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Getting to the heart of hERG K+ channel gating

PubMed Central

Perry, Matthew D; Ng, Chai-Ann; Mann, Stefan A; Sadrieh, Arash; Imtiaz, Mohammad; Hill, Adam P; Vandenberg, Jamie I

2015-01-01

Potassium ion channels encoded by the human ether-a-go-go related gene (hERG) form the ion-conducting subunit of the rapid delayed rectifier potassium current (IKr). Although hERG channels exhibit a widespread tissue distribution they play a particularly important role in the heart. There has been considerable interest in hERG K+ channels for three main reasons. First, they have very unusual gating kinetics, most notably rapid and voltage-dependent inactivation coupled to slow deactivation, which has led to the suggestion that they may play a specific role in the suppression of arrhythmias. Second, mutations in hERG are the cause of 30–40% of cases of congenital long QT syndrome (LQTS), the commonest inherited primary arrhythmia syndrome. Third, hERG is the molecular target for the vast majority of drugs that cause drug-induced LQTS, the commonest cause of drug-induced arrhythmias and cardiac death. Drug-induced LQTS has now been reported for a large range of both cardiac and non-cardiac drugs, in which this side effect is entirely undesired. In recent years there have been comprehensive reviews published on hERG K+ channels (Vandenberg et al. 2012) and we will not re-cover this ground. Rather, we focus on more recent work on the structural basis and dynamics of hERG gating with an emphasis on how the latest developments may facilitate translational research in the area of stratifying risk of arrhythmias. PMID:25820318

High-risk Long QT Syndrome Mutations in the Kv7.1 (KCNQ1) Pore Disrupt the Molecular Basis for Rapid K+ Permeation

PubMed Central

Burgess, Don E.; Bartos, Daniel C.; Reloj, Allison R.; Campbell, Kenneth S.; Johnson, Jonathan N.; Tester, David J.; Ackerman, Michael J.; Fressart, Véronique; Denjoy, Isabelle; Guicheney, Pascale; Moss, Arthur J.; Ohno, Seiko; Horie, Minoru; Delisle, Brian P.

2012-01-01

Type 1 long QT syndrome (LQT1) syndrome is caused by loss-of-function mutations in the KCNQ1, which encodes the K+ channel (Kv7.1) that underlies the slowly activating delayed rectifier K+ current in the heart. Intragenic risk stratification suggests LQT1 mutations that disrupt conserved amino acid residues in the pore are an independent risk factor for LQT1-related cardiac events. The purpose of this study is to determine possible molecular mechanisms that underlie the loss-of-function for these high-risk mutations. Extensive genotype-phenotype analyses of LQT1 patients showed that T322M-, T322A-, or G325R-Kv7.1 confer a high risk for LQT1-related cardiac events. Heterologous expression of these mutations with KCNE1 revealed they generated non-functional channels and caused dominant negative suppression of WT-Kv7.1 current. Molecular dynamic simulations (MDS) of analogous mutations in KcsA (T85M-, T85A-, and G88R-KcsA) demonstrated that they disrupted the symmetrical distribution of the carbonyl oxygen atoms in the selectivity filter, which upset the balance between the strong attractive and K+-K+ repulsive forces required for rapid K+ permeation. We conclude high-risk LQT1 mutations in the pore likely disrupt the architectural and physical properties of the K+ channel selectivity filter. PMID:23092362

BK potassium channels facilitate high-frequency firing and cause early spike frequency adaptation in rat CA1 hippocampal pyramidal cells

PubMed Central

Gu, Ning; Vervaeke, Koen; Storm, Johan F

2007-01-01

Neuronal potassium (K+) channels are usually regarded as largely inhibitory, i.e. reducing excitability. Here we show that BK-type calcium-activated K+ channels enhance high-frequency firing and cause early spike frequency adaptation in neurons. By combining slice electrophysiology and computational modelling, we investigated functions of BK channels in regulation of high-frequency firing in rat CA1 pyramidal cells. Blockade of BK channels by iberiotoxin (IbTX) selectively reduced the initial discharge frequency in response to strong depolarizing current injections, thus reducing the early spike frequency adaptation. IbTX also blocked the fast afterhyperpolarization (fAHP), slowed spike rise and decay, and elevated the spike threshold. Simulations with a computational model of a CA1 pyramidal cell confirmed that the BK channel-mediated rapid spike repolarization and fAHP limits activation of slower K+ channels (in particular the delayed rectifier potassium current (IDR)) and Na+ channel inactivation, whereas M-, sAHP- or SK-channels seem not to be important for the early facilitating effect. Since the BK current rapidly inactivates, its facilitating effect diminishes during the initial discharge, thus producing early spike frequency adaptation by an unconventional mechanism. This mechanism is highly frequency dependent. Thus, IbTX had virtually no effect at spike frequencies < 40 Hz. Furthermore, extracellular field recordings demonstrated (and model simulations supported) that BK channels contribute importantly to high-frequency burst firing in response to excitatory synaptic input to distal dendrites. These results strongly support the idea that BK channels play an important role for early high-frequency, rapidly adapting firing in hippocampal pyramidal neurons, thus promoting the type of bursting that is characteristic of these cells in vivo, during behaviour. PMID:17303637

Rab11-dependent Recycling of the Human Ether-a-go-go-related Gene (hERG) Channel*

PubMed Central

Chen, Jeffery; Guo, Jun; Yang, Tonghua; Li, Wentao; Lamothe, Shawn M.; Kang, Yudi; Szendrey, John A.; Zhang, Shetuan

2015-01-01

The human ether-a-go-go-related gene (hERG) encodes the pore-forming subunit of the rapidly activating delayed rectifier potassium channel (IKr). A reduction in the hERG current causes long QT syndrome, which predisposes affected individuals to ventricular arrhythmias and sudden death. We reported previously that hERG channels in the plasma membrane undergo vigorous internalization under low K+ conditions. In the present study, we addressed whether hERG internalization occurs under normal K+ conditions and whether/how internalized channels are recycled back to the plasma membrane. Using patch clamp, Western blot, and confocal imaging analyses, we demonstrated that internalized hERG channels can effectively recycle back to the plasma membrane. Low K+-enhanced hERG internalization is accompanied by an increased rate of hERG recovery in the plasma membrane upon reculture following proteinase K-mediated clearance of cell-surface proteins. The increased recovery rate is not due to enhanced protein synthesis, as hERG mRNA expression was not altered by low K+ exposure, and the increased recovery was observed in the presence of the protein biosynthesis inhibitor cycloheximide. GTPase Rab11, but not Rab4, is involved in the recycling of hERG channels. Interfering with Rab11 function not only delayed hERG recovery in cells after exposure to low K+ medium but also decreased hERG expression and function in cells under normal culture conditions. We concluded that the recycling pathway plays an important role in the homeostasis of plasma membrane-bound hERG channels. PMID:26152716

The delayed rectifier potassium conductance in the sarcolemma and the transverse tubular system membranes of mammalian skeletal muscle fibers

PubMed Central

DiFranco, Marino; Quinonez, Marbella

2012-01-01

A two-microelectrode voltage clamp and optical measurements of membrane potential changes at the transverse tubular system (TTS) were used to characterize delayed rectifier K currents (IKV) in murine muscle fibers stained with the potentiometric dye di-8-ANEPPS. In intact fibers, IKV displays the canonical hallmarks of KV channels: voltage-dependent delayed activation and decay in time. The voltage dependence of the peak conductance (gKV) was only accounted for by double Boltzmann fits, suggesting at least two channel contributions to IKV. Osmotically treated fibers showed significant disconnection of the TTS and displayed smaller IKV, but with similar voltage dependence and time decays to intact fibers. This suggests that inactivation may be responsible for most of the decay in IKV records. A two-channel model that faithfully simulates IKV records in osmotically treated fibers comprises a low threshold and steeply voltage-dependent channel (channel A), which contributes ∼31% of gKV, and a more abundant high threshold channel (channel B), with shallower voltage dependence. Significant expression of the IKV1.4 and IKV3.4 channels was demonstrated by immunoblotting. Rectangular depolarizing pulses elicited step-like di-8-ANEPPS transients in intact fibers rendered electrically passive. In contrast, activation of IKV resulted in time- and voltage-dependent attenuations in optical transients that coincided in time with the peaks of IKV records. Normalized peak attenuations showed the same voltage dependence as peak IKV plots. A radial cable model including channels A and B and K diffusion in the TTS was used to simulate IKV and average TTS voltage changes. Model predictions and experimental data were compared to determine what fraction of gKV in the TTS accounted simultaneously for the electrical and optical data. Best predictions suggest that KV channels are approximately equally distributed in the sarcolemma and TTS membranes; under these conditions, >70% of IKV arises from the TTS. PMID:22851675

Junction barrier Schottky rectifier with an improved P-well region

NASA Astrophysics Data System (ADS)

Wang, Ying; Li, Ting; Cao, Fei; Shao, Lei; Chen, Yu-Xian

2012-12-01

A junction barrier Schottky (JBS) rectifier with an improved P-well on 4H—SiC is proposed to improve the VF—IR trade-off and the breakdown voltage. The reverse current density of the proposed JBS rectifier at 300 K and 800 V is about 3.3×10-8 times that of the common JBS rectifier at no expense of the forward voltage drop. This is because the depletion layer thickness in the P-well region at the same reverse voltage is larger than in the P+ grid, resulting in a lower spreading current and tunneling current. As a result, the breakdown voltage of the proposed JBS rectifier is over 1.6 kV, that is about 0.8 times more than that of the common JBS rectifier due to the uniform electric field. Although the series resistance of the proposed JBS rectifier is a little larger than that of the common JBS rectifier, the figure of merit (FOM) of the proposed JBS rectifier is about 2.9 times that of the common JBS rectifier. Based on simulating the values of susceptibility of the two JBS rectifiers to electrostatic discharge (ESD) in the human body model (HBM) circuits, the failure energy of the proposed JBS rectifier increases 17% compared with that of the common JBS rectifier.

Inactivation and pharmacological properties of sqKv1A homotetramers in Xenopus oocytes cannot account for behavior of the squid "delayed rectifier" K(+) conductance.

PubMed Central

Jerng, Henry H; Gilly, William F

2002-01-01

Considerable published evidence suggests that alpha-subunits of the cloned channel sqKv1A compose the "delayed rectifier" in the squid giant axon system, but discrepancies regarding inactivation properties of cloned versus native channels exist. In this paper we define the mechanism of inactivation for sqKv1A channels in Xenopus oocytes to investigate these and other discrepancies. Inactivation of sqKv1A in Xenopus oocytes was found to be unaffected by genetic truncation of the N-terminus, but highly sensitive to certain amino acid substitutions around the external mouth of the pore. External TEA and K(+) ions slowed inactivation of sqKv1A channels in oocytes, and chloramine T (Chl-T) accelerated inactivation. These features are all consistent with a C-type inactivation mechanism as defined for Shaker B channels. Treatment of native channels in giant fiber lobe neurons with TEA or high K(+) does not slow inactivation, nor does Chl-T accelerate it. Pharmacological differences between the two channel types were also found for 4-aminopyridine (4AP). SqKv1A's affinity for 4AP was poor at rest and increased after activation, whereas 4AP block occurred much more readily at rest with native channels than when they were activated. These results suggest that important structural differences between sqKv1A homotetramers and native squid channels are likely to exist around the external and internal mouths of the pore. PMID:12023225

Rate dependency of delayed rectifier currents during the guinea-pig ventricular action potential

PubMed Central

Rocchetti, Marcella; Besana, Alessandra; Gurrola, Georgina B; Possani, Lourival D; Zaza, Antonio

2001-01-01

The action potential clamp technique was exploited to evaluate the rate dependency of delayed rectifier currents (IKr and IKs) during physiological electrical activity. IKr and IKs were measured in guinea-pig ventricular myocytes at pacing cycle lengths (CL) of 1000 and 250 ms.A shorter CL, with the attendant changes in action potential shape, was associated with earlier activation and increased magnitude of both IKr and IKs. Nonetheless, the relative contributions of IKr and IKs to total transmembrane current were independent of CL.Shortening of diastolic interval only (constant action potential shape) enhanced IKs, but not IKr.IKr was increased by a change in the action potential shape only (constant diastolic interval).In ramp clamp experiments, IKr amplitude was directly proportional to repolarization rate at values within the low physiological range (< 1.0 V s−1); at higher repolarization rates proportionality became shallower and finally reversed.When action potential duration (APD) was modulated by constant current injection (I-clamp), repolarization rates > 1.0 V s−1 were associated with a reduced effect of IKr block on APD. The effect of changes in repolarization rate was independent of CL and occurred in the presence of IKs blockade.In spite of its complexity, the behaviour of IKr was accurately predicted by a numerical model based entirely on known kinetic properties of the current.Both IKr and IKs may be increased at fast heart rates, but this may occur through completely different mechanisms. The mechanisms identified are such as to contribute to abnormal rate dependency of repolarization in prolonged repolarization syndromes. PMID:11483703

Forskolin Suppresses Delayed-Rectifier K+ Currents and Enhances Spike Frequency-Dependent Adaptation of Sympathetic Neurons

PubMed Central

Castro, Elena; Cruzblanca, Humberto

2015-01-01

In signal transduction research natural or synthetic molecules are commonly used to target a great variety of signaling proteins. For instance, forskolin, a diterpene activator of adenylate cyclase, has been widely used in cellular preparations to increase the intracellular cAMP level. However, it has been shown that forskolin directly inhibits some cloned K+ channels, which in excitable cells set up the resting membrane potential, the shape of action potential and regulate repetitive firing. Despite the growing evidence indicating that K+ channels are blocked by forskolin, there are no studies yet assessing the impact of this mechanism of action on neuron excitability and firing patterns. In sympathetic neurons, we find that forskolin and its derivative 1,9-Dideoxyforskolin, reversibly suppress the delayed rectifier K+ current (IKV). Besides, forskolin reduced the spike afterhyperpolarization and enhanced the spike frequency-dependent adaptation. Given that IKV is mostly generated by Kv2.1 channels, HEK-293 cells were transfected with cDNA encoding for the Kv2.1 α subunit, to characterize the mechanism of forskolin action. Both drugs reversible suppressed the Kv2.1-mediated K+ currents. Forskolin inhibited Kv2.1 currents and IKV with an IC50 of ~32 μM and ~24 µM, respectively. Besides, the drug induced an apparent current inactivation and slowed-down current deactivation. We suggest that forskolin reduces the excitability of sympathetic neurons by enhancing the spike frequency-dependent adaptation, partially through a direct block of their native Kv2.1 channels. PMID:25962132

Changes in the mRNA levels of delayed rectifier potassium channels in human atrial fibrillation.

PubMed

Lai, L P; Su, M J; Lin, J L; Lin, F Y; Tsai, C H; Chen, Y S; Tseng, Y Z; Lien, W P; Huang, S K

1999-01-01

We measured mRNA levels of delayed rectifier potassium channels in human atrial tissue to investigate the mechanism of the shortening of the atrial effective refractory period and the loss of rate-adaptive shortening of the atrial effective refractory period in human atrial fibrillation. A total of 34 patients undergoing open heart surgery were included. Atrial tissue was obtained from the right atrial free wall, right atrial appendage, left atrial free wall and left atrial appendage, respectively. The mRNA amounts of KVLQT1 (IKs), minK (beta-subunit of IKs), HERG (IKr), and KV1.5 (IKur) were measured by reverse transcription-polymerase chain reaction and normalized to the mRNA amount of GAPDH. We found that the mRNA levels of KV1.5, HERG and KVLQT1 were all significantly decreased in patients with persistent atrial fibrillation for more than 3 months. In contrast, the mRNA level of minK was significantly increased in patients with persistent atrial fibrillation for more than 3 months. We further showed that these changes were independent of the underlying cardiac disease, atrial filling pressure, gender and age. We also found that there was no spatial dispersion of mRNA levels among the four atrial sampling sites. Because the decrease in potassium currents results in a prolonged action potential, the shortening of the atrial effective refractory period in atrial fibrillation should be attributed to other factors. However, the decrease in IKs might contribute, at least in part, to the loss of rate-adaptive shortening of the atrial refractory period.

Effects of allocryptopine on outward potassium current and slow delayed rectifier potassium current in rabbit myocardium.

PubMed

Fu, Yi-Cheng; Zhang, Yu; Tian, Liu-Yang; Li, Nan; Chen, Xi; Cai, Zhong-Qi; Zhu, Chao; Li, Yang

2016-05-01

Allocryptopine (ALL) is an effective alkaloid of Corydalis decumbens (Thunb.) Pers. Papaveraceae and has proved to be anti-arrhythmic. The purpose of our study is to investigate the effects of ALL on transmural repolarizing ionic ingredients of outward potassium current (I to) and slow delayed rectifier potassium current (I Ks). The monophasic action potential (MAP) technique was used to record the MAP duration of the epicardium (Epi), myocardium (M) and endocardium (Endo) of the rabbit heart and the whole cell patch clamp was used to record I to and I Ks in cardiomyocytes of Epi, M and Endo layers that were isolated from rabbit ventricles. The effects of ALL on MAP of Epi, M and Endo layers were disequilibrium. ALL could effectively reduce the transmural dispersion of repolarization (TDR) in rabbit transmural ventricular wall. ALL decreased the current densities of I to and I Ks in a voltage and concentration dependent way and narrowed the repolarizing differences among three layers. The analysis of gating kinetics showed ALL accelerated the channel activation of I to in M layers and partly inhibit the channel openings of I to in Epi, M and Endo cells. On the other hand, ALL mainly slowed channel deactivation of I Ks channel in Epi and Endo layers without affecting its activation. Our study gives partially explanation about the mechanisms of transmural inhibition of I to and I Ks channels by ALL in rabbit myocardium. These findings provide novel perspective regarding the anti-arrhythmogenesis application of ALL in clinical settings.

Wireless power transmission for biomedical implants: The role of near-zero threshold CMOS rectifiers.

PubMed

Mohammadi, Ali; Redoute, Jean-Michel; Yuce, Mehmet R

2015-01-01

Biomedical implants require an electronic power conditioning circuitry to provide a stable electrical power supply. The efficiency of wireless power transmission is strongly dependent on the power conditioning circuitry specifically the rectifier. A cross-connected CMOS bridge rectifier is implemented to demonstrate the impact of thresholds of rectifiers on wireless power transfer. The performance of the proposed rectifier is experimentally compared with a conventional Schottky diode full wave rectifier over 9 cm distance of air and tissue medium between the transmitter and receiver. The output voltage generated by the CMOS rectifier across a 1 KΩ resistive load is around twice as much as the Schottky rectifier.

Development of a hardware-based AC microgrid for AC stability assessment

NASA Astrophysics Data System (ADS)

Swanson, Robert R.

As more power electronic-based devices enable the development of high-bandwidth AC microgrids, the topic of microgrid power distribution stability has become of increased interest. Recently, researchers have proposed a relatively straightforward method to assess the stability of AC systems based upon the time-constants of sources, the net bus capacitance, and the rate limits of sources. In this research, a focus has been to develop a hardware test system to evaluate AC system stability. As a first step, a time domain model of a two converter microgrid was established in which a three phase inverter acts as a power source and an active rectifier serves as an adjustable constant power AC load. The constant power load can be utilized to create rapid power flow transients to the generating system. As a second step, the inverter and active rectifier were designed using a Smart Power Module IGBT for switching and an embedded microcontroller as a processor for algorithm implementation. The inverter and active rectifier were designed to operate simultaneously using a synchronization signal to ensure each respective local controller operates in a common reference frame. Finally, the physical system was created and initial testing performed to validate the hardware functionality as a variable amplitude and variable frequency AC system.

The Role of Potassium Channels in Arabidopsis thaliana Long Distance Electrical Signalling: AKT2 Modulates Tissue Excitability While GORK Shapes Action Potentials.

PubMed

Cuin, Tracey Ann; Dreyer, Ingo; Michard, Erwan

2018-03-21

Fast responses to an external threat depend on the rapid transmission of signals through a plant. Action potentials (APs) are proposed as such signals. Plant APs share similarities with their animal counterparts; they are proposed to depend on the activity of voltage-gated ion channels. Nonetheless, despite their demonstrated role in (a)biotic stress responses, the identities of the associated voltage-gated channels and transporters remain undefined in higher plants. By demonstrating the role of two potassium-selective channels in Arabidopsis thaliana in AP generation and shaping, we show that the plant AP does depend on similar Kv -like transport systems to those of the animal signal. We demonstrate that the outward-rectifying potassium-selective channel GORK limits the AP amplitude and duration, while the weakly-rectifying channel AKT2 affects membrane excitability. By computational modelling of plant APs, we reveal that the GORK activity not only determines the length of an AP but also the steepness of its rise and the maximal amplitude. Thus, outward-rectifying potassium channels contribute to both the repolarisation phase and the initial depolarisation phase of the signal. Additionally, from modelling considerations we provide indications that plant APs might be accompanied by potassium waves, which prime the excitability of the green cable.

Characterization of ionic currents of cells of the subfornical organ that project to the supraoptic nuclei

NASA Technical Reports Server (NTRS)

Johnson, R. F.; Beltz, T. G.; Jurzak, M.; Wachtel, R. E.; Johnson, A. K.

1999-01-01

The subfornical organ (SFO) is a forebrain structure that converts peripheral blood-borne signals reflecting the hydrational state of the body to neural signals and then through efferent fibers conveys this information to several central nervous system structures. One of the forebrain areas receiving input from the SFO is the supraoptic nucleus (SON), a source of vasopressin synthesis and control of release from the posterior pituitary. Little is known of the transduction and transmission processes by which this conversion of systemic information to brain input occurs. As a step in elucidating these mechanisms, the present study characterized the ionic currents of dissociated cells of the SFO that were identified as neurons that send efferents to the SON. A retrograde tracer was injected into the SON area in eleven-day-old rats. After three days for retrograde transport of the label, the SFOs of these animals were dissociated and plated for tissue culture. The retrograde tracer was used to identify the soma of SFO cells projecting to the SON so that voltage-dependent ionic currents using whole-cell voltage clamp methods could be studied. The three types of currents in labeled SFO neurons were characterized as a 1) rapid, transient inward current that can be blocked by tetrodotoxin (TTX) characteristic of a sodium current; 2) slow-onset sustained outward current that can be blocked by tetraethylammonium (TEA) characteristic of a delayed rectifier potassium current; and 3) remaining outward current that has a rapid-onset and transient characteristic of a potassium A-type current. Copyright 1999 Elsevier Science B.V.

Rotor termination is critically dependent on kinetic properties of I kur inhibitors in an in silico model of chronic atrial fibrillation.

PubMed

Scholz, Eberhard P; Carrillo-Bustamante, Paola; Fischer, Fathima; Wilhelms, Mathias; Zitron, Edgar; Dössel, Olaf; Katus, Hugo A; Seemann, Gunnar

2013-01-01

Inhibition of the atrial ultra-rapid delayed rectifier potassium current (I Kur) represents a promising therapeutic strategy in the therapy of atrial fibrillation. However, experimental and clinical data on the antiarrhythmic efficacy remain controversial. We tested the hypothesis that antiarrhythmic effects of I Kur inhibitors are dependent on kinetic properties of channel blockade. A mathematical description of I Kur blockade was introduced into Courtemanche-Ramirez-Nattel models of normal and remodeled atrial electrophysiology. Effects of five model compounds with different kinetic properties were analyzed. Although a reduction of dominant frequencies could be observed in two dimensional tissue simulations for all compounds, a reduction of spiral wave activity could be only be detected in two cases. We found that an increase of the percent area of refractory tissue due to a prolongation of the wavelength seems to be particularly important. By automatic tracking of spiral tip movement we find that increased refractoriness resulted in rotor extinction caused by an increased spiral-tip meandering. We show that antiarrhythmic effects of I Kur inhibitors are dependent on kinetic properties of blockade. We find that an increase of the percent area of refractory tissue is the underlying mechanism for an increased spiral-tip meandering, resulting in the extinction of re-entrant circuits.

Rotor Termination Is Critically Dependent on Kinetic Properties of I Kur Inhibitors in an In Silico Model of Chronic Atrial Fibrillation

PubMed Central

Scholz, Eberhard P.; Carrillo-Bustamante, Paola; Fischer, Fathima; Wilhelms, Mathias; Zitron, Edgar; Dössel, Olaf; Katus, Hugo A.; Seemann, Gunnar

2013-01-01

Inhibition of the atrial ultra-rapid delayed rectifier potassium current (I Kur) represents a promising therapeutic strategy in the therapy of atrial fibrillation. However, experimental and clinical data on the antiarrhythmic efficacy remain controversial. We tested the hypothesis that antiarrhythmic effects of I Kur inhibitors are dependent on kinetic properties of channel blockade. A mathematical description of I Kur blockade was introduced into Courtemanche-Ramirez-Nattel models of normal and remodeled atrial electrophysiology. Effects of five model compounds with different kinetic properties were analyzed. Although a reduction of dominant frequencies could be observed in two dimensional tissue simulations for all compounds, a reduction of spiral wave activity could be only be detected in two cases. We found that an increase of the percent area of refractory tissue due to a prolongation of the wavelength seems to be particularly important. By automatic tracking of spiral tip movement we find that increased refractoriness resulted in rotor extinction caused by an increased spiral-tip meandering. We show that antiarrhythmic effects of I Kur inhibitors are dependent on kinetic properties of blockade. We find that an increase of the percent area of refractory tissue is the underlying mechanism for an increased spiral-tip meandering, resulting in the extinction of re-entrant circuits. PMID:24376659

Flecainide-induced proarrhythmia is attributed to abnormal changes in repolarization and refractoriness in perfused guinea-pig heart.

PubMed

Osadchii, Oleg E

2012-11-01

Flecainide is nonselective Na(+) channel blocker which may also inhibit I(Kr), the rapid component of the delayed rectifier. This study was designed to explore if proarrhythmic responses to flecainide noted in cardiac patients may be partly attributed to abnormal changes in repolarization and refractoriness. Monophasic action potential duration (APD) and effective refractory periods (ERP) were assessed at distinct epicardial and endocardial sites along with volume-conducted ECG recordings in isolated perfused guinea-pig heart preparations. Flecainide was found to prolong ventricular repolarization, with effect being greater at the left ventricular compared with the right ventricular epicardium. This change translated to reversal of the normal right ventricular-to-left ventricular transepicardial APD difference determined before drug infusion. An inverse correlation between local epicardial APD and corresponding activation time values seen at baseline was eliminated in flecainide-treated hearts, indicating the activation-to-repolarization uncoupling. Over transmural plane, flecainide produced a greater ERP lengthening at endocardium than epicardium, thus markedly increasing ERP dispersion across ventricular wall. Spontaneous short-lasting episodes of monomorphic ventricular tachycardia were observed in 45% of heart preparations upon flecainide infusion. In conclusion, in nonischemic guinea-pig heart, flecainide-induced proarrhythmia may be partly attributed to abnormal spatial gradients in repolarization and refractoriness and impaired transepicardial activation-to-repolarization coupling.

RF rectifiers for EM power harvesting in a Deep Brain Stimulating device.

PubMed

Hosain, Md Kamal; Kouzani, Abbas Z; Tye, Susannah; Kaynak, Akif; Berk, Michael

2015-03-01

A passive deep brain stimulation (DBS) device can be equipped with a rectenna, consisting of an antenna and a rectifier, to harvest energy from electromagnetic fields for its operation. This paper presents optimization of radio frequency rectifier circuits for wireless energy harvesting in a passive head-mountable DBS device. The aim is to achieve a compact size, high conversion efficiency, and high output voltage rectifier. Four different rectifiers based on the Delon doubler, Greinacher voltage tripler, Delon voltage quadrupler, and 2-stage charge pumped architectures are designed, simulated, fabricated, and evaluated. The design and simulation are conducted using Agilent Genesys at operating frequency of 915 MHz. A dielectric substrate of FR-4 with thickness of 1.6 mm, and surface mount devices (SMD) components are used to fabricate the designed rectifiers. The performance of the fabricated rectifiers is evaluated using a 915 MHz radio frequency (RF) energy source. The maximum measured conversion efficiency of the Delon doubler, Greinacher tripler, Delon quadrupler, and 2-stage charge pumped rectifiers are 78, 75, 73, and 76 % at -5 dBm input power and for load resistances of 5-15 kΩ. The conversion efficiency of the rectifiers decreases significantly with the increase in the input power level. The Delon doubler rectifier provides the highest efficiency at both -5 and 5 dBm input power levels, whereas the Delon quadrupler rectifier gives the lowest efficiency for the same inputs. By considering both efficiency and DC output voltage, the charge pump rectifier outperforms the other three rectifiers. Accordingly, the optimised 2-stage charge pumped rectifier is used together with an antenna to harvest energy in our DBS device.

Activity of Palythoa caribaeorum Venom on Voltage-Gated Ion Channels in Mammalian Superior Cervical Ganglion Neurons.

PubMed

Lazcano-Pérez, Fernando; Castro, Héctor; Arenas, Isabel; García, David E; González-Muñoz, Ricardo; Arreguín-Espinosa, Roberto

2016-05-05

The Zoanthids are an order of cnidarians whose venoms and toxins have been poorly studied. Palythoa caribaeorum is a zoanthid commonly found around the Mexican coastline. In this study, we tested the activity of P. caribaeorum venom on voltage-gated sodium channel (NaV1.7), voltage-gated calcium channel (CaV2.2), the A-type transient outward (IA) and delayed rectifier (IDR) currents of KV channels of the superior cervical ganglion (SCG) neurons of the rat. These results showed that the venom reversibly delays the inactivation process of voltage-gated sodium channels and inhibits voltage-gated calcium and potassium channels in this mammalian model. The compounds responsible for these effects seem to be low molecular weight peptides. Together, these results provide evidence for the potential use of zoanthids as a novel source of cnidarian toxins active on voltage-gated ion channels.

Activity of Palythoa caribaeorum Venom on Voltage-Gated Ion Channels in Mammalian Superior Cervical Ganglion Neurons

PubMed Central

Lazcano-Pérez, Fernando; Castro, Héctor; Arenas, Isabel; García, David E.; González-Muñoz, Ricardo; Arreguín-Espinosa, Roberto

2016-01-01

The Zoanthids are an order of cnidarians whose venoms and toxins have been poorly studied. Palythoa caribaeorum is a zoanthid commonly found around the Mexican coastline. In this study, we tested the activity of P. caribaeorum venom on voltage-gated sodium channel (NaV1.7), voltage-gated calcium channel (CaV2.2), the A-type transient outward (IA) and delayed rectifier (IDR) currents of KV channels of the superior cervical ganglion (SCG) neurons of the rat. These results showed that the venom reversibly delays the inactivation process of voltage-gated sodium channels and inhibits voltage-gated calcium and potassium channels in this mammalian model. The compounds responsible for these effects seem to be low molecular weight peptides. Together, these results provide evidence for the potential use of zoanthids as a novel source of cnidarian toxins active on voltage-gated ion channels. PMID:27164140

Vascular Inward Rectifier K+ Channels as External K+ Sensors in the Control of Cerebral Blood Flow

PubMed Central

LONGDEN, THOMAS A.; NELSON, MARK T.

2015-01-01

For decades it has been known that external potassium (K+) ions are rapid and potent vasodilators that increase cerebral blood flow (CBF). Recent studies have implicated the local release of K+ from astrocytic endfeet—which encase the entirety of the parenchymal vasculature—in the dynamic regulation of local CBF during neurovascular coupling (NVC). It has been proposed that the activation of strong inward rectifier K+ (KIR) channels in the vascular wall by external K+ is a central component of these hyperemic responses; however, a number of significant gaps in our knowledge remain. Here, we explore the concept that vascular KIR channels are the major extracellular K+ sensors in the control of CBF. We propose that K+ is an ideal mediator of NVC, and discuss KIR channels as effectors that produce rapid hyperpolarization and robust vasodilation of cerebral arterioles. We provide evidence that KIR channels, of the KIR2 subtype in particular, are present in both the endothelial and smooth muscle cells of parenchymal arterioles and propose that this dual positioning of KIR2 channels increases the robustness of the vasodilation to external K+, enables the endothelium to be actively engaged in neurovascular coupling, and permits electrical signaling through the endothelial syncytium to promote upstream vasodilation to modulate CBF. PMID:25641345

Voltage balanced multilevel voltage source converter system

DOEpatents

Peng, Fang Zheng; Lai, Jih-Sheng

1997-01-01

A voltage balanced multilevel converter for high power AC applications such as adjustable speed motor drives and back-to-back DC intertie of adjacent power systems. This converter provides a multilevel rectifier, a multilevel inverter, and a DC link between the rectifier and the inverter allowing voltage balancing between each of the voltage levels within the multilevel converter. The rectifier is equipped with at least one phase leg and a source input node for each of the phases. The rectifier is further equipped with a plurality of rectifier DC output nodes. The inverter is equipped with at least one phase leg and a load output node for each of the phases. The inverter is further equipped with a plurality of inverter DC input nodes. The DC link is equipped with a plurality of rectifier charging means and a plurality of inverter discharging means. The plurality of rectifier charging means are connected in series with one of the rectifier charging means disposed between and connected in an operable relationship with each adjacent pair of rectifier DC output nodes. The plurality of inverter discharging means are connected in series with one of the inverter discharging means disposed between and connected in an operable relationship with each adjacent pair of inverter DC input nodes. Each of said rectifier DC output nodes are individually electrically connected to the respective inverter DC input nodes. By this means, each of the rectifier DC output nodes and each of the inverter DC input nodes are voltage balanced by the respective charging and discharging of the rectifier charging means and the inverter discharging means.

Voltage balanced multilevel voltage source converter system

DOEpatents

Peng, F.Z.; Lai, J.S.

1997-07-01

Disclosed is a voltage balanced multilevel converter for high power AC applications such as adjustable speed motor drives and back-to-back DC intertie of adjacent power systems. This converter provides a multilevel rectifier, a multilevel inverter, and a DC link between the rectifier and the inverter allowing voltage balancing between each of the voltage levels within the multilevel converter. The rectifier is equipped with at least one phase leg and a source input node for each of the phases. The rectifier is further equipped with a plurality of rectifier DC output nodes. The inverter is equipped with at least one phase leg and a load output node for each of the phases. The inverter is further equipped with a plurality of inverter DC input nodes. The DC link is equipped with a plurality of rectifier charging means and a plurality of inverter discharging means. The plurality of rectifier charging means are connected in series with one of the rectifier charging means disposed between and connected in an operable relationship with each adjacent pair of rectifier DC output nodes. The plurality of inverter discharging means are connected in series with one of the inverter discharging means disposed between and connected in an operable relationship with each adjacent pair of inverter DC input nodes. Each of said rectifier DC output nodes are individually electrically connected to the respective inverter DC input nodes. By this means, each of the rectifier DC output nodes and each of the inverter DC input nodes are voltage balanced by the respective charging and discharging of the rectifier charging means and the inverter discharging means. 15 figs.

Nicotine depresses the functions of multiple cardiac potassium channels.

PubMed

Wang, H; Shi, H; Wang, Z

1999-01-01

Nicotine is the main constituent of tobacco smoke responsible for the elevated risk of the cardiovascular disease and sudden coronary death associated with smoking, presumably by provoking cardiac arrhythmias. The cellular mechanisms may be related to the ability of nicotine to prolong action potentials and to depolarize membrane potential. However, the underlying ionic mechanisms remained unknown. We showed here that nicotine blocked multiple types of K+ currents, including the native currents in canine ventricular myocytes and the cloned channels expressed in Xenopus oocytes: A-type K+ currents (I(to)/Kv4.3), delayed rectifier K+ currents (I(Kr)/HERG) and inward rectifier K+ currents (I(K1)/Kir2.1). Most noticeably, nicotine at a concentration as low as of 10 nM significantly suppressed I(to) and Kv4.3 by approximately 20%. The effects of nicotine were independent of nicotinic receptor simulation or catecholamine release. Our results indicate that nicotine is a non-specific blocker of K+ channels and the inhibitory effects are the consequence of direct interactions between nicotine molecules and the channel proteins. Our study provided for the first time the evidence for the direct inhibition of cardiac K+ channels by nicotine and established a novel aspect of nicotine pharmacology.

[Ca2+]i Elevation and Oxidative Stress Induce KCNQ1 Protein Translocation from the Cytosol to the Cell Surface and Increase Slow Delayed Rectifier (IKs) in Cardiac Myocytes*

PubMed Central

Wang, Yuhong; Zankov, Dimitar P.; Jiang, Min; Zhang, Mei; Henderson, Scott C.; Tseng, Gea-Ny

2013-01-01

Our goals are to simultaneously determine the three-dimensional distribution patterns of KCNQ1 and KCNE1 in cardiac myocytes and to study the mechanism and functional implications for variations in KCNQ1/KCNE1 colocalization in myocytes. We monitored the distribution patterns of KCNQ1, KCNE1, and markers for subcellular compartments/organelles using immunofluorescence/confocal microscopy and confirmed the findings in ventricular myocytes by directly observing fluorescently tagged KCNQ1-GFP and KCNE1-dsRed expressed in these cells. We also monitored the effects of stress on KCNQ1-GFP and endoplasmic reticulum (ER) remodeling during live cell imaging. The data showed that 1) KCNE1 maintained a stable cell surface localization, whereas KCNQ1 exhibited variations in the cytosolic compartment (striations versus vesicles) and the degree of presence on the cell surface; 2) the degree of cell surface KCNQ1/KCNE1 colocalization was positively correlated with slow delayed rectifier (IKs) current density; 3) KCNQ1 and calnexin (an ER marker) shared a cytosolic compartment; and 4) in response to stress ([Ca2+]i elevation, oxidative overload, or AT1R stimulation), KCNQ1 exited the cytosolic compartment and trafficked to the cell periphery in vesicles. This was accompanied by partial ER fragmentation. We conclude that the cellular milieu regulates KCNQ1 distribution in cardiac myocytes and that stressful conditions can increase IKs by inducing KCNQ1 movement to the cell surface. This represents a hitherto unrecognized mechanism by which IKs fulfills its function as a repolarization reserve in ventricular myocytes. PMID:24142691

Enhanced excitability and down-regulated voltage-gated potassium channels in colonic drg neurons from neonatal maternal separation rats.

PubMed

Luo, Jia-Lie; Qin, Hong-Yan; Wong, Chun-Kit; Tsang, Suk-Ying; Huang, Yu; Bian, Zhao-Xiang

2011-05-01

Irritable bowel syndrome (IBS), characterized mainly by abdominal pain, is a functional bowel disorder. The present study aimed to examine changes in the excitability and the activity of the voltage-gated K(+) channel in dorsal root ganglia (DRG) neurons innervating the colon of rats subjected to neonatal maternal separation (NMS). Colonic DRG neurons from NMS rats as identified by FAST DiI™ labeling showed an increased cell size compared with those from nonhandled (NH) rats. Whole cell current-clamp recordings showed that colonic DRG neurons from NMS rats displayed: 1) depolarized resting membrane potential; 2) increased input resistance; 3) a dramatic reduction in rheobase; and 4) a significant increase in the number of action potentials evoked at twice rheobase. Whole cell voltage-clamp recordings revealed that neurons from both groups exhibited transient A-type (I(A)) and delayed rectifier (I(K)) K(+) currents. Compared with NH rat neurons, the averaged density of I(K) was significantly reduced in NMS rat neurons. Furthermore, the Kv1.2 expression was significantly decreased in NMS rat colonic DRG neurons. These results suggest that NMS increases the excitability of colonic DRG neurons mainly by suppressing the I(K) current, which is likely accounted for by the downregulation of the Kv1.2 expression and somal hypertrophy. This study demonstrates the alteration of delayed rectifier K current and Kv1.2 expression in DRG neurons from IBS model rats, representing a molecular mechanism underlying visceral pain and sensitization in IBS, suggesting the potential of Kv1.2 as a therapeutic target for the treatment of IBS. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

Role of action potential configuration and the contribution of Ca2+ and K+ currents to isoprenaline-induced changes in canine ventricular cells

PubMed Central

Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, PP

2012-01-01

BACKGROUND AND PURPOSE Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca2+ current (ICa), slow delayed rectifier K+ current (IKs) and fast delayed rectifier K+ current (IKr) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. EXPERIMENTAL APPROACH Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. KEY RESULTS In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the IKr blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the IKs blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the ICa blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating ICa followed by a rise in IKs, both currents increased with increasing the cycle length. CONCLUSIONS AND IMPLICATIONS The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of IKs– but not IKr– may be responsible for the observed shortening of action potentials. PMID:22563726

Role of action potential configuration and the contribution of C²⁺a and K⁺ currents to isoprenaline-induced changes in canine ventricular cells.

PubMed

Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, P P

2012-10-01

Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca²⁺ current (I(Ca)), slow delayed rectifier K⁺ current (I(Ks)) and fast delayed rectifier K⁺ current (I(Kr)) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the I(Kr) blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the I(Ks) blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the I(Ca) blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating I(Ca) followed by a rise in I(Ks) , both currents increased with increasing the cycle length. The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of I(Ks) - but not I(Kr) - may be responsible for the observed shortening of action potentials. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Heterogeneity in Kv2 Channel Expression Shapes Action Potential Characteristics and Firing Patterns in CA1 versus CA2 Hippocampal Pyramidal Neurons

PubMed Central

Chevaleyre, Vivien; Murray, Karl D.; Piskorowski, Rebecca A.

2017-01-01

Abstract The CA1 region of the hippocampus plays a critical role in spatial and contextual memory, and has well-established circuitry, function and plasticity. In contrast, the properties of the flanking CA2 pyramidal neurons (PNs), important for social memory, and lacking CA1-like plasticity, remain relatively understudied. In particular, little is known regarding the expression of voltage-gated K+ (Kv) channels and the contribution of these channels to the distinct properties of intrinsic excitability, action potential (AP) waveform, firing patterns and neurotransmission between CA1 and CA2 PNs. In the present study, we used multiplex fluorescence immunolabeling of mouse brain sections, and whole-cell recordings in acute mouse brain slices, to define the role of heterogeneous expression of Kv2 family Kv channels in CA1 versus CA2 pyramidal cell excitability. Our results show that the somatodendritic delayed rectifier Kv channel subunits Kv2.1, Kv2.2, and their auxiliary subunit AMIGO-1 have region-specific differences in expression in PNs, with the highest expression levels in CA1, a sharp decrease at the CA1-CA2 boundary, and significantly reduced levels in CA2 neurons. PNs in CA1 exhibit a robust contribution of Guangxitoxin-1E-sensitive Kv2-based delayed rectifier current to AP shape and after-hyperpolarization potential (AHP) relative to that seen in CA2 PNs. Our results indicate that robust Kv2 channel expression confers a distinct pattern of intrinsic excitability to CA1 PNs, potentially contributing to their different roles in hippocampal network function. PMID:28856240

Effects of Nitric Oxide on Voltage-Gated K⁺ Currents in Human Cardiac Fibroblasts through the Protein Kinase G and Protein Kinase A Pathways but Not through S-Nitrosylation.

PubMed

Bae, Hyemi; Choi, Jeongyoon; Kim, Young-Won; Lee, Donghee; Kim, Jung-Ha; Ko, Jae-Hong; Bang, Hyoweon; Kim, Taeho; Lim, Inja

2018-03-12

This study investigated the expression of voltage-gated K⁺ (K V ) channels in human cardiac fibroblasts (HCFs), and the effect of nitric oxide (NO) on the K V currents, and the underlying phosphorylation mechanisms. In reverse transcription polymerase chain reaction, two types of K V channels were detected in HCFs: delayed rectifier K⁺ channel and transient outward K⁺ channel. In whole-cell patch-clamp technique, delayed rectifier K⁺ current (I K ) exhibited fast activation and slow inactivation, while transient outward K⁺ current (I to ) showed fast activation and inactivation kinetics. Both currents were blocked by 4-aminopyridine. An NO donor, S -nitroso- N -acetylpenicillamine (SNAP), increased the amplitude of I K in a concentration-dependent manner with an EC 50 value of 26.4 µM, but did not affect I to . The stimulating effect of SNAP on I K was blocked by pretreatment with 1H-(1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or by KT5823. 8-bromo-cyclic GMP stimulated the I K . The stimulating effect of SNAP on I K was also blocked by pretreatment with KT5720 or by SQ22536. Forskolin and 8-bromo-cyclic AMP each stimulated I K . On the other hand, the stimulating effect of SNAP on I K was not blocked by pretreatment of N -ethylmaleimide or by DL-dithiothreitol. Our data suggest that NO enhances I K , but not I to , among K V currents of HCFs, and the stimulating effect of NO on I K is through the PKG and PKA pathways, not through S -nitrosylation.

Computational Modeling Reveals Key Contributions of KCNQ and hERG Currents to the Malleability of Uterine Action Potentials Underpinning Labor

PubMed Central

Tong, Wing-Chiu; Tribe, Rachel M.; Smith, Roger; Taggart, Michael J.

2014-01-01

The electrical excitability of uterine smooth muscle cells is a key determinant of the contraction of the organ during labor and is manifested by spontaneous, periodic action potentials (APs). Near the end of term, APs vary in shape and size reflecting an ability to change the frequency, duration and amplitude of uterine contractions. A recent mathematical model quantified several ionic features of the electrical excitability in uterine smooth muscle cells. It replicated many of the experimentally recorded uterine AP configurations but its limitations were evident when trying to simulate the long-duration bursting APs characteristic of labor. A computational parameter search suggested that delayed rectifying K+ currents could be a key model component requiring improvement to produce the longer-lasting bursting APs. Of the delayed rectifying K+ currents family it is of interest that KCNQ and hERG channels have been reported to be gestationally regulated in the uterus. These currents exhibit features similar to the broadly defined uterine I K1 of the original mathematical model. We thus formulated new quantitative descriptions for several I KCNQ and I hERG. Incorporation of these currents into the uterine cell model enabled simulations of the long-lasting bursting APs. Moreover, we used this modified model to simulate the effects of different contributions of I KCNQ and I hERG on AP form. Our findings suggest that the alterations in expression of hERG and KCNQ channels can potentially provide a mechanism for fine tuning of AP forms that lends a malleability for changing between plateau-like and long-lasting bursting-type APs as uterine cells prepare for parturition. PMID:25474527

Adenosine A₂A receptors inhibit delayed rectifier potassium currents and cell differentiation in primary purified oligodendrocyte cultures.

PubMed

Coppi, Elisabetta; Cellai, Lucrezia; Maraula, Giovanna; Pugliese, Anna Maria; Pedata, Felicita

2013-10-01

Oligodendrocyte progenitor cells (OPCs) are a population of cycling cells which persist in the adult central nervous system (CNS) where, under opportune stimuli, they differentiate into mature myelinating oligodendrocytes. Adenosine A(2A) receptors are Gs-coupled P1 purinergic receptors which are widely distributed throughout the CNS. It has been demonstrated that OPCs express A(2A) receptors, but their functional role in these cells remains elusive. Oligodendrocytes express distinct voltage-gated ion channels depending on their maturation. Here, by electrophysiological recordings coupled with immunocytochemical labeling, we studied the effects of adenosine A(2A) receptors on membrane currents and differentiation of purified primary OPCs isolated from the rat cortex. We found that the selective A(2A) agonist, CGS21680, inhibits sustained, delayed rectifier, K(+) currents (I(K)) without modifying transient (I(A)) conductances. The effect was observed in all cells tested, independently from time in culture. CGS21680 inhibition of I(K) current was concentration-dependent (10-200 nM) and blocked in the presence of the selective A(2A) antagonist SCH58261 (100 nM). It is known that I(K) currents play an important role during OPC development since their block decreases cell proliferation and differentiation. In light of these data, our further aim was to investigate whether A(2A) receptors modulate these processes. CGS21680, applied at 100 nM in the culture medium of oligodendrocyte cultures, inhibits OPC differentiation (an effect prevented by SCH58261) without affecting cell proliferation. Data demonstrate that cultured OPCs express functional A(2A) receptors whose activation negatively modulate I(K) currents. We propose that, by this mechanism, A(2A) adenosine receptors inhibit OPC differentiation. Copyright © 2013 Elsevier Ltd. All rights reserved.

The comprehensive electrophysiological study of curcuminoids on delayed-rectifier K+ currents in insulin-secreting cells.

PubMed

Kuo, Ping-Chung; Yang, Chia-Jung; Lee, Yu-Chi; Chen, Pei-Chun; Liu, Yen-Chin; Wu, Sheng-Nan

2018-01-15

Curcumin (CUR) has been demonstrated to induce insulin release from pancreatic β-cells; however, how curcuminoids (including demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC)) exert any possible effects on membrane ion currents inherently in insulin-secreting cells remains largely unclear. The effects of CUR and other structurally similar curcuminoids on ion currents in rat insulin-secreting (INS-1) insulinoma cells were therefore investigated in this study. The effects of these compounds on ionic currents and membrane potential were studied by patch-clamp technique. CUR suppressed the amplitude of delayed-rectifier K + current (I K(DR) ) in a time-, state- and concentration-dependent manner in these cells and the inhibition was not reversed by diazoxide, nicorandil or chlorotoxin. The value of dissociation constant for CUR-induced suppression of I K(DR) in INS-1 cells was 1.26μM. Despite the inability of CUR to alter the activation rate of I K(DR) , it accelerated current inactivation elicited by membrane depolarization. Increasing CUR concentrations shifted the inactivation curve of I K(DR) to hyperpolarized potential and slowed the recovery of I K(DR) inactivation. CUR, DMC, and BDMC all exerted depressant actions on I K(DR) amplitude to a similar magnitude, although DMC and BDMC did not increase current inactivation clearly. CUR slightly suppressed the peak amplitude of voltage-gated Na + current. CUR, DMC and BDMC depolarized the resting potential and increased firing frequency of action potentials. The CUR-mediated decrease of I K(DR) and the increase of current inactivation also occurred in βTC-6 INS-1 cells. Taken these results together, these effects may be one of the possible mechanisms contributing their insulin-releasing effect. Copyright © 2017 Elsevier B.V. All rights reserved.

Ginseng gintonin activates the human cardiac delayed rectifier K+ channel: involvement of Ca2+/calmodulin binding sites.

PubMed

Choi, Sun-Hye; Lee, Byung-Hwan; Kim, Hyeon-Joong; Jung, Seok-Won; Kim, Hyun-Sook; Shin, Ho-Chul; Lee, Jun-Hee; Kim, Hyoung-Chun; Rhim, Hyewhon; Hwang, Sung-Hee; Ha, Tal Soo; Kim, Hyun-Ji; Cho, Hana; Nah, Seung-Yeol

2014-09-01

Gintonin, a novel, ginseng-derived G protein-coupled lysophosphatidic acid (LPA) receptor ligand, elicits [Ca(2+)]i transients in neuronal and non-neuronal cells via pertussis toxin-sensitive and pertussis toxin-insensitive G proteins. The slowly activating delayed rectifier K(+) (I(Ks)) channel is a cardiac K(+) channel composed of KCNQ1 and KCNE1 subunits. The C terminus of the KCNQ1 channel protein has two calmodulin-binding sites that are involved in regulating I(Ks) channels. In this study, we investigated the molecular mechanisms of gintonin-mediated activation of human I(Ks) channel activity by expressing human I(Ks) channels in Xenopus oocytes. We found that gintonin enhances IKs channel currents in concentration- and voltage-dependent manners. The EC50 for the I(Ks) channel was 0.05 ± 0.01 μg/ml. Gintonin-mediated activation of the I(Ks) channels was blocked by an LPA1/3 receptor antagonist, an active phospholipase C inhibitor, an IP3 receptor antagonist, and the calcium chelator BAPTA. Gintonin-mediated activation of both the I(Ks) channel was also blocked by the calmodulin (CaM) blocker calmidazolium. Mutations in the KCNQ1 [Ca(2+)]i/CaM-binding IQ motif sites (S373P, W392R, or R539W)blocked the action of gintonin on I(Ks) channel. However, gintonin had no effect on hERG K(+) channel activity. These results show that gintonin-mediated enhancement of I(Ks) channel currents is achieved through binding of the [Ca(2+)]i/CaM complex to the C terminus of KCNQ1 subunit.

Hydrogen peroxide-induced reduction of delayed rectifier potassium current in hippocampal neurons involves oxidation of sulfhydryl groups.

PubMed

Hasan, Sonia M K; Redzic, Zoran B; Alshuaib, Waleed B

2013-07-03

This study examined the effect of H2O2 on the delayed rectifier potassium current (IKDR) in isolated hippocampal neurons. Whole-cell voltage-clamp experiments were performed on freshly dissociated hippocampal CA1 neurons of SD rats before and after treatment with H2O2. To reveal the mechanism behind H2O2-induced changes in IKDR, cells were treated with different oxidizing and reducing agents. External application of membrane permeable H2O2 reduced the amplitude and voltage-dependence of IKDR in a concentration dependent manner. Desferoxamine (DFO), an iron-chelator that prevents hydroxyl radical (OH) generation, prevented H2O2-induced reduction in IKDR. Application of the sulfhydryl-oxidizing agent 5,5 dithio-bis-nitrobenzoic acid (DTNB) mimicked the effect of H2O2. Sulfhydryl-reducing agents dithiothreitol (DTT) and glutathione (GSH) alone did not affect IKDR; however, DTT and GSH reversed and prevented the H2O2-induced inhibition of IKDR, respectively. Membrane impermeable agents GSH and DTNB showed effects only when added intracellularly identifying intracellular sulfhydryl groups as potential targets for hydroxyl-mediated oxidation. However, the inhibitory effects of DTNB and H2O2 at the positive test potentials were completely and partially abolished by DTT, respectively, suggesting an additional mechanism of action for H2O2, that is not shared by DTNB. In summary, this study provides evidence for the redox modulation of IKDR, identifies hydroxyl radical as an intermediate oxidant responsible for the H2O2-induced decrease in current amplitude and identifies intracellular sulfhydryl groups as an oxidative target. Copyright © 2013 Elsevier B.V. All rights reserved.

Sex differences in repolarization and slow delayed rectifier potassium current and their regulation by sympathetic stimulation in rabbits.

PubMed

Zhu, Yujie; Ai, Xun; Oster, Robert A; Bers, Donald M; Pogwizd, Steven M

2013-06-01

Slow delayed rectifier potassium current (IKs) is important in action potential (AP) repolarization and repolarization reserve. We tested the hypothesis that there are sex-specific differences in IKs, AP, and their regulation by β-adrenergic receptors (β-AR's) using whole-cell patch-clamp. AP duration (APD90) was significantly longer in control female (F) than in control male (M) myocytes. Isoproterenol (ISO, 500 nM) shortened APD90 comparably in M and F, and was largely reversed by β1-AR blocker CGP 20712A (CGP, 300 nM). Inhibition of IKs with chromanol 293B (10 μM) resulted in less APD prolongation in F at baseline (3.0 vs 8.9 %, p < 0.05 vs M) and even in the presence of ISO (5.4 vs 20.9 %, p < 0.05). This suggests that much of the ISO-induced APD abbreviation in F is independent of IKs. In F, baseline IKs was 42 % less and was more weakly activated by ISO (19 vs 68 % in M, p < 0.01). ISO enhancement of IKs was comparably attenuated by CGP in M and F. After ovariectomy, IKs in F had greater enhancement by ISO (72 %), now comparable to control M. After orchiectomy, IKs in M was only slightly enhanced by ISO (23 %), comparable to control F. Pretreatment with thapsigargin (to block SR Ca release) had bigger impact on ISO-induced APD shortening in F than that in M (p < 0.01). In conclusion, we found that there are sex differences in IKs, AP, and their regulation by β-AR's that are modulated by sex hormones, suggesting the potential for sex-specific antiarrhythmic therapy.

Isoflurane depolarizes bronchopulmonary C neurons by inhibiting transient A-type and delayed rectifier potassium channels.

PubMed

Zhang, Zhenxiong; Zhuang, Jianguo; Zhang, Cancan; Xu, Fadi

2013-04-01

Inhalation of isoflurane (ISO), a widely used volatile anesthetic, can produce clinical tachypnea. In dogs, this response is reportedly mediated by bronchopulmonary C-fibers (PCFs), but the relevant mechanisms remain unclear. Activation of transient A-type potassium current (IA) channels and delayed rectifier potassium current (IK) channels hyperpolarizes neurons, and inhibition of both channels by ISO increases neural firing. Due to the presence of these channels in the cell bodies of rat PCFs, we determined whether ISO could stimulate PCFs to produce tachypnea in anesthetized rats, and, if so, whether this response resulted from ISO-induced depolarization of the pulmonary C neurons via the inhibition of IA and IK. We recorded ventilatory responses to 5% ISO exposure in anesthetized rats before and after blocking PCF conduction and the responses of pulmonary C neurons (extracellularly recorded) to ISO exposure. ISO-induced (1mM) changes in pulmonary C neuron membrane potential and IA/IK were tested using the perforated patch clamp technique. We found that: (1) ISO inhalation evoked a brief tachypnea (∼7s) and that this response disappeared after blocking PCF conduction; (2) the ISO significantly elevated (by 138%) the firing rate of most pulmonary C neurons (17 out of 21) in the nodose ganglion; and (3) ISO perfusion depolarized the pulmonary C neurons in the vitro and inhibited both IA and IK, and this evoked-depolarization was largely diminished after blocking both IA and IK. Our results suggest that ISO is able to stimulate PCFs to elicit tachypnea in rats, at least partly, via inhibiting IA and IK, thereby depolarizing the pulmonary C neurons. Copyright © 2013. Published by Elsevier B.V.

Feedback loop compensates for rectifier nonlinearity

NASA Technical Reports Server (NTRS)

1966-01-01

Signal processing circuit with two negative feedback loops rectifies two sinusoidal signals which are 180 degrees out of phase and produces a single full-wave rectified output signal. Each feedback loop incorporates a feedback rectifier to compensate for the nonlinearity of the circuit.

High-speed switching of biphoton delays through electro-optic pump frequency modulation

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

Odele, Ogaga D.; Lukens, Joseph M.; Jaramillo-Villegas, Jose A.

The realization of high-speed tunable delay control has received significant attention in the scene of classical photonics. In quantum optics, however, such rapid delay control systems for entangled photons have remained undeveloped. Here for the first time, we demonstrate rapid (2.5 MHz) modulation of signal-idler arrival times through electro-optic pump frequency modulation. Our technique applies the quantum phenomenon of nonlocal dispersion cancellation along with pump frequency tuning to control the relative delay between photon pairs. Chirped fiber Bragg gratings are employed to provide large amounts of dispersion which result in biphoton delays exceeding 30 ns. This rapid delay modulation schememore » could be useful for on-demand single-photon distribution in addition to quantum versions of pulse position modulation.« less

High-speed switching of biphoton delays through electro-optic pump frequency modulation

DOE PAGES

Odele, Ogaga D.; Lukens, Joseph M.; Jaramillo-Villegas, Jose A.; ...

2016-12-08

The realization of high-speed tunable delay control has received significant attention in the scene of classical photonics. In quantum optics, however, such rapid delay control systems for entangled photons have remained undeveloped. Here for the first time, we demonstrate rapid (2.5 MHz) modulation of signal-idler arrival times through electro-optic pump frequency modulation. Our technique applies the quantum phenomenon of nonlocal dispersion cancellation along with pump frequency tuning to control the relative delay between photon pairs. Chirped fiber Bragg gratings are employed to provide large amounts of dispersion which result in biphoton delays exceeding 30 ns. This rapid delay modulation schememore » could be useful for on-demand single-photon distribution in addition to quantum versions of pulse position modulation.« less

46 CFR 183.360 - Semiconductor rectifier systems.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 7 2011-10-01 2011-10-01 false Semiconductor rectifier systems. 183.360 Section 183.360... TONS) ELECTRICAL INSTALLATION Power Sources and Distribution Systems § 183.360 Semiconductor rectifier systems. (a) Each semiconductor rectifier system must have an adequate heat removal system that prevents...

46 CFR 183.360 - Semiconductor rectifier systems.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Semiconductor rectifier systems. 183.360 Section 183.360... TONS) ELECTRICAL INSTALLATION Power Sources and Distribution Systems § 183.360 Semiconductor rectifier systems. (a) Each semiconductor rectifier system must have an adequate heat removal system that prevents...

An RF Energy Harvester System Using UHF Micropower CMOS Rectifier Based on a Diode Connected CMOS Transistor

PubMed Central

Shokrani, Mohammad Reza; Hamidon, Mohd Nizar B.; Rokhani, Fakhrul Zaman; Shafie, Suhaidi Bin

2014-01-01

This paper presents a new type diode connected MOS transistor to improve CMOS conventional rectifier's performance in RF energy harvester systems for wireless sensor networks in which the circuits are designed in 0.18 μm TSMC CMOS technology. The proposed diode connected MOS transistor uses a new bulk connection which leads to reduction in the threshold voltage and leakage current; therefore, it contributes to increment of the rectifier's output voltage, output current, and efficiency when it is well important in the conventional CMOS rectifiers. The design technique for the rectifiers is explained and a matching network has been proposed to increase the sensitivity of the proposed rectifier. Five-stage rectifier with a matching network is proposed based on the optimization. The simulation results shows 18.2% improvement in the efficiency of the rectifier circuit and increase in sensitivity of RF energy harvester circuit. All circuits are designed in 0.18 μm TSMC CMOS technology. PMID:24782680

An RF energy harvester system using UHF micropower CMOS rectifier based on a diode connected CMOS transistor.

PubMed

Shokrani, Mohammad Reza; Khoddam, Mojtaba; Hamidon, Mohd Nizar B; Kamsani, Noor Ain; Rokhani, Fakhrul Zaman; Shafie, Suhaidi Bin

2014-01-01

This paper presents a new type diode connected MOS transistor to improve CMOS conventional rectifier's performance in RF energy harvester systems for wireless sensor networks in which the circuits are designed in 0.18  μm TSMC CMOS technology. The proposed diode connected MOS transistor uses a new bulk connection which leads to reduction in the threshold voltage and leakage current; therefore, it contributes to increment of the rectifier's output voltage, output current, and efficiency when it is well important in the conventional CMOS rectifiers. The design technique for the rectifiers is explained and a matching network has been proposed to increase the sensitivity of the proposed rectifier. Five-stage rectifier with a matching network is proposed based on the optimization. The simulation results shows 18.2% improvement in the efficiency of the rectifier circuit and increase in sensitivity of RF energy harvester circuit. All circuits are designed in 0.18 μm TSMC CMOS technology.

Molecular Coupling between Voltage Sensor and Pore Opening in the Arabidopsis Inward Rectifier K+ Channel KAT1

PubMed Central

Latorre, Ramon; Olcese, Riccardo; Basso, Claudia; Gonzalez, Carlos; Muñoz, Fabian; Cosmelli, Diego; Alvarez, Osvaldo

2003-01-01

Animal and plant voltage-gated ion channels share a common architecture. They are made up of four subunits and the positive charges on helical S4 segments of the protein in animal K+ channels are the main voltage-sensing elements. The KAT1 channel cloned from Arabidopsis thaliana, despite its structural similarity to animal outward rectifier K+ channels is, however, an inward rectifier. Here we detected KAT1-gating currents due to the existence of an intrinsic voltage sensor in this channel. The measured gating currents evoked in response to hyperpolarizing voltage steps consist of a very fast (τ = 318 ± 34 μs at −180 mV) and a slower component (4.5 ± 0.5 ms at −180 mV) representing charge moved when most channels are closed. The observed gating currents precede in time the ionic currents and they are measurable at voltages (less than or equal to −60) at which the channel open probability is negligible (≈10−4). These two observations, together with the fact that there is a delay in the onset of the ionic currents, indicate that gating charge transits between several closed states before the KAT1 channel opens. To gain insight into the molecular mechanisms that give rise to the gating currents and lead to channel opening, we probed external accessibility of S4 domain residues to methanethiosulfonate-ethyltrimethylammonium (MTSET) in both closed and open cysteine-substituted KAT1 channels. The results demonstrate that the putative voltage–sensing charges of S4 move inward when the KAT1 channels open. PMID:14517271

Histamine facilitates GABAergic transmission in the rat entorhinal cortex: Roles of H1 and H2 receptors, Na+ -permeable cation channels, and inward rectifier K+ channels.

PubMed

Cilz, Nicholas I; Lei, Saobo

2017-05-01

In the brain, histamine (HA) serves as a neuromodulator and a neurotransmitter released from the tuberomammillary nucleus (TMN). HA is involved in wakefulness, thermoregulation, energy homeostasis, nociception, and learning and memory. The medial entorhinal cortex (MEC) receives inputs from the TMN and expresses HA receptors (H 1 , H 2 , and H 3 ). We investigated the effects of HA on GABAergic transmission in the MEC and found that HA significantly increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) with an EC 50 of 1.3 µM, but failed to significantly alter sIPSC amplitude. HA-induced increases in sIPSC frequency were sensitive to tetrodotoxin (TTX), required extracellular Ca 2+ , and persisted when GDP-β-S, a G-protein inactivator, was applied postsynaptically via the recording pipettes, indicating that HA increased GABA release by facilitating the excitability of GABAergic interneurons in the MEC. Recordings from local MEC interneurons revealed that HA significantly increased their excitability as determined by membrane depolarization, generation of an inward current at -65 mV, and augmentation of action potential firing frequency. Both H 1 and H 2 receptors were involved in HA-induced increases in sIPSCs and interneuron excitability. Immunohistochemical staining showed that both H 1 and H 2 receptors are expressed on GABAergic interneurons in the MEC. HA-induced depolarization of interneurons involved a mixed ionic mechanism including activation of a Na + -permeable cation channel and inhibition of a cesium-sensitive inward rectifier K + channel, although HA also inhibited the delayed rectifier K + channels. Our results may provide a cellular mechanism, at least partially, to explain the roles of HA in the brain. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Electrophysiological properties of myocytes isolated from the mouse atrioventricular node: L-type ICa, IKr, If, and Na-Ca exchange

PubMed Central

Choisy, Stéphanie C; Cheng, Hongwei; Orchard, Clive H; James, Andrew F; Hancox, Jules C

2015-01-01

The atrioventricular node (AVN) is a key component of the cardiac pacemaker-conduction system. This study investigated the electrophysiology of cells isolated from the AVN region of adult mouse hearts, and compared murine ionic current magnitude with that of cells from the more extensively studied rabbit AVN. Whole-cell patch-clamp recordings of ionic currents, and perforated-patch recordings of action potentials (APs), were made at 35–37°C. Hyperpolarizing voltage commands from −40 mV elicited a Ba2+-sensitive inward rectifier current that was small at diastolic potentials. Some cells (Type 1; 33.4 ± 2.2 pF; n = 19) lacked the pacemaker current, If, whilst others (Type 2; 34.2 ± 1.5 pF; n = 21) exhibited a clear If, which was larger than in rabbit AVN cells. On depolarization from −40 mV L-type Ca2+ current, ICa,L, was elicited with a half maximal activation voltage (V0.5) of −7.6 ± 1.2 mV (n = 24). ICa,L density was smaller than in rabbit AVN cells. Rapid delayed rectifier (IKr) tail currents sensitive to E-4031 (5 μmol/L) were observed on repolarization to −40 mV, with an activation V0.5 of −10.7 ± 4.7 mV (n = 8). The IKr magnitude was similar in mouse and rabbit AVN. Under Na-Ca exchange selective conditions, mouse AVN cells exhibited 5 mmol/L Ni-sensitive exchange current that was inwardly directed negative to the holding potential (−40 mV). Spontaneous APs (5.2 ± 0.5 sec−1; n = 6) exhibited an upstroke velocity of 37.7 ± 16.2 V/s and ceased following inhibition of sarcoplasmic reticulum Ca2+ release by 1 μmol/L ryanodine, implicating intracellular Ca2+ cycling in murine AVN cell electrogenesis. PMID:26607172

46 CFR 129.360 - Semiconductor-rectifier systems.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 4 2011-10-01 2011-10-01 false Semiconductor-rectifier systems. 129.360 Section 129.360... INSTALLATIONS Power Sources and Distribution Systems § 129.360 Semiconductor-rectifier systems. (a) Each semiconductor-rectifier system must have an adequate heat-removal system to prevent overheating. (b) If a...

46 CFR 120.360 - Semiconductor rectifier systems.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 4 2011-10-01 2011-10-01 false Semiconductor rectifier systems. 120.360 Section 120.360... INSTALLATION Power Sources and Distribution Systems § 120.360 Semiconductor rectifier systems. (a) Each semiconductor rectifier system must have an adequate heat removal system that prevents overheating. (b) Where a...

46 CFR 129.360 - Semiconductor-rectifier systems.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Semiconductor-rectifier systems. 129.360 Section 129.360... INSTALLATIONS Power Sources and Distribution Systems § 129.360 Semiconductor-rectifier systems. (a) Each semiconductor-rectifier system must have an adequate heat-removal system to prevent overheating. (b) If a...

46 CFR 120.360 - Semiconductor rectifier systems.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Semiconductor rectifier systems. 120.360 Section 120.360... INSTALLATION Power Sources and Distribution Systems § 120.360 Semiconductor rectifier systems. (a) Each semiconductor rectifier system must have an adequate heat removal system that prevents overheating. (b) Where a...

Resonant Rectifier ICs for Piezoelectric Energy Harvesting Using Low-Voltage Drop Diode Equivalents

PubMed Central

Din, Amad Ud; Chandrathna, Seneke Chamith; Lee, Jong-Wook

2017-01-01

Herein, we present the design technique of a resonant rectifier for piezoelectric (PE) energy harvesting. We propose two diode equivalents to reduce the voltage drop in the rectifier operation, a minuscule-drop-diode equivalent (MDDE) and a low-drop-diode equivalent (LDDE). The diode equivalents are embedded in resonant rectifier integrated circuits (ICs), which use symmetric bias-flip to reduce the power used for charging and discharging the internal capacitance of a PE transducer. The self-startup function is supported by synchronously generating control pulses for the bias-flip from the PE transducer. Two resonant rectifier ICs, using both MDDE and LDDE, are fabricated in a 0.18 μm CMOS process and their performances are characterized under external and self-power conditions. Under the external-power condition, the rectifier using LDDE delivers an output power POUT of 564 μW and a rectifier output voltage VRECT of 3.36 V with a power transfer efficiency of 68.1%. Under self-power conditions, the rectifier using MDDE delivers a POUT of 288 μW and a VRECT of 2.4 V with a corresponding efficiency of 78.4%. Using the proposed bias-flip technique, the power extraction capability of the proposed rectifier is 5.9 and 3.0 times higher than that of a conventional full-bridge rectifier. PMID:28422085

Resonant Rectifier ICs for Piezoelectric Energy Harvesting Using Low-Voltage Drop Diode Equivalents.

PubMed

Din, Amad Ud; Chandrathna, Seneke Chamith; Lee, Jong-Wook

2017-04-19

Herein, we present the design technique of a resonant rectifier for piezoelectric (PE) energy harvesting. We propose two diode equivalents to reduce the voltage drop in the rectifier operation, a minuscule-drop-diode equivalent (MDDE) and a low-drop-diode equivalent (LDDE). The diode equivalents are embedded in resonant rectifier integrated circuits (ICs), which use symmetric bias-flip to reduce the power used for charging and discharging the internal capacitance of a PE transducer. The self-startup function is supported by synchronously generating control pulses for the bias-flip from the PE transducer. Two resonant rectifier ICs, using both MDDE and LDDE, are fabricated in a 0.18 μm CMOS process and their performances are characterized under external and self-power conditions. Under the external-power condition, the rectifier using LDDE delivers an output power P OUT of 564 μW and a rectifier output voltage V RECT of 3.36 V with a power transfer efficiency of 68.1%. Under self-power conditions, the rectifier using MDDE delivers a P OUT of 288 μW and a V RECT of 2.4 V with a corresponding efficiency of 78.4%. Using the proposed bias-flip technique, the power extraction capability of the proposed rectifier is 5.9 and 3.0 times higher than that of a conventional full-bridge rectifier.

Complex expression and localization of inactivating Kv channels in cultured hippocampal astrocytes.

PubMed

Bekar, Lane K; Loewen, Matthew E; Cao, Kun; Sun, Xianfeng; Leis, Jerome; Wang, Rui; Forsyth, George W; Walz, Wolfgang

2005-03-01

Voltage-gated potassium channels are well established as critical for setting action potential frequency, membrane potential, and neurotransmitter release in neurons. However, their role in the "nonexcitable" glial cell type is yet to be fully understood. We used whole cell current kinetics, pharmacology, immunocytochemistry, and RT-PCR to characterize A-type current in hippocampal astrocyte cultures to better understand its function. Pharmacological analysis suggests that approximately 70, 10, and <5% of total A current is associated with Kv4, Kv3, and Kv1 channels, respectively. In addition, pharmacology and kinetics provide evidence for a significant contribution of KChIP accessory proteins to astrocytic A-channel composition. Localization of the Shaw Kv3.4 channel to astrocytic processes and the Shal Kv4.3 channel to soma suggest that these channels serve a specific function. Given this complex A-type channel expression pattern, we assessed the role of A currents in membrane voltage oscillations in response to current injections. Although TEA-sensitive delayed-rectifying currents are involved in the extent of repolarization, 4-AP-sensitive A currents serve to increase the rate. As in neurons, this effect may enable astrocytes to respond rapidly to high-frequency synaptic events. Our results indicate that hippocampal astrocytes in vitro express multiple A-type Kv channel alpha-subunits with accessory, possibly Ca(2+)-sensitive, cytoplasmic subunits that appear to be specifically localized to subcellular membrane compartments. Function of these channels remains to be determined in a physiological setting. However, this study suggests that they enable astrocytes to respond rapidly with membrane voltage oscillations to high-frequency incoming signals, possibly synchronizing astrocyte function to neuronal activity.

High voltage pulse generator. [Patent application

DOEpatents

Fasching, G.E.

1975-06-12

An improved high-voltage pulse generator is described which is especially useful in ultrasonic testing of rock core samples. An N number of capacitors are charged in parallel to V volts and at the proper instance are coupled in series to produce a high-voltage pulse of N times V volts. Rapid switching of the capacitors from the paralleled charging configuration to the series discharging configuration is accomplished by using silicon-controlled rectifiers which are chain self-triggered following the initial triggering of the first rectifier connected between the first and second capacitors. A timing and triggering circuit is provided to properly synchronize triggering pulses to the first SCR at a time when the charging voltage is not being applied to the parallel-connected charging capacitors. The output voltage can be readily increased by adding additional charging networks. The circuit allows the peak level of the output to be easily varied over a wide range by using a variable autotransformer in the charging circuit.

Two-dimensional non-volatile programmable p-n junctions

NASA Astrophysics Data System (ADS)

Li, Dong; Chen, Mingyuan; Sun, Zhengzong; Yu, Peng; Liu, Zheng; Ajayan, Pulickel M.; Zhang, Zengxing

2017-09-01

Semiconductor p-n junctions are the elementary building blocks of most electronic and optoelectronic devices. The need for their miniaturization has fuelled the rapid growth of interest in two-dimensional (2D) materials. However, the performance of a p-n junction considerably degrades as its thickness approaches a few nanometres and traditional technologies, such as doping and implantation, become invalid at the nanoscale. Here we report stable non-volatile programmable p-n junctions fabricated from the vertically stacked all-2D semiconductor/insulator/metal layers (WSe2/hexagonal boron nitride/graphene) in a semifloating gate field-effect transistor configuration. The junction exhibits a good rectifying behaviour with a rectification ratio of 104 and photovoltaic properties with a power conversion efficiency up to 4.1% under a 6.8 nW light. Based on the non-volatile programmable properties controlled by gate voltages, the 2D p-n junctions have been exploited for various electronic and optoelectronic applications, such as memories, photovoltaics, logic rectifiers and logic optoelectronic circuits.

Two-dimensional non-volatile programmable p-n junctions.

PubMed

Li, Dong; Chen, Mingyuan; Sun, Zhengzong; Yu, Peng; Liu, Zheng; Ajayan, Pulickel M; Zhang, Zengxing

2017-09-01

Semiconductor p-n junctions are the elementary building blocks of most electronic and optoelectronic devices. The need for their miniaturization has fuelled the rapid growth of interest in two-dimensional (2D) materials. However, the performance of a p-n junction considerably degrades as its thickness approaches a few nanometres and traditional technologies, such as doping and implantation, become invalid at the nanoscale. Here we report stable non-volatile programmable p-n junctions fabricated from the vertically stacked all-2D semiconductor/insulator/metal layers (WSe 2 /hexagonal boron nitride/graphene) in a semifloating gate field-effect transistor configuration. The junction exhibits a good rectifying behaviour with a rectification ratio of 10 4 and photovoltaic properties with a power conversion efficiency up to 4.1% under a 6.8 nW light. Based on the non-volatile programmable properties controlled by gate voltages, the 2D p-n junctions have been exploited for various electronic and optoelectronic applications, such as memories, photovoltaics, logic rectifiers and logic optoelectronic circuits.

p - n junction diodes fabricated from isolated electrospun fibers of (P(NDI2ODT2)) and an inorganic p-doped semiconductor

NASA Astrophysics Data System (ADS)

Rosado, Alexander; Pinto, Nicholas

2013-03-01

A simple method to fabricate, under ambient conditions and within seconds, p - n diodes using an individual electrospun poly{[N, N'-bis(2-octyldodecyl)-naphthalene-1,4,5,8-bis(dicarboximide)-2,6-diyl]-alt-5,5'-(2,2'-bithiophene)}-(P(NDI2ODT2)) fiber and a commercially available p-doped Si/SiO2 substrate is presented. Band bending at the fiber/Si+ interface leads to asymmetric I-V characteristic curves resembling that of a diode. The diode turn-on voltage was in the range 1V and was unaffected via UV light irradiation. The rectification ratio however could be tuned reversibly thereby making this device multifunctional. In addition to being a rectifier, the advantage of our design is the complete exposure of the rectifying junction to the surrounding environment. This has the advantage of making them attractive candidates in the potential fabrication of low power, sensitive and rapid response photo-sensors. NSF

75 FR 24747 - SCI, LLC/Zener-Rectifier Operations Division A Wholly Owned Subsidiary of SCI, LLC/ON...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-05

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-70,235] SCI, LLC/Zener-Rectifier... Adjustment Assistance on October 19, 2009, applicable to workers of SCI LLC/Zener-Rectifier, Operations... Technical Resources were employed on-site at the Phoenix Arizona location of SCI LLC/Zener-Rectifier...

Discounting of money and sex: effects of commodity and temporal position in stimulant-dependent men and women.

PubMed

Jarmolowicz, David P; Landes, Reid D; Christensen, Darren R; Jones, Bryan A; Jackson, Lisa; Yi, Richard; Bickel, Warren K

2014-11-01

Research on delay discounting has contributed to the understanding of numerous addiction-related phenomena. For example, studies have shown that substance dependent individuals discount their addictive substances (e.g., cocaine) more rapidly than they do other commodities (e.g., money). Recent research has shown that substance dependent individuals discount delayed sex more rapidly than delayed money, and their discounting rates for delayed sex were higher than those of non-addicted individuals. The particular reason that delay discounting rates for sex are higher than those for money, however, are unclear. Do individuals discount delayed sex rapidly because immediate sex is particularly appealing or because delayed sex does not retain its value? Moreover, do the same factors influence men and women's choices? The current study examined delay discounting in four conditions (money now versus money later; sex now versus sex later; money now, versus sex later; sex now versus money later) in cocaine dependent men and women. The procedures used isolated the role of the immediate versus delayed commodity. For men, the higher rates of delay discounting for sex were because delayed sex did not retain its value, whereas both the immediate and delayed commodity influenced the female participants' decisions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Apparatus for controlling the firing of rectifiers in polyphase rectifying circuits

DOEpatents

Yarema, R.J.

1979-09-18

A polyphase rectifier is controlled with precision by a circuit that filters and shifts a reference signal associated with each phase and that starts a ramp signal at a zero crossing of the shifted reference signal. The difference between the ramp signal and an external trigger signal is used to generate a pulse that switches power rectifiers into conduction. The circuit reduces effects of variations that introduce subharmonics into a rectified signal and it can be used for constant or time-varying external trigger signals.

Increased Response to β2-Adrenoreceptor Stimulation Augments Inhibition of IKr in Heart Failure Ventricular Myocytes

PubMed Central

Wang, Hegui; Chen, Yanhong; Zhu, Hongjun; Wang, Sen; Zhang, Xiwen; Xu, Dongjie; Cao, Kejiang; Zou, Jiangang

2012-01-01

Background Increasing evidence indicates that the rapid component of delayed rectifier potassium current (IKr) is modulated by α- and β-adrenergic stimulation. However, the role and mechanism regulating IKr through β2-adrenoreceptor (β-AR) stimulation in heart failure (HF) are unclear. Methodology/Principal Findings In the present study, we investigated the effects of fenoterol, a highly selective β2-AR agonist, on IKr in left ventricular myocytes obtained from control and guinea pigs with HF induced by descending aortic banding. IKr was measured by using whole cell patch clamp technique. In control myocytes, superfusion of fenoterol (10 µM) caused a 17% decrease in IKr. In HF myocytes, the same concentration of fenoterol produced a significantly greater decrease (33%) in IKr. These effects were not modified by the incubation of myocytes with CGP-20712A, a β1-AR antagonist, but were abolished by pretreatment of myocytes with ICI-118551, a β2-AR antagonist. An inhibitory cAMP analog, Rp-cAMPS and PKA inhibitor significantly attenuated fenoterol-induced inhibition of IKr in HF myocytes. Moreover, fenoterol markedly prolonged action potential durations at 90% (APD90) repolarization in HF ventricular myocytes. Conclusions The results indicate that inhibition of IKr induced by β2-AR stimulation is increased in HF. The inhibitory effect is likely to be mediated through a cAMP/PKA pathway in HF ventricular myocytes. PMID:23029432

Long-term bradycardia caused by atrioventricular block can remodel the canine heart to detect the histamine H1 blocker terfenadine-induced torsades de pointes arrhythmias.

PubMed

Takahara, Akira; Sugiyama, Atsushi; Ishida, Yuko; Satoh, Yoshioki; Wang, Kai; Nakamura, Yuji; Hashimoto, Keitaro

2006-03-01

Although a second-generation histamine H(1) blocker terfenadine induced torsades de pointes (TdP) arrhythmias in patients via the blockade of a rapid component of delayed rectifier K(+) current (I(Kr)), such action of terfenadine has not been detected in previous animal models. We analysed the potential of the canine persistent atrioventricular block heart, a new in vivo proarrhythmia model, to detect a torsadogenic effect of terfenadine of an oral dose of 3 or 30 mg kg(-1). The doses can provide therapeutic to supra-therapeutic plasma concentrations as an anti-histamine. In 2 weeks of bradycardiac heart model, there were no significant changes in any of the electrocardiogram parameters after the administration of both doses of terfenadine. In 4-6 weeks of bradycardiac heart model, the low dose of terfenadine hardly affected any of the electrocardiogram parameters except that it induced TdP in one out of six animals. The high dose significantly decreased the atrial rate and ventricular rate, prolonged the QT interval, and induced TdP in five out of six animals. Moreover, temporal variability of repolarization increased after the high-dose administration. These results suggest that long-term bradycardia caused by atrioventricular block can remodel the canine heart to detect terfenadine-induced TdP.

CNFET-based voltage rectifier circuit for biomedical implantable applications

NASA Astrophysics Data System (ADS)

Tu, Yonggen; Qian, Libo; Xia, Yinshui

2017-02-01

Carbon nanotube field effect transistor (CNFET) shows lower threshold voltage and smaller leakage current in comparison to its CMOS counterpart. In this paper, two kinds of CNFET-based rectifiers, full-wave rectifiers and voltage doubler rectifiers are presented for biomedical implantable applications. Based on the standard 32 nm CNFET model, the electrical performance of CNFET rectifiers is analyzed and compared. Simulation results show the voltage conversion efficiency (VCE) and power conversion efficiency (PCE) achieve 70.82% and 72.49% for CNFET full-wave rectifiers and 56.60% and 61.17% for CNFET voltage double rectifiers at typical 1.0 V input voltage excitation, which are higher than that of CMOS design. Moreover, considering the controllable property of CNFET threshold voltage, the effect of various design parameters on the electrical performance is investigated. It is observed that the VCE and PCE of CNFET rectifier increase with increasing CNT diameter and number of tubes. The proposed results would provide some guidelines for design and optimization of CNFET-based rectifier circuits. Project supported by the National Natural Science Foundation of China (Nos. 61131001, 61404077, 61571248), the Science and Technology Fund of Zhejiang Province (No. 2015C31090), the Natural Science Foundation of Ningbo (No. 2014A610147), State Key Laboratory of ASIC & System (No. 2015KF006) and the K. C. Wong Magna Fund in Ningbo University.

Pharmacological Conversion of a Cardiac Inward Rectifier into an Outward Rectifier Potassium Channel.

PubMed

Moreno-Galindo, Eloy G; Sanchez-Chapula, Jose A; Tristani-Firouzi, Martin; Navarro-Polanco, Ricardo A

2016-09-01

Potassium (K(+)) channels are crucial for determining the shape, duration, and frequency of action-potential firing in excitable cells. Broadly speaking, K(+) channels can be classified based on whether their macroscopic current outwardly or inwardly rectifies, whereby rectification refers to a change in conductance with voltage. Outwardly rectifying K(+) channels conduct greater current at depolarized membrane potentials, whereas inward rectifier channels conduct greater current at hyperpolarized membrane potentials. Under most circumstances, outward currents through inwardly rectifying K(+) channels are reduced at more depolarized potentials. However, the acetylcholine-gated K(+) channel (KACh) conducts current that inwardly rectifies when activated by some ligands (such as acetylcholine), and yet conducts current that outwardly rectifies when activated by other ligands (for example, pilocarpine and choline). The perplexing and paradoxical behavior of KACh channels is due to the intrinsic voltage sensitivity of the receptor that activates KACh channels, the M2 muscarinic receptor (M2R). Emerging evidence reveals that the affinity of M2R for distinct ligands varies in a voltage-dependent and ligand-specific manner. These intrinsic receptor properties determine whether current conducted by KACh channels inwardly or outwardly rectifies. This review summarizes the most recent concepts regarding the intrinsic voltage sensitivity of muscarinic receptors and the consequences of this intriguing behavior on cardiac physiology and pharmacology of KACh channels. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

High-voltage 4H-SiC trench MOS barrier Schottky rectifier with low forward voltage drop using enhanced sidewall layer

NASA Astrophysics Data System (ADS)

Cho, Doohyung; Sim, Seulgi; Park, Kunsik; Won, Jongil; Kim, Sanggi; Kim, Kwangsoo

2015-12-01

In this paper, a 4H-SiC trench MOS barrier Schottky (TMBS) rectifier with an enhanced sidewall layer (ESL) is proposed. The proposed structure has a high doping concentration at the trench sidewall. This high doping concentration improves both the reverse blocking and forward characteristics of the structure. The ESL-TMBS rectifier has a 7.4% lower forward voltage drop and a 24% higher breakdown voltage. However, this structure has a reverse leakage current that is approximately three times higher than that of a conventional TMBS rectifier owing to the reduction in energy barrier height. This problem is solved when ESL is used partially, since its use provides a reverse leakage current that is comparable to that of a conventional TMBS rectifier. Thus, the forward voltage drop and breakdown voltage improve without any loss in static and dynamic characteristics in the ESL-TMBS rectifier compared with the performance of a conventional TMBS rectifier.

Timing and teamwork--an observational pilot study of patients referred to a Rapid Response Team with the aim of identifying factors amenable to re-design of a Rapid Response System.

PubMed

Peebles, Emma; Subbe, Christian P; Hughes, Paul; Gemmell, Les

2012-06-01

Rapid Response Teams aim to accelerate recognition and treatment of acutely unwell patients. Delays in delivery might undermine efficiency of the intervention. Our understanding of the causes of these delays is, as yet, incomplete. To identify modifiable causes of delays in the treatment of critically ill patients outside intensive care with a focus on factors amenable to system design. Review of care records and direct observation with process mapping of care delivered to 17 acutely unwell patients attended by a Rapid Response Team in a District General Hospital in the United Kingdom. Delays were defined as processes with no added value for patient care. Essential diagnostic and therapeutic procedures accounted for only 31% of time of care processes. Causes for delays could be classified into themes as (1) delays in call-out of the Rapid Response Team, (2) problems with team cohesion including poor communication and team efficiency and (3) lack of resources including lack of first line antibiotics, essential equipment, experienced staff and critical care beds. We identified a number of potentially modifiable causes for delays in care of acutely ill patients. Improved process design could include automated call-outs, a dedicated kit for emergency treatment in relevant clinical areas, increased usage of standard operating procedures and staff training using crew resource management techniques. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Rectenna for high-voltage applications

NASA Technical Reports Server (NTRS)

Epp, Larry W. (Inventor); Khan, Abdur R. (Inventor)

2002-01-01

An energy transfer system is disclosed. The system includes patch elements, shielding layers, and energy rectifying circuits. The patch elements receive and couple radio frequency energy. The shielding layer includes at least one opening that allows radio frequency energy to pass through. The openings are formed and positioned to receive the radio frequency energy and to minimize any re-radiating back toward the source of energy. The energy rectifying circuit includes a circuit for rectifying the radio frequency energy into dc energy. A plurality of energy rectifying circuits is arranged in an array to provide a sum of dc energy generated by the energy rectifying circuit.

27 CFR 1.21 - Domestic producers, rectifiers, blenders, and warehousemen.

Code of Federal Regulations, 2011 CFR

2011-04-01

... in the business of distilling distilled spirits, producing wine, rectifying or blending distilled... or indirectly or through an affiliate, distilled spirits or wine so distilled, produced, rectified...

Generator voltage stabilisation for series-hybrid electric vehicles.

PubMed

Stewart, P; Gladwin, D; Stewart, J; Cowley, R

2008-04-01

This paper presents a controller for use in speed control of an internal combustion engine for series-hybrid electric vehicle applications. Particular reference is made to the stability of the rectified DC link voltage under load disturbance. In the system under consideration, the primary power source is a four-cylinder normally aspirated gasoline internal combustion engine, which is mechanically coupled to a three-phase permanent magnet AC generator. The generated AC voltage is subsequently rectified to supply a lead-acid battery, and permanent magnet traction motors via three-phase full bridge power electronic inverters. Two complementary performance objectives exist. Firstly to maintain the internal combustion engine at its optimal operating point, and secondly to supply a stable 42 V supply to the traction drive inverters. Achievement of these goals minimises the transient energy storage requirements at the DC link, with a consequent reduction in both weight and cost. These objectives imply constant velocity operation of the internal combustion engine under external load disturbances and changes in both operating conditions and vehicle speed set-points. An electronically operated throttle allows closed loop engine velocity control. System time delays and nonlinearities render closed loop control design extremely problematic. A model-based controller is designed and shown to be effective in controlling the DC link voltage, resulting in the well-conditioned operation of the hybrid vehicle.

Mibefradil (Ro 40-5967) inhibits several Ca2+ and K+ currents in human fusion-competent myoblasts

PubMed Central

Liu, Jian-Hui; Bijlenga, Philippe; Occhiodoro, Teresa; Fischer-Lougheed, Jacqueline; Bader, Charles R; Bernheim, Laurent

1999-01-01

The effect of mibefradil (Ro 40-5967), an inhibitor of T-type Ca2+ current (ICa(T)), on myoblast fusion and on several voltage-gated currents expressed by fusion-competent myoblasts was examined.At a concentration of 5 μM, mibefradil decreases myoblast fusion by 57%. At this concentration, the peak amplitudes of ICa(T) and L-type Ca2+ current (ICa(L)) measured in fusion-competent myoblasts are reduced by 95 and 80%, respectively. The IC50 of mibefradil for ICa(T) and ICa(L) are 0.7 and 2 μM, respectively.At low concentrations, mibefradil increased the amplitude of ICa(L) with respect to control.Mibefradil blocked three voltage-gated K+ currents expressed by human fusion-competent myoblasts: a delayed rectifier K+ current, an ether-à-go-go K+ current, and an inward rectifier K+ current, with a respective IC50 of 0.3, 0.7 and 5.6 μM.It is concluded that mibefradil can interfere with myoblast fusion, a mechanism fundamental to muscle growth and repair, and that the interpretation of the effect of mibefradil in a given system should take into account the action of this drug on ionic currents other than Ca2+ currents. PMID:10051142

Effects of astragaloside IV on action potentials and ionic currents in guinea-pig ventricular myocytes.

PubMed

Zhao, Meimi; Zhao, Jinsheng; He, Guilin; Sun, Xuefei; Huang, Xueshi; Hao, Liying

2013-01-01

Astragaloside IV (AS-IV) is one of the main active constituents of Astragalus membranaceus, which has various actions on the cardiovascular system. However, its electrophysiological mechanisms are not clear. In the present study, we investigated the effects of AS-IV on action potentials and membrane currents using the whole-cell patch clamp technique in isolated guinea-pig ventricular myocytes. AS-IV prolonged the action potential duration (APD) at all three tested concentrations. The peak effect was achieved with 1×10(-6) M, at which concentration AS-IV significantly prolonged the APD at 95% repolarization from 313.1±38.9 to 785.3±83.7 ms. AS-IV at 1×10(-6) M also enhanced the inward rectifier K(+) currents (I(K1)) and inhibited the delayed rectifier K(+) currents (I(K)). AS-IV (1×10(-6) M) strongly depressed the peak of voltage-dependent Ca(2+) channel current (I(CaL)) from -607.3±37.5 to -321.1±38.3 pA. However, AS-IV was not found to affect the Na(+) currents. Taken together, AS-IV prolonged APD of guinea-pig ventricular myocytes, which might be explained by its inhibition of I(K). AS-IV also influences Ca(2+) signaling through suppressing ICaL.

3-D printed 2.4 GHz rectifying antenna for wireless power transfer applications

NASA Astrophysics Data System (ADS)

Skinner, Matthew

In this work, a 3D printed rectifying antenna that operates at the 2.4GHz WiFi band was designed and manufactured. The printed material did not have the same properties of bulk material, so the printed materials needed to be characterized. The antenna and rectifying circuit was printed out of Acrylonitrile Butadiene Styrene (ABS) filament and a conductive silver paste, with electrical components integrated into the circuit. Before printing the full rectifying antenna, each component was printed and evaluated. The printed antenna operated at the desired frequency with a return loss of -16 dBm with a bandwidth of 70MHz. The radiation pattern was measured in an anechoic chamber with good matching to the model. The rectifying circuit was designed in Ansys Circuit Simulation using Schottky diodes to enable the circuit to operate at lower input power levels. Two rectifying circuits were manufactured, one by printing the conductive traces with silver ink, and one with traces made from copper. The printed silver ink is less conductive than the bulk copper and therefore the output voltage of the printed rectifier was lower than the copper circuit. The copper circuit had an efficiency of 60% at 0dBm and the printed silver circuit had an efficiency of 28.6% at 0dBm. The antenna and rectifying circuits were then connected to each other and the performance was compared to a fully printed integrated rectifying antenna. The rectifying antennas were placed in front of a horn antenna while changing the power levels at the antenna. The efficiency of the whole system was lower than the individual components but an efficiency of 11% at 10dBm was measured.

Mechanisms of Firing Patterns in Fast-Spiking Cortical Interneurons

PubMed Central

Golomb, David; Donner, Karnit; Shacham, Liron; Shlosberg, Dan; Amitai, Yael; Hansel, David

2007-01-01

Cortical fast-spiking (FS) interneurons display highly variable electrophysiological properties. Their spike responses to step currents occur almost immediately following the step onset or after a substantial delay, during which subthreshold oscillations are frequently observed. Their firing patterns include high-frequency tonic firing and rhythmic or irregular bursting (stuttering). What is the origin of this variability? In the present paper, we hypothesize that it emerges naturally if one assumes a continuous distribution of properties in a small set of active channels. To test this hypothesis, we construct a minimal, single-compartment conductance-based model of FS cells that includes transient Na+, delayed-rectifier K+, and slowly inactivating d-type K+ conductances. The model is analyzed using nonlinear dynamical system theory. For small Na+ window current, the neuron exhibits high-frequency tonic firing. At current threshold, the spike response is almost instantaneous for small d-current conductance, g d, and it is delayed for larger g d. As g d further increases, the neuron stutters. Noise substantially reduces the delay duration and induces subthreshold oscillations. In contrast, when the Na+ window current is large, the neuron always fires tonically. Near threshold, the firing rates are low, and the delay to firing is only weakly sensitive to noise; subthreshold oscillations are not observed. We propose that the variability in the response of cortical FS neurons is a consequence of heterogeneities in their g d and in the strength of their Na+ window current. We predict the existence of two types of firing patterns in FS neurons, differing in the sensitivity of the delay duration to noise, in the minimal firing rate of the tonic discharge, and in the existence of subthreshold oscillations. We report experimental results from intracellular recordings supporting this prediction. PMID:17696606

Mechanisms of firing patterns in fast-spiking cortical interneurons.

PubMed

Golomb, David; Donner, Karnit; Shacham, Liron; Shlosberg, Dan; Amitai, Yael; Hansel, David

2007-08-01

Cortical fast-spiking (FS) interneurons display highly variable electrophysiological properties. Their spike responses to step currents occur almost immediately following the step onset or after a substantial delay, during which subthreshold oscillations are frequently observed. Their firing patterns include high-frequency tonic firing and rhythmic or irregular bursting (stuttering). What is the origin of this variability? In the present paper, we hypothesize that it emerges naturally if one assumes a continuous distribution of properties in a small set of active channels. To test this hypothesis, we construct a minimal, single-compartment conductance-based model of FS cells that includes transient Na(+), delayed-rectifier K(+), and slowly inactivating d-type K(+) conductances. The model is analyzed using nonlinear dynamical system theory. For small Na(+) window current, the neuron exhibits high-frequency tonic firing. At current threshold, the spike response is almost instantaneous for small d-current conductance, gd, and it is delayed for larger gd. As gd further increases, the neuron stutters. Noise substantially reduces the delay duration and induces subthreshold oscillations. In contrast, when the Na(+) window current is large, the neuron always fires tonically. Near threshold, the firing rates are low, and the delay to firing is only weakly sensitive to noise; subthreshold oscillations are not observed. We propose that the variability in the response of cortical FS neurons is a consequence of heterogeneities in their gd and in the strength of their Na(+) window current. We predict the existence of two types of firing patterns in FS neurons, differing in the sensitivity of the delay duration to noise, in the minimal firing rate of the tonic discharge, and in the existence of subthreshold oscillations. We report experimental results from intracellular recordings supporting this prediction.

Effects of 22 MeV protons on single junction and silicon controlled rectifiers

NASA Technical Reports Server (NTRS)

Beatty, M. E., III

1972-01-01

The effects of 22-MeV protons on various types of silicon single junction and silicon controlled rectifiers were investigated. The results show that low-leakage devices and silicon controlled rectifiers are the most susceptable to radiation damage. There are also differences noted between single junction rectifiers of the same type made by different manufacturers, which emphasizes the need for better selection of devices used in spacecraft.

Automatic method of measuring silicon-controlled-rectifier holding current

NASA Technical Reports Server (NTRS)

Maslowski, E. A.

1972-01-01

Development of automated silicon controlled rectifier circuit for measuring minimum anode current required to maintain rectifiers in conducting state is discussed. Components of circuit are described and principles of operation are explained. Illustration of circuit is provided.

Inhibition of cardiac inward rectifier currents by cationic amphiphilic drugs.

PubMed

van der Heyden, M A G; Stary-Weinzinger, A; Sanchez-Chapula, J A

2013-09-01

Cardiac inward rectifier channels belong to three different classes of the KIR channel protein family. The KIR2.x proteins generate the classical inward rectifier current, IK1, while KIR3 and KIR6 members are responsible for the acetylcholine responsive and ATP sensitive inward rectifier currents IKAch and IKATP, respectively. Aberrant function of these channels has been correlated with severe cardiac arrhythmias, indicating their significant contribution to normal cardiac electrophysiology. A common feature of inward rectifier channels is their dependence on the lipid phosphatidyl-4,5-bisphospate (PIP2) interaction for functional activity. Cationic amphiphilic drugs (CADs) are one of the largest classes of pharmaceutical compounds. Several widely used CADs have been associated with inward rectifier current disturbances, and recent evidence points to interference of the channel-PIP2 interaction as the underlying mechanism of action. Here, we will review how six of these well known drugs, used for treatment in various different conditions, interfere in cardiac inward rectifier functioning. In contrast, KIR channel inhibition by the anionic anesthetic thiopental is achieved by a different mechanism of channel-PIP2 interference. We will discuss the latest basic science insights of functional inward rectifier current characteristics, recently derived KIR channel structures and specific PIP2-receptor interactions at the molecular level and provide insight in how these drugs interfere in the structure-function relationships.

Floating-Gate Manipulated Graphene-Black Phosphorus Heterojunction for Nonvolatile Ambipolar Schottky Junction Memories, Memory Inverter Circuits, and Logic Rectifiers.

PubMed

Li, Dong; Chen, Mingyuan; Zong, Qijun; Zhang, Zengxing

2017-10-11

The Schottky junction is an important unit in electronics and optoelectronics. However, its properties greatly degrade with device miniaturization. The fast development of circuits has fueled a rapid growth in the study of two-dimensional (2D) crystals, which may lead to breakthroughs in the semiconductor industry. Here we report a floating-gate manipulated nonvolatile ambipolar Schottky junction memory from stacked all-2D layers of graphene-BP/h-BN/graphene (BP, black phosphorus; h-BN, hexagonal boron nitride) in a designed floating-gate field-effect Schottky barrier transistor configuration. By manipulating the voltage pulse applied to the control gate, the device exhibits ambipolar characteristics and can be tuned to act as graphene-p-BP or graphene-n-BP junctions with reverse rectification behavior. Moreover, the junction exhibits good storability properties of more than 10 years and is also programmable. On the basis of these characteristics, we further demonstrate the application of the device to dual-mode nonvolatile Schottky junction memories, memory inverter circuits, and logic rectifiers.

Initial segment Kv2.2 channels mediate a slow delayed rectifier and maintain high frequency action potential firing in medial nucleus of the trapezoid body neurons

PubMed Central

Johnston, Jamie; Griffin, Sarah J; Baker, Claire; Skrzypiec, Anna; Chernova, Tatanya; Forsythe, Ian D

2008-01-01

The medial nucleus of the trapezoid body (MNTB) is specialized for high frequency firing by expression of Kv3 channels, which minimize action potential (AP) duration, and Kv1 channels, which suppress multiple AP firing, during each calyceal giant EPSC. However, the outward K+ current in MNTB neurons is dominated by another unidentified delayed rectifier. It has slow kinetics and a peak conductance of ∼37 nS; it is half-activated at −9.2 ± 2.1 mV and half-inactivated at −35.9 ± 1.5 mV. It is blocked by several non-specific potassium channel antagonists including quinine (100 μm) and high concentrations of extracellular tetraethylammonium (TEA; IC50 = 11.8 mm), but no specific antagonists were found. These characteristics are similar to recombinant Kv2-mediated currents. Quantitative RT-PCR showed that Kv2.2 mRNA was much more prevalent than Kv2.1 in the MNTB. A Kv2.2 antibody showed specific staining and Western blots confirmed that it recognized a protein ∼110 kDa which was absent in brainstem tissue from a Kv2.2 knockout mouse. Confocal imaging showed that Kv2.2 was highly expressed in axon initial segments of MNTB neurons. In the absence of a specific antagonist, Hodgkin–Huxley modelling of voltage-gated conductances showed that Kv2.2 has a minor role during single APs (due to its slow activation) but assists recovery of voltage-gated sodium channels (Nav) from inactivation by hyperpolarizing interspike potentials during repetitive AP firing. Current-clamp recordings during high frequency firing and characterization of Nav inactivation confirmed this hypothesis. We conclude that Kv2.2-containing channels have a distinctive initial segment location and crucial function in maintaining AP amplitude by regulating the interspike potential during high frequency firing. PMID:18511484

Effects of electrical loads containing non-resistive components on electromagnetic vibration energy harvester performance

NASA Astrophysics Data System (ADS)

Zhang, Hui; Corr, Lawrence R.; Ma, Tianwei

2018-02-01

To further advance the existing knowledge base on rectified vibration energy harvester design, this study investigates the fundamental effects of electrical loads containing non-resistive components (e.g., rectifiers and capacitors) on electromagnetic energy harvester performance. Three types of electrical loads, namely (I) a resistor with a rectifier, (II) a resistor with a rectifier and a capacitor, and (III) a simple charging circuit consisting of a rectifier and a capacitor, were considered. A linear electromagnetic energy harvester was used as an illustrative example. Results have verified that device performance obtained from pure-resistive loads cannot be generalized to applications involving rectifier and/or capacitor loads. Such generalization caused not only an overestimation in the maximum power delivered to the load resistance for cases (I) and (II), but also an underestimation of the optimal load resistance and an overestimation of device natural frequency for case (II). Results obtained from case (II) also showed that it is possible to tune the mechanical natural frequency of device using an adjustable regulating capacitor. For case (III), it was found that a larger storing capacitor, with a low rectifier voltage drop, improves the performance of the electromagnetic harvester.

New Analysis and Design of a RF Rectifier for RFID and Implantable Devices

PubMed Central

Liu, Dong-Sheng; Li, Feng-Bo; Zou, Xue-Cheng; Liu, Yao; Hui, Xue-Mei; Tao, Xiong-Fei

2011-01-01

New design and optimization of charge pump rectifiers using diode-connected MOS transistors is presented in this paper. An analysis of the output voltage and Power Conversion Efficiency (PCE) is given to guide and evaluate the new design. A novel diode-connected MOS transistor for UHF rectifiers is presented and optimized, and a high efficiency N-stage charge pump rectifier based on this new diode-connected MOS transistor is designed and fabricated in a SMIC 0.18-μm 2P3M CMOS embedded EEPROM process. The new diode achieves 315 mV turn-on voltage and 415 nA reverse saturation leakage current. Compared with the traditional rectifier, the one based on the proposed diode-connected MOS has higher PCE, higher output voltage and smaller ripple coefficient. When the RF input is a 900-MHz sinusoid signal with the power ranging from −15 dBm to −4 dBm, PCEs of the charge pump rectifier with only 3-stage are more than 30%, and the maximum output voltage is 5.5 V, and its ripple coefficients are less than 1%. Therefore, the rectifier is especially suitableto passive UHF RFID tag IC and implantable devices. PMID:22163968

New analysis and design of a RF rectifier for RFID and implantable devices.

PubMed

Liu, Dong-Sheng; Li, Feng-Bo; Zou, Xue-Cheng; Liu, Yao; Hui, Xue-Mei; Tao, Xiong-Fei

2011-01-01

New design and optimization of charge pump rectifiers using diode-connected MOS transistors is presented in this paper. An analysis of the output voltage and Power Conversion Efficiency (PCE) is given to guide and evaluate the new design. A novel diode-connected MOS transistor for UHF rectifiers is presented and optimized, and a high efficiency N-stage charge pump rectifier based on this new diode-connected MOS transistor is designed and fabricated in a SMIC 0.18-μm 2P3M CMOS embedded EEPROM process. The new diode achieves 315 mV turn-on voltage and 415 nA reverse saturation leakage current. Compared with the traditional rectifier, the one based on the proposed diode-connected MOS has higher PCE, higher output voltage and smaller ripple coefficient. When the RF input is a 900-MHz sinusoid signal with the power ranging from -15 dBm to -4 dBm, PCEs of the charge pump rectifier with only 3-stage are more than 30%, and the maximum output voltage is 5.5 V, and its ripple coefficients are less than 1%. Therefore, the rectifier is especially suitable to passive UHF RFID tag IC and implantable devices.

46 CFR 129.360 - Semiconductor-rectifier systems.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 4 2014-10-01 2014-10-01 false Semiconductor-rectifier systems. 129.360 Section 129.360 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OFFSHORE SUPPLY VESSELS ELECTRICAL INSTALLATIONS Power Sources and Distribution Systems § 129.360 Semiconductor-rectifier systems. (a) Each...

46 CFR 129.360 - Semiconductor-rectifier systems.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 4 2013-10-01 2013-10-01 false Semiconductor-rectifier systems. 129.360 Section 129.360 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OFFSHORE SUPPLY VESSELS ELECTRICAL INSTALLATIONS Power Sources and Distribution Systems § 129.360 Semiconductor-rectifier systems. (a) Each...

46 CFR 129.360 - Semiconductor-rectifier systems.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 4 2012-10-01 2012-10-01 false Semiconductor-rectifier systems. 129.360 Section 129.360 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OFFSHORE SUPPLY VESSELS ELECTRICAL INSTALLATIONS Power Sources and Distribution Systems § 129.360 Semiconductor-rectifier systems. (a) Each...

Effect of dissolved gases in water on acoustic cavitation and bubble growth rate in 0.83 MHz megasonic of interest to wafer cleaning.

PubMed

Kang, Bong-Kyun; Kim, Min-Su; Park, Jin-Goo

2014-07-01

Changes in the cavitation intensity of gases dissolved in water, including H2, N2, and Ar, have been established in studies of acoustic bubble growth rates under ultrasonic fields. Variations in the acoustic properties of dissolved gases in water affect the cavitation intensity at a high frequency (0.83 MHz) due to changes in the rectified diffusion and bubble coalescence rate. It has been proposed that acoustic bubble growth rates rapidly increase when water contains a gas, such as hydrogen faster single bubble growth due to rectified diffusion, and a higher rate of coalescence under Bjerknes forces. The change of acoustic bubble growth rate in rectified diffusion has an effect on the damping constant and diffusivity of gas at the acoustic bubble and liquid interface. It has been suggested that the coalescence reaction of bubbles under Bjerknes forces is a reaction determined by the compressibility and density of dissolved gas in water associated with sound velocity and density in acoustic bubbles. High acoustic bubble growth rates also contribute to enhanced cavitation effects in terms of dissolved gas in water. On the other hand, when Ar gas dissolves into water under ultrasound field, cavitation behavior was reduced remarkably due to its lower acoustic bubble growth rate. It is shown that change of cavitation intensity in various dissolved gases were verified through cleaning experiments in the single type of cleaning tool such as particle removal and pattern damage based on numerically calculated acoustic bubble growth rates. Copyright © 2014 Elsevier B.V. All rights reserved.

An overview of self-switching diode rectifiers using green materials

NASA Astrophysics Data System (ADS)

Kasjoo, Shahrir Rizal; Zailan, Zarimawaty; Zakaria, Nor Farhani; Isa, Muammar Mohamad; Arshad, Mohd Khairuddin Md; Taking, Sanna

2017-09-01

A unipolar two-terminal nanodevice, known as the self-switching diode (SSD), has recently been demonstrated as a room-temperature rectifier at microwave and terahertz frequencies due to its nonlinear current-voltage characteristic. The planar architecture of SSD not only makes the fabrication process of the device faster, simpler and at a lower cost when compared with other rectifying diodes, but also allows the use of various materials to realize and fabricate SSDs. This includes the utilization of `green' materials such as organic and graphene thin films for environmental sustainability. This paper reviews the properties of current `green' SSD rectifiers with respect to their operating frequencies and rectifying performances, including responsivity and noise-equivalent power of the devices, along with the applications.

46 CFR 183.360 - Semiconductor rectifier systems.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 7 2014-10-01 2014-10-01 false Semiconductor rectifier systems. 183.360 Section 183.360 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS (UNDER 100 GROSS TONS) ELECTRICAL INSTALLATION Power Sources and Distribution Systems § 183.360 Semiconductor rectifier...

46 CFR 183.360 - Semiconductor rectifier systems.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 7 2012-10-01 2012-10-01 false Semiconductor rectifier systems. 183.360 Section 183.360 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS (UNDER 100 GROSS TONS) ELECTRICAL INSTALLATION Power Sources and Distribution Systems § 183.360 Semiconductor rectifier...

46 CFR 183.360 - Semiconductor rectifier systems.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 7 2013-10-01 2013-10-01 false Semiconductor rectifier systems. 183.360 Section 183.360 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS (UNDER 100 GROSS TONS) ELECTRICAL INSTALLATION Power Sources and Distribution Systems § 183.360 Semiconductor rectifier...

Electrophysiological properties of myocytes isolated from the mouse atrioventricular node: L-type ICa, IKr, If, and Na-Ca exchange.

PubMed

Choisy, Stéphanie C; Cheng, Hongwei; Orchard, Clive H; James, Andrew F; Hancox, Jules C

2015-11-01

The atrioventricular node (AVN) is a key component of the cardiac pacemaker-conduction system. This study investigated the electrophysiology of cells isolated from the AVN region of adult mouse hearts, and compared murine ionic current magnitude with that of cells from the more extensively studied rabbit AVN. Whole-cell patch-clamp recordings of ionic currents, and perforated-patch recordings of action potentials (APs), were made at 35-37°C. Hyperpolarizing voltage commands from -40 mV elicited a Ba(2+)-sensitive inward rectifier current that was small at diastolic potentials. Some cells (Type 1; 33.4 ± 2.2 pF; n = 19) lacked the pacemaker current, If, whilst others (Type 2; 34.2 ± 1.5 pF; n = 21) exhibited a clear If, which was larger than in rabbit AVN cells. On depolarization from -40 mV L-type Ca(2+) current, IC a,L, was elicited with a half maximal activation voltage (V0.5) of -7.6 ± 1.2 mV (n = 24). IC a,L density was smaller than in rabbit AVN cells. Rapid delayed rectifier (IK r) tail currents sensitive to E-4031 (5 μmol/L) were observed on repolarization to -40 mV, with an activation V0.5 of -10.7 ± 4.7 mV (n = 8). The IK r magnitude was similar in mouse and rabbit AVN. Under Na-Ca exchange selective conditions, mouse AVN cells exhibited 5 mmol/L Ni-sensitive exchange current that was inwardly directed negative to the holding potential (-40 mV). Spontaneous APs (5.2 ± 0.5 sec(-1); n = 6) exhibited an upstroke velocity of 37.7 ± 16.2 V/s and ceased following inhibition of sarcoplasmic reticulum Ca(2+) release by 1 μmol/L ryanodine, implicating intracellular Ca(2+) cycling in murine AVN cell electrogenesis. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

The Role of Monoubiquitination in Endocytic Degradation of Human Ether-a-go-go-related Gene (hERG) Channels under Low K+ Conditions*

PubMed Central

Sun, Tao; Guo, Jun; Shallow, Heidi; Yang, Tonghua; Xu, Jianmin; Li, Wentao; Hanson, Christian; Wu, James G.; Li, Xian; Massaeli, Hamid; Zhang, Shetuan

2011-01-01

A reduction in extracellular K+ concentration ([K+]o) causes cardiac arrhythmias and triggers internalization of the cardiac rapidly activating delayed rectifier potassium channel (IKr) encoded by the human ether-a-go-go-related gene (hERG). We investigated the role of ubiquitin (Ub) in endocytic degradation of hERG channels stably expressed in HEK cells. Under low K+ conditions, UbKO, a lysine-less mutant Ub that only supports monoubiquitination, preferentially interacted and selectively enhanced degradation of the mature hERG channels. Overexpression of Vps24 protein, also known as charged multivesicular body protein 3, significantly accelerated degradation of mature hERG channels, whereas knockdown of Vps24 impeded this process. Moreover, the lysosomal inhibitor bafilomycin A1 inhibited degradation of the internalized mature hERG channels. Thus, monoubiquitination directs mature hERG channels to degrade through the multivesicular body/lysosome pathway. Interestingly, the protease inhibitor lactacystin inhibited the low K+-induced hERG endocytosis and concomitantly led to an accumulation of monoubiquitinated mature hERG channels, suggesting that deubiquitination is also required for the endocytic degradation. Consistently, overexpression of the endosomal deubiquitinating enzyme signal transducing adaptor molecule-binding protein significantly accelerated whereas knockdown of endogenous signal transducing adaptor molecule-binding protein impeded degradation of the mature hERG channels under low K+ conditions. Thus, monoubiquitin dynamically mediates endocytic degradation of mature hERG channels under low K+ conditions. PMID:21177251

Involvement of Caveolin in Low K+-induced Endocytic Degradation of Cell-surface Human Ether-a-go-go-related Gene (hERG) Channels*

PubMed Central

Massaeli, Hamid; Sun, Tao; Li, Xian; Shallow, Heidi; Wu, Jimmy; Xu, Jianmin; Li, Wentao; Hanson, Christian; Guo, Jun; Zhang, Shetuan

2010-01-01

Reduction in the rapidly activating delayed rectifier K+ channel current (IKr) due to either mutations in the human ether-a-go-go-related gene (hERG) or drug block causes inherited or drug-induced long QT syndrome. A reduction in extracellular K+ concentration ([K+]o) exacerbates long QT syndrome. Recently, we demonstrated that lowering [K+]o promotes degradation of IKr in rabbit ventricular myocytes and of the hERG channel stably expressed in HEK 293 cells. In this study, we investigated the degradation pathways of hERG channels under low K+ conditions. We demonstrate that under low K+ conditions, mature hERG channels and caveolin-1 (Cav1) displayed a parallel time-dependent reduction. Mature hERG channels coprecipitated with Cav1 in co-immunoprecipitation analysis, and internalized hERG channels colocalized with Cav1 in immunocytochemistry analysis. Overexpression of Cav1 accelerated internalization of mature hERG channels in 0 mm K+o, whereas knockdown of Cav1 impeded this process. In addition, knockdown of dynamin 2 using siRNA transfection significantly impeded hERG internalization and degradation under low K+o conditions. In cultured neonatal rat ventricular myocytes, knockdown of caveolin-3 significantly impeded low K+o-induced reduction of IKr. Our data indicate that a caveolin-dependent endocytic route is involved in low K+o-induced degradation of mature hERG channels. PMID:20605793

Increased response to β₂-adrenoreceptor stimulation augments inhibition of IKr in heart failure ventricular myocytes.

PubMed

Wang, Hegui; Chen, Yanhong; Zhu, Hongjun; Wang, Sen; Zhang, Xiwen; Xu, Dongjie; Cao, Kejiang; Zou, Jiangang

2012-01-01

Increasing evidence indicates that the rapid component of delayed rectifier potassium current (I(Kr)) is modulated by α- and β-adrenergic stimulation. However, the role and mechanism regulating I(Kr) through β(2)-adrenoreceptor (β-AR) stimulation in heart failure (HF) are unclear. In the present study, we investigated the effects of fenoterol, a highly selective β(2)-AR agonist, on I(Kr) in left ventricular myocytes obtained from control and guinea pigs with HF induced by descending aortic banding. I(Kr) was measured by using whole cell patch clamp technique. In control myocytes, superfusion of fenoterol (10 µM) caused a 17% decrease in I(Kr). In HF myocytes, the same concentration of fenoterol produced a significantly greater decrease (33%) in I(Kr). These effects were not modified by the incubation of myocytes with CGP-20712A, a β(1)-AR antagonist, but were abolished by pretreatment of myocytes with ICI-118551, a β(2)-AR antagonist. An inhibitory cAMP analog, Rp-cAMPS and PKA inhibitor significantly attenuated fenoterol-induced inhibition of I(Kr) in HF myocytes. Moreover, fenoterol markedly prolonged action potential durations at 90% (APD(90)) repolarization in HF ventricular myocytes. The results indicate that inhibition of I(Kr) induced by β(2)-AR stimulation is increased in HF. The inhibitory effect is likely to be mediated through a cAMP/PKA pathway in HF ventricular myocytes.

NMR solution structure of the N-terminal domain of hERG and its interaction with the S4-S5 linker

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

Li, Qingxin; Gayen, Shovanlal; Chen, Angela Shuyi

Research highlights: {yields} The N-terminal domain (NTD, eag domain) containing 135 residues of hERG was expressed and purified from E. coli cells. {yields} Solution structure of NTD was determined with NMR spectroscopy. {yields} The alpha-helical region (residues 13-23) was demonstrated to possess the characteristics of an amphipathic helix. {yields} NMR titration confirmed the interaction between NTD and the peptide from the S4-S5 linker. -- Abstract: The human Ether-a-go-go Related Gene (hERG) potassium channel mediates the rapid delayed rectifier current (IKr) in the cardiac action potential. Mutations in the 135 amino acid residue N-terminal domain (NTD) cause channel dysfunction or mis-translocation.more » To study the structure of NTD, it was overexpressed and purified from Escherichia coli cells using affinity purification and gel filtration chromatography. The purified protein behaved as a monomer under purification conditions. Far- and near-UV, circular dichroism (CD) and solution nuclear magnetic resonance (NMR) studies showed that the purified protein was well-folded. The solution structure of NTD was obtained and the N-terminal residues 13-23 forming an amphipathic helix which may be important for the protein-protein or protein-membrane interactions. NMR titration experiment also demonstrated that residues from 88 to 94 in NTD are important for the molecular interaction with the peptide derived from the S4-S5 linker.« less

27 CFR 1.21 - Domestic producers, rectifiers, blenders, and warehousemen.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Domestic producers, rectifiers, blenders, and warehousemen. 1.21 Section 1.21 Alcohol, Tobacco Products and Firearms ALCOHOL AND... BOTTLING OF DISTILLED SPIRITS Basic Permits When Required § 1.21 Domestic producers, rectifiers, blenders...

27 CFR 26.40 - Marking containers of distilled spirits.

Code of Federal Regulations, 2010 CFR

2010-04-01

... spirits. The distiller, rectifier, or bottler shall serially number each case, barrel, cask, or similar... the container, the distiller, rectifier, or bottler shall plainly print, stamp, or stencil with..., rectifier, or bottler. (b) The brand name and kind of liquor; (c) The wine and proof gallon contents; or...

Brushless exciters using a high temperature superconducting field winding

DOEpatents

Garces, Luis Jose [Schenectady, NY; Delmerico, Robert William [Clifton Park, NY; Jansen, Patrick Lee [Scotia, NY; Parslow, John Harold [Scotia, NY; Sanderson, Harold Copeland [Tribes Hill, NY; Sinha, Gautam [Chesterfield, MO

2008-03-18

A brushless exciter for a synchronous generator or motor generally includes a stator and a rotor rotatably disposed within the stator. The rotor has a field winding and a voltage rectifying bridge circuit connected in parallel to the field winding. A plurality of firing circuits are connected the voltage rectifying bridge circuit. The firing circuit is configured to fire a signal at an angle of less than 90.degree. or at an angle greater than 90.degree.. The voltage rectifying bridge circuit rectifies the AC voltage to excite or de-excite the field winding.

Tunable all-optical plasmonic rectifier in nanoscale metal-insulator-metal waveguides.

PubMed

Xu, Yi; Wang, Xiaomeng; Deng, Haidong; Guo, Kangxian

2014-10-15

We propose a tunable all-optical plasmonic rectifier based on the nonlinear Fano resonance in a metal-insulator-metal plasmonic waveguide and cavities coupling system. We develop a theoretical model based on the temporal coupled-mode theory to study the device physics of the nanoscale rectifier. We further demonstrate via the finite difference time domain numerical experiment that our idea can be realized in a plasmonic system with an ultracompact size of ~120×800  nm². The tunable plasmonic rectifier could facilitate the all-optical signal processing in nanoscale.

Changes in Inward Rectifier K+ Channels in Hepatic Stellate Cells During Primary Culture

PubMed Central

Lee, Dong Hyeon; Kong, In Deok; Lee, Joong-Woo

2008-01-01

Purpose This study examined the expression and function of inward rectifier K+ channels in cultured rat hepatic stellate cells (HSC). Materials and Methods The expression of inward rectifier K+ channels was measured using real-time RT-PCR, and electrophysiological properties were determined using the gramicidin-perforated patch-clamp technique. Results The dominant inward rectifier K+ channel subtypes were Kir2.1 and Kir6.1. These dominant K+ channel subtypes decreased significantly during the primary culture throughout activation process. HSC can be classified into two subgroups: one with an inward-rectifying K+ current (type 1) and the other without (type 2). The inward current was blocked by Ba2+ (100 µM) and enhanced by high K+ (140 mM), more prominently in type 1 HSC. There was a correlation between the amplitude of the Ba2+-sensitive current and the membrane potential. In addition, Ba2+ (300 µM) depolarized the membrane potential. After the culture period, the amplitude of the inward current decreased and the membrane potential became depolarized. Conclusion HSC express inward rectifier K+ channels, which physiologically regulate membrane potential and decrease during the activation process. These results will potentially help determine properties of the inward rectifier K+ channels in HSC as well as their roles in the activation process. PMID:18581597

Photojunction field-effect transistor based on a colloidal quantum dot absorber channel layer.

PubMed

Adinolfi, Valerio; Kramer, Illan J; Labelle, André J; Sutherland, Brandon R; Hoogland, S; Sargent, Edward H

2015-01-27

The performance of photodetectors is judged via high responsivity, fast speed of response, and low background current. Many previously reported photodetectors based on size-tuned colloidal quantum dots (CQDs) have relied either on photodiodes, which, since they are primary photocarrier devices, lack gain; or photoconductors, which provide gain but at the expense of slow response (due to delayed charge carrier escape from sensitizing centers) and an inherent dark current vs responsivity trade-off. Here we report a photojunction field-effect transistor (photoJFET), which provides gain while breaking prior photoconductors' response/speed/dark current trade-off. This is achieved by ensuring that, in the dark, the channel is fully depleted due to a rectifying junction between a deep-work-function transparent conductive top contact (MoO3) and a moderately n-type CQD film (iodine treated PbS CQDs). We characterize the rectifying behavior of the junction and the linearity of the channel characteristics under illumination, and we observe a 10 μs rise time, a record for a gain-providing, low-dark-current CQD photodetector. We prove, using an analytical model validated using experimental measurements, that for a given response time the device provides a two-orders-of-magnitude improvement in photocurrent-to-dark-current ratio compared to photoconductors. The photoJFET, which relies on a junction gate-effect, enriches the growing family of CQD photosensitive transistors.

Improving Heat Transfer at the Bottom of Vials for Consistent Freeze Drying with Unidirectional Structured Ice.

PubMed

Rosa, Mónica; Tiago, João M; Singh, Satish K; Geraldes, Vítor; Rodrigues, Miguel A

2016-10-01

The quality of lyophilized products is dependent of the ice structure formed during the freezing step. Herein, we evaluate the importance of the air gap at the bottom of lyophilization vials for consistent nucleation, ice structure, and cake appearance. The bottom of lyophilization vials was modified by attaching a rectified aluminum disc with an adhesive material. Freezing was studied for normal and converted vials, with different volumes of solution, varying initial solution temperature (from 5°C to 20°C) and shelf temperature (from -20°C to -40°C). The impact of the air gap on the overall heat transfer was interpreted with the assistance of a computational fluid dynamics model. Converted vials caused nucleation at the bottom and decreased the nucleation time up to one order of magnitude. The formation of ice crystals unidirectionally structured from bottom to top lead to a honeycomb-structured cake after lyophilization of a solution with 4% mannitol. The primary drying time was reduced by approximately 35%. Converted vials that were frozen radially instead of bottom-up showed similar improvements compared with normal vials but very poor cake quality. Overall, the curvature of the bottom of glass vials presents a considerable threat to consistency by delaying nucleation and causing radial ice growth. Rectifying the vials bottom with an adhesive material revealed to be a relatively simple alternative to overcome this inconsistency.

Regional analysis of whole cell currents from hair cells of the turtle posterior crista.

PubMed

Brichta, Alan M; Aubert, Anne; Eatock, Ruth Anne; Goldberg, Jay M

2002-12-01

The turtle posterior crista is made up of two hemicristae, each consisting of a central zone containing type I and type II hair cells and a surrounding peripheral zone containing only type II hair cells and extending from the planum semilunatum to the nonsensory torus. Afferents from various regions of a hemicrista differ in their discharge properties. To see if afferent diversity is related to the basolateral currents of the hair cells innervated, we selectively harvested type I and II hair cells from the central zone and type II hair cells from two parts of the peripheral zone, one near the planum and the other near the torus. Voltage-dependent currents were studied with the whole cell, ruptured-patch method and characterized in voltage-clamp mode. We found regional differences in both outwardly and inwardly rectifying voltage-sensitive currents. As in birds and mammals, type I hair cells have a distinctive outwardly rectifying current (I(K,L)), which begins activating at more hyperpolarized voltages than do the outward currents of type II hair cells. Activation of I(K,L) is slow and sigmoidal. Maximal outward conductances are large. Outward currents in type II cells vary in their activation kinetics. Cells with fast kinetics are associated with small conductances and with partial inactivation during 200-ms depolarizing voltage steps. Almost all type II cells in the peripheral zone and many in the central zone have fast kinetics. Some type II cells in the central zone have large outward currents with slow kinetics and little inactivation. Although these currents resemble I(K,L), they can be distinguished from the latter both electrophysiologically and pharmacologically. There are two varieties of inwardly rectifying currents in type II hair cells: activation of I(K1) is rapid and monoexponential, whereas that of I(h) is slow and sigmoidal. Many type II cells either have both inward currents or only have I(K1); very few cells only have I(h). Inward currents are less conspicuous in type I cells. Type II cells near the torus have smaller outwardly rectifying currents and larger inwardly rectifying currents than those near the planum, but the differences are too small to account for variations in discharge properties of bouton afferents innervating the two regions of the peripheral zone. The large outward conductances seen in central cells, by lowering impedances, may contribute to the low rotational gains of some central-zone afferents.

Characterization of two distinct depolarization-activated K+ currents in isolated adult rat ventricular myocytes

PubMed Central

1991-01-01

Depolarization-activated outward K+ currents in isolated adult rat ventricular myocytes were characterized using the whole-cell variation of the patch-clamp recording technique. During brief depolarizations to potentials positive to -40 mV, Ca(2+)-independent outward K+ currents in these cells rise to a transient peak, followed by a slower decay to an apparent plateau. The analyses completed here reveal that the observed outward current waveforms result from the activation of two kinetically distinct voltage-dependent K+ currents: one that activates and inactivates rapidly, and one that activates and inactivates slowly, on membrane depolarization. These currents are referred to here as Ito (transient outward) and IK (delayed rectifier), respectively, because their properties are similar (although not identical) to these K+ current types in other cells. Although the voltage dependences of Ito and IK activation are similar, Ito activates approximately 10-fold and inactivates approximately 30-fold more rapidly than IK at all test potentials. In the composite current waveforms measured during brief depolarizations, therefore, the peak current predominantly reflects Ito, whereas IK is the primary determinant of the plateau. There are also marked differences in the voltage dependences of steady-state inactivation of these two K+ currents: IK undergoes steady-state inactivation at all potentials positive to -120 mV, and is 50% inactivated at -69 mV; Ito, in contrast, is insensitive to steady-state inactivation at membrane potentials negative to -50 mV. In addition, Ito recovers from steady-state inactivation faster than IK: at -90 mV, for example, approximately 70% recovery from the inactivation produced at -20 mV is observed within 20 ms for Ito; IK recovers approximately 25-fold more slowly. The pharmacological properties of Ito and IK are also distinct: 4-aminopyridine preferentially attenuates Ito, and tetraethylammonium suppresses predominantly IK. The voltage- and time- dependent properties of these currents are interpreted here in terms of a model in which Ito underlies the initial, rapid repolarization phase of the action potential (AP), and IK is responsible for the slower phase of AP repolarization back to the resting membrane potential, in adult rat ventricular myocytes. PMID:1865177

Inward rectifier potassium currents in mammalian skeletal muscle fibres

PubMed Central

DiFranco, Marino; Yu, Carl; Quiñonez, Marbella; Vergara, Julio L

2015-01-01

Inward rectifying potassium (Kir) channels play a central role in maintaining the resting membrane potential of skeletal muscle fibres. Nevertheless their role has been poorly studied in mammalian muscles. Immunohistochemical and transgenic expression were used to assess the molecular identity and subcellular localization of Kir channel isoforms. We found that Kir2.1 and Kir2.2 channels were targeted to both the surface andthe transverse tubular system membrane (TTS) compartments and that both isoforms can be overexpressed up to 3-fold 2 weeks after transfection. Inward rectifying currents (IKir) had the canonical features of quasi-instantaneous activation, strong inward rectification, depended on the external [K+], and could be blocked by Ba2+ or Rb+. In addition, IKir records show notable decays during large 100 ms hyperpolarizing pulses. Most of these properties were recapitulated by model simulations of the electrical properties of the muscle fibre as long as Kir channels were assumed to be present in the TTS. The model also simultaneously predicted the characteristics of membrane potential changes of the TTS, as reported optically by a fluorescent potentiometric dye. The activation of IKir by large hyperpolarizations resulted in significant attenuation of the optical signals with respect to the expectation for equal magnitude depolarizations; blocking IKir with Ba2+ (or Rb+) eliminated this attenuation. The experimental data, including the kinetic properties of IKir and TTS voltage records, and the voltage dependence of peak IKir, while measured at widely dissimilar bulk [K+] (96 and 24 mm), were closely predicted by assuming Kir permeability (PKir) values of ∼5.5 × 10−6 cm s−1 and equal distribution of Kir channels at the surface and TTS membranes. The decay of IKir records and the simultaneous increase in TTS voltage changes were mostly explained by K+ depletion from the TTS lumen. Most importantly, aside from allowing an accurate estimation of most of the properties of IKir in skeletal muscle fibres, the model demonstrates that a substantial proportion of IKir (>70%) arises from the TTS. Overall, our work emphasizes that measured intrinsic properties (inward rectification and external [K] dependence) and localization of Kir channels in the TTS membranes are ideally suited for re-capturing potassium ions from the TTS lumen during, and immediately after, repetitive stimulation under physiological conditions. Key points This paper provides a comprehensive electrophysiological characterization of the external [K+] dependence and inward rectifying properties of Kir channels in fast skeletal muscle fibres of adult mice. Two isoforms of inward rectifier K channels (IKir2.1 and IKir2.2) are expressed in both the surface and the transverse tubular system (TTS) membranes of these fibres. Optical measurements demonstrate that Kir currents (IKir) affect the membrane potential changes in the TTS membranes, and result in a reduction in luminal [K+]. A model of the muscle fibre assuming that functional Kir channels are equally distributed between the surface and TTS membranes accounts for both the electrophysiological and the optical data. Model simulations demonstrate that the more than 70% of IKir arises from the TTS membranes. [K+] increases in the lumen of the TTS resulting from the activation of K delayed rectifier channels (Kv) lead to drastic enhancements of IKir, and to right-shifts in their reversal potential. These changes are predicted by the model. PMID:25545278

Comparison between Phase-Shift Full-Bridge Converters with Noncoupled and Coupled Current-Doubler Rectifier

PubMed Central

Tsai, Cheng-Tao; Tseng, Sheng-Yu

2013-01-01

This paper presents comparison between phase-shift full-bridge converters with noncoupled and coupled current-doubler rectifier. In high current capability and high step-down voltage conversion, a phase-shift full-bridge converter with a conventional current-doubler rectifier has the common limitations of extremely low duty ratio and high component stresses. To overcome these limitations, a phase-shift full-bridge converter with a noncoupled current-doubler rectifier (NCDR) or a coupled current-doubler rectifier (CCDR) is, respectively, proposed and implemented. In this study, performance analysis and efficiency obtained from a 500 W phase-shift full-bridge converter with two improved current-doubler rectifiers are presented and compared. From their prototypes, experimental results have verified that the phase-shift full-bridge converter with NCDR has optimal duty ratio, lower component stresses, and output current ripple. In component count and efficiency comparison, CCDR has fewer components and higher efficiency at full load condition. For small size and high efficiency requirements, CCDR is relatively suitable for high step-down voltage and high efficiency applications. PMID:24381521

A metamaterial electromagnetic energy rectifying surface with high harvesting efficiency

NASA Astrophysics Data System (ADS)

Duan, Xin; Chen, Xing; Zhou, Lin

2016-12-01

A novel metamaterial rectifying surface (MRS) for electromagnetic energy capture and rectification with high harvesting efficiency is presented. It is fabricated on a three-layer printed circuit board, which comprises an array of periodic metamaterial particles in the shape of mirrored split rings, a metal ground, and integrated rectifiers employing Schottky diodes. Perfect impedance matching is engineered at two interfaces, i.e. one between free space and the surface, and the other between the metamaterial particles and the rectifiers, which are connected through optimally positioned vias. Therefore, the incident electromagnetic power is captured with almost no reflection by the metamaterial particles, then channeled maximally to the rectifiers, and finally converted to direct current efficiently. Moreover, the rectifiers are behind the metal ground, avoiding the disturbance of high power incident electromagnetic waves. Such a MRS working at 2.45 GHz is designed, manufactured and measured, achieving a harvesting efficiency up to 66.9% under an incident power density of 5 mW/cm2, compared with a simulated efficiency of 72.9%. This high harvesting efficiency makes the proposed MRS an effective receiving device in practical microwave power transmission applications.

Comparison between phase-shift full-bridge converters with noncoupled and coupled current-doubler rectifier.

PubMed

Tsai, Cheng-Tao; Su, Jye-Chau; Tseng, Sheng-Yu

2013-01-01

This paper presents comparison between phase-shift full-bridge converters with noncoupled and coupled current-doubler rectifier. In high current capability and high step-down voltage conversion, a phase-shift full-bridge converter with a conventional current-doubler rectifier has the common limitations of extremely low duty ratio and high component stresses. To overcome these limitations, a phase-shift full-bridge converter with a noncoupled current-doubler rectifier (NCDR) or a coupled current-doubler rectifier (CCDR) is, respectively, proposed and implemented. In this study, performance analysis and efficiency obtained from a 500 W phase-shift full-bridge converter with two improved current-doubler rectifiers are presented and compared. From their prototypes, experimental results have verified that the phase-shift full-bridge converter with NCDR has optimal duty ratio, lower component stresses, and output current ripple. In component count and efficiency comparison, CCDR has fewer components and higher efficiency at full load condition. For small size and high efficiency requirements, CCDR is relatively suitable for high step-down voltage and high efficiency applications.

Memory effects in funnel ratchet of self-propelled particles

NASA Astrophysics Data System (ADS)

Hu, Cai-Tian; Wu, Jian-Chun; Ai, Bao-Quan

2017-05-01

The transport of self-propelled particles with memory effects is investigated in a two-dimensional periodic channel. Funnel-shaped barriers are regularly arrayed in the channel. Due to the asymmetry of the barriers, the self-propelled particles can be rectified. It is found that the memory effects of the rotational diffusion can strongly affect the rectified transport. The memory effects do not always break the rectified transport, and there exists an optimal finite value of correlation time at which the rectified efficiency takes its maximal value. We also find that the optimal values of parameters (the self-propulsion speed, the translocation diffusion coefficient, the rotational noise intensity, and the self-rotational diffusion coefficient) can facilitate the rectified transport. When introducing a finite load, particles with different self-propulsion speeds move to different directions and can be separated.

PHASE DETECTOR

DOEpatents

Kippenhan, D.O.

1959-09-01

A phase detector circuit is described for use at very high frequencies of the order of 50 megacycles. The detector circuit includes a pair of rectifiers inverted relative to each other. One voltage to be compared is applied to the two rectifiers in phase opposition and the other voltage to be compared is commonly applied to the two rectifiers. The two result:ng d-c voltages derived from the rectifiers are combined in phase opposition to produce a single d-c voltage having amplitude and polarity characteristics dependent upon the phase relation between the signals to be compared. Principal novelty resides in the employment of a half-wave transmission line to derive the phase opposing signals from the first voltage to be compared for application to the two rectifiers in place of the transformer commonly utilized for such purpose in phase detector circuits for operation at lower frequency.

Delay Discounting in Lewis and Fischer 344 Rats: Steady-state and Rapid-determination Adjusting-amount Procedures

PubMed Central

Stein, Jeffrey S; Pinkston, Jonathan W; Brewer, Adam T; Francisco, Monica T; Madden, Gregory J

2012-01-01

Lewis rats have been shown to make more impulsive choices than Fischer 344 rats in discrete-trial choice procedures that arrange fixed (i.e., nontitrating) reinforcement parameters. However, nontitrating procedures yield only gross estimates of preference, as choice measures in animal subjects are rarely graded at the level of the individual subject. The present study was designed to examine potential strain differences in delay discounting using an adjusting-amount procedure, in which distributed (rather than exclusive) choice is observed due to dynamic titration of reinforcer magnitude across trials. Using a steady-state version of the adjusting-amount procedure in which delay was manipulated between experimental conditions, steeper delay discounting was observed in Lewis rats compared to Fischer 344 rats; further, delay discounting in both strains was well described by the traditional hyperbolic discounting model. However, upon partial completion of the present study, a study published elsewhere (Wilhelm & Mitchell, 2009) demonstrated no difference in delay discounting between these strains with the use of a more rapid version of the adjusting-amount procedure (i.e., in which delay is manipulated daily). Thus, following completion of the steady-state assessment in the present study, all surviving Lewis and Fischer 344 rats completed an approximation of this rapid-determination procedure in which no strain difference in delay discounting was observed. PMID:22693360

Delay discounting in Lewis and Fischer 344 rats: steady-state and rapid-determination adjusting-amount procedures.

PubMed

Stein, Jeffrey S; Pinkston, Jonathan W; Brewer, Adam T; Francisco, Monica T; Madden, Gregory J

2012-05-01

Lewis rats have been shown to make more impulsive choices than Fischer 344 rats in discrete-trial choice procedures that arrange fixed (i.e., nontitrating) reinforcement parameters. However, nontitrating procedures yield only gross estimates of preference, as choice measures in animal subjects are rarely graded at the level of the individual subject. The present study was designed to examine potential strain differences in delay discounting using an adjusting-amount procedure, in which distributed (rather than exclusive) choice is observed due to dynamic titration of reinforcer magnitude across trials. Using a steady-state version of the adjusting-amount procedure in which delay was manipulated between experimental conditions, steeper delay discounting was observed in Lewis rats compared to Fischer 344 rats; further, delay discounting in both strains was well described by the traditional hyperbolic discounting model. However, upon partial completion of the present study, a study published elsewhere (Wilhelm & Mitchell, 2009) demonstrated no difference in delay discounting between these strains with the use of a more rapid version of the adjusting-amount procedure (i.e., in which delay is manipulated daily). Thus, following completion of the steady-state assessment in the present study, all surviving Lewis and Fischer 344 rats completed an approximation of this rapid-determination procedure in which no strain difference in delay discounting was observed.

Synchronous Half-Wave Rectifier

NASA Technical Reports Server (NTRS)

Rippel, Wally E.

1989-01-01

Synchronous rectifying circuit behaves like diode having unusually low voltage drop during forward-voltage half cycles. Circuit particularly useful in power supplies with potentials of 5 Vdc or less, where normal forward-voltage drops in ordinary diodes unacceptably large. Fabricated as monolithic assembly or as hybrid. Synchronous half-wave rectifier includes active circuits to attain low forward voltage drop and high rectification efficiency.

Identification of a pharmacological target for genioglossus reactivation throughout sleep.

PubMed

Grace, Kevin P; Hughes, Stuart W; Horner, Richard L

2014-01-01

Obstructive sleep apnea (OSA) is a significant public health problem caused by repeated episodes of upper airway closure that occur only during sleep. Attempts to treat OSA pharmacologically have been unsuccessful because there has not been identification of a target operating at cranial motor nuclei, blockade of which can reactivate pharyngeal muscle activity throughout sleep. Increasing potassium conductance is a common mechanism by which state-dependent neuromodulators reduce motoneuron excitability. Therefore, we aimed to determine if potassium channel blockade is an effective strategy to reactivate the pharyngeal musculature throughout sleep. In rats chronically instrumented for recording sleep-wake states and respiratory motor activities, we locally microperfused pharmacological agents into the hypoglossal motor pool to modulate potassium channels of three major classes: inwardly rectifying, two-pore domain, and voltage-gated. Microperfusion of the inwardly rectifying potassium channel blocker, barium, as well as the voltage-gated potassium channel blockers, tetraethylammonium and 4-aminopyridine, increased tonic and respiratory-related genioglossus activities throughout nonrapid eye movement (non-REM) and rapid eye movement (REM) sleep to 133-300% of levels present during baseline wakefulness. In contrast, microperfusion of methanandamide (TWIK-related acid-sensitive potassium [TASK] channel blocker/cannabinoid receptor agonist) activated genioglossus in wakefulness but not in sleep. These findings establish proof-of-principle that targeted blockade of certain potassium channels at the hypoglossal motor pool is an effective strategy for reversing upper airway hypotonia and causing sustained reactivation of genioglossus throughout nonrapid eye movement and rapid eye movement sleep. These findings identify an important new direction for translational approaches to the pharmacological treatment of obstructive sleep apnea.

Interannual variability in the atmospheric CO2 rectification over a boreal forest region

NASA Astrophysics Data System (ADS)

Chen, Baozhang; Chen, Jing M.; Worthy, Douglas E. J.

2005-08-01

Ecosystem CO2 exchange with the atmosphere and the planetary boundary layer (PBL) dynamics are correlated diurnally and seasonally. The strength of this kind of covariation is quantified as the rectifier effect, and it affects the vertical gradient of CO2 and thus the global CO2 distribution pattern. An 11-year (1990-1996, 1999-2002), continuous CO2 record from Fraserdale, Ontario (49°52'29.9″N, 81°34'12.3″W), along with a coupled vertical diffusion scheme (VDS) and ecosystem model named Boreal Ecosystem Productivity Simulator (BEPS), are used to investigate the interannual variability of the rectifier effect over a boreal forest region. The coupled model performed well (r2 = 0.70 and 0.87, at 40 m at hourly and daily time steps, respectively) in simulating CO2 vertical diffusion processes. The simulated annual atmospheric rectifier effect varies from 3.99 to 5.52 ppm, while the diurnal rectifying effect accounted for about a quarter of the annual total (22.8˜28.9%).The atmospheric rectification of CO2 is not simply influenced by terrestrial source and sink strengths, but by seasonal and diurnal variations in the land CO2 flux and their interaction with PBL dynamics. Air temperature and moisture are found to be the dominant climatic factors controlling the rectifier effect. The annual rectifier effect is highly correlated with annual mean temperature (r2 = 0.84), while annual mean air relative humidity can explain 51% of the interannual variation in rectification. Seasonal rectifier effect is also found to be more sensitive to climate variability than diurnal rectifier effect.

Ion channels in plants.

PubMed

Hedrich, Rainer

2012-10-01

Since the first recordings of single potassium channel activities in the plasma membrane of guard cells more than 25 years ago, patch-clamp studies discovered a variety of ion channels in all cell types and plant species under inspection. Their properties differed in a cell type- and cell membrane-dependent manner. Guard cells, for which the existence of plant potassium channels was initially documented, advanced to a versatile model system for studying plant ion channel structure, function, and physiology. Interestingly, one of the first identified potassium-channel genes encoding the Shaker-type channel KAT1 was shown to be highly expressed in guard cells. KAT1-type channels from Arabidopsis thaliana and its homologs from other species were found to encode the K(+)-selective inward rectifiers that had already been recorded in early patch-clamp studies with guard cells. Within the genome era, additional Arabidopsis Shaker-type channels appeared. All nine members of the Arabidopsis Shaker family are localized at the plasma membrane, where they either operate as inward rectifiers, outward rectifiers, weak voltage-dependent channels, or electrically silent, but modulatory subunits. The vacuole membrane, in contrast, harbors a set of two-pore K(+) channels. Just very recently, two plant anion channel families of the SLAC/SLAH and ALMT/QUAC type were identified. SLAC1/SLAH3 and QUAC1 are expressed in guard cells and mediate Slow- and Rapid-type anion currents, respectively, that are involved in volume and turgor regulation. Anion channels in guard cells and other plant cells are key targets within often complex signaling networks. Here, the present knowledge is reviewed for the plant ion channel biology. Special emphasis is drawn to the molecular mechanisms of channel regulation, in the context of model systems and in the light of evolution.

Molecular basis of slow activation of the human ether-á-go-go related gene potassium channel

PubMed Central

Subbiah, Rajesh N; Clarke, Catherine E; Smith, David J; Zhao, JingTing; Campbell, Terence J; Vandenberg, Jamie I

2004-01-01

The human ether-á-go-go related gene (HERG) encodes the pore forming α-subunit of the rapid delayed rectifier K+ channel which is central to the repolarization phase of the cardiac action potential. HERG K+ channels have unusual kinetics characterized by slow activation and deactivation, yet rapid inactivation. The fourth transmembrane domain (S4) of HERG, like other voltage-gated K+ channels, contains multiple positive charges and is the voltage sensor for activation. In this study, we mutated each of the positively charged residues in this region to glutamine (Q), expressed the mutant and wild-type (WT) channels in Xenopus laevis oocytes and studied them using two-electrode voltage clamp methods. K525Q channels activated at more hyperpolarized potentials than WT, whereas all the other mutant channels activated at more depolarized potentials. All mutants except for R531Q also had a reduction in apparent gating charge associated with activation. Mutation of K525 to cysteine (C) resulted in a less dramatic phenotype than K525Q. The addition of the positively charged MTSET to K525C altered the phenotype to one more similar to K525Q than to WT. Therefore it is not charge per se, but the specific lysine side chain at position 525, that is crucial for stabilizing the closed state. When rates of activation and deactivation for WT and mutant channels were compared at equivalent total (chemical + electrostatic) driving forces, K525Q and R528Q accelerated activation but had no effect on deactivation, R531Q slowed activation and deactivation, R534Q accelerated activation but slowed deactivation and R537Q accelerated deactivation but had no effect on activation. The main conclusions we can draw from these data are that in WT channels K525 stabilizes the closed state, R531 stabilizes the open state and R534 participates in interactions that stabilize pre-open closed states. PMID:15181157

KCNJ11: Genetic Polymorphisms and Risk of Diabetes Mellitus

PubMed Central

Mohamed, Zahurin; Abdullah, Nor Azizan; Haghvirdizadeh, Pantea; Haerian, Monir Sadat

2015-01-01

Diabetes mellitus (DM) is a major worldwide health problem and its prevalence has been rapidly increasing in the last century. It is caused by defects in insulin secretion or insulin action or both, leading to hyperglycemia. Of the various types of DM, type 2 occurs most frequently. Multiple genes and their interactions are involved in the insulin secretion pathway. Insulin secretion is mediated through the ATP-sensitive potassium (KATP) channel in pancreatic beta cells. This channel is a heteromeric protein, composed of four inward-rectifier potassium ion channel (Kir6.2) tetramers, which form the pore of the KATP channel, as well as sulfonylurea receptor 1 subunits surrounding the pore. Kir6.2 is encoded by the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene, a member of the potassium channel genes. Numerous studies have reported the involvement of single nucleotide polymorphisms of the KCNJ11 gene and their interactions in the susceptibility to DM. This review discusses the current evidence for the contribution of common KCNJ11 genetic variants to the development of DM. Future studies should concentrate on understanding the exact role played by these risk variants in the development of DM. PMID:26448950

Control system adds to precipitator efficiency

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

Gurrole, G.

1978-02-01

An electrostatic precipitator in use at Lion Oil Co., Martinez, Calif., in a fluid catalytic cracking and CO boiler application, was upgraded by mechanical sectionalization of the gas passage and a new electronic control system. The electrostatic precipitator is installed upstream of the CO boiler to handle gas flow up to 4.77 ft/sec, and pressure to 4.5 psi. The independent gas chambers in the electrostatic precipitator were divided by installing gas-tight partition walls to form a total of four electrostatic fields. The precipitator was also equipped with adjustable inlet gas flow-control baffles for even gas distribution. Rows of grounded collectingmore » electrodes are parallel with the flow of gas. The emitting electrode system, powered by separate high-energy transformers for each collecting field, uses silicon-controlled rectifiers and analog electronic networks for rapid response to changing gas and dust conditions. Regulatory requirements call for efficient collection of catalyst fines with no more than 40 lb/hr escaping through the boiler stack. Currently, stack losses average about 38 lb/hr. The installation of two additional control systems with transformers and rectifiers should reduce stack losses to 34 lb/hr.« less

Artificial neural networks for control of a grid-connected rectifier/inverter under disturbance, dynamic and power converter switching conditions.

PubMed

Li, Shuhui; Fairbank, Michael; Johnson, Cameron; Wunsch, Donald C; Alonso, Eduardo; Proaño, Julio L

2014-04-01

Three-phase grid-connected converters are widely used in renewable and electric power system applications. Traditionally, grid-connected converters are controlled with standard decoupled d-q vector control mechanisms. However, recent studies indicate that such mechanisms show limitations in their applicability to dynamic systems. This paper investigates how to mitigate such restrictions using a neural network to control a grid-connected rectifier/inverter. The neural network implements a dynamic programming algorithm and is trained by using back-propagation through time. To enhance performance and stability under disturbance, additional strategies are adopted, including the use of integrals of error signals to the network inputs and the introduction of grid disturbance voltage to the outputs of a well-trained network. The performance of the neural-network controller is studied under typical vector control conditions and compared against conventional vector control methods, which demonstrates that the neural vector control strategy proposed in this paper is effective. Even in dynamic and power converter switching environments, the neural vector controller shows strong ability to trace rapidly changing reference commands, tolerate system disturbances, and satisfy control requirements for a faulted power system.

Ripple feedback for the resonant-filter unity-power-factor rectifier

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

Streng, S.A.; King, R.J.

1992-07-01

An unusual bucklike unity-power-factor rectifier with a resonant load-balancing network permits current-limited operation down to zero output voltage in a single-stage-topology. However, this rectifier has been found to be sensitive to ac-line voltage distortion and is potentially unstable with realistic values of ac-line impedance. In this paper, a new ripple feedback is proposed that solves both problems. A large-signal time-varying analysis is given along with incremental, quasi-static, and low-frequency approximations. Experimental verification is provided by a 500-W 50-kHz rectifier operating from the 120-V 60-Hz distribution system.

Rectifying behavior in the GaN/graded-AlxGa1‑xN/GaN double heterojunction structure

NASA Astrophysics Data System (ADS)

Wang, Caiwei; Jiang, Yang; Ma, Ziguang; Zuo, Peng; Yan, Shen; Die, Junhui; Wang, Lu; Jia, Haiqiang; Wang, Wenxin; Chen, Hong

2018-05-01

Rectifying characteristics induced by the polarization fields are achieved in the GaN/graded-AlxGa1‑xN/GaN double heterojunction structure (DHS). By grading AlxGa1‑xN from x  =  0.4(0.3) to 0.1, the DHS displays a better conductivity for smaller reverse bias than for forward bias voltages (reverse rectifying behavior) which is opposite to p–n junction rectifying characteristics. The mechanism of reverse rectifying behavior is illustrated via calculating the energy band structures of the samples. The band gap narrowing caused by decreasing Al composition could compensate the for the band tilt due to the polarization effect in AlxGa1‑xN barriers, thus lowering the barrier height for electron transport from top to bottom. The reverse rectifying behavior could be enhanced by increasing the Al content and the thickness of the multi-layer graded AlxGa1‑xN barriers. This work gives a better understanding of the mechanism of carrier transport in a DHS and makes it possible to realize novel GaN-based heterojunction transistors.

Photomultiplier circuit including means for rapidly reducing the sensitivity thereof. [and protection from radiation damage

NASA Technical Reports Server (NTRS)

Mcclenahan, J. O. (Inventor)

1974-01-01

A simple, reliable and inexpensive control circuit is described for rapidly reducing the bias voltage across one or more of the dynode stages of a photomultiplier, to substantially decrease its sensitivity to incoming light at those times where excess light intensity might damage the tube. The control circuit comprises a switching device, such as a silicon controlled rectifier (SCR), coupled between a pair of the electrodes in the tube, preferably the cathode and first dynode, or the first and second dynodes, the switching device operating in response to a trigger pulse applied to its gate to short circuit the two electrodes. To insure the desired reduction in sensitivity, two switching stages, the devices be employed between two of the electrode stages, the devices being operated simultaneously to short circuit both stages.

Silicon Controlled Switch for Detection of Ionizing Radiation

DTIC Science & Technology

2015-12-01

sensitivity of previous NPS silicon controlled rectifier (SCR) based circuits. Additionally, the circuit in this thesis was able to detect AM-241 and...sensitivity of previous NPS silicon controlled rectifier (SCR) based circuits. Additionally, the circuit in this thesis was able to detect AM-241 and...Controlled Rectifier SCS Silicon-Controlled Switch SONAR SOund Navigation and Ranging VBIAS Applied Bias Voltage VH Holding Voltage VS Standalone SCS

[Research progress in the role of aquaproin-4 and inward rectifying potassium channel 4.1 in spinal cord edema].

PubMed

Chen, Tiege; Dang, Yuexiu; Wang, Ming; Zhang, Dongliang; Guo, Yongqiang; Zhang, Haihong

2018-05-28

Spinal edema is a very important pathophysiological basis for secondary spinal cord injury, which affects the repair and prognosis of spinal cord injury. Aquaporin-4 is widely distributed in various organs of the body, and is highly expressed in the brain and spinal cord. Inward rectifying potassium channel 4.1 is a protein found in astrocytes of central nervous system. It interacts with aquaporins in function. Aquaporin-4 and inward rectifying potassium channel 4.1 play an important role in the formation and elimination of spinal cord edema, inhibition of glial scar formation and promotion of excitotoxic agents exclusion. The distribution and function of aquaporin-4 and inward rectifying potassium channel 4.1 in the central nervous system and their expression after spinal cord injury have multiple effects on spinal edema. Studies of aquaporin-4 and inward rectifying potassium channel 4.1 in the spinal cord may provide new ideas for the elimination and treatment of spinal edema.

Power converter for raindrop energy harvesting application: Half-wave rectifier

NASA Astrophysics Data System (ADS)

Izrin, Izhab Muhammad; Dahari, Zuraini

2017-10-01

Harvesting raindrop energy by capturing vibration from impact of raindrop have been explored extensively. Basically, raindrop energy is generated by converting the kinetic energy of raindrop into electrical energy by using polyvinylidene fluoride (PVDF) piezoelectric. In this paper, a power converter using half-wave rectifier for raindrop harvesting energy application is designed and proposed to convert damping alternating current (AC) generated by PVDF into direct current (DC). This research presents parameter analysis of raindrop simulation used in the experiment and resistive load effect on half-wave rectifier converter. The experiment is conducted by using artificial raindrop from the height of 1.3 m to simulate the effect of different resistive load on the output of half-wave rectifier converter. The results of the 0.68 MΩ resistive load showed the best performance of the half-wave rectifier converter used in raindrop harvesting energy system, which generated 3.18 Vaverage. The peak instantaneous output generated from this experiment is 15.36 µW.

A high speed PE-ALD ZnO Schottky diode rectifier with low interface-state density

NASA Astrophysics Data System (ADS)

Jin, Jidong; Zhang, Jiawei; Shaw, Andrew; Kudina, Valeriya N.; Mitrovic, Ivona Z.; Wrench, Jacqueline S.; Chalker, Paul R.; Balocco, Claudio; Song, Aimin; Hall, Steve

2018-02-01

Zinc oxide (ZnO) has recently attracted attention for its potential application to high speed electronics. In this work, a high speed Schottky diode rectifier was fabricated based on a ZnO thin film deposited by plasma-enhanced atomic layer deposition and a PtOx Schottky contact deposited by reactive radio-frequency sputtering. The rectifier shows an ideality factor of 1.31, an effective barrier height of 0.79 eV, a rectification ratio of 1.17  ×  107, and cut-off frequency as high as 550 MHz. Low frequency noise measurements reveal that the rectifier has a low interface-state density of 5.13  ×  1012 cm-2 eV-1, and the noise is dominated by the mechanism of a random walk of electrons at the PtO x /ZnO interface. The work shows that the rectifier can be used for both noise sensitive and high frequency electronics applications.

A high-efficiency low-voltage CMOS rectifier for harvesting energy in implantable devices.

PubMed

Hashemi, S Saeid; Sawan, Mohamad; Savaria, Yvon

2012-08-01

We present, in this paper, a new full-wave CMOS rectifier dedicated for wirelessly-powered low-voltage biomedical implants. It uses bootstrapped capacitors to reduce the effective threshold voltage of selected MOS switches. It achieves a significant increase in its overall power efficiency and low voltage-drop. Therefore, the rectifier is good for applications with low-voltage power supplies and large load current. The rectifier topology does not require complex circuit design. The highest voltages available in the circuit are used to drive the gates of selected transistors in order to reduce leakage current and to lower their channel on-resistance, while having high transconductance. The proposed rectifier was fabricated using the standard TSMC 0.18 μm CMOS process. When connected to a sinusoidal source of 3.3 V peak amplitude, it allows improving the overall power efficiency by 11% compared to the best recently published results given by a gate cross-coupled-based structure.

Energy Harvesting from Energetic Porous Silicon

DTIC Science & Technology

2016-07-01

ignition. Here we investigate a means to convert this mechanical energy to electrical energy via a piezoelectric cantilever and rectifying circuit. This...mechanical energy to electrical energy via a piezoelectric cantilever and an associated rectifying circuit. A small PSi sample is placed on the...cantilever is wired to a direct current (DC) full-bridge rectifier circuit (EHE001NC) also purchased from Midé. Test points have been added at the

A self-powered piezoelectric energy harvesting interface circuit with efficiency-enhanced P-SSHI rectifier

NASA Astrophysics Data System (ADS)

Liu, Lianxi; Pang, Yanbo; Yuan, Wenzhi; Zhu, Zhangming; Yang, Yintang

2018-04-01

The key to self-powered technique is initiative to harvest energy from the surrounding environment. Harvesting energy from an ambient vibration source utilizing piezoelectrics emerged as a popular method. Efficient interface circuits become the main limitations of existing energy harvesting techniques. In this paper, an interface circuit for piezoelectric energy harvesting is presented. An active full bridge rectifier is adopted to improve the power efficiency by reducing the conduction loss on the rectifying path. A parallel synchronized switch harvesting on inductor (P-SSHI) technique is used to improve the power extraction capability from piezoelectric harvester, thereby trying to reach the theoretical maximum output power. An intermittent power management unit (IPMU) and an output capacitor-less low drop regulator (LDO) are also introduced. Active diodes (AD) instead of traditional passive ones are used to reduce the voltage loss over the rectifier, which results in a good power efficiency. The IPMU with hysteresis comparator ensures the interface circuit has a large transient output power by limiting the output voltage ranges from 2.2 to 2 V. The design is fabricated in a SMIC 0.18 μm CMOS technology. Simulation results show that the flipping efficiency of the P-SSHI circuit is over 80% with an off-chip inductor value of 820 μH. The output power the proposed rectifier can obtain is 44.4 μW, which is 6.7× improvement compared to the maximum output power of a traditional rectifier. Both the active diodes and the P-SSHI help to improve the output power of the proposed rectifier. LDO outputs a voltage of 1.8 V with the maximum 90% power efficiency. The proposed P-SSHI rectifier interface circuit can be self-powered without the need for additional power supply. Project supported by the National Natural Science Foundation of China (Nos. 61574103, U1709218) and the Key Research and Development Program of Shaanxi Province (No. 2017ZDXM-GY-006).

Phospholipase C-independent effects of 3M3FBS in murine colon.

PubMed

Dwyer, Laura; Kim, Hyun Jin; Koh, Byoung Ho; Koh, Sang Don

2010-02-25

The muscarinic receptor subtype M(3) is coupled to Gq/11 proteins. Muscarinic receptor agonists such as carbachol stimulate these receptors that result in activation of phospholipase C (PLC) which hydrolyzes phosphatidylinositol 4,5-bisphosphate into diacylglycerol and Ins(1,4,5)P(3). This pathway leads to excitation and smooth muscle contraction. In this study the PLC agonist, 2, 4, 6-trimethyl-N-(meta-3-trifluoromethyl-phenyl)-benezenesulfonamide (m-3M3FBS), was used to investigate whether direct PLC activation mimics carbachol-induced excitation. We examined the effects of m-3M3FBS and 2, 4, 6-trimethyl-N-(ortho-3-trifluoromethyl-phenyl)-benzenesulfonamide (o-3M3FBS), on murine colonic smooth muscle tissue and cells by performing conventional microelectrode recordings, isometric force measurements and patch clamp experiments. Application of m-3M3FBS decreased spontaneous contractility in murine colonic smooth muscle without affecting the resting membrane potential. Patch clamp studies revealed that delayed rectifier K(+) channels were reversibly inhibited by m-3M3FBS and o-3M3FBS. The PLC inhibitor, 1-(6-((17b-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122), did not prevent this inhibition by m-3M3FBS. Both m-3M3FBS and o-3M3FBS decreased two components of delayed rectifier K(+) currents in the presence of tetraethylammonium chloride or 4-aminopyridine. Ca(2+) currents were significantly suppressed by m-3M3FBS and o-3M3FBS with a simultaneous increase in intracellular Ca(2+). Pretreatment with U73122 did not prevent the decrease in Ca(2+) currents upon m-3M3FBS application. In conclusion, both m-3M3FBS and o-3M3FBS inhibit inward and outward currents via mechanisms independent of PLC acting in an antagonistic manner. In contrast, both compounds also caused an increase in [Ca(2+)](i) in an agonistic manner. Therefore caution must be employed when interpreting their effects at the tissue and cellular level.

Portable Plating System

NASA Technical Reports Server (NTRS)

Flores, R.

1984-01-01

Plating system mounted on portable cart includes 30-gallon (23.5 liter) electrolyte tank, filler pump, heaters, replenishing anodes, plating rectifiers and tank rectifier to continously remove contaminants.

A deep learning model observer for use in alterative forced choice virtual clinical trials

NASA Astrophysics Data System (ADS)

Alnowami, M.; Mills, G.; Awis, M.; Elangovanr, P.; Patel, M.; Halling-Brown, M.; Young, K. C.; Dance, D. R.; Wells, K.

2018-03-01

Virtual clinical trials (VCTs) represent an alternative assessment paradigm that overcomes issues of dose, high cost and delay encountered in conventional clinical trials for breast cancer screening. However, to fully utilize the potential benefits of VCTs requires a machine-based observer that can rapidly and realistically process large numbers of experimental conditions. To address this, a Deep Learning Model Observer (DLMO) was developed and trained to identify lesion targets from normal tissue in small (200 x 200 pixel) image segments, as used in Alternative Forced Choice (AFC) studies. The proposed network consists of 5 convolutional layers with 2x2 kernels and ReLU (Rectified Linear Unit) activations, followed by max pooling with size equal to the size of the final feature maps and three dense layers. The class outputs weights from the final fully connected dense layer are used to consider sets of n images in an n-AFC paradigm to determine the image most likely to contain a target. To examine the DLMO performance on clinical data, a training set of 2814 normal and 2814 biopsy-confirmed malignant mass targets were used. This produced a sensitivity of 0.90 and a specificity of 0.92 when presented with a test data set of 800 previously unseen clinical images. To examine the DLMOs minimum detectable contrast, a second dataset of 630 simulated backgrounds and 630 images with simulated lesion and spherical targets (4mm and 6mm diameter), produced contrast thresholds equivalent to/better than human observer performance for spherical targets, and comparable (12 % difference) for lesion targets.

David Triggle: Research collaborations and scientific exchanges with the China Pharmaceutical University, Nanjing, China.

PubMed

Dai, De-Zai

2015-11-15

Over the period 1995-2012, David Triggle was a frequent visitor to the China Pharmaceutical University in Nanjing, China making many important contributions that enhanced the activities of the Research Division of Pharmacology at the University. In addition to providing collegial advice and facilitating interactions with the international pharmacological community, Professor Triggle's international reputation as a thought leader in the field of ion channel research and drug discovery provided important insights into the potential pathophysiological and therapeutic effects of targeting ion channels. This included the L-type calcium channel and the outward delayed rectified potassium currents of rapid (IKr) and slow (IKs) components in the myocardium. The Nanjing research team had been particularly interested in ion channel dysfunction in the context of cardiac arrhythmias, remodeling and drug discovery. With Professor Triggle's assistance, the relationship between an increase in ICa.L and other biological events including an enhancement of IKr and IKr currents, NADPH oxidase and endothelin receptor activation, down regulation of calcium modulating protein FKBP12.6, sarco/endoplasmic reticulum Ca(2+)ATPse (SERCA2A) and calsequens 2 (CASQ2), calcium leak at the diastole and endoplasmic reticulum stress, were evaluated and are discussed. Additionally, the organization of several international symposia was greatly enhanced by input from Professor Triggle as were the published research manuscripts in international pharmacology journals. During his association with the China Pharmaceutical University, Professor Triggle aided in enhancing the scientific standing of the Pharmacology department and was a highly effective ambassador for international research cooperation. Copyright © 2015. Published by Elsevier Inc.

Cell Surface Expression of Human Ether-a-go-go-related Gene (hERG) Channels Is Regulated by Caveolin-3 Protein via the Ubiquitin Ligase Nedd4-2*

PubMed Central

Guo, Jun; Wang, Tingzhong; Li, Xian; Shallow, Heidi; Yang, Tonghua; Li, Wentao; Xu, Jianmin; Fridman, Michael D.; Yang, Xiaolong; Zhang, Shetuan

2012-01-01

The human ether-a-go-go-related gene (hERG) encodes the rapidly activating delayed rectifier potassium channel (IKr) which plays an important role in cardiac repolarization. A reduction or increase in hERG current can cause long or short QT syndrome, respectively, leading to fatal cardiac arrhythmias. The channel density in the plasma membrane is a key determinant of the whole cell current amplitude. To gain insight into the molecular mechanisms for the regulation of hERG density at the plasma membrane, we used whole cell voltage clamp, Western blotting, and immunocytochemical methods to investigate the effects of an integral membrane protein, caveolin-3 (Cav3) on hERG expression levels. Our data demonstrate that Cav3, hERG, and ubiquitin-ligase Nedd4-2 interact with each other and form a complex. Expression of Cav3 thus enhances the hERG-Nedd4-2 interaction, leading to an increased ubiquitination and degradation of mature, plasma-membrane localized hERG channels. Disrupting Nedd4-2 interaction with hERG by mutations eliminates the effects of Cav3 on hERG channels. Knockdown of endogenous Cav3 or Nedd4-2 in cultured neonatal rat ventricular myocytes using siRNA led to an increase in native IKr. Our data demonstrate that hERG expression in the plasma membrane is regulated by Cav3 via Nedd4-2. These findings extend our understanding of the regulation of hERG channels and cardiac electrophysiology. PMID:22879586

Potassium channel KCNH2 K897T polymorphism and cardiac repolarization during exercise test: The Finnish Cardiovascular Study.

PubMed

Koskela, J; Laiho, J; KäHönen, M; Rontu, R; Lehtinen, R; Viik, J; Niemi, M; Niemelä, K; Kööbi, T; Turjanmaa, V; Pörsti, I; Lehtimäki, T; Nieminen, T

2008-01-01

Cardiac repolarization is regulated, in part, by the KCNH2 gene, which encodes a rapidly activating component of the delayed rectifier potassium channel. The gene expresses a functional single nucleotide polymorphism, K897T, which changes the biophysical properties of the channel. The objective of this study was to evaluate whether this polymorphism influences two indices of repolarization--the QT interval and T-wave alternans (TWA)--during different phases of a physical exercise test. The cohort consisted of 1,975 patients undergoing an exercise test during which on-line electrocardiographic data were registered. Information on coronary risk factors and medication was recorded. The 2690A>C nucleotide variation in the KCNH2 gene corresponding to the K897T amino acid change was analysed after polymerase chain reaction with allele-specific TaqMan probes. Among all subjects, the QTc intervals did not differ between the three genotype groups (p> or =0.31, RANOVA). Women with the CC genotype tended to have longer QT intervals during the exercise test, but the difference was statistically significant only at rest (p = 0.011, ANOVA). This difference was also detected when the analysis was adjusted for several factors influencing the QT interval. No statistically significant effects of the K897T polymorphism on TWA were observed among all subjects (p = 0.16, RANOVA), nor in men and women separately. The K897T polymorphism of the KCNH2 gene may not be a major genetic determinant for the TWA, but the influence of the CC genotype on QT interval deserves further research among women.

Nicotine inhibits potassium currents in Aplysia bag cell neurons

PubMed Central

White, Sean H.; Sturgeon, Raymond M.

2016-01-01

Acetylcholine and the archetypal cholinergic agonist, nicotine, are typically associated with the opening of ionotropic receptors. In the bag cell neurons, which govern the reproductive behavior of the marine snail, Aplysia californica, there are two cholinergic responses: a relatively large acetylcholine-induced current and a relatively small nicotine-induced current. Both currents are readily apparent at resting membrane potential and result from the opening of distinct ionotropic receptors. We now report a separate current response elicited by applying nicotine to cultured bag cell neurons under whole cell voltage-clamp. This current was ostensibly inward, best resolved at depolarized voltages, presented a noncooperative dose-response with a half-maximal concentration near 1.5 mM, and associated with a decrease in membrane conductance. The unique nicotine-evoked response was not altered by intracellular perfusion with the G protein blocker GDPβS or exposure to classical nicotinic antagonists but was occluded by replacing intracellular K+ with Cs+. Consistent with an underlying mechanism of direct inhibition of one or more K+ channels, nicotine was found to rapidly reduce the fast-inactivating A-type K+ current as well as both components of the delayed-rectifier K+ current. Finally, nicotine increased bag cell neuron excitability, which manifested as reduction in spike threshold, greater action potential height and width, and markedly more spiking to continuous depolarizing current injection. In contrast to conventional transient activation of nicotinic ionotropic receptors, block of K+ channels could represent a nonstandard means for nicotine to profoundly alter the electrical properties of neurons over prolonged periods of time. PMID:26864763

Effects of sildenafil on cardiac repolarization.

PubMed

Chiang, Chern-En; Luk, Hsiang-Ning; Wang, Tsui-Min; Ding, Philip Yu-An

2002-08-01

Sudden death has occasionally been reported in patients taking sildenafil. The objective of this study was to investigate the effect of sildenafil on cardiac repolarization. We used conventional microelectrode recording technique in isolated guinea pig papillary muscles and canine Purkinje fibers, whole-cell patch clamp techniques in guinea pig ventricular myocytes, and in vivo ECG measurements in guinea pigs. Action potential duration at 90% repolarization (APD(90)) was not affected by sildenafil in the therapeutic ranges (< or =1 microM), but shortened by higher concentration (> or =10 microM) in both guinea pig papillary muscles and canine Purkinje fibers. D-Sotalol prolonged APD(90) in the same preparations with concentrations > or =1 microM in a reverse frequency-dependent manner. Co-administration of sildenafil (10 and 30 microM) abolished the APD-prolonging effects of D-sotalol (30 microM) and amiodarone (100 microM). Sildenafil, with concentrations up to 30 microM, had no significant effect on both the rapid (I(Kr)) and the slow (I(Ks)) components of the delayed rectifier potassium currents in guinea pig ventricular myocytes. Sildenafil dose-dependently blocked L-type Ca(2+) current (I(Ca,L)), but had no effect on persistent Na(+) current in guinea pig ventricular myocytes. ECG recordings in intact guinea pigs revealed significant shortening of QTc interval by sildenafil (10 and 30 mg/kg orally). The QT-prolonging effects by D,L-sotalol (50 mg/kg) and amiodarone (100 mg/kg) were abolished by sildenafil (30 mg/kg). Sildenafil does not prolong cardiac repolarization. Instead, in supra-therapeutic concentrations, it accelerates cardiac repolarization, presumably through its blocking effect on I(Ca,L).

Dofetilide promotes repolarization abnormalities in perfused Guinea-pig heart.

PubMed

Osadchii, Oleg E

2012-12-01

Dofetilide is class III antiarrhythmic agent which prolongs cardiac action potential duration because of selective inhibition of I (Kr), the rapid component of the delayed rectifier K(+) current. Although clinical studies reported on proarrhythmic risk associated with dofetilide treatment, the contributing electrophysiological mechanisms remain poorly understood. This study was designed to determine if dofetilide-induced proarrhythmia may be attributed to abnormalities in ventricular repolarization and refractoriness. The monophasic action potential duration and effective refractory periods (ERP) were assessed at distinct epicardial and endocardial sites along with volume-conducted ECG recordings in isolated, perfused guinea-pig heart preparations. Dofetilide was found to produce the reverse rate-dependent prolongation of ventricular repolarization, increased the steepness of action potential duration rate adaptation, and amplified transepicardial variability in electrical restitution kinetics. Dofetilide also prolonged the T peak-to-end interval on ECG, and elicited a greater prolongation of endocardial than epicardial ERP, thereby increasing transmural dispersion of refractoriness. At epicardium, dofetilide prolonged action potential duration to a greater extent than ERP, thus extending the critical interval for ventricular re-excitation. This change was associated with triangulation of epicardial action potential because of greater dofetilide-induced prolonging effect at 90 % than 30 % repolarization. Premature ectopic beats and spontaneous short-lasting episodes of monomorphic ventricular tachycardia were observed in 44 % of dofetilide-treated heart preparations. Proarrhythmic potential of dofetilide in guinea-pig heart is attributed to steepened electrical restitution, increased transepicardial variability in electrical restitution kinetics, amplified transmural dispersion of refractoriness, increased critical interval for ventricular re-excitation, and triangulation of epicardial action potential.

Possibility designing half-wave and full-wave molecular rectifiers by using single benzene molecule

NASA Astrophysics Data System (ADS)

Abbas, Mohammed A.; Hanoon, Falah H.; Al-Badry, Lafy F.

2018-02-01

This work focused on possibility designing half-wave and full-wave molecular rectifiers by using single and two benzene rings, respectively. The benzene rings were threaded by a magnetic flux that changes over time. The quantum interference effect was considered as the basic idea in the rectification action, the para and meta configurations were investigated. All the calculations are performed by using steady-state theoretical model, which is based on the time-dependent Hamiltonian model. The electrical conductance and the electric current are considered as DC output signals of half-wave and full-wave molecular rectifiers. The finding in this work opens up the exciting potential to use these molecular rectifiers in molecular electronics.

Clinical Concentrations of Local Anesthetics Bupivacaine and Lidocaine Differentially Inhibit Human Kir2.x Inward Rectifier K+ Channels.

PubMed

Nakahira, Kei; Oshita, Kensuke; Itoh, Masayuki; Takano, Makoto; Sakaguchi, Yoshiro; Ishihara, Keiko

2016-04-01

Inward rectifier K channels of the Kir2.x subfamily are widely expressed in neuronal tissues, controlling neuronal excitability. Previous studies reported that local anesthetics (LAs) do not affect Kir2 channels. However, the effects have not been studied at large concentrations used in regional anesthesia. This study used the patch-clamp technique to examine the effects of bupivacaine and lidocaine on Kir2.1, Kir2.2, and Kir2.3 channels expressed in human embryonic kidney 293 cells. When applied extracellularly in whole-cell recordings, both LAs inhibited Kir2.x currents in a voltage-independent manner. Inhibition with bupivacaine was slow and irreversible, whereas that with lidocaine was fast and reversible. Kir2.3 displayed a greater sensitivity to bupivacaine than Kir2.1 and Kir2.2 (50% inhibitory concentrations at approximately 5 minutes, 0.6 vs 8-10 mM), whereas their sensitivities to lidocaine were similar (50% inhibitory concentrations, 1.5-2.7 mM). Increases in the charged/neutral ratio of the LAs at an acidic extracellular pH attenuated their inhibitory effects, and a permanently charged lidocaine derivative QX-314 exhibited no effects when applied extracellularly. Inside-out experiments demonstrated that inhibition of Kir2.1 with cytoplasmic lidocaine and QX-314 was rapid and reversible, whereas that induced by bupivacaine was slow and irreversible. Furthermore, dose-inhibition relations for the charged form of bupivacaine and lidocaine obtained at different cytoplasmic pHs could be approximated by a single relation for each LA. The results indicate that both LAs at clinical concentrations equilibrated rapidly with the intracellular milieu, differentially inhibiting Kir2.x channel function from the cytoplasmic side.

27 CFR 5.61 - Application.

Code of Federal Regulations, 2010 CFR

2010-04-01

... § 5.61 Application. No person engaged in business as a distiller, rectifier, importer, wholesaler, or... distiller, rectifier, importer, wholesaler, or warehouseman and bottler of distilled spirits, directly or...

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

PubMed

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

2013-04-01

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

Oscillations in motor unit discharge are reflected in the low-frequency component of rectified surface EMG and the rate of change in force.

PubMed

Yoshitake, Yasuhide; Shinohara, Minoru

2013-11-01

Common drive to a motor unit (MU) pool manifests as low-frequency oscillations in MU discharge rate, producing fluctuations in muscle force. The aim of the study was to examine the temporal correlation between instantaneous MU discharge rate and rectified EMG in low frequencies. Additionally, we attempted to examine whether there is a temporal correlation between the low-frequency oscillations in MU discharge rate and the first derivative of force (dF/dt). Healthy young subjects produced steady submaximal force with their right finger as a single task or while maintaining a pinch-grip force with the left hand as a dual task. Surface EMG and fine-wire MU potentials were recorded from the first dorsal interosseous muscle in the right hand. Surface EMG was band-pass filtered (5-1,000 Hz) and full-wave rectified. Rectified surface EMG and the instantaneous discharge rate of MUs were smoothed by a Hann-window of 400 ms duration (equivalent to 2 Hz low-pass filtering). In each of the identified MUs, the smoothed MU discharge rate was positively correlated with the rectified-and-smoothed EMG as confirmed by the distinct peak in cross-correlation function with greater values in the dual task compared with the single task. Additionally, the smoothed MU discharge rate was temporally correlated with dF/dt more than with force and with rectified-and-smoothed EMG. The results indicated that the low-frequency component of rectified surface EMG and the first derivative of force provide temporal information on the low-frequency oscillations in the MU discharge rate.

Design and test of a 2.25-MW transformer rectifier assembly

NASA Technical Reports Server (NTRS)

Cormier, R.; Daeges, J.

1989-01-01

A new 2.25-MW transformer rectifier assembly was fabricated for DSS-13 at Goldstone, California. The transformer rectifier will provide constant output power of 2.25 MW at any voltage from 31 kV to 125 kV. This will give a new capability of 1 MW of RF power at X-band, provided appropriate microwave tubes are in the power amplifier. A description of the design and test results is presented.

Power combining in an array of microwave power rectifiers

NASA Technical Reports Server (NTRS)

Gutmann, R. J.; Borrego, J. M.

1979-01-01

This work analyzes the resultant efficiency degradation when identical rectifiers operate at different RF power levels as caused by the power beam taper. Both a closed-form analytical circuit model and a detailed computer-simulation model are used to obtain the output dc load line of the rectifier. The efficiency degradation is nearly identical with series and parallel combining, and the closed-form analytical model provides results which are similar to the detailed computer-simulation model.

27 CFR 4.60 - Application.

Code of Federal Regulations, 2010 CFR

2010-04-01

... person engaged in the business as a producer, rectifier, blender, importer, or wholesaler of wine... engaged in business as a producer, rectifier, blender, importer, or wholesaler of wine, directly or...

High-speed optical coherence tomography using fiberoptic acousto-optic phase modulation

NASA Astrophysics Data System (ADS)

Xie, Tuqiang; Wang, Zhenguo; Pan, Yingtian

2003-12-01

We report a new rapid-scanning optical delay device suitable for high-speed optical coherence tomography (OCT) in which an acousto-optic modulator (AOM) is used to independently modulate the Doppler frequency shift of the reference light beam for optical heterodyne detection. Experimental results show that the fluctuation of the measured Doppler frequency shift is less than +/-0.2% over 95% duty cycle of OCT imaging, thus allowing for enhanced signal-to-noise ratio of optical heterodyne detection. The increased Doppler frequency shift by AOM also permits complete envelop demodulation without the compromise of reducing axial resolution; if used with a resonant rapid-scanning optical delay, it will permit high-performance real-time OCT imaging. Potentially, this new rapid-scanning optical delay device will improve the performance of high-speed Doppler OCT techniques.

RNA Editing Underlies Temperature Adaptation in K+ Channels from Polar Octopuses

PubMed Central

Garrett, Sandra; Rosenthal, Joshua J.C.

2014-01-01

To operate in the extreme cold, ion channels from psychrophiles must have evolved structural changes to compensate for their thermal environment. A reasonable assumption would be that the underlying adaptations lie within the encoding genes. Here we show that delayed rectifier K+ channel genes from an Antarctic and a tropical octopus encode channels that differ at only four positions and display very similar behavior when expressed in Xenopus oocytes. However, the transcribed mRNAs are extensively edited, creating functional diversity. One editing site, which recodes an isoleucine to a valine in the channel’s pore, greatly accelerates gating kinetics by destabilizing the open state. This site is extensively edited in both Antarctic and Arctic species, but mostly unedited in tropical species. Thus A-to-I RNA editing can respond to the physical environment. PMID:22223739

Two-dimensional coherent spectroscopy of a THz quantum cascade laser: observation of multiple harmonics.

PubMed

Markmann, Sergej; Nong, Hanond; Pal, Shovon; Fobbe, Tobias; Hekmat, Negar; Mohandas, Reshma A; Dean, Paul; Li, Lianhe; Linfield, Edmund H; Davies, A Giles; Wieck, Andreas D; Jukam, Nathan

2017-09-04

Two-dimensional spectroscopy is performed on a terahertz (THz) frequency quantum cascade laser (QCL) with two broadband THz pulses. Gain switching is used to amplify the first THz pulse and the second THz pulse is used to probe the system. Fourier transforms are taken with respect to the delay time between the two THz pulses and the sampling time of the THz probe pulse. The two-dimensional spectrum consists of three peaks at (ω τ = 0, ω t = ω 0 ), (ω τ = ω 0 , ω t = ω 0 ), and (ω τ = 2ω 0 , ω t = ω 0 ) where ω 0 denotes the lasing frequency. The peak at ω τ = 0 represents the response of the probe to the zero-frequency (rectified) component of the instantaneous intensity and can be used to measure the gain recovery.

30 CFR 75.380 - Escapeways; bituminous and lignite mines.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Underground transformer stations, battery charging stations, substations, and rectifiers except— (A) Where... rectifiers and power centers with transformers that are either dry-type or contain nonflammable liquid...

Driver circuit for solid state light sources

DOEpatents

Palmer, Fred; Denvir, Kerry; Allen, Steven

2016-02-16

A driver circuit for a light source including one or more solid state light sources, a luminaire including the same, and a method of so driving the solid state light sources are provided. The driver circuit includes a rectifier circuit that receives an alternating current (AC) input voltage and provides a rectified AC voltage. The driver circuit also includes a switching converter circuit coupled to the light source. The switching converter circuit provides a direct current (DC) output to the light source in response to the rectified AC voltage. The driver circuit also includes a mixing circuit, coupled to the light source, to switch current through at least one solid state light source of the light source in response to each of a plurality of consecutive half-waves of the rectified AC voltage.

Theoretical study on the rectifying performance of organoimido derivatives of hexamolybdates.

PubMed

Wen, Shizheng; Yang, Guochun; Yan, Likai; Li, Haibin; Su, Zhongmin

2013-02-25

We design a new type of molecular diode, based on the organoimido derivatives of hexamolybdates, by exploring the rectifying performances using density functional theory combined with the non-equilibrium Green's function. Asymmetric current-voltage characteristics were obtained for the models with an unexpected large rectification ratio. The rectifying behavior can be understood by the asymmetrical shift of the transmission peak observed under different polarities. It is interesting to find that the preferred electron-transport direction in our studied system is different from that of the organic D-bridge-A system. The results show that the studied organic-inorganic hybrid systems have an intrinsically robust rectifying ratio, which should be taken into consideration in the design of the molecular diodes. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of Asymmetric Local Joule Heating on Silicon Nanowire-Based Devices Formed by Dielectrophoresis Alignment Across Pt Electrodes

NASA Astrophysics Data System (ADS)

Ho, Hsiang-Hsi; Lin, Chun-Lung; Tsai, Wei-Che; Hong, Liang-Zheng; Lyu, Cheng-Han; Hsu, Hsun-Feng

2018-01-01

We demonstrate the fabrication and characterization of silicon nanowire-based devices in metal-nanowire-metal configuration using direct current dielectrophoresis. The current-voltage characteristics of the devices were found rectifying, and their direction of rectification could be determined by voltage sweep direction due to the asymmetric Joule heating effect that occurred in the electrical measurement process. The photosensing properties of the rectifying devices were investigated. It reveals that when the rectifying device was in reverse-biased mode, the excellent photoresponse was achieved due to the strong built-in electric field at the junction interface. It is expected that rectifying silicon nanowire-based devices through this novel and facile method can be potentially applied to other applications such as logic gates and sensors.

The Use of Uas for Rapid 3d Mapping in Geomatics Education

NASA Astrophysics Data System (ADS)

Teo, Tee-Ann; Tian-Yuan Shih, Peter; Yu, Sz-Cheng; Tsai, Fuan

2016-06-01

With the development of technology, UAS is an advance technology to support rapid mapping for disaster response. The aim of this study is to develop educational modules for UAS data processing in rapid 3D mapping. The designed modules for this study are focused on UAV data processing from available freeware or trial software for education purpose. The key modules include orientation modelling, 3D point clouds generation, image georeferencing and visualization. The orientation modelling modules adopts VisualSFM to determine the projection matrix for each image station. Besides, the approximate ground control points are measured from OpenStreetMap for absolute orientation. The second module uses SURE and the orientation files from previous module for 3D point clouds generation. Then, the ground point selection and digital terrain model generation can be archived by LAStools. The third module stitches individual rectified images into a mosaic image using Microsoft ICE (Image Composite Editor). The last module visualizes and measures the generated dense point clouds in CloudCompare. These comprehensive UAS processing modules allow the students to gain the skills to process and deliver UAS photogrammetric products in rapid 3D mapping. Moreover, they can also apply the photogrammetric products for analysis in practice.

46 CFR 111.33-1 - General.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Power Semiconductor Rectifier Systems § 111.33-1 General. This subpart is applicable to all power semiconductor rectifier systems. In addition to the regulations contained in this subpart, the requirements of...

Requirements for effective use of CFD in aerospace design

NASA Technical Reports Server (NTRS)

Raj, Pradeep

1995-01-01

This paper presents a perspective on the requirements that Computational Fluid Dynamics (CFD) technology must meet for its effective use in aerospace design. General observations are made on current aerospace design practices and deficiencies are noted that must be rectified for the U.S. aerospace industry to maintain its leadership position in the global marketplace. In order to rectify deficiencies, industry is transitioning to an integrated product and process development (IPPD) environment and design processes are undergoing radical changes. The role of CFD in producing data that design teams need to support flight vehicle development is briefly discussed. An overview of the current state of the art in CFD is given to provide an assessment of strengths and weaknesses of the variety of methods currently available, or under development, to produce aerodynamic data. Effectiveness requirements are examined from a customer/supplier view point with design team as customer and CFD practitioner as supplier. Partnership between the design team and CFD team is identified as an essential requirement for effective use of CFD. Rapid turnaround, reliable accuracy, and affordability are offered as three key requirements that CFD community must address if CFD is to play its rightful role in supporting the IPPD design environment needed to produce high quality yet affordable designs.

Fabrication and characterization of the organic rectifying junctions by electrolysis

NASA Astrophysics Data System (ADS)

Karimov, Khasan; Ahmad, Zubair; Ali, Rashid; Noor, Adnan; Akmal, M.; Najeeb, M. A.; Shakoor, R. A.

2017-08-01

Unlike the conventional solution processable deposition techniques, in this study, we propose a novel and economical method for the fabrication of organic rectifying junctions. The solutions of the orange dye, copper phthalocyanine and NaCl were deposited on the surface-type interdigitated silver electrodes using electrolysis technique. Using the current-voltage (I-V) characteristics, the presence of rectifying behavior in the samples has been confirmed. This phenomenon, in principle, can be used for fabrication of the diodes, transistors and memory devices.

Flutter Generator Control and Force Computer.

DTIC Science & Technology

1985-07-01

exciter module 2. Mechanical load 3. Rectifier and triac 4. Overall system 5. Velocity control 6. Microprocessor 7. Operation in 1 ’g’ environment 8...amplifier Output voltage from the rectifier/ triac circuit (figure 3) is a function of the conduction angle of each triac . In a 400 Hz 3-phase system...3IIGCICI FIRING CIRCUIT FIRING CIRCUIT TO MOTOR Figure 3. Rectifier and triac _____ -=low AEL-0242-TNI Figure 4 DEMAND(V V49 -9 APIFE M O T OR

37 CFR 201.7 - Cancellation of completed registrations.

Code of Federal Regulations, 2011 CFR

2011-07-01

... or omissions which would generally have been rectified before registration, the Copyright Office will attempt to rectify the error through correspondence with the remitter. Except in those cases enumerated in...

27 CFR 26.206 - Marking packages and cases.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., rectifier, or bottler shall serially number each case, barrel, cask, or similar container of distilled... distiller, rectifier, or bottler shall plainly print, stamp, or stencil with durable coloring material, in...

46 CFR 111.33-9 - Ventilation exhaust.

Code of Federal Regulations, 2010 CFR

2010-10-01

... REQUIREMENTS Power Semiconductor Rectifier Systems § 111.33-9 Ventilation exhaust. The exhaust of each forced-air semiconductor rectifier system must: (a) Terminate in a location other than a hazardous location...

46 CFR 111.33-7 - Alarms and shutdowns.

Code of Federal Regulations, 2010 CFR

2010-10-01

... REQUIREMENTS Power Semiconductor Rectifier Systems § 111.33-7 Alarms and shutdowns. Each power semiconductor rectifier must have a high temperature alarm or shutdown, except as provided in § 111.33-11. ...

"ATP1A3" Mutations in Infants: A New Rapid-Onset Dystonia-Parkinsonism Phenotype Characterized by Motor Delay and Ataxia

ERIC Educational Resources Information Center

Brashear, Allison; Mink, Jonathan W.; Hill, Deborah F.; Boggs, Niki; McCall, W. Vaughn; Stacy, Mark A.; Snively, Beverly; Light, Laney S.; Sweadner, Kathleen J.; Ozelius, Laurie J.; Morrison, Leslie

2012-01-01

We report new clinical features of delayed motor development, hypotonia, and ataxia in two young children with mutations (R756H and D923N) in the "ATP1A3" gene. In adults, mutations in "ATP1A3" cause rapid-onset dystonia-Parkinsonism (RDP, DYT12) with abrupt onset of fixed dystonia. The parents and children were examined and videotaped, and…

Tags, wireless communication systems, tag communication methods, and wireless communications methods

DOEpatents

Scott,; Jeff W. , Pratt; Richard, M [Richland, WA

2006-09-12

Tags, wireless communication systems, tag communication methods, and wireless communications methods are described. In one aspect, a tag includes a plurality of antennas configured to receive a plurality of first wireless communication signals comprising data from a reader, a plurality of rectifying circuits coupled with. respective individual ones of the antennas and configured to provide rectified signals corresponding to the first wireless communication signals, wherein the rectified signals are combined to produce a composite signal, an adaptive reference circuit configured to vary a reference signal responsive to the composite signal, a comparator coupled with the adaptive reference circuit and the rectifying circuits and configured to compare the composite signal with respect to the reference signal and to output the data responsive to the comparison, and processing circuitry configured to receive the data from the comparator and to process the data.

A Novel Phase-Shift Control of Semibridgeless Active Rectifier for Wireless Power Transfer

DOE PAGES

Colak, Kerim; Asa, Erdem; Bojarski, Mariusz; ...

2015-05-12

We investigated a novel phase-shift control of a semibridgeless active rectifier (S-BAR) in order to utilize the S-BAR in wireless energy transfer applications. The standard receiver-side rectifier topology is developed by replacing rectifier lower diodes with synchronous switches controlled by a phase-shifted PWM signal. Moreover, theoretical and simulation results showthat with the proposed control technique, the output quantities can be regulated without communication between the receiver and transmitter. In order to confirm the performance of the proposed converter and control, experimental results are provided using 8-, 15-, and 23-cm air gap coreless transformer which has dimension of 76 cm xmore » 76 cm, with 120-V input and the output power range of 0 to 1kW with a maximum efficiency of 94.4%.« less

How long can fisheries management delay action in response to ecosystem and climate change?

PubMed

Brown, Christopher J; Fulton, Elizabeth A; Possingham, Hugh P; Richardson, Anthony J

2012-01-01

Sustainable management of fisheries is often compromised by management delaying implementation of regulations that reduce harvest, in order to maintain higher catches in the short-term. Decreases or increases in fish population growth rate driven by environmental change, including ecosystem and climate change, affect the harvest that can be taken sustainably. If not acted on rapidly, environmental change could result in unsustainable fishing or missed opportunity for higher catches. Using simulation models of harvested fish populations influenced by environmental change, we explore how long fisheries managers can afford to wait before changing harvest regulations in response to changes in population growth. If environmental change causes population declines, delays greater than five years increase the probability of population collapse. Species with fast and highly variable population growth rates are more susceptible to collapse under delays and should be a priority for revised management where delays occur. Generally, the long-term cost of delay, in terms of lost fishing opportunity, exceeds the short-term benefits of overfishing. Lowering harvest limits and monitoring for environmental change can alleviate the impact of delays; however, these measures may be more costly than reducing delays. We recommend that management systems that allow rapid responses to population growth changes be enacted for fisheries management to adapt to ecosystem and climate change.

Construction procedures using self hardening fly ash

NASA Astrophysics Data System (ADS)

Thornton, S. I.; Parker, D. G.

1980-07-01

Fly ash produced in Arkansas from burning Wyoming low sulfur coal is self-hardening and can be effective as a soil stabilizing agent for clays and sands. The strength of soil-self hardening fly ash develops rapidly when compacted immediately after mixing. Seven day unconfined compressive strengths up to 1800 psi were obtained from 20% fly ash and 80% sand mixtures. A time delay between mixing the fly ash with the soil and compaction of the mixture reduced the strength. With two hours delay, over a third of the strength was lost and with four hours delay, the loss was over half. Gypsum and some commercial concrete retarders were effective in reducing the detrimental effect of delayed compaction. Adequate mixing of the soil and fly ash and rapid compaction of the mixtures were found to be important parameters in field construction of stabilized bases.

The changes of potassium currents in rabbit ventricle with healed myocardial infarction.

PubMed

Liu, Nian; Niu, Huiyan; Li, Yang; Zhang, Cuntai; Zhou, Qiang; Ruan, Yanfei; Pu, Jun; Lu, Zaiying

2004-01-01

To elucidate the mechanism of arrhythmia in healed myocardial infarction (HMI), the changes of action potential duration (APD), transient outward potassium current (Ito), delayed rectifier potassium current (IK) and inward rectifier potassium current (IK1) of left ventricular myocytes in non-infarcted zone of HMI were investigated. Rabbits were randomly assigned into two groups: HMI group, in which animals were subjected to thoracotomy and ligation of the circumflex coronary and sham-operated group, in which rabbits underwent thoracotomy but no conorary ligation. 3 months after the operation, the whole myocyte patch clamp technique was used to record APD, Ito, IK, and IK1 of ventricular myocytes in non-infarcted zone. Our results showed that the membrane capacitance was larger in HMI group than in sham-operated group. Action potential duration was significantly lengthened in HMI group and early afterdepolarization (EAD) appeared in HMI group. The densities of Ito, I(K, tail), and IK1 were reduced significantly in HMI group, from 6.72 +/- 0.42 pA/pF, 1.54 +/- 0.13 pA/pF and 25.6 +/- 2.6 pA/pF in sham-operated group to 4.03 +/- 0.33 pA/pF, 1.14 +/- 0.11 pA/pF and 17.6 +/- 2.3 pA/pF, respectively. It is concluded that the reduced densities of Ito, I(K, tail) and IK1 in ventricular myocytes of non-infarcted zone in HMI were responsible for the prolongation of APD and the presentation of EAD which played important roles in the development of malignant arrhythmia in HMI.

INCREASED VOLUNTARY DRIVE IS ASSOCIATED WITH CHANGES IN COMMON OSCILLATIONS FROM 13 TO 60 HZ OF INTERFERENCE BUT NOT RECTIFIED ELECTROMYOGRAPHY

PubMed Central

NETO, OSMAR P.; BAWEJA, HARSIMRAN S.; CHRISTOU, EVANGELOS A.

2013-01-01

The purpose of this study was to compare the capability of interference and rectified electromyography (EMG) to detect changes in the beta (13–30-HZ) and Piper (30–60-HZ) bands when voluntary force is increased. Twenty adults exerted a constant force abduction of the index finger at 15% and 50% of maximum. The common oscillations at various frequency bands (0–500 HZ) were estimated from the first dorsal interosseous muscle using cross wavelets of interference and rectified EMG. For the interference EMG signals, normalized power significantly (P < 0.01) increased with force in the beta (9.0 ± 0.9 vs. 15.5 ± 2.1%) and Piper (13.6 ± 0.9 vs. 21 ± 1.7%) bands. For rectified EMG signals, however, the beta and Piper bands remained unchanged (P > 0.4). Although rectified EMG is used in many clinical studies to identify changes in the oscillatory drive to the muscle, our findings suggest that only interference EMG can accurately capture the increase in oscillatory drive from 13 to 60 HZ with voluntary force. PMID:20589885

Self-Rectifying Effect in Resistive Switching Memory Using Amorphous InGaZnO

NASA Astrophysics Data System (ADS)

Lee, Jin-Woo; Kwon, Hyeon-Min; Kim, Myeong-Ho; Lee, Seung-Ryul; Kim, Young-Bae; Choi, Duck-Kyun

2014-05-01

Resistance random access memory (ReRAM) has received attention as next-generation memory because of its excellent operating properties and high density integration capability as a crossbar array. However, the application of the existing ReRAM as a crossbar array may lead to crosstalk between adjacent cells due to its symmetric I- V characteristics. In this study, the self-rectifying effect of contact between amorphous In-Ga-Zn-O (a-IGZO) and TaO x was examined in a Pt/a-IGZO/TaO x /Al2O3/W structure. The experimental results show not only self-rectifying behavior but also forming-free characteristics. During the deposition of a-IGZO on the TaO x , an oxygen-rich TaO x interfacial layer was formed. The rectifying effect was observed regardless of the interface formation and is believed to be associated with Schottky contact formation between a-IGZO and TaO x . The current level remained unchanged despite repeated DC sweep cycles. The low resistance state/high resistance state ratio was about 101 at a read voltage of -0.5 V, and the rectifying ratio was about 103 at ±2 V.

Better concrete mixes for rapid repair in Wisconsin.

DOT National Transportation Integrated Search

2017-04-01

With the increasing demands on the highway system and increasing costs of user delay, the use and development of rapid-repairtechniques are expected to grow rapidly. High early strength (HES) portland cement concrete can help reduce the duration oftr...

Revealing unobserved factors underlying cortical activity with a rectified latent variable model applied to neural population recordings.

PubMed

Whiteway, Matthew R; Butts, Daniel A

2017-03-01

The activity of sensory cortical neurons is not only driven by external stimuli but also shaped by other sources of input to the cortex. Unlike external stimuli, these other sources of input are challenging to experimentally control, or even observe, and as a result contribute to variability of neural responses to sensory stimuli. However, such sources of input are likely not "noise" and may play an integral role in sensory cortex function. Here we introduce the rectified latent variable model (RLVM) in order to identify these sources of input using simultaneously recorded cortical neuron populations. The RLVM is novel in that it employs nonnegative (rectified) latent variables and is much less restrictive in the mathematical constraints on solutions because of the use of an autoencoder neural network to initialize model parameters. We show that the RLVM outperforms principal component analysis, factor analysis, and independent component analysis, using simulated data across a range of conditions. We then apply this model to two-photon imaging of hundreds of simultaneously recorded neurons in mouse primary somatosensory cortex during a tactile discrimination task. Across many experiments, the RLVM identifies latent variables related to both the tactile stimulation as well as nonstimulus aspects of the behavioral task, with a majority of activity explained by the latter. These results suggest that properly identifying such latent variables is necessary for a full understanding of sensory cortical function and demonstrate novel methods for leveraging large population recordings to this end. NEW & NOTEWORTHY The rapid development of neural recording technologies presents new opportunities for understanding patterns of activity across neural populations. Here we show how a latent variable model with appropriate nonlinear form can be used to identify sources of input to a neural population and infer their time courses. Furthermore, we demonstrate how these sources are related to behavioral contexts outside of direct experimental control. Copyright © 2017 the American Physiological Society.

Inward rectifier potassium current IKir promotes intrinsic pacemaker activity of thalamocortical neurons.

PubMed

Amarillo, Yimy; Tissone, Angela I; Mato, Germán; Nadal, Marcela S

2018-06-01

Slow repetitive burst firing by hyperpolarized thalamocortical (TC) neurons correlates with global slow rhythms (<4 Hz), which are the physiological oscillations during non-rapid eye movement sleep or pathological oscillations during idiopathic epilepsy. The pacemaker activity of TC neurons depends on the expression of several subthreshold conductances, which are modulated in a behaviorally dependent manner. Here we show that upregulation of the small and neglected inward rectifier potassium current I Kir induces repetitive burst firing at slow and delta frequency bands. We demonstrate this in mouse TC neurons in brain slices by manipulating the Kir maximum conductance with dynamic clamp. We also performed a thorough theoretical analysis that explains how the unique properties of I Kir enable this current to induce slow periodic bursting in TC neurons. We describe a new ionic mechanism based on the voltage- and time-dependent interaction of I Kir and hyperpolarization-activated cationic current I h that endows TC neurons with the ability to oscillate spontaneously at very low frequencies, even below 0.5 Hz. Bifurcation analysis of conductance-based models of increasing complexity demonstrates that I Kir induces bistability of the membrane potential at the same time that it induces sustained oscillations in combination with I h and increases the robustness of low threshold-activated calcium current I T -mediated oscillations. NEW & NOTEWORTHY The strong inwardly rectifying potassium current I Kir of thalamocortical neurons displays a region of negative slope conductance in the current-voltage relationship that generates potassium currents activated by hyperpolarization. Bifurcation analysis shows that I Kir induces bistability of the membrane potential; generates sustained subthreshold oscillations by interacting with the hyperpolarization-activated cationic current I h ; and increases the robustness of oscillations mediated by the low threshold-activated calcium current I T . Upregulation of I Kir in thalamocortical neurons induces repetitive burst firing at slow and delta frequency bands (<4 Hz).

The function and molecular identity of inward rectifier channels in vestibular hair cells of the mouse inner ear

PubMed Central

Levin, Michaela E.

2012-01-01

Inner ear hair cells respond to mechanical stimuli with graded receptor potentials. These graded responses are modulated by a host of voltage-dependent currents that flow across the basolateral membrane. Here, we examine the molecular identity and the function of a class of voltage-dependent ion channels that carries the potassium-selective inward rectifier current known as IK1. IK1 has been identified in vestibular hair cells of various species, but its molecular composition and functional contributions remain obscure. We used quantitative RT-PCR to show that the inward rectifier gene, Kir2.1, is highly expressed in mouse utricle between embryonic day 15 and adulthood. We confirmed Kir2.1 protein expression in hair cells by immunolocalization. To examine the molecular composition of IK1, we recorded voltage-dependent currents from type II hair cells in response to 50-ms steps from −124 to −54 in 10-mV increments. Wild-type cells had rapidly activating inward currents with reversal potentials close to the K+ equilibrium potential and a whole-cell conductance of 4.8 ± 1.5 nS (n = 46). In utricle hair cells from Kir2.1-deficient (Kir2.1−/−) mice, IK1 was absent at all stages examined. To identify the functional contribution of Kir2.1, we recorded membrane responses in current-clamp mode. Hair cells from Kir2.1−/− mice had significantly (P < 0.001) more depolarized resting potentials and larger, slower membrane responses than those of wild-type cells. These data suggest that Kir2.1 is required for IK1 in type II utricle hair cells and contributes to hyperpolarized resting potentials and fast, small amplitude receptor potentials in response to current inputs, such as those evoked by hair bundle deflections. PMID:22496522

31 CFR 27.7 - Final Notice of Assessment.

Code of Federal Regulations, 2011 CFR

2011-07-01

... civil or equitable remedy deemed necessary to rectify the potential for a continued misuse or harm from... determined, and the terms of any civil or equitable remedy deemed necessary to rectify the potential for a...

31 CFR 27.7 - Final Notice of Assessment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... civil or equitable remedy deemed necessary to rectify the potential for a continued misuse or harm from... determined, and the terms of any civil or equitable remedy deemed necessary to rectify the potential for a...

78 FR 60186 - Airworthiness Directives; AgustaWestland S.p.A. (Agusta) Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-01

... avionics bay and the baggage compartment resulting from an Auto Transformer Rectifier Unit internal circuit... resulting in failure of the FIPS Auto Transformer Rectifier Unit to contain the internal circuit overload...

Storing wind energy into electrical accumulators

NASA Astrophysics Data System (ADS)

Dordescu, M.; Petrescu, D. I.; Erdodi, G. M.

2016-12-01

Shall be determined, in this work, the energy stored in the accumulators electrical, AE, at a wind system operating at wind speeds time-varying. mechanical energy caught in the turbine from the wind, (TV), is transformed into electrical energy by the generator synchronous with the permanent magnets, GSMP. The Generator synchronous with the permanent magnets saws, via a rectifier, energy in a battery AE, finished in a choice of two: variant 1-unregulated rectifier and variant of the 2-controlled rectifier and task adapted. Through simulation determine the differences between the two versions

Recovery Act: High-Efficiency, Wideband Three-Phase Rectifiers and Adaptive Rectifier Management for Telecomm Central Office and Large Data Center Applications

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

Mark A. Johnson

2012-06-29

Lineage Power and Verizon teamed up to address a DOE funding opportunity focused on improving the power conversion chain in telecommunications facilities and data centers. The project had three significant elements: the design and development of high efficiency and high power three-phase rectifiers by Lineage Power, design and development of software to optimize overall plant energy efficiency by Lineage Power, and a field trial in active Verizon telecommunications facilities where energy consumption was measured before and after efficiency upgrades.

Shear Wave Splitting Inversion in a Complex Crust

NASA Astrophysics Data System (ADS)

Lucas, A.

2015-12-01

Shear wave splitting (SWS) inversion presents a method whereby the upper crust can be interrogated for fracture density. It is caused when a shear wave traverses an area of anisotropy, splits in two, with each wave experiencing a different velocity resulting in an observable separation in arrival times. A SWS observation consists of the first arrival polarization direction and the time delay. Given the large amount of data common in SWS studies, manual inspection for polarization and time delay is considered prohibitively time intensive. All automated techniques used can produce high amounts of observations falsely interpreted as SWS. Thus introducing error into the interpretation. The technique often used for removing these false observations is to manually inspect all SWS observations defined as high quality by the automated routine, and remove false identifications. We investigate the nature of events falsely identified compared to those correctly identified. Once this identification is complete we conduct a inversion for crack density from SWS time delay. The current body of work on linear SWS inversion utilizes an equation that defines the time delay between arriving shear waves with respect to fracture density. This equation makes the assumption that no fluid flow occurs as a result of the passing shear wave, a situation called squirt flow. We show that the assumption is not applicable in all geological situations. When it is not true, its use in an inversion produces a result which is negatively affected by the assumptions. This is shown to be the case at the test case of 6894 SWS observations gathered in a small area at Puna geothermal field, Hawaii. To rectify this situation, a series of new time delay formulae, applicable to linear inversion, are derived from velocity equations presented in literature. The new formula use a 'fluid influence parameter' which indicates the degree to which squirt flow is influencing the SWS. It is found that accounting for squirt flow better fits the data and is more applicable. The fluid influence factor that best describes the data can be identified prior to solving the inversion. Implementing this formula in a linear inversion has a significantly improved fit to the time delay observations than that of the current methods.

GaN Microwave DC-DC Converters

NASA Astrophysics Data System (ADS)

Ramos Franco, Ignacio

Increasing the operating frequency of switching converters can have a direct impact in the miniaturization and integration of power converters. The size of energy-storage passive components and the difficulty to integrate them with the rest of the circuitry is a major challenge in the development of a fully integrated power supply on a chip. The work presented in this thesis attempts to address some of the difficulties encountered in the design of high-frequency converters by applying concepts and techniques usually used in the design of high-efficiency power amplifiers and high-efficiency rectifiers at microwave frequencies. The main focus is in the analysis, design, and characterization of dc-dc converters operating at microwave frequencies in the low gigahertz range. The concept of PA-rectifier duality, where a high-efficiency power amplifier operates as a high-efficiency rectifier is investigated through non-linear simulations and experimentally validated. Additionally, the concept of a self-synchronous rectifier, where a transistor rectifier operates synchronously without the need of a RF source or driver is demonstrated. A theoretical analysis of a class-E self-synchronous rectifier is presented and validated through non-linear simulations and experiments. Two GaN class-E2 dc-dc converters operating at a switching frequency of 1 and 1.2 GHz are demonstrated. The converters achieve 80 % and 75 % dc-dc efficiency respectively and are among the highest-frequency and highest-efficiency reported in the literature. The application of the concepts established in the analysis of a self-synchronous rectifier to a power amplifier culminated in the development of an oscillating, self-synchronous class-E 2 dc-dc converter. Finally, a proof-of-concept fully integrated GaN MMIC class-E 2 dc-dc converter switching at 4.6 GHz is demonstrated for the first time to the best of our knowledge. The 3.8 mm x 2.6 mm chip contains distributed inductors and does not require any external components. The maximum measured dc-dc efficiency is approximately 45%.

Membrane augmented distillation to separate solvents from water

DOEpatents

Huang, Yu; Baker, Richard W.; Daniels, Rami; Aldajani, Tiem; Ly, Jennifer H.; Alvarez, Franklin R.; Vane, Leland M.

2012-09-11

Processes for removing water from organic solvents, such as ethanol. The processes include distillation to form a rectified overhead vapor, compression of the rectified vapor, and treatment of the compressed vapor by two sequential membrane separation steps.

Thin-film semiconductor rectifier has improved properties

NASA Technical Reports Server (NTRS)

1966-01-01

Cadmium selenide-zinc selenide film is used as a thin film semiconductor rectifier. The film is vapor-deposited in a controlled concentration gradient into a glass substrate to form the required junctions between vapor-deposited gold electrodes.

Gate-Controlled BP-WSe2 Heterojunction Diode for Logic Rectifiers and Logic Optoelectronics.

PubMed

Li, Dong; Wang, Biao; Chen, Mingyuan; Zhou, Jun; Zhang, Zengxing

2017-06-01

p-n junctions play an important role in modern semiconductor electronics and optoelectronics, and field-effect transistors are often used for logic circuits. Here, gate-controlled logic rectifiers and logic optoelectronic devices based on stacked black phosphorus (BP) and tungsten diselenide (WSe 2 ) heterojunctions are reported. The gate-tunable ambipolar charge carriers in BP and WSe 2 enable a flexible, dynamic, and wide modulation on the heterojunctions as isotype (p-p and n-n) and anisotype (p-n) diodes, which exhibit disparate rectifying and photovoltaic properties. Based on such characteristics, it is demonstrated that BP-WSe 2 heterojunction diodes can be developed for high-performance logic rectifiers and logic optoelectronic devices. Logic optoelectronic devices can convert a light signal to an electric one by applied gate voltages. This work should be helpful to expand the applications of 2D crystals. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Temperature-gated thermal rectifier for active heat flow control.

PubMed

Zhu, Jia; Hippalgaonkar, Kedar; Shen, Sheng; Wang, Kevin; Abate, Yohannes; Lee, Sangwook; Wu, Junqiao; Yin, Xiaobo; Majumdar, Arun; Zhang, Xiang

2014-08-13

Active heat flow control is essential for broad applications of heating, cooling, and energy conversion. Like electronic devices developed for the control of electric power, it is very desirable to develop advanced all-thermal solid-state devices that actively control heat flow without consuming other forms of energy. Here we demonstrate temperature-gated thermal rectification using vanadium dioxide beams in which the environmental temperature actively modulates asymmetric heat flow. In this three terminal device, there are two switchable states, which can be regulated by global heating. In the "Rectifier" state, we observe up to 28% thermal rectification. In the "Resistor" state, the thermal rectification is significantly suppressed (<1%). To the best of our knowledge, this is the first demonstration of solid-state active-thermal devices with a large rectification in the Rectifier state. This temperature-gated rectifier can have substantial implications ranging from autonomous thermal management of heating and cooling systems to efficient thermal energy conversion and storage.

Competitive inhibition can linearize dose-response and generate a linear rectifier.

PubMed

Savir, Yonatan; Tu, Benjamin P; Springer, Michael

2015-09-23

Many biological responses require a dynamic range that is larger than standard bi-molecular interactions allow, yet the also ability to remain off at low input. Here we mathematically show that an enzyme reaction system involving a combination of competitive inhibition, conservation of the total level of substrate and inhibitor, and positive feedback can behave like a linear rectifier-that is, a network motif with an input-output relationship that is linearly sensitive to substrate above a threshold but unresponsive below the threshold. We propose that the evolutionarily conserved yeast SAGA histone acetylation complex may possess the proper physiological response characteristics and molecular interactions needed to perform as a linear rectifier, and we suggest potential experiments to test this hypothesis. One implication of this work is that linear responses and linear rectifiers might be easier to evolve or synthetically construct than is currently appreciated.

Experimental verification of arm-locking for LISA using electronic phase delay [rapid communication

NASA Astrophysics Data System (ADS)

Thorpe, J. I.; Mueller, G.

2005-07-01

We present results of an electronic model of arm-locking, a proposed technique for reducing the laser phase noise in the laser interferometer space antenna (LISA). The model is based on a delay of 500 ms, achieved using the electronic phase delay (EPD) method. The observed behavior is consistent with predictions.

Specific residues of the cytoplasmic domains of cardiac inward rectifier potassium channels are effective antifibrillatory targets

PubMed Central

Noujaim, Sami F.; Stuckey, Jeanne A.; Ponce-Balbuena, Daniela; Ferrer-Villada, Tania; López-Izquierdo, Angelica; Pandit, Sandeep; Calvo, Conrado J.; Grzeda, Krzysztof R.; Berenfeld, Omer; Sánchez Chapula, José A.; Jalife, José

2010-01-01

Atrial and ventricular tachyarrhythmias can be perpetuated by up-regulation of inward rectifier potassium channels. Thus, it may be beneficial to block inward rectifier channels under conditions in which their function becomes arrhythmogenic (e.g., inherited gain-of-function mutation channelopathies, ischemia, and chronic and vagally mediated atrial fibrillation). We hypothesize that the antimalarial quinoline chloroquine exerts potent antiarrhythmic effects by interacting with the cytoplasmic domains of Kir2.1 (IK1), Kir3.1 (IKACh), or Kir6.2 (IKATP) and reducing inward rectifier potassium currents. In isolated hearts of three different mammalian species, intracoronary chloroquine perfusion reduced fibrillatory frequency (atrial or ventricular), and effectively terminated the arrhythmia with resumption of sinus rhythm. In patch-clamp experiments chloroquine blocked IK1, IKACh, and IKATP. Comparative molecular modeling and ligand docking of chloroquine in the intracellular domains of Kir2.1, Kir3.1, and Kir6.2 suggested that chloroquine blocks or reduces potassium flow by interacting with negatively charged amino acids facing the ion permeation vestibule of the channel in question. These results open a novel path toward discovering antiarrhythmic pharmacophores that target specific residues of the cytoplasmic domain of inward rectifier potassium channels.—Noujaim, S. F., Stuckey, J. A., Ponce-Balbuena, D., Ferrer-Villada, T., López-Izquierdo, A., Pandit, S., Calvo, C. J., Grzeda, K. R., Berenfeld, O., Sánchez Chapula, J. A., Jalife, J. Specific residues of the cytoplasmic domains of cardiac inward rectifier potassium channels are effective antifibrillatory targets. PMID:20585026

Effect of SSRI antidepressants on ejaculation: a double-blind, randomized, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine, and sertraline.

PubMed

Waldinger, M D; Hengeveld, M W; Zwinderman, A H; Olivier, B

1998-08-01

Depression is a common cause of sexual dysfunction, but also antidepressant medication is often associated with sexual side effects. This article includes two related studies. The first double-blind, placebo-controlled study was conducted in men with lifelong rapid ejaculation and aimed to assess putative differences between the major selective serotonin reuptake inhibitors (SSRIs) (fluoxetine, fluvoxamine, paroxetine, and sertraline) with regard to their ejaculation-delaying effect. Sixty men with an intravaginal ejaculation latency time (IELT) of 1 minute or less were randomly assigned to receive fluoxetine 20 mg/day, fluvoxamine 100 mg/day, paroxetine 20 mg/day, sertraline 50 mg/day, or placebo for 6 weeks. During the 1-month baseline and 6-week treatment periods, the men measured their IELT at home using a stopwatch. The trial was completed by 51 men. During the 6-week treatment period, the geometric mean IELT in the placebo group was constant at approximately 20 seconds. Analysis of variance revealed a between-groups difference in the evolution of IELT delay (p = 0.0004); in the paroxetine, fluoxetine, and sertraline groups there was a gradual increase to about 110 seconds, whereas in the fluvoxamine group, IELT was increased to only approximately 40 seconds. The paroxetine, fluoxetine, and sertraline groups differed significantly (p < 0.001, p < 0.001, p = 0.017, respectively) from placebo but the fluvoxamine group did not (p = 0.38). Compared with baseline, paroxetine exerted the strongest delay in ejaculation, followed by fluoxetine and sertraline. There was no clinically relevant delay in ejaculation with fluvoxamine. In men with lifelong rapid ejaculation, paroxetine delayed ejaculation most strongly, whereas fluvoxamine delayed ejaculation the least. The second double-blind, placebo-controlled study was carried out in men with lifelong rapid ejaculation (IELT < or = 1 minute) and in men with lifelong less-rapid ejaculation (IELT > 1 minute) to investigate whether data about SSRI-induced delayed ejaculation in men with rapid ejaculation may be extrapolated to men with less-rapid ejaculation. After measurement of IELT at home (using a stopwatch) during a 1-month baseline assessment, 32 men with an IELT of 1 minute or less (group 1) or more than 1 minute (group 2) were randomly assigned to receive paroxetine 20 mg/day or placebo for 6 weeks in a double-blind manner. Patients continued to measure their IELTs at home during the 6 weeks of the study. At baseline, 24 patients consistently had IELTs of one minute or less (group 1), and eight patients had IELTs of more than 1 minute (group 2). The geometric mean IELT was 14 seconds in group 1 and 83 seconds in group 2. Twelve patients in group 1 and five in group 2 were randomized to the paroxetine 20 mg/day. The percentage increase in the geometric mean IELT compared with baseline in patients treated with paroxetine was 420% (95% confidence interval [CI], 216-758%) in group 1 and 480% (95% CI, 177-1,118%) in group 2 (p = 0.81). After 6 weeks of treatment with paroxetine, the geometric mean IELT was 92 seconds in group 1 and 602 seconds in group 2 (p < 0.001). Therefore, the paroxetine-induced percentage increase in IELT seems to be independent of the baseline IELT. This suggests that ejaculation-delaying side effects of some SSRIs investigated in men with lifelong rapid ejaculation may be generalized to men with less-rapid ejaculation.

Influence of load type on power factor and harmonic composition of three-phase rectifier current

NASA Astrophysics Data System (ADS)

Nikolayzin, N. V.; Vstavskaya, E. V.; Konstantinov, V. I.; Konstantinova, O. V.

2018-05-01

This article is devoted to research of the harmonic composition of the three-phase rectifier current consumed when it operates with different types of load. The results are compared with Standard requirements.

27 CFR 70.31 - Entry of premises for examination of taxable objects.

Code of Federal Regulations, 2011 CFR

2011-04-01

... by day, enter any plant or any other premises where distilled spirits are produced or rectified, or... premises where spirits are produced or rectified, or any ground adjoining or near to such plant or premises...

Homeostatic effect of laughter on diabetic cardiovascular complications: The myth turned to fact.

PubMed

Noureldein, Mohamed H; Eid, Assaad A

2018-01-01

Laughter has been used for centuries to alleviate pain in morbid conditions. It was not until 1976 that scientists thought about laughter as a form of therapy that can modulate hormonal and immunological parameters that affect the outcome of many serious diseases. Moreover, laughter therapy was shown to be beneficial in type 2 diabetes mellitus (T2DM) by delaying the onset of many diabetic complications. Laughter is also described to influence the cardiovascular and endothelial functions and thus may protect against diabetic cardiovascular complications. In this review, we outline the different biochemical, physiological and immunological mechanisms by which laughter may influence the overall state of wellbeing and enhance disease prognosis. We also focus on the biological link between laughter therapy and diabetic cardiovascular complications as well as the underlying mechanisms involved in T2DM. Reviewing all the essential databases for "laughter" and "type 2 diabetes mellitus". Although laughter therapy is still poorly investigated, recent studies show that laughter may retard the onset of diabetic complications, enhance cardiovascular functions and rectify homeostatic abnormalities associated with T2DM. Laughter therapy is effective in delaying diabetic complications and should be used as an adjuvant therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Sotos Syndrome. Clinical Exchange.

ERIC Educational Resources Information Center

Shuey, Elaine M.; Jamison, Kristen

1996-01-01

Sotos syndrome is characterized by high birth length, rapid bone growth, distinctive facial features, and possible verbal and motor delays. It is more common in males than females. Developmental deficits, specific learning problems, and speech/language delays may also occur. (DB)

Cholesterol regulates HERG K+ channel activation by increasing phospholipase C β1 expression.

PubMed

Chun, Yoon Sun; Oh, Hyun Geun; Park, Myoung Kyu; Cho, Hana; Chung, Sungkwon

2013-01-01

Human ether-a-go-go-related gene (HERG) K(+) channel underlies the rapidly activating delayed rectifier K(+) conductance (IKr) during normal cardiac repolarization. Also, it may regulate excitability in many neuronal cells. Recently, we showed that enrichment of cell membrane with cholesterol inhibits HERG channels by reducing the levels of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] due to the activation of phospholipase C (PLC). In this study, we further explored the effect of cholesterol enrichment on HERG channel kinetics. When membrane cholesterol level was mildly increased in human embryonic kidney (HEK) 293 cells expressing HERG channel, the inactivation and deactivation kinetics of HERG current were not affected, but the activation rate was significantly decelerated at all voltages tested. The application of PtdIns(4,5)P2 or inhibitor for PLC prevented the effect of cholesterol enrichment, while the presence of antibody against PtdIns(4,5)P2 in pipette solution mimicked the effect of cholesterol enrichment. These results indicate that the effect of cholesterol enrichment on HERG channel is due to the depletion of PtdIns(4,5)P2. We also found that cholesterol enrichment significantly increases the expression of β1 and β3 isoforms of PLC (PLCβ1, PLCβ3) in the membrane. Since the effects of cholesterol enrichment on HERG channel were prevented by inhibiting transcription or by inhibiting PLCβ1 expression, we conclude that increased PLCβ1 expression leads to the deceleration of HERG channel activation rate via downregulation of PtdIns(4,5)P2. These results confirm a crosstalk between two plasma membrane-enriched lipids, cholesterol and PtdIns(4,5)P2, in the regulation of HERG channels.

In silico assessment of drug safety in human heart applied to late sodium current blockers

PubMed Central

Trenor, Beatriz; Gomis-Tena, Julio; Cardona, Karen; Romero, Lucia; Rajamani, Sridharan; Belardinelli, Luiz; Giles, Wayne R; Saiz, Javier

2013-01-01

Drug-induced action potential (AP) prolongation leading to Torsade de Pointes is a major concern for the development of anti-arrhythmic drugs. Nevertheless the development of improved anti-arrhythmic agents, some of which may block different channels, remains an important opportunity. Partial block of the late sodium current (INaL) has emerged as a novel anti-arrhythmic mechanism. It can be effective in the settings of free radical challenge or hypoxia. In addition, this approach can attenuate pro-arrhythmic effects of blocking the rapid delayed rectifying K+ current (IKr). The main goal of our computational work was to develop an in-silico tool for preclinical anti-arrhythmic drug safety assessment, by illustrating the impact of IKr/INaL ratio of steady-state block of drug candidates on “torsadogenic” biomarkers. The O’Hara et al. AP model for human ventricular myocytes was used. Biomarkers for arrhythmic risk, i.e., AP duration, triangulation, reverse rate-dependence, transmural dispersion of repolarization and electrocardiogram QT intervals, were calculated using single myocyte and one-dimensional strand simulations. Predetermined amounts of block of INaL and IKr were evaluated. “Safety plots” were developed to illustrate the value of the specific biomarker for selected combinations of IC50s for IKr and INaL of potential drugs. The reference biomarkers at baseline changed depending on the “drug” specificity for these two ion channel targets. Ranolazine and GS967 (a novel potent inhibitor of INaL) yielded a biomarker data set that is considered safe by standard regulatory criteria. This novel in-silico approach is useful for evaluating pro-arrhythmic potential of drugs and drug candidates in the human ventricle. PMID:23696033

Direct block of hERG potassium channels by the protein kinase C inhibitor bisindolylmaleimide I (GF109203X).

PubMed

Thomas, Dierk; Hammerling, Bettina C; Wimmer, Anna-Britt; Wu, Kezhong; Ficker, Eckhard; Kuryshev, Yuri A; Scherer, Daniel; Kiehn, Johann; Katus, Hugo A; Schoels, Wolfgang; Karle, Christoph A

2004-12-01

The human ether-a-go-go-related gene (hERG) encodes the rapid component of the cardiac repolarizing delayed rectifier potassium current, I(Kr). The direct interaction of the commonly used protein kinase C (PKC) inhibitor bisindolylmaleimide I (BIM I) with hERG, KvLQT1/minK, and I(Kr) currents was investigated in this study. hERG and KvLQT1/minK channels were heterologously expressed in Xenopus laevis oocytes, and currents were measured using the two-microelectrode voltage clamp technique. In addition, hERG currents in stably transfected human embryonic kidney (HEK 293) cells, native I(Kr) currents and action potentials in isolated guinea pig ventricular cardiomyocytes were recorded using whole-cell patch clamp electrophysiology. Bisindolylmaleimide I blocked hERG currents in HEK 293 cells and Xenopus oocytes in a concentration-dependent manner with IC(50) values of 1.0 and 13.2 muM, respectively. hERG channels were primarily blocked in the open state in a frequency-independent manner. Analysis of the voltage-dependence of block revealed a reduction of inhibition at positive membrane potentials. BIM I caused a shift of -20.3 mV in the voltage-dependence of inactivation. The point mutations tyrosine 652 alanine (Y652A) and phenylalanine 656 alanine (F656A) attenuated hERG current blockade, indicating that BIM I binds to a common drug receptor within the pore region. KvLQT1/minK currents were not significantly altered by BIM I. Finally, 1 muM BIM I reduced native I(Kr) currents by 69.2% and lead to action potential prolongation. In summary, PKC-independent effects have to be carefully considered when using BIM I as PKC inhibitor in experimental models involving hERG channels and I(Kr) currents.

Block of voltage-gated potassium channels by Pacific ciguatoxin-1 contributes to increased neuronal excitability in rat sensory neurons

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

Birinyi-Strachan, Liesl C.; Gunning, Simon J.; Lewis, Richard J.

2005-04-15

The present study investigated the actions of the polyether marine toxin Pacific ciguatoxin-1 (P-CTX-1) on neuronal excitability in rat dorsal root ganglion (DRG) neurons using patch-clamp recording techniques. Under current-clamp conditions, bath application of 2-20 nM P-CTX-1 caused a rapid, concentration-dependent depolarization of the resting membrane potential in neurons expressing tetrodotoxin (TTX)-sensitive voltage-gated sodium (Na{sub v}) channels. This action was completely suppressed by the addition of 200 nM TTX to the external solution, indicating that this effect was mediated through TTX-sensitive Na{sub v} channels. In addition, P-CTX-1 also prolonged action potential and afterhyperpolarization (AHP) duration. In a subpopulation of neurons,more » P-CTX-1 also produced tonic action potential firing, an effect that was not accompanied by significant oscillation of the resting membrane potential. Conversely, in neurons expressing TTX-resistant Na{sub v} currents, P-CTX-1 failed to alter any parameter of neuronal excitability examined in this study. Under voltage-clamp conditions in rat DRG neurons, P-CTX-1 inhibited both delayed-rectifier and 'A-type' potassium currents in a dose-dependent manner, actions that occurred in the absence of alterations to the voltage dependence of activation. These actions appear to underlie the prolongation of the action potential and AHP, and contribute to repetitive firing. These data indicate that a block of potassium channels contributes to the increase in neuronal excitability, associated with a modulation of Na{sub v} channel gating, observed clinically in response to ciguatera poisoning.« less

Calcium Currents of Olfactory Bulb Juxtaglomerular Cells: Profile and Multiple Conductance Plateau Potential Simulation

PubMed Central

Masurkar, Arjun V.; Chen, Wei R.

2011-01-01

The olfactory glomerulus is the locus of information transfer between olfactory sensory neurons and output neurons of the olfactory bulb. Juxtaglomerular cells (JGCs) may influence intraglomerular processing by firing plateau potentials that support multiple spikes. It is unclear what inward currents mediate this firing pattern. In previous work, we characterized potassium currents of JGCs. We focus here on the inward currents using whole cell current clamp and voltage recording in a rat in vitro slice preparation, as well as computer simulation. We first showed that sodium current was not required to mediate plateau potentials. Voltage clamp characterization of calcium current (ICa) determined that ICa consisted of a slow activating, rapidly inactivating (τ10%–90% rise 6–8ms, τinactivation 38–77ms) component Icat1, similar to T-type currents, and a sustained (τinactivation≫500ms) component Icat2, likely composed of L-type and P/Q-type currents. We used computer simulation to test their roles in plateau potential firing. We robustly modeled Icat1 and Icat2 to Hodgkin-Huxley schemes (m3h and m2, respectively) and simulated a JGC plateau potential with 6 conductances: calcium currents as above, potassium currents from our prior study (A-type Ikt1, D-type Ikt2, delayed rectifier Ikt3), and a fast sodium current (INa). We demonstrated that Icat1 was required for mediating the plateau potential, unlike INa and Icat2, and its τinactivation determined plateau duration. We also found that Ikt1 dictated plateau potential shape more than Ikt2 and Ikt3. The influence of these two transient and opposing conductances suggests a unique mechanism of plateau potential physiology. PMID:21704681

Properties and ionic mechanisms of action potential adaptation, restitution, and accommodation in canine epicardium.

PubMed

Decker, Keith F; Heijman, Jordi; Silva, Jonathan R; Hund, Thomas J; Rudy, Yoram

2009-04-01

Computational models of cardiac myocytes are important tools for understanding ionic mechanisms of arrhythmia. This work presents a new model of the canine epicardial myocyte that reproduces a wide range of experimentally observed rate-dependent behaviors in cardiac cell and tissue, including action potential (AP) duration (APD) adaptation, restitution, and accommodation. Model behavior depends on updated formulations for the 4-aminopyridine-sensitive transient outward current (I(to1)), the slow component of the delayed rectifier K(+) current (I(Ks)), the L-type Ca(2+) channel current (I(Ca,L)), and the Na(+)-K(+) pump current (I(NaK)) fit to data from canine ventricular myocytes. We found that I(to1) plays a limited role in potentiating peak I(Ca,L) and sarcoplasmic reticulum Ca(2+) release for propagated APs but modulates the time course of APD restitution. I(Ks) plays an important role in APD shortening at short diastolic intervals, despite a limited role in AP repolarization at longer cycle lengths. In addition, we found that I(Ca,L) plays a critical role in APD accommodation and rate dependence of APD restitution. Ca(2+) entry via I(Ca,L) at fast rate drives increased Na(+)-Ca(2+) exchanger Ca(2+) extrusion and Na(+) entry, which in turn increases Na(+) extrusion via outward I(NaK). APD accommodation results from this increased outward I(NaK). Our simulation results provide valuable insight into the mechanistic basis of rate-dependent phenomena important for determining the heart's response to rapid and irregular pacing rates (e.g., arrhythmia). Accurate simulation of rate-dependent phenomena and increased understanding of their mechanistic basis will lead to more realistic multicellular simulations of arrhythmia and identification of molecular therapeutic targets.

Direct negative chronotropic action of desflurane on sinoatrial node pacemaker activity in the guinea pig heart.

PubMed

Kojima, Akiko; Ito, Yuki; Kitagawa, Hirotoshi; Matsuura, Hiroshi; Nosaka, Shuichi

2014-06-01

Desflurane inhalation is associated with sympathetic activation and concomitant increase in heart rate in humans and experimental animals. There is, however, little information concerning the direct effects of desflurane on electrical activity of sinoatrial node pacemaker cells that determines the intrinsic heart rate. Whole-cell patch-clamp experiments were conducted on guinea pig sinoatrial node pacemaker cells to record spontaneous action potentials and ionic currents contributing to sinoatrial node automaticity, namely, hyperpolarization-activated cation current (If), T-type and L-type Ca currents (ICa,T and ICa,L, respectively), Na/Ca exchange current (INCX), and rapidly and slowly activating delayed rectifier K currents (IKr and IKs, respectively). Electrocardiograms were recorded from ex vivo Langendorff-perfused hearts and in vivo hearts. Desflurane at 6 and 12% decreased spontaneous firing rate of sinoatrial node action potentials by 15.9% (n = 11) and 27.6% (n = 10), respectively, which was associated with 20.4% and 42.5% reductions in diastolic depolarization rate, respectively. Desflurane inhibited If, ICa,T, ICa,L, INCX, and IKs but had little effect on IKr. The negative chronotropic action of desflurane was reasonably well reproduced in sinoatrial node computer model. Desflurane reduced the heart rate in Langendorff-perfused hearts. High concentration (12%) of desflurane inhalation was associated with transient tachycardia, which was totally abolished by pretreatment with the β-adrenergic blocker propranolol. Desflurane has a direct negative chronotropic action on sinoatrial node pacemaking activity, which is mediated by its inhibitory action on multiple ionic currents. This direct inhibitory action of desflurane on sinoatrial node automaticity seems to be counteracted by sympathetic activation associated with desflurane inhalation in vivo.

Postnatal development of A-type and Kv1- and Kv2-mediated potassium channel currents in neocortical pyramidal neurons

PubMed Central

Guan, Dongxu; Horton, Leslie R.; Armstrong, William E.

2011-01-01

Potassium channels regulate numerous aspects of neuronal excitability, and several voltage-gated K+ channel subunits have been identified in pyramidal neurons of rat neocortex. Previous studies have either considered the development of outward current as a whole or divided currents into transient, A-type and persistent, delayed rectifier components but did not differentiate between current components defined by α-subunit type. To facilitate comparisons of studies reporting K+ currents from animals of different ages and to understand the functional roles of specific current components, we characterized the postnatal development of identified Kv channel-mediated currents in pyramidal neurons from layers II/III from rat somatosensory cortex. Both the persistent/slowly inactivating and transient components of the total K+ current increased in density with postnatal age. We used specific pharmacological agents to test the relative contributions of putative Kv1- and Kv2-mediated currents (100 nM α-dendrotoxin and 600 nM stromatoxin, respectively). A combination of voltage protocol, pharmacology, and curve fitting was used to isolate the rapidly inactivating A-type current. We found that the density of all identified current components increased with postnatal age, approaching a plateau at 3–5 wk. We found no significant changes in the relative proportions or kinetics of any component between postnatal weeks 1 and 5, except that the activation time constant for A-type current was longer at 1 wk. The putative Kv2-mediated component was the largest at all ages. Immunocytochemistry indicated that protein expression for Kv4.2, Kv4.3, Kv1.4, and Kv2.1 increased between 1 wk and 4–5 wk of age. PMID:21451062

Postnatal development of A-type and Kv1- and Kv2-mediated potassium channel currents in neocortical pyramidal neurons.

PubMed

Guan, Dongxu; Horton, Leslie R; Armstrong, William E; Foehring, Robert C

2011-06-01

Potassium channels regulate numerous aspects of neuronal excitability, and several voltage-gated K(+) channel subunits have been identified in pyramidal neurons of rat neocortex. Previous studies have either considered the development of outward current as a whole or divided currents into transient, A-type and persistent, delayed rectifier components but did not differentiate between current components defined by α-subunit type. To facilitate comparisons of studies reporting K(+) currents from animals of different ages and to understand the functional roles of specific current components, we characterized the postnatal development of identified Kv channel-mediated currents in pyramidal neurons from layers II/III from rat somatosensory cortex. Both the persistent/slowly inactivating and transient components of the total K(+) current increased in density with postnatal age. We used specific pharmacological agents to test the relative contributions of putative Kv1- and Kv2-mediated currents (100 nM α-dendrotoxin and 600 nM stromatoxin, respectively). A combination of voltage protocol, pharmacology, and curve fitting was used to isolate the rapidly inactivating A-type current. We found that the density of all identified current components increased with postnatal age, approaching a plateau at 3-5 wk. We found no significant changes in the relative proportions or kinetics of any component between postnatal weeks 1 and 5, except that the activation time constant for A-type current was longer at 1 wk. The putative Kv2-mediated component was the largest at all ages. Immunocytochemistry indicated that protein expression for Kv4.2, Kv4.3, Kv1.4, and Kv2.1 increased between 1 wk and 4-5 wk of age.

A Reduced Antigen Load In Vivo, Rather Than Weak Inflammation, Causes a Substantial Delay in CD8+ T Cell Priming against Mycobacterium bovis (Bacillus Calmette-Guérin)1

PubMed Central

Russell, Marsha S.; Iskandar, Monica; Mykytczuk, Oksana L.; Nash, John H. E.; Krishnan, Lakshmi; Sad, Subash

2014-01-01

Regardless of the dose of Ag, Ag presentation occurs rapidly within the first few days which results in rapid expansion of the CD8+ T cell response that peaks at day 7. However, we have previously shown that this rapid priming of CD8+ T cells is absent during infection of mice with Mycobacterium bovis (bacillus Calmette-Guérin (BCG)). In this study, we have evaluated the mechanisms responsible for the delayed CD8+ T cell priming. Because BCG replicates poorly and survives within phagosomes we considered whether 1) generation of reduced amounts of Ag or 2) weaker activation by pathogen-associated molecular patterns (PAMPs) during BCG infection is responsible for the delay in CD8+ T cell priming. Using rOVA-expressing bacteria, our results indicate that infection of mice with BCG-OVA generates greatly reduced levels of OVA, which are 70-fold lower in comparison to the levels generated during infection of mice with Listeria monocytogenes-expressing OVA. Furthermore, increasing the dose of OVA, but not PAMP signaling during BCG-OVA infection resulted in rapid Ag presentation and consequent expansion of the CD8+ T cell response, indicating that the generation of reduced Ag levels, not lack of PAMP-associated inflammation, was responsible for delayed priming of CD8+ T cells. There was a strong correlation between the relative timing of Ag presentation and the increase in the level of OVA in vivo. Taken together, these results reveal that some slowly replicating pathogens, such as mycobacteria, may facilitate their chronicity by generating reduced Ag levels which causes a substantial delay in the development of acquired immune responses. PMID:17579040

99. POWER DISTRIBUTION UNITS FOR BATTERIES AND RECTIFIERS, NORTHEAST SIDE ...

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

99. POWER DISTRIBUTION UNITS FOR BATTERIES AND RECTIFIERS, NORTHEAST SIDE OF LANDLINE INSTRUMENTATION ROOM (106), LSB (BLDG. 770) - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

40 CFR 63.341 - Definitions and nomenclature.

Code of Federal Regulations, 2010 CFR

2010-07-01

... electrical insulation) using a chromic acid solution. In chromium anodizing, the part to be anodized acts as... chromium anodizing: rectifiers fitted with controls to allow for voltage adjustments, heat exchanger... electroplating: Rectifiers, anodes, heat exchanger equipment, circulation pumps, and air agitation systems...

Rectifier cabinet static breaker

DOEpatents

Costantino, Jr, Roger A.; Gliebe, Ronald J.

1992-09-01

A rectifier cabinet static breaker replaces a blocking diode pair with an SCR and the installation of a power transistor in parallel with the latch contactor to commutate the SCR to the off state. The SCR serves as a static breaker with fast turnoff capability providing an alternative way of achieving reactor scram in addition to performing the function of the replaced blocking diodes. The control circuitry for the rectifier cabinet static breaker includes on-line test capability and an LED indicator light to denote successful test completion. Current limit circuitry provides high-speed protection in the event of overload.

CMOS-Compatible Room-Temperature Rectifier Toward Terahertz Radiation Detection

NASA Astrophysics Data System (ADS)

Varlamava, Volha; De Amicis, Giovanni; Del Monte, Andrea; Perticaroli, Stefano; Rao, Rosario; Palma, Fabrizio

2016-08-01

In this paper, we present a new rectifying device, compatible with the technology of CMOS image sensors, suitable for implementing a direct-conversion detector operating at room temperature for operation at up to terahertz frequencies. The rectifying device can be obtained by introducing some simple modifications of the charge-storage well in conventional CMOS integrated circuits, making the proposed solution easy to integrate with the existing imaging systems. The rectifying device is combined with the different elements of the detector, composed of a 3D high-performance antenna and a charge-storage well. In particular, its position just below the edge of the 3D antenna takes maximum advantage of the high electric field concentrated by the antenna itself. In addition, the proposed structure ensures the integrity of the charge-storage well of the detector. In the structure, it is not necessary to use very scaled and costly technological nodes, since the CMOS transistor only provides the necessary integrated readout electronics. On-wafer measurements of RF characteristics of the designed junction are reported and discussed. The overall performances of the entire detector in terms of noise equivalent power (NEP) are evaluated by combining low-frequency measurements of the rectifier with numerical simulations of the 3D antenna and the semiconductor structure at 1 THz, allowing prediction of the achievable NEP.

A transparent diode with high rectifying ratio using amorphous indium-gallium-zinc oxide/SiN{sub x} coupled junction

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

Choi, Myung-Jea; Kim, Myeong-Ho; Choi, Duck-Kyun, E-mail: duck@hanyang.ac.kr

2015-08-03

We introduce a transparent diode that shows both high rectifying ratio and low leakage current at process temperature below 250 °C. This device is clearly distinguished from all previous transparent diodes in that the rectifying behavior results from the junction between a semiconductor (amorphous indium-gallium-zinc oxide (a-IGZO)) and insulator (SiN{sub x}). We systematically study the properties of each junction within the device structure and demonstrate that the a-IGZO/SiN{sub x} junction is the source of the outstanding rectification. The electrical characteristics of this transparent diode are: 2.8 A/cm{sup 2} on-current density measured at −7 V; lower than 7.3 × 10{sup −9} A/cm{sup 2} off-currentmore » density; 2.53 ideality factor; and high rectifying ratio of 10{sup 8}–10{sup 9}. Furthermore, the diode structure has a transmittance of over 80% across the visible light range. The operating principle of the indium-tin oxide (ITO)/a-IGZO/SiN{sub x}/ITO device was examined with an aid of the energy band diagram and we propose a preliminary model for the rectifying behavior. Finally, we suggest further directions for research on this transparent diode.« less

Evaluating waste printed circuit boards recycling: Opportunities and challenges, a mini review.

PubMed

Awasthi, Abhishek Kumar; Zlamparet, Gabriel Ionut; Zeng, Xianlai; Li, Jinhui

2017-04-01

Rapid generation of waste printed circuit boards has become a very serious issue worldwide. Numerous techniques have been developed in the last decade to resolve the pollution from waste printed circuit boards, and also recover valuable metals from the waste printed circuit boards stream on a large-scale. However, these techniques have their own certain specific drawbacks that need to be rectified properly. In this review article, these recycling technologies are evaluated based on a strength, weaknesses, opportunities and threats analysis. Furthermore, it is warranted that, the substantial research is required to improve the current technologies for waste printed circuit boards recycling in the outlook of large-scale applications.

46 CFR 111.33-5 - Installation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 4 2014-10-01 2014-10-01 false Installation. 111.33-5 Section 111.33-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Power Semiconductor Rectifier Systems § 111.33-5 Installation. Each semiconductor rectifier system...

46 CFR 111.33-5 - Installation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 4 2012-10-01 2012-10-01 false Installation. 111.33-5 Section 111.33-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Power Semiconductor Rectifier Systems § 111.33-5 Installation. Each semiconductor rectifier system...

46 CFR 111.33-5 - Installation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 4 2013-10-01 2013-10-01 false Installation. 111.33-5 Section 111.33-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Power Semiconductor Rectifier Systems § 111.33-5 Installation. Each semiconductor rectifier system...

46 CFR 111.33-5 - Installation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 4 2011-10-01 2011-10-01 false Installation. 111.33-5 Section 111.33-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Power Semiconductor Rectifier Systems § 111.33-5 Installation. Each semiconductor rectifier system...

76 FR 37660 - Amendment of the Schedule of Application Fees Set Forth In Sections 1.1102 Through 1.1109 of the...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-28

.... This clarification is intended to rectify a possible inconsistency throughout the Commission's rules... fee need not accompany a high bidder's long-form application, on the other. To rectify this...

Harmonic Characteristics of Rectifier Substations and Their Impact on Audio Frequency Track Circuits

DOT National Transportation Integrated Search

1982-05-01

This report describes the basic operation of substation rectifier equipment and the modes of possible interference with audio frequency track circuits used for train detection, cab signalling, and vehicle speed control. It also includes methods of es...

46 CFR 111.33-5 - Installation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Installation. 111.33-5 Section 111.33-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Power Semiconductor Rectifier Systems § 111.33-5 Installation. Each semiconductor rectifier system...

Can arousing feedback rectify lapses in driving? Prediction from EEG power spectra.

PubMed

Lin, Chin-Teng; Huang, Kuan-Chih; Chuang, Chun-Hsiang; Ko, Li-Wei; Jung, Tzyy-Ping

2013-10-01

This study explores the neurophysiological changes, measured using an electroencephalogram (EEG), in response to an arousing warning signal delivered to drowsy drivers, and predicts the efficacy of the feedback based on changes in the EEG. Eleven healthy subjects participated in sustained-attention driving experiments. The driving task required participants to maintain their cruising position and compensate for randomly induced lane deviations using the steering wheel, while their EEG and driving performance were continuously monitored. The arousing warning signal was delivered to participants who experienced momentary behavioral lapses, failing to respond rapidly to lane-departure events (specifically the reaction time exceeded three times the alert reaction time). The results of our previous studies revealed that arousing feedback immediately reversed deteriorating driving performance, which was accompanied by concurrent EEG theta- and alpha-power suppression in the bilateral occipital areas. This study further proposes a feedback efficacy assessment system to accurately estimate the efficacy of arousing warning signals delivered to drowsy participants by monitoring the changes in their EEG power spectra immediately thereafter. The classification accuracy was up 77.8% for determining the need for triggering additional warning signals. The findings of this study, in conjunction with previous studies on EEG correlates of behavioral lapses, might lead to a practical closed-loop system to predict, monitor and rectify behavioral lapses of human operators in attention-critical settings.

Mapping coral reefs using consumer-grade drones and structure from motion photogrammetry techniques

NASA Astrophysics Data System (ADS)

Casella, Elisa; Collin, Antoine; Harris, Daniel; Ferse, Sebastian; Bejarano, Sonia; Parravicini, Valeriano; Hench, James L.; Rovere, Alessio

2017-03-01

We propose a novel technique to measure the small-scale three-dimensional features of a shallow-water coral reef using a small drone equipped with a consumer-grade camera, a handheld GPS and structure from motion (SfM) algorithms. We used a GoPro HERO4 with a modified lens mounted on a DJI Phantom 2 drone (maximum total take-off weight <2 kg) to perform a 10 min flight and collect 306 aerial images with an overlap equal or greater than 90%. We mapped an area of 8380 m2, obtaining as output an ortho-rectified aerial photomosaic and a bathymetric digital elevation model (DEM) with a resolution of 0.78 and 1.56 cm pixel-1, respectively. Through comparison with airborne LiDAR data for the same area, we verified that the location of the ortho-rectified aerial photomosaic is accurate within 1.4 m. The bathymetric difference between our DEM and the LiDAR dataset is -0.016 ± 0.45 m (1σ). Our results show that it is possible, in conditions of calm waters, low winds and minimal sun glint, to deploy consumer-grade drones as a relatively low-cost and rapid survey technique to produce multispectral and bathymetric data on shallow-water coral reefs. We discuss the utility of such data to monitor temporal changes in topographic complexity of reefs and associated biological processes.

Familial diagnostic experiences in paediatric oncology.

PubMed

Evans, N T; Wakefield, C E; McLoone, J K; Cohn, R J

2015-01-06

Diagnostic delays may not have significant prognostic implications in paediatric oncology, but psychological impacts remain understudied. Interviews exploring diagnostic experiences were conducted with childhood cancer survivors (n=19), parents (n=78) and siblings (n=15). Median diagnostic time was 3 weeks. Participants described a mixture of rapid diagnoses (28.9%), plus delayed appraisal intervals (that is, parent- or patient-associated diagnostic delays; 40.0%) and diagnostic intervals (that is, healthcare-associated delays; 46.7%). Families experiencing delays described guilt and anger and deleterious impacts on the family-clinician relationship. Some believed delays impacted on treatment and prognosis. The effect of the diagnostic experience can be considerable.

Interannual Variability In the Atmospheric CO2 Rectification Over Boreal Forests Based On A Coupled Ecosystem-Atmosphere Model

NASA Astrophysics Data System (ADS)

Chen, B.; Chen, J. M.; Worthy, D.

2004-05-01

Ecosystem CO2 exchange and the planetary boundary layer (PBL) are correlated diurnally and seasonally. The simulation of this atmospheric rectifier effect is important in understanding the global CO2 distribution pattern. A 12-year (1990-1996, 1999-2003), continuous CO2 measurement record from Fraserdale, Ontario (located ~150 km north of Timmons), along with a coupled Vertical Diffusion Scheme (VDS) and ecosystem model (Boreal Ecosystem Productivity Simulator, BEPS), is used to investigate the interannual variability in this effect over a boreal forest region. The coupled model performed well in simulating CO2 vertical diffusion processes. Simulated annual atmospheric rectifier effects, (including seasonal and diurnal), quantified as the variation in the mean CO2 concentration from the surface to the top of the PBL, varied from 2.8 to 4.1 ppm, even though the modeled seasonal variations in the PBL depth were similar throughout the 12-year period. The differences in the interannual rectifier effect primarily resulted from changes in the biospheric CO2 uptake and heterotrophic respiration. Correlations in the year-to year variations of the CO2 rectification were found with mean annual air temperatures, simulated gross primary productivity (GPP) and heterotrophic respiration (Rh) (r2=0.5, 0.46, 0.42, respectively). A small increasing trend in the CO2 rectification was also observed. The year-to-year variation in the vertical distribution of the monthly mean CO2 mixing ratios (reflecting differences in the diurnal rectifier effect) was related to interannual climate variability, however, the seasonal rectifier effects were found to be more sensitive to climate variability than the diurnal rectifier effects.

Direct block of native and cloned (Kir2.1) inward rectifier K+ channels by chloroethylclonidine

PubMed Central

Barrett-Jolley, R; Dart, C; Standen, N B

1999-01-01

We have investigated the inhibition of inwardly rectifying potassium channels by the α-adrenergic agonist/antagonist chloroethylclonidine (CEC). We used two preparations; two-electrode voltage-clamp of rat isolated flexor digitorum brevis muscle and whole-cell patch-clamp of cell lines transfected with Kir2.1 (IRK1).In skeletal muscle and at a membrane potential of −50 mV, chloroethylclonidine (CEC), an agonist at α2-adrenergic receptors and an antagonist at α1x-receptors, was found to inhibit the inward rectifier current with a Ki of 30 μM.The inhibition of skeletal muscle inward rectifier current by CEC was not mimicked by clonidine, adrenaline or noradrenaline and was not sensitive to high concentrations of α1-(prazosin) or α2-(rauwolscine) antagonists.The degree of current inhibition by CEC was found to vary with the membrane potential (approximately 70% block at −50 mV c.f. ∼10% block at −190 mV). The kinetics of this voltage dependence were further investigated using recombinant inward rectifier K+ channels (Kir2.1) expressed in the MEL cell line. Using a two pulse protocol, we calculated the time constant for block to be ∼8 s at 0 mV, and the rate of unblock was described by the relationship τ=exp((Vm+149)/22) s.This block was effective when CEC was applied to either the inside or the outside of patch clamped cells, but ineffective when a polyamine binding site (aspartate 172) was mutated to asparagine.The data suggest that the clonidine-like imidazoline compound, CEC, inhibits inward rectifier K+ channels independently of α-receptors by directly blocking the channel pore, possibly at an intracellular polyamine binding site. PMID:10516659

Calcium currents in a fast-twitch skeletal muscle of the rat.

PubMed

Donaldson, P L; Beam, K G

1983-10-01

Slow ionic currents were measured in the rat omohyoid muscle with the three-microelectrode voltage-clamp technique. Sodium and delayed rectifier potassium currents were blocked pharmacologically. Under these conditions, depolarizing test pulses elicited an early outward current, followed by a transient slow inward current, followed in turn by a late outward current. The early outward current appeared to be a residual delayed rectifier current. The slow inward current was identified as a calcium current on the basis that (a) its magnitude depended on extracellular calcium concentration, (b) it was blocked by the addition of the divalent cations cadmium or nickel, and reduced in magnitude by the addition of manganese or cobalt, and (c) barium was able to replace calcium as an inward current carrier. The threshold potential for inward calcium current was around -20 mV in 10mM extracellular calcium and about -35 mV in 2 mM calcium. Currents were net inward over part of their time course for potentials up to at least +30 mV. At temperatures of 20-26 degrees C, the peak inward current (at approximately 0 mV) was 139 +/- 14 microA/cm2 (mean +/- SD), increasing to 226 +/- 28 microA/cm2 at temperatures of 27-37 degrees C. The late outward current exhibited considerable fiber-to-fiber variability. In some fibers it was primarily a time-independent, nonlinear leakage current. In other fibers it was primarily a time-independent, nonlinear leakage current. In other fibers it appeared to be the sum of both leak and a slowly activated outward current. The rate of activation of inward calcium current was strongly temperature dependent. For example, in a representative fiber, the time-to-peak inward current for a +10-mV test pulse decreased from approximately 250 ms at 20 degrees C to 100 ms at 30 degrees C. At 37 degrees C, the time-to-peak current was typically approximately 25 ms. The earliest phase of activation was difficult to quantify because the ionic current was partially obscured by nonlinear charge movement. Nonetheless, at physiological temperatures, the rate of calcium channel activation in rat skeletal muscle is about five times faster than activation of calcium channels in frog muscle. This pathway may be an important source of calcium entry in mammalian muscle.

Electrophysiological heterogeneity of pacemaker cells in the rabbit intercaval region, including the SA node: insights from recording multiple ion currents in each cell.

PubMed

Monfredi, Oliver; Tsutsui, Kenta; Ziman, Bruce; Stern, Michael D; Lakatta, Edward G; Maltsev, Victor A

2018-03-01

Cardiac pacemaker cells, including cells of the sinoatrial node, are heterogeneous in size, morphology, and electrophysiological characteristics. The exact extent to which these cells differ electrophysiologically is unclear yet is critical to understanding their functioning. We examined major ionic currents in individual intercaval pacemaker cells (IPCs) sampled from the paracristal, intercaval region (including the sinoatrial node) that were spontaneously beating after enzymatic isolation from rabbit hearts. The beating rate was measured at baseline and after inhibition of the Ca 2+ pump with cyclopiazonic acid. Thereafter, in each cell, we consecutively measured the density of funny current ( I f ), delayed rectifier K + current ( I K ) (a surrogate of repolarization capacity), and L-type Ca 2+ current ( I Ca,L ) using whole cell patch clamp . The ionic current densities varied to a greater extent than previously appreciated, with some IPCs demonstrating very small or zero I f . The density of none of the currents was correlated with cell size, while I Ca,L and I f densities were related to baseline beating rates. I f density was correlated with I K density but not with that of I Ca,L . Inhibition of Ca 2+ cycling had a greater beating rate slowing effect in IPCs with lower I f densities. Our numerical model simulation indicated that 1) IPCs with small (or zero) I f or small I Ca,L can operate via a major contribution of Ca 2+ clock, 2) I f -Ca 2+ -clock interplay could be important for robust pacemaking function, and 3) coupled I f - I K function could regulate maximum diastolic potential. Thus, we have demonstrated marked electrophysiological heterogeneity of IPCs. This heterogeneity is manifested in basal beating rate and response to interference of Ca 2+ cycling, which is linked to I f . NEW & NOTEWORTHY In the present study, a hitherto unrecognized range of heterogeneity of ion currents in pacemaker cells from the intercaval region is demonstrated. Relationships between basal beating rate and L-type Ca 2+ current and funny current ( I f ) density are uncovered, along with a positive relationship between I f and delayed rectifier K + current. Links are shown between the response to Ca 2+ cycling blockade and I f density.

Protein kinase C epsilon mediates the inhibition of angiotensin II on the slowly activating delayed-rectifier potassium current through channel phosphorylation.

PubMed

Gou, Xiangbo; Wang, Wenying; Zou, Sihao; Qi, Yajuan; Xu, Yanfang

2018-03-01

The slowly activating delayed rectifier K + current (I Ks ) is one of the main repolarizing currents in the human heart. Evidence has shown that angiotensin II (Ang II) regulates I Ks through the protein kinase C (PKC) pathway, but the related results are controversial. This study was designed to identify PKC isoenzymes involved in the regulation of I Ks by Ang II and the underlying molecular mechanism. The whole-cell patch-clamp technique was used to record I Ks in isolated guinea pig ventricular cardiomyocytes and in human embryonic kidney (HEK) 293 cells co-transfected with human KCNQ1/KCNE1 genes and Ang II type 1 receptor genes. Ang II inhibited I Ks in a concentration-dependent manner in native cardiomyocytes. A broad PKC inhibitor Gö6983 (not inhibiting PKCε) and a selective cPKC inhibitor Gö6976 did not affect the inhibitory action of Ang II. In contrast, the inhibition was significantly attenuated by PKCε-selective peptide inhibitor εV1-2. However, direct activation of PKC by phorbol 12-myristate 13-acetate (PMA) increased the cloned human I Ks in HEK293 cells. Similarly, the cPKC peptide activator significantly enhanced the current. In contrast, the PKCε peptide activator inhibited the current. Further evidence showed that PKCε knockdown by siRNA antagonized the Ang II-induced inhibition on KCNQ1/KCNE1 current, whereas knockdown of cPKCs (PKCα and PKCβ) attenuated the potentiation of the current by PMA. Moreover, deletion of four putative phosphorylation sites in the C-terminus of KCNQ1 abolished the action of PMA. Mutation of two putative phosphorylation sites in the N-terminus of KCNQ1 and one site in KCNE1 (S102) blocked the inhibition of Ang II. Our results demonstrate that PKCε isoenzyme mediates the inhibitory action of Ang II on I Ks and by phosphorylating distinct sites in KCNQ1/KCNE1, cPKC and PKCε isoenzymes produce the contrary regulatory effects on the channel. These findings have provided new insight into the molecular mechanism underlying the modulation of the KCNQ1/KCNE1 channel. Copyright © 2018 Elsevier Ltd. All rights reserved.

Dissolvable fluidic time delays for programming multi-step assays in instrument-free paper diagnostics.

PubMed

Lutz, Barry; Liang, Tinny; Fu, Elain; Ramachandran, Sujatha; Kauffman, Peter; Yager, Paul

2013-07-21

Lateral flow tests (LFTs) are an ingenious format for rapid and easy-to-use diagnostics, but they are fundamentally limited to assay chemistries that can be reduced to a single chemical step. In contrast, most laboratory diagnostic assays rely on multiple timed steps carried out by a human or a machine. Here, we use dissolvable sugar applied to paper to create programmable flow delays and present a paper network topology that uses these time delays to program automated multi-step fluidic protocols. Solutions of sucrose at different concentrations (10-70% of saturation) were added to paper strips and dried to create fluidic time delays spanning minutes to nearly an hour. A simple folding card format employing sugar delays was shown to automate a four-step fluidic process initiated by a single user activation step (folding the card); this device was used to perform a signal-amplified sandwich immunoassay for a diagnostic biomarker for malaria. The cards are capable of automating multi-step assay protocols normally used in laboratories, but in a rapid, low-cost, and easy-to-use format.

Dissolvable fluidic time delays for programming multi-step assays in instrument-free paper diagnostics

PubMed Central

Lutz, Barry; Liang, Tinny; Fu, Elain; Ramachandran, Sujatha; Kauffman, Peter; Yager, Paul

2013-01-01

Lateral flow tests (LFTs) are an ingenious format for rapid and easy-to-use diagnostics, but they are fundamentally limited to assay chemistries that can be reduced to a single chemical step. In contrast, most laboratory diagnostic assays rely on multiple timed steps carried out by a human or a machine. Here, we use dissolvable sugar applied to paper to create programmable flow delays and present a paper network topology that uses these time delays to program automated multi-step fluidic protocols. Solutions of sucrose at different concentrations (10-70% of saturation) were added to paper strips and dried to create fluidic time delays spanning minutes to nearly an hour. A simple folding card format employing sugar delays was shown to automate a four-step fluidic process initiated by a single user activation step (folding the card); this device was used to perform a signal-amplified sandwich immunoassay for a diagnostic biomarker for malaria. The cards are capable of automating multi-step assay protocols normally used in laboratories, but in a rapid, low-cost, and easy-to-use format. PMID:23685876

35 GHz integrated circuit rectifying antenna with 33 percent efficiency

NASA Technical Reports Server (NTRS)

Yoo, T.-W.; Chang, K.

1991-01-01

A 35 GHz integrated circuit rectifying antenna (rectenna) has been developed using a microstrip dipole antenna and beam-lead mixer diode. Greater than 33 percent conversion efficiency has been achieved. The circuit should have applications in microwave/millimeter-wave power transmission and detection.

Silicon carbide semiconductor device fabrication and characterization

NASA Technical Reports Server (NTRS)

Davis, R. F.; Das, K.

1990-01-01

A number of basic building blocks i.e., rectifying and ohmic contacts, implanted junctions, MOS capacitors, pnpn diodes and devices, such as, MESFETs on both alpha and beta SiC films were fabricated and characterized. Gold forms a rectifying contact on beta SiC. Since Au contacts degrade at high temperatures, these are not considered to be suitable for high temperature device applications. However, it was possible to utilize Au contact diodes for electrically characterizing SiC films. Preliminary work indicates that sputtered Pt or Pt/Si contacts on beta SiC films are someways superior to Au contacts. Sputtered Pt layers on alpha SiC films form excellent rectifying contacts, whereas Ni layers following anneal at approximately 1050 C provide an ohmic contact. It has demonstrated that ion implantation of Al in substrates held at 550 C can be successfully employed for the fabrication of rectifying junction diodes. Feasibility of fabricating pnpn diodes and platinum gated MESFETs on alpha SiC films was also demonstrated.

High static gain single-phase PFC based on a hybrid boost converter

NASA Astrophysics Data System (ADS)

Flores Cortez, Daniel; Maccarini, Marcello C.; Mussa, Samir A.; Barbi, Ivo

2017-05-01

In this paper, a single-phase unity power factor rectifier, based on a hybrid boost converter, resulting from the integration of a conventional dc-dc boost converter and a switched-capacitor voltage doubler is proposed, analysed, designed and tested. The high-power rectifier is controlled by two feedback loops with the same control strategy employed in the conventional boost-based rectifier. The main feature of the proposed rectifier is its ability to output a dc voltage larger than the double of the peak value of the input line voltage, while subjecting the power switches to half of the dc-link voltage, which contributes to reducing the cost and increasing the efficiency. Experimental data were obtained from a laboratory prototype with an input voltage of 220 Vrms, line frequency of 60 Hz, output voltage of 800 Vdc, load power of 1000 W and switching frequency of 50 kHz. The efficiency of the prototype, measured in the laboratory, was 96.5% for full load and 97% for half load.

NASA Ames Research Center 60 MW Power Supply Modernization

NASA Technical Reports Server (NTRS)

Choy, Yuen Ching; Ilinets, Boris V.; Miller, Ted; Nagel, Kirsten (Technical Monitor)

2001-01-01

The NASA Ames Research Center 60 MW DC Power Supply was built in 1974 to provide controlled DC power for the Thermophysics Facility Arc Jet Laboratory. The Power Supply has gradually losing reliability due to outdated technology and component life limitation. NASA has decided to upgrade the existing rectifier modules with contemporary high-power electronics and control equipment. NASA plans to complete this project in 2001. This project includes a complete replacement of obsolete thyristor stacks in all six rectifier modules and rectifier bridge control system. High power water-cooled thyristors and freewheeling diodes will be used. The rating of each of the six modules will be 4000 A at 5500 V. The control firing angle signal will be sent from the Facility Control System to six modules via fiberoptic cable. The Power Supply control and monitoring system will include a Master PLC in the Facility building and a Slave PLC in each rectifier module. This system will also monitor each thyristor level in each stack and the auxiliary equipment.

Thermal rectification in thin films driven by gradient grain microstructure

NASA Astrophysics Data System (ADS)

Cheng, Zhe; Foley, Brian M.; Bougher, Thomas; Yates, Luke; Cola, Baratunde A.; Graham, Samuel

2018-03-01

As one of the basic components of phononics, thermal rectifiers transmit heat current asymmetrically similar to electronic rectifiers in microelectronics. Heat can be conducted through them easily in one direction while being blocked in the other direction. In this work, we report a thermal rectifier that is driven by the gradient grain structure and the inherent gradient in thermal properties as found in these materials. To demonstrate their thermal rectification properties, we build a spectral thermal conductivity model with complete phonon dispersion relationships using the thermophysical properties of chemical vapor deposited (CVD) diamond films which possess gradient grain microstructures. To explain the observed significant thermal rectification, the temperature and thermal conductivity distribution are studied. Additionally, the effects of temperature bias and film thickness are discussed, which shed light on tuning the thermal rectification based on the gradient microstructures. Our results show that the columnar grain microstructure makes CVD materials unique candidates for mesoscale thermal rectifiers without a sharp temperature change.

Failure Detecting Method of Fault Current Limiter System with Rectifier

NASA Astrophysics Data System (ADS)

Tokuda, Noriaki; Matsubara, Yoshio; Asano, Masakuni; Ohkuma, Takeshi; Sato, Yoshibumi; Takahashi, Yoshihisa

A fault current limiter (FCL) is extensively needed to suppress fault current, particularly required for trunk power systems connecting high-voltage transmission lines, such as 500kV class power system which constitutes the nucleus of the electric power system. We proposed a new type FCL system (rectifier type FCL), consisting of solid-state diodes, DC reactor and bypass AC reactor, and demonstrated the excellent performances of this FCL by developing the small 6.6kV and 66kV model. It is important to detect the failure of power devices used in the rectifier under the normal operating condition, for keeping the excellent reliability of the power system. In this paper, we have proposed a new failure detecting method of power devices most suitable for the rectifier type FCL. This failure detecting system is simple and compact. We have adapted the proposed system to the 66kV prototype single-phase model and successfully demonstrated to detect the failure of power devices.

Fast switching wideband rectifying circuit for future RF energy harvesting

NASA Astrophysics Data System (ADS)

Asmeida, Akrem; Mustam, Saizalmursidi Md; Abidin, Z. Z.; Ashyap, A. Y. I.

2017-09-01

This paper presents the design and simulation of fast switching microwave rectifying circuit for ultra wideband patch antenna over a dual-frequency band (1.8 GHz for GSM and 2.4 GHz for ISM band). This band was chosen due to its high signal availability in the surrounding environment. New rectifying circuit topology with pair-matching trunks is designed using Advanced Design System (ADS) software. These trunks are interfaced with power divider to achieve good bandwidth, fast switching and high efficiency. The power divider acts as a good isolator between the trunks and its straightforward design structure makes it a good choice for a single feed UWB antenna. The simulated results demonstrate that the maximum output voltage is 2.13 V with an input power of -5 dBm. Moreover, the rectifier offers maximum efficiency of 86% for the input power of -5 dBm at given band, which could easily power up wireless sensor networks (WSN) and other small devices sufficiently.

Modelling a single phase voltage controlled rectifier using Laplace transforms

NASA Technical Reports Server (NTRS)

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.

Microfluidic rectifier based on poly(dimethylsiloxane) membrane and its application to a micropump

PubMed Central

Wang, Yao-Nan; Tsai, Chien-Hsiung; Fu, Lung-Ming; Lin Liou, Lung-Kai

2013-01-01

A microfluidic rectifier incorporating an obstructed microchannel and a PDMS membrane is proposed. During forward flow, the membrane deflects in the upward direction; thereby allowing the fluid to pass over the obstacle. Conversely, during reverse flow, the membrane seals against the obstacle, thereby closing the channel and preventing flow. It is shown that the proposed device can operate over a wide pressure range by increasing or decreasing the membrane thickness as required. A microfluidic pump is realized by integrating the rectifier with a simple stepper motor mechanism. The experimental results show that the pump can achieve a vertical left height of more than 2 m. Moreover, it is shown that a maximum flow rate of 6.3 ml/min can be obtained given a membrane thickness of 200 μm and a motor velocity of 80 rpm. In other words, the proposed microfluidic rectifier not only provides an effective means of preventing reverse flow but also permits the realization of a highly efficient microfluidic pump. PMID:24404051

Microfluidic rectifier based on poly(dimethylsiloxane) membrane and its application to a micropump.

PubMed

Wang, Yao-Nan; Tsai, Chien-Hsiung; Fu, Lung-Ming; Lin Liou, Lung-Kai

2013-01-01

A microfluidic rectifier incorporating an obstructed microchannel and a PDMS membrane is proposed. During forward flow, the membrane deflects in the upward direction; thereby allowing the fluid to pass over the obstacle. Conversely, during reverse flow, the membrane seals against the obstacle, thereby closing the channel and preventing flow. It is shown that the proposed device can operate over a wide pressure range by increasing or decreasing the membrane thickness as required. A microfluidic pump is realized by integrating the rectifier with a simple stepper motor mechanism. The experimental results show that the pump can achieve a vertical left height of more than 2 m. Moreover, it is shown that a maximum flow rate of 6.3 ml/min can be obtained given a membrane thickness of 200 μm and a motor velocity of 80 rpm. In other words, the proposed microfluidic rectifier not only provides an effective means of preventing reverse flow but also permits the realization of a highly efficient microfluidic pump.

Efficient Direct-Matching Rectenna Design for RF Power Transfer Applications

NASA Astrophysics Data System (ADS)

Keyrouz, Shady; Visser, Huib

2013-12-01

This paper presents the design, simulation, fabrication and measurements of a 50 ohm rectenna system. The paper investigates each part (in terms of input impedance) of the rectenna system starting from the antenna, followed by the matching network, to the rectifier. The system consists of an antenna, which captures the transmitted RF signal, connected to a rectifier which converts the AC captured signal into a DC power signal. For maximum power transfer, a matching network is designed between the rectifier and the antenna. At an input power level of -10 dBm, the system is able to achieve an RF/DC power conversion efficiency of 49.7%.

Static analysis of rectifier cabinet for nuclear power generating stations based on finite element method

NASA Astrophysics Data System (ADS)

Yin, Qiang; Chen, Tian-jin; Li, Wei-yang; Xiong, Ze-cheng; Ma, Rui

2017-09-01

In order to obtain the deformation map and equivalent stress distribution of rectifier cabinet for nuclear power generating stations, the quality distribution of structure and electrical are described, the tensile bond strengths of the rings are checked, and the finite element model of cabinet is set up by ANSYS. The transport conditions of the hoisting state and fork loading state are analyzed. The deformation map and equivalent stress distribution are obtained. The attentive problems are put forward. It is a reference for analysis method and the obtained results for the transport of rectifier cabinet for nuclear power generating stations.

Field-effect P-N junction

DOEpatents

Regan, William; Zettl, Alexander

2015-05-05

This disclosure provides systems, methods, and apparatus related to field-effect p-n junctions. In one aspect, a device includes an ohmic contact, a semiconductor layer disposed on the ohmic contact, at least one rectifying contact disposed on the semiconductor layer, a gate including a layer disposed on the at least one rectifying contact and the semiconductor layer and a gate contact disposed on the layer. A lateral width of the rectifying contact is less than a semiconductor depletion width of the semiconductor layer. The gate contact is electrically connected to the ohmic contact to create a self-gating feedback loop that is configured to maintain a gate electric field of the gate.

LC-oscillator with automatic stabilized amplitude via bias current control. [power supply circuit for transducers

NASA Technical Reports Server (NTRS)

Hamlet, J. F. (Inventor)

1974-01-01

A stable excitation supply for measurement transducers is described. It consists of a single-transistor oscillator with a coil connected to the collector and a capacitor connected from the collector to the emitter. The output of the oscillator is rectified and the rectified signal acts as one input to a differential amplifier; the other input being a reference potential. The output of the amplifier is connected at a point between the emitter of the transistor and ground. When the rectified signal is greater than the reference signal, the differential amplifier produces a signal of polarity to reduce bias current and, consequently, amplification.

Combustion chemistry of ethanol: Ignition and speciation studies in a rapid compression facility [On the combustion chemistry of ethanol: Ignition and speciation studies in a rapid compression facility

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

Barraza-Botet, Cesar L.; Wagnon, Scott W.; Wooldridge, Margaret S.

Here, ethanol remains the most important alternative fuel for the transportation sector. This work presents new experimental data on ethanol ignition, including stable species measurements, obtained with the University of Michigan rapid compression facility. Ignition delay times were determined from pressure histories of ignition experiments with stoichiometric ethanol–air mixtures at pressures of ~3–10 atm. Temperatures (880–1150 K) were controlled by varying buffer gas composition (Ar, N 2, CO 2). High-speed imaging was used to record chemiluminescence during the experiments, which showed homogeneous ignition events. The results for ignition delay time agreed well with trends on the basis of previous experimentalmore » measurements. Speciation experiments were performed using fast gas sampling and gas chromatography to identify and quantify ethanol and 11 stable intermediate species formed during the ignition delay period. Simulations were carried out using a chemical kinetic mechanism available in the literature, and the agreement with the experimental results for ignition delay time and the intermediate species measured was excellent for the majority of the conditions studied. From the simulation results, ethanol + HO 2 was identified as an important reaction at the experimental conditions for both the ignition delay time and intermediate species measurements. Further studies to improve the accuracy of the rate coefficient for ethanol + HO 2 would improve the predictive understanding of intermediate and low-temperature ethanol combustion.« less

Combustion chemistry of ethanol: Ignition and speciation studies in a rapid compression facility [On the combustion chemistry of ethanol: Ignition and speciation studies in a rapid compression facility

DOE PAGES

Barraza-Botet, Cesar L.; Wagnon, Scott W.; Wooldridge, Margaret S.

2016-08-31

Here, ethanol remains the most important alternative fuel for the transportation sector. This work presents new experimental data on ethanol ignition, including stable species measurements, obtained with the University of Michigan rapid compression facility. Ignition delay times were determined from pressure histories of ignition experiments with stoichiometric ethanol–air mixtures at pressures of ~3–10 atm. Temperatures (880–1150 K) were controlled by varying buffer gas composition (Ar, N 2, CO 2). High-speed imaging was used to record chemiluminescence during the experiments, which showed homogeneous ignition events. The results for ignition delay time agreed well with trends on the basis of previous experimentalmore » measurements. Speciation experiments were performed using fast gas sampling and gas chromatography to identify and quantify ethanol and 11 stable intermediate species formed during the ignition delay period. Simulations were carried out using a chemical kinetic mechanism available in the literature, and the agreement with the experimental results for ignition delay time and the intermediate species measured was excellent for the majority of the conditions studied. From the simulation results, ethanol + HO 2 was identified as an important reaction at the experimental conditions for both the ignition delay time and intermediate species measurements. Further studies to improve the accuracy of the rate coefficient for ethanol + HO 2 would improve the predictive understanding of intermediate and low-temperature ethanol combustion.« less

46 CFR 111.33-3 - Nameplate data.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 4 2013-10-01 2013-10-01 false Nameplate data. 111.33-3 Section 111.33-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Power Semiconductor Rectifier Systems § 111.33-3 Nameplate data. (a) Each semiconductor rectifier...

46 CFR 111.33-3 - Nameplate data.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 4 2014-10-01 2014-10-01 false Nameplate data. 111.33-3 Section 111.33-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Power Semiconductor Rectifier Systems § 111.33-3 Nameplate data. (a) Each semiconductor rectifier...

46 CFR 111.33-3 - Nameplate data.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 4 2012-10-01 2012-10-01 false Nameplate data. 111.33-3 Section 111.33-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Power Semiconductor Rectifier Systems § 111.33-3 Nameplate data. (a) Each semiconductor rectifier...

46 CFR 111.33-3 - Nameplate data.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Nameplate data. 111.33-3 Section 111.33-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Power Semiconductor Rectifier Systems § 111.33-3 Nameplate data. (a) Each semiconductor rectifier...

46 CFR 111.33-3 - Nameplate data.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 4 2011-10-01 2011-10-01 false Nameplate data. 111.33-3 Section 111.33-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Power Semiconductor Rectifier Systems § 111.33-3 Nameplate data. (a) Each semiconductor rectifier...

Pulse generator using transistors and silicon controlled rectifiers produces high current pulses with fast rise and fall times

NASA Technical Reports Server (NTRS)

Woolfson, M. G.

1966-01-01

Electrical pulse generator uses power transistors and silicon controlled rectifiers for producing a high current pulse having fast rise and fall times. At quiescent conditions, the standby power consumption of the circuit is equal to zero.

Serotonin regulates voltage-dependent currents in type Ie(A) and Ii interneurons of Hermissenda

PubMed Central

Jin, Nan Ge

2011-01-01

Serotonin (5-HT) has both direct and modulatory actions on central neurons contributing to behavioral arousal and cellular-synaptic plasticity in diverse species. In Hermissenda, 5-HT produces changes in intrinsic excitability of different types of identified interneurons in the circumesophageal nervous system. Using whole cell patch-clamp techniques we have examined membrane conductance changes produced by 5-HT that contribute to intrinsic excitability in two identified classes of interneurons, types Ii and IeA. Whole cell currents were examined before and after 5-HT application to the isolated nervous system. A 4-aminopyridine-sensitive transient outward K+ current [IK(A)], a tetraethylammonium-sensitive delayed rectifier K+ current [IK(V)], an inward rectifier K+ current [IK(IR)], and a hyperpolarization-activated current (Ih) were characterized. 5-HT decreased the amplitude of IK(A) and IK(V) in both type Ii and IeA interneurons. However, differences in 5-HT's effects on the activation-inactivation kinetics were observed in different types of interneurons. 5-HT produced a depolarizing shift in the activation curve of IK(V) and a hyperpolarizing shift in the inactivation curve of IK(A) in type Ii interneurons. In contrast, 5-HT produced a depolarizing shift in the activation curve and a hyperpolarizing shift in the inactivation curve of both IK(V) and IK(A) in type IeA interneurons. In addition, 5-HT decreased the amplitude of IK(IR) in type Ii interneurons and increased the amplitude of Ih in type IeA interneurons. These results indicate that 5-HT-dependent changes in IK(A), IK(V), IK(IR), and Ih contribute to multiple mechanisms that synergistically support modulation of increased intrinsic excitability associated with different functional classes of identified type I interneurons. PMID:21813747

Long-Term Fish Oil Supplementation Induces Cardiac Electrical Remodeling by Changing Channel Protein Expression in the Rabbit Model

PubMed Central

Xu, Xulin; Jiang, Min; Wang, Yuhong; Smith, Timothy; Baumgarten, Clive M.; Wood, Mark A.; Tseng, Gea-Ny

2010-01-01

Clinical trials and epidemiological studies have suggested that dietary fish oil (FO) supplementation can provide an anti-arrhythmic benefit in some patient populations. The underlying mechanisms are not entirely clear. We wanted to understand how FO supplementation (for 4 weeks) affected the action potential configuration/duration of ventricular myocytes, and the ionic mechanism(s)/molecular basis for these effects. The experiments were conducted on adult rabbits, a widely used animal model for cardiac electrophysiology and pathophysiology. We used gas chromatography - mass spectroscopy to confirm that FO feeding produced a marked increase in the content of n-3 polyunsaturated fatty acids in the phospholipids of rabbit hearts. Left ventricular myocytes were used in current and voltage clamp experiments to monitor action potentials and ionic currents, respectively. Action potentials of myocytes from FO-fed rabbits exhibited much more positive plateau voltages and prolonged durations. These changes could be explained by an increase in the L-type Ca current (ICaL) and a decrease in the transient outward current (Ito) in these myocytes. FO feeding did not change the delayed rectifier or inward rectifier current. Immunoblot experiments showed that the FO-feeding induced changes in ICaL and Ito were associated with corresponding changes in the protein levels of major pore-forming subunits of these channels: increase in Cav1.2 and decrease in Kv4.2 and Kv1.4. There was no change in other channel subunits (Cav1.1, Kv4.3, KChIP2, and ERG1). We conclude that long-term fish oil supplementation can impact on cardiac electrical activity at least partially by changing channel subunit expression in cardiac myocytes. PMID:20405051

Effects of phloretin and phloridzin on Ca2+ handling, the action potential, and ion currents in rat ventricular myocytes.

PubMed

Olson, Marnie L; Kargacin, Margaret E; Ward, Christopher A; Kargacin, Gary J

2007-06-01

The effects of the phytoestrogens phloretin and phloridzin on Ca(2+) handling, cell shortening, the action potential, and Ca(2+) and K(+) currents in freshly isolated cardiac myocytes from rat ventricle were examined. Phloretin increased the amplitude and area and decreased the rate of decline of electrically evoked Ca(2+) transients in the myocytes. These effects were accompanied by an increase in the Ca(2+) load of the sarcoplasmic reticulum, as determined by the area of caffeine-evoked Ca(2+) transients. An increase in the extent of shortening of the myocytes in response to electrically evoked action potentials was also observed in the presence of phloretin. To further examine possible mechanisms contributing to the observed changes in Ca(2+) handling and contractility, the effects of phloretin on the cardiac action potential and plasma membrane Ca(2+) and K(+) currents were examined. Phloretin markedly increased the action potential duration in the myocytes, and it inhibited the Ca(2+)-independent transient outward K(+) current (I(to)). The inwardly rectifying K(+) current, the sustained outward delayed rectifier K(+) current, and L-type Ca(2+) currents were not significantly different in the presence and absence of phloretin, nor was there any evidence that the Na(+)/Ca(2+) exchanger was affected. The effects of phloretin on Ca(2+) handling in the myocytes are consistent with its effects on I(to). Phloridzin did not significantly alter the amplitude or area of electrically evoked Ca(2+) transients in the myocytes, nor did it have detectable effects on the sarcoplasmic reticulum Ca(2+) load, cell shortening, or the action potential.

Reduction of I(Ca,L) and I(to1) density in hypertrophied right ventricular cells by simulated high altitude in adult rats.

PubMed

Chouabe, C; Espinosa, L; Megas, P; Chakir, A; Rougier, O; Freminet, A; Bonvallet, R

1997-01-01

The present paper describes the effect of a simulated hypobaric condition (at the altitude of 4500 m) on morphological characteristics and on some ionic currents in ventricular cells of adult rats. According to current data, chronic high-altitude exposure led to mild right ventricular hypertrophy. Increase in right ventricular weight appeared to be due wholly or partly to an enlargement of myocytes. The whole-cell patch-clamp technique was used and this confirmed, by cell capacitance measurement, that chronic high-altitude exposure induced an increase in the size of the right ventricular cells. Hypertrophied cells showed prolongation of action potential (AP). Four ionic currents, playing a role along with many others in the precise balance of inward and outward currents that control the duration of cardiac AP, were investigated. We report a significant decrease in the transient outward (I(to1)) and in the L-type calcium current (I(Ca,L)) densities while there was no significant difference in the delayed rectifier current (I(K)) or in the inward rectifier current (I(K1)) densities in hypertrophied right ventricular cells compared to control cells. At a given potential the decrease in I(to 1) density was relatively more important than the decrease in I(Ca,L) density. In both cell types, all the currents displayed the same voltage dependence. The inactivation kinetics of I(to 1) and I(Ca,L) or the steady-state activation and inactivation relationships were not significantly modified by chronic high-altitude exposure. We conclude that chronic high-altitude exposure induced true right ventricular myocyte hypertrophy and that the decrease in I(to 1) density might account for the lengthened action potential, or have a partial effect.

Acute desensitization of acetylcholine and endothelin-1 activated inward rectifier K+ current in myocytes from the cardiac atrioventricular node.

PubMed

Choisy, Stéphanie C M; James, Andrew F; Hancox, Jules C

2012-07-06

The atrioventricular node (AVN) is a vital component of the pacemaker-conduction system of the heart, co-ordinating conduction of electrical excitation from cardiac atria to ventricles and acting as a secondary pacemaker. The electrical behaviour of the AVN is modulated by vagal activity via activation of muscarinic potassium current, IKACh. However, it is not yet known if this response exhibits 'fade' or desensitization in the AVN, as established for the heart's primary pacemaker--the sinoatrial node. In this study, acute activation of IKACh in rabbit single AVN cells was investigated using whole-cell patch clamp at 37 °C. 0.1-1 μM acetylcholine (ACh) rapidly activated a robust IKACh in AVN myocytes during a descending voltage-ramp protocol. This response was inhibited by tertiapin-Q (TQ; 300 nM) and by the M2 muscarinic ACh receptor antagonist AFDX-116 (1 μM). During sustained ACh exposure the elicited IKACh exhibited bi-exponential fade (τf of 2.0 s and τs 76.9 s at -120 mV; 1 μM ACh). 10 nM ET-1 elicited a current similar to IKACh, which faded with a mono-exponential time-course (τ of 52.6 s at -120 mV). When ET-1 was applied following ACh, the ET-1 activated response was greatly attenuated, demonstrating that ACh could desensitize the response to ET-1. For neither ACh nor ET-1 was the rate of current fade dependent upon the initial response magnitude, which is inconsistent with K+ flux mediated changes in electrochemical driving force as the underlying mechanism. Collectively, these findings demonstrate that TQ sensitive inwardly rectifying K+ current in cardiac AVN cells, elicited by M2 muscarinic receptor or ET-1 receptor activation, exhibits fade due to rapid desensitization. Copyright © 2012 Elsevier Inc. All rights reserved.

Comparison of Rectified and Unrectified Sockets for Transtibial Amputees.

PubMed

Engsberg, Jack R; Sprouse, S Wayne; Uhrich, Mary L; Ziegler, Barbara R; Luitjohan, F Daniel

2008-01-01

The current method for fabricating prosthetic sockets is to modify a positive mold to account for the non-homogeneity of the residual limb to tolerate load (i.e., rectified socket). We tested unrectified sockets by retaining the shape of the residual limb, except for a distal end pad, using an alginate gel process instead of casting. This investigation compared rectified and unrectified sockets. Forty-three adults with unilateral transtibial amputations were tested after randomly wearing both rectified and unrectified sockets for at least 4 weeks. Testing included a gait analysis, energy expenditure and Prosthesis Evaluation Questionnaire (PEQ). Results indicated no differences between sockets for gait speed and timing, gait kinematics and kinetics, and gait energy expenditure. There were also no differences in the Prosthetic Evaluation Questionnaire and 16 subjects selected the rectified socket, 25 selected the unrectified socket, and 2 subjects selected to use both sockets as their exit socket. Results seemed to indicate that more than one paradigm exists for shaping prosthetic sockets, and this paradigm may be helpful in understanding the mechanisms of socket fit. The alginate gel fabrication method was simpler than the traditional method. The method could be helpful in other countries where prosthetic care is lacking, may be helpful with new amputees, and may be helpful in typical clinics to reduce costs and free the prosthetist to focus more time on patient needs.

Comparison of Rectified and Unrectified Sockets for Transtibial Amputees

PubMed Central

Engsberg, Jack R.; Sprouse, S. Wayne; Uhrich, Mary L.; Ziegler, Barbara R.; Luitjohan, F. Daniel

2008-01-01

The current method for fabricating prosthetic sockets is to modify a positive mold to account for the non-homogeneity of the residual limb to tolerate load (i.e., rectified socket). We tested unrectified sockets by retaining the shape of the residual limb, except for a distal end pad, using an alginate gel process instead of casting. This investigation compared rectified and unrectified sockets. Forty-three adults with unilateral transtibial amputations were tested after randomly wearing both rectified and unrectified sockets for at least 4 weeks. Testing included a gait analysis, energy expenditure and Prosthesis Evaluation Questionnaire (PEQ). Results indicated no differences between sockets for gait speed and timing, gait kinematics and kinetics, and gait energy expenditure. There were also no differences in the Prosthetic Evaluation Questionnaire and 16 subjects selected the rectified socket, 25 selected the unrectified socket, and 2 subjects selected to use both sockets as their exit socket. Results seemed to indicate that more than one paradigm exists for shaping prosthetic sockets, and this paradigm may be helpful in understanding the mechanisms of socket fit. The alginate gel fabrication method was simpler than the traditional method. The method could be helpful in other countries where prosthetic care is lacking, may be helpful with new amputees, and may be helpful in typical clinics to reduce costs and free the prosthetist to focus more time on patient needs. PMID:18776945

Hindrance of conservation biology by delays in the submission of manuscripts.

PubMed

O'Donnell, Ryan P; Supp, Sarah R; Cobbold, Stephanie M

2010-04-01

Timely dissemination of scientific findings depends not only on rapid publication of submitted manuscripts, a topic which has received much discussion, but also on rapid submission of research after the research is completed. We measured submission delay (time from the last date of data collection to the submission of a manuscript) for every paper from 14 journals in 2007 and compared these submission delays among four fields of biology (conservation, taxonomy, behavior, and evolution). Manuscripts published in leading journals in the field of conservation biology have the longest delays in publication of accepted manuscripts and the longest intervals between completion of research and submission of the manuscript. Delay in manuscript submission accounts for more than half of the total time from last date of data collection to publication. Across fields, the number of authors was significantly negatively correlated with submission delay, but conservation journals had the second highest number of authors and the greatest submission delay, so submission of conservation manuscripts was not hindered by a shortage of collaboration relative to other fields. Rejection rates were greater in conservation journals than in behavior and evolution, but rejection times were faster; thus, there were no obvious net differences among fields in the time papers spent waiting to be rejected. Publication delay has been reduced significantly in the last 7 years, but was still greater in conservation journals than in any of the other three fields we studied. Thus, the urgent field of conservation biology is hindered in both preparation and publication of manuscripts.

Research and Development of Hazardous/Toxic Waste Analytical Screening Procedures. Available Field Methods for Rapid Screening of Hazardous Waste Materials at Waste Sites (Class A Poisons).

DTIC Science & Technology

1982-01-01

bromide is listed as a positive interference. Nitric oxide and nitrogen dioxide can be detected by using the Draeger nitrous fumes detector tube. A... fumes exhibit a delay from the time of exposure to the onset of symptoms. This time delay would not be conducive for a rapid field screening test. It...Dangerous when strongly heated, emits highly toxic fumes . THRESHOLD LIMIT VALUE: No information available PHYSIOLOGICAL EFFECTS: A. Intensely irritating to

Use of rapid needs assessment as a tool to identify vaccination delays in Guatemala and Peru.

PubMed

D'Ardenne, Katie K; Darrow, Juliana; Furniss, Anna; Chavez, Catia; Hernandez, Herminio; Berman, Stephen; Asturias, Edwin J

2016-03-29

To explore the use of rapid needs assessment (RNA) surveys to determine the prevalence and factors contributing to delays in vaccination of children in two low middle-income countries (LMIC). Data from two RNA surveys performed as part of program improvement evaluations in Guatemala and Peru were used for this analysis. The primary endpoint was the timeliness of immunization with delay defined as administration of vaccines beyond 28 days from recommended age for DTwP-HepB-Hib (Penta) and measles-mumps-rubella (MMR) vaccines, as well as past age-restrictions for rotavirus vaccine. Independent risk factors analyzed included child's gender, birth year, number of children in household, maternal age, maternal education, and food insecurity. Vaccine information was available from 811 children from 838 households surveyed. High rate of immunization delays was observed, with 75.6% of children in Guatemala and 57.8% of children in Peru being delayed for the third dose of Penta primary series. Factors associated with delayed vaccination in Guatemala included advanced maternal age and increased number of children in household. In Peru, significant associations were birth year before 2009, lower maternal education level, and increased number of children in household. RNA is a fast and effective method to identify timely vaccine coverage and derive a hypothesis of factors possibly associated with vaccination delay. Copyright © 2016 Elsevier Ltd. All rights reserved.

WASTE MINIMIZATION ASSESSMENT FOR A MANUFACTURER OF SILICON-CONTROLLED RECTIFIERS AND SCHOTTKY RECTIFIERS

EPA Science Inventory

The U.S. Environmental Protection Agency (EPA) has funded a pilot project to assist small- and medium-size manufacturers who want to minimize their generation of waste but who lack the expertise to do so. In an effort to assist these manufacturers Waste Minimization Assessment Ce...

76 FR 62671 - Airworthiness Directives; Dassault Aviation Model FALCON 7X Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-11

... product. The MCAI describes the unsafe condition as: The manufacturer of the Transformer Rectifier Unit... MCAI states: The manufacturer of the Transformer Rectifier Unit (TRU) part of the Ram Air Turbine (RAT..., all serial numbers, certificated in any category; equipped with any Ram Air Turbine (RAT) Transformer...

77 FR 3 - Airworthiness Directives; Dassault Aviation Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-03

... (RAT) transformer rectifier units (TRUs). This AD was prompted by a report of incorrect design of the... an unsafe condition for the specified products. The MCAI states: The manufacturer of the Transformer..., certificated in any category; equipped with any ram air turbine (RAT) transformer rectifier unit (TRU) having...

INTELLIGENCE SUPPORT TO JOINT TARGETING IN THE A2/AD ENVIRONMENT

DTIC Science & Technology

2016-02-10

budgets. Finally, the dismal state of targeting personnel training and development must be rectified . These steps must be taken before the United... rectified . These steps must be taken before the United States faces a near-peer adversary employing A2/AD capabilities. Bibliography ACC/A2. Air Force

Relativistic effects in photoionization: Wigner time delay for the noble gases and IIB atoms

NASA Astrophysics Data System (ADS)

Banerjee, Sourav; Deshmukh, Pranawa; Dolmatov, Valeriy; Kheifets, Anatoli; Manson, Steven

2017-04-01

Time delay in atomic photoionization has been observed in several experiments, and various theoretical and experimental approaches are developing rapidly to obtain a better understanding of this phenomena. Theoretical methods that account for many body correlations include the relativistic random phase approximation (RRPA) and its non-relativistic analogue, RPAE. Calculations using RRPA are performed and the impact of relativistic interactions on Wigner time delay are explored via comparison of this result with RPAE results. In addition, results on Wigner time delay for Zn Cd and Hg are presented.

Acute alteration of cardiac ECG, action potential, I{sub Kr} and the human ether-a-go-go-related gene (hERG) K{sup +} channel by PCB 126 and PCB 77

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

Park, Mi-Hyeong; Park, Won Sun; Jo, Su-Hyun, E-mail: suhyunjo@kangwon.ac.kr

2012-07-01

Polychlorinated biphenyls (PCBs) have been known as serious persistent organic pollutants (POPs), causing developmental delays and motor dysfunction. We have investigated the effects of two PCB congeners, 3,3′,4,4′-tetrachlorobiphenyl (PCB 77) and 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) on ECG, action potential, and the rapidly activating delayed rectifier K{sup +} current (I{sub Kr}) of guinea pigs' hearts, and hERG K{sup +} current expressed in Xenopus oocytes. PCB 126 shortened the corrected QT interval (QTc) of ECG and decreased the action potential duration at 90% (APD{sub 90}), and 50% of repolarization (APD{sub 50}) (P < 0.05) without changing the action potential duration at 20% (APD{submore » 20}). PCB 77 decreased APD{sub 20} (P < 0.05) without affecting QTc, APD{sub 90}, and APD{sub 50}. The PCB 126 increased the I{sub Kr} in guinea-pig ventricular myocytes held at 36 °C and hERG K{sup +} current amplitude at the end of the voltage steps in voltage-dependent mode (P < 0.05); however, PCB 77 did not change the hERG K{sup +} current amplitude. The PCB 77 increased the diastolic Ca{sup 2+} and decreased Ca{sup 2+} transient amplitude (P < 0.05), however PCB 126 did not change. The results suggest that PCB 126 shortened the QTc and decreased the APD{sub 90} possibly by increasing I{sub Kr}, while PCB 77 decreased the APD{sub 20} possibly by other modulation related with intracellular Ca{sup 2+}. The present data indicate that the environmental toxicants, PCBs, can acutely affect cardiac electrophysiology including ECG, action potential, intracellular Ca{sup 2+}, and channel activity, resulting in toxic effects on the cardiac function in view of the possible accumulation of the PCBs in human body. -- Highlights: ► PCBs are known as serious environmental pollutants and developmental disruptors. ► PCB 126 shortened QT interval of ECG and action potential duration. ► PCB 126 increased human ether-a-go-go-related K{sup +} current and I{sub Kr}. ► PCB 77 decreased action potential duration and increased intracellular Ca{sup 2+} content. ► PCBs acutely change cardiac electrophysiology and rhythmicity.« less

Development and fabrication of improved Schottky power diodes

NASA Technical Reports Server (NTRS)

Cordes, L. F.; Garfinkel, M.; Taft, E. A.

1975-01-01

Reproducible methods for the fabrication of silicon Schottky diodes have been developed for tungsten, aluminum, conventional platinum silicide, and low temperature platinum silicide. Barrier heights and barrier lowering under reverse bias have been measured, permitting the accurate prediction of forward and reverse diode characteristics. Processing procedures have been developed that permit the fabrication of large area (about 1 sq cm) mesageometry power Schottky diodes with forward and reverse characteristics that approach theoretical values. A theoretical analysis of the operation of bridge rectifier circuits has been performed, which indicates the ranges of frequency and voltage for which Schottky rectifiers are preferred to p-n junctions. Power Schottky rectifiers have been fabricated and tested for voltage ratings up to 140 volts.

Ionization tube simmer current circuit

DOEpatents

Steinkraus, R.F. Jr.

1994-12-13

A highly efficient flash lamp simmer current circuit utilizes a fifty percent duty cycle square wave pulse generator to pass a current over a current limiting inductor to a full wave rectifier. The DC output of the rectifier is then passed over a voltage smoothing capacitor through a reverse current blocking diode to a flash lamp tube to sustain ionization in the tube between discharges via a small simmer current. An alternate embodiment of the circuit combines the pulse generator and inductor in the form of an FET off line square wave generator with an impedance limited step up output transformer which is then applied to the full wave rectifier as before to yield a similar simmer current. 6 figures.

Development of a Thermal Rectifier Usable at High Temperature

NASA Astrophysics Data System (ADS)

Takeuchi, Tsunehiro; Goto, Hiroki; Toyama, Yasuhiro; Itoh, Takashi; Mikami, Masashi

2011-05-01

By using Al-based metallic alloys characterized by a disordered structure and a narrow pseudogap of a few hundred meV in energy width persisting at the Fermi level, we succeeded in preparing materials possessing a large increase of thermal conductivity with increasing temperature. This unusual increase of thermal conductivity is caused by the electronic structure effect known as the bipolar diffusion effect (BDE) in the context of the two-band model. A thermal rectifier was constructed using materials exhibiting the BDE. By showing the thermal rectification of the bulk sample prepared in this study, we demonstrate that our newly proposed idea of a thermal rectifier using the BDE is applicable for practical use.

Transport of particles and microorganisms in microfluidic channels using rectified ac electro-osmotic flow

PubMed Central

Wu, Wen-I; Selvaganapathy, P. Ravi; Ching, Chan Y.

2011-01-01

A new method is demonstrated to transport particles, cells, and other microorganisms using rectified ac electro-osmotic flows in open microchannels. The rectified flow is obtained by synchronous zeta potential modulation with the driving potential in the microchannel. Experiments were conducted to transport both neutral, charged particles, and microorganisms of various sizes. A maximum speed of 50 μm∕s was obtained for 8 μm polystyrene beads, without any electrolysis, using a symmetrical square waveform driving electric field of 5 V∕mm at 10 Hz and a 360 V gate potential with its polarity synchronized with the driving potential (phase lag=0°). PMID:21522497

CMOS single-stage input-powered bridge rectifier with boost switch and duty cycle control

NASA Astrophysics Data System (ADS)

Radzuan, Roskhatijah; Mohd Salleh, Mohd Khairul; Hamzah, Mustafar Kamal; Ab Wahab, Norfishah

2017-06-01

This paper presents a single-stage input-powered bridge rectifier with boost switch for wireless-powered devices such as biomedical implants and wireless sensor nodes. Realised using CMOS process technology, it employs a duty cycle switch control to achieve high output voltage using boost technique, leading to a high output power conversion. It has only six external connections with the boost inductance. The input frequency of the bridge rectifier is set at 50 Hz, while the switching frequency is 100 kHz. The proposed circuit is fabricated on a single 0.18-micron CMOS die with a space area of 0.024 mm2. The simulated and measured results show good agreement.

Ionization tube simmer current circuit

DOEpatents

Steinkraus, Jr., Robert F.

1994-01-01

A highly efficient flash lamp simmer current circuit utilizes a fifty percent duty cycle square wave pulse generator to pass a current over a current limiting inductor to a full wave rectifier. The DC output of the rectifier is then passed over a voltage smoothing capacitor through a reverse current blocking diode to a flash lamp tube to sustain ionization in the tube between discharges via a small simmer current. An alternate embodiment of the circuit combines the pulse generator and inductor in the form of an FET off line square wave generator with an impedance limited step up output transformer which is then applied to the full wave rectifier as before to yield a similar simmer current.

Solid state circuit controls direction, speed, and braking of dc motor

NASA Technical Reports Server (NTRS)

Hanna, M. F.

1966-01-01

Full-wave bridge rectifier circuit controls the direction, speed, and braking of a dc motor. Gating in the circuit of Silicon Controlled Rectifiers /SCRS/ controls output polarity and braking is provided by an SCR that is gated to short circuit the reverse voltage generated by reversal of motor rotation.

125. JOB NO. LINE 5044, INTERNATIONAL RECTIFIER CORP., RACHELLE LABORATORIES, ...

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

125. JOB NO. LINE 5044, INTERNATIONAL RECTIFIER CORP., RACHELLE LABORATORIES, INC., LONG BEACH, CA, BY J.C. FULTON, SEPTEMBER 1982, LINE 5044, CLIFTON AND CO., ON FILE ENGINEERS DEPARTMENT, PORT OF LONG BEACH - Ford Motor Company Long Beach Assembly Plant, Assembly Building, 700 Henry Ford Avenue, Long Beach, Los Angeles County, CA

Role of inward rectifier potassium channels in salivary gland function and sugar feeding of the fruit fly, Drosophila melanogaster

USDA-ARS?s Scientific Manuscript database

The arthropod salivary gland is of critical importance for horizontal transmission of pathogens, yet a detailed understanding of the ion conductance pathways responsible for saliva production and excretion is lacking. A superfamily of potassium ion channels, known as inward rectifying potassium (Ki...

AGOR 28: SIO Shipyard Representative Bi-Weekly Progress Report

DTIC Science & Technology

2016-06-18

failed due to shorted temperature sensor at the Tunnel Thruster motor. A small rectifier was found to have failed in the terminal block found in the...Active Front End (AFE). The 1n4007 Rectifier is readily available for 16-cents. Will order additional diodes for spares. Siemens to make repairs

Power Conditioning for MEMS-Based Waste Vibrational Energy Harvester

DTIC Science & Technology

2015-06-01

circuits ...........................................................................................18 Figure 18. Full-wave passive MOSFET rectifier...ABBREVIATIONS AC Alternative Current AlN Aluminum Nitride DC Direct Current LIA Lock-In Amplifier MEMS Microelectromechanical Systems MOSFET ...efficiency is achieved when input voltage is over 2–3 V [14]. Using metal-oxide-semiconductor field-effect transistors ( MOSFETs ) in a rectifier instead of

High-temperature, gas-filled ceramic rectifiers, thyratrons, and voltage-reference tubes

NASA Technical Reports Server (NTRS)

Baum, E. A.

1969-01-01

Thyratron, capable of being operated as a rectifier and a voltage-reference tube, was constructed and tested for 1000 hours at temperatures to 800 degrees C. With current levels at 15 amps and peak voltages of 2000 volts and frequencies at 6000 cps, tube efficiency was greater than 97 percent.

Low leakage current Ni/CdZnTe/In diodes for X/ γ-ray detectors

NASA Astrophysics Data System (ADS)

Sklyarchuk, V. M.; Gnatyuk, V. A.; Pecharapa, W.

2018-01-01

The electrical characteristics of the Ni/Cd1-xZnxTe/In structures with a metal-semiconductor rectifying contact are investigated. The diodes, fabricated on the base of In-doped n-type Cd1-xZnxTe (CZT) crystals with resistivity of ∼1010 Ω ṡ cm, have low leakage current and can be used as X/ γ-ray detectors. The rectifying contact was obtained by vacuum deposition of Ni on the semiconductor surface pretreated with argon plasma. The high barrier rectifying contact allowed us to increase applied reverse bias voltage up to 2500 V at the CZT crystal thickness of 1 mm. Dark (leakage) currents of the diodes with the rectifying contact area of 4 mm2 did not exceed 3-5 nA at bias voltage of 2000 V and room temperature. The charge transport mechanisms in the Ni/CZT/In structures have been interpreted as generation-recombination in the space charge region within the range of reverse bias of 5-100 V and as currents limited by space charge at both forward and reverse bias at V >100 V.

Low cost, p-ZnO/n-Si, rectifying, nano heterojunction diode: Fabrication and electrical characterization.

PubMed

Kabra, Vinay; Aamir, Lubna; Malik, M M

2014-01-01

A low cost, highly rectifying, nano heterojunction (p-ZnO/n-Si) diode was fabricated using solution-processed, p-type, ZnO nanoparticles and an n-type Si substrate. p-type ZnO nanoparticles were synthesized using a chemical synthesis route and characterized by XRD and a Hall effect measurement system. The device was fabricated by forming thin film of synthesized p-ZnO nanoparticles on an n-Si substrate using a dip coating technique. The device was then characterized by current-voltage (I-V) and capacitance-voltage (C-V) measurements. The effect of UV illumination on the I-V characteristics was also explored and indicated the formation of a highly rectifying, nano heterojunction with a rectification ratio of 101 at 3 V, which increased nearly 2.5 times (232 at 3 V) under UV illumination. However, the cut-in voltage decreases from 1.5 V to 0.9 V under UV illumination. The fabricated device could be used in switches, rectifiers, clipper and clamper circuits, BJTs, MOSFETs and other electronic circuitry.

Reconfigurable Resonant Regulating Rectifier With Primary Equalization for Extended Coupling- and Loading-Range in Bio-Implant Wireless Power Transfer.

PubMed

Li, Xing; Meng, Xiaodong; Tsui, Chi-Ying; Ki, Wing-Hung

2015-12-01

Wireless power transfer using reconfigurable resonant regulating (R(3)) rectification suffers from limited range in accommodating varying coupling and loading conditions. A primary-assisted regulation principle is proposed to mitigate these limitations, of which the amplitude of the rectifier input voltage on the secondary side is regulated by accordingly adjusting the voltage amplitude Veq on the primary side. A novel current-sensing method and calibration scheme track Veq on the primary side. A ramp generator simultaneously provides three clock signals for different modules. Both the primary equalizer and the R(3) rectifier are implemented as custom integrated circuits fabricated in a 0.35 μm CMOS process, with the global control implemented in FPGA. Measurements show that with the primary equalizer, the workable coupling and loading ranges are extended by 250% at 120 mW load and 300% at 1.2 cm coil distance compared to the same system without the primary equalizer. A maximum rectifier efficiency of 92.5% and a total system efficiency of 62.4% are demonstrated.

Rectifying the output of vibrational piezoelectric energy harvester using quantum dots

NASA Astrophysics Data System (ADS)

Li, Lijie

2017-03-01

Piezoelectric energy harvester scavenges mechanical vibrations and generates electricity. Researchers have strived to optimize the electromechanical structures and to design necessary external power management circuits, aiming to deliver high power and rectified outputs ready for serving as batteries. Complex deformation of the mechanical structure results in charges with opposite polarities appearing on same surface, leading to current loss in the attached metal electrode. External power management circuits such as rectifiers comprise diodes that consume power and have undesirable forward bias. To address the above issues, we devise a novel integrated piezoelectric energy harvesting device that is structured by stacking a layer of quantum dots (QDs) and a layer of piezoelectric material. We find that the QD can rectify electrical charges generated from the piezoelectric material because of its adaptable conductance to the electrochemical potentials of both sides of the QDs layer, so that electrical current causing energy loss on the same surface of the piezoelectric material can be minimized. The QDs layer has the potential to replace external rectification circuits providing a much more compact and less power-consumption solution.

Effects of a Word-Learning Training on Children With Cochlear Implants

PubMed Central

Lund, Emily

2014-01-01

Preschool children with hearing loss who use cochlear implants demonstrate vocabulary delays when compared to their peers without hearing loss. These delays may be a result of deficient word-learning abilities; children with cochlear implants perform more poorly on rapid word-learning tasks than children with normal hearing. This study explored the malleability of rapid word learning of preschoolers with cochlear implants by evaluating the effects of a word-learning training on rapid word learning. A single-subject, multiple probe design across participants measured the impact of the training on children’s rapid word-learning performance. Participants included 5 preschool children with cochlear implants who had an expressive lexicon of less than 150 words. An investigator guided children to identify, repeat, and learn about unknown sets of words in 2-weekly sessions across 10 weeks. The probe measure, a rapid word-learning task with a different set of words than those taught during training, was collected in the baseline, training, and maintenance conditions. All participants improved their receptive rapid word-learning performance in the training condition. The functional relation indicates that the receptive rapid word-learning performance of children with cochlear implants is malleable. PMID:23981321

Optics to rectify CORONA panoramic photographs for map making

NASA Astrophysics Data System (ADS)

Hilbert, Robert S.

2006-08-01

In the 1960's, accurate maps of the United States were available to all, from the U.S. Government, but maps of the Soviet Union were not, and in fact were classified. Maps of the Soviet Union were needed by the U.S. Government, including for U.S. targeting of Soviet ICBM sites, and for negotiating the SALT ICBM disarmament treaty. Although mapping cameras were historically frame cameras with low distortion, the CORONA panoramic film coverage was used to identify any ICBM sites. If distortion-free photographs could be produced from this inherently distorted panoramic material, accurate maps could be produced that would be valuable. Use of the stereo photographs from CORONA, for developing accurate topographical maps, was the mission of Itek's Gamma Rectifier. Bob Shannon's department at Itek was responsible for designing the optics for the Gamma Rectifier. He assigned the design to the author. The optical requirements of this system are described along with the optical design solution, which allowed the inherent panoramic distortion of the original photographs to be "rectified" to a very high level of accuracy, in enlarged photographs. These rectifiers were used three shifts a day, for over a decade, and produced the most accurate maps of the earth's surface, that existed at that time. The results facilitated the success of the Strategic Arms Limitation Talks (SALT) Treaty signed by the US and the Soviet Union in 1972, which were verified by "national means of verification" (i.e. space reconnaissance).

Angiotensin II and angiotensin II receptor blocker modulate the arrhythmogenic activity of pulmonary veins.

PubMed

Chen, Yi-Jen; Chen, Yao-Chang; Tai, Ching-Tai; Yeh, Hung-I; Lin, Cheng-I; Chen, Shih-Ann

2006-01-01

Angiotensin II receptor blockers (AIIRBs) have been shown to prevent atrial fibrillation. The pulmonary veins (PVs) are the most important focus for the generation of atrial fibrillation. The aim of this study was to evaluate whether angiotensin II or AIIRB may change the arrhythmogenic activity of the PVs. Conventional microelectrodes and whole-cell patch clamps were used to investigate the action potentials (APs) and ionic currents in isolated rabbit PV tissue and single cardiomyocytes before and after administering angiotensin II or losartan (AIIRB). In the tissue preparations, angiotensin II induced delayed after-depolarizations (1, 10, and 100 nM) and accelerated the automatic rhythm (10 and 100 nM). Angiotensin II (100 nM) prolonged the AP duration and increased the contractile force (10 and 100 nM). Losartan (1 and 10 microM) inhibited the automatic rhythm. Losartan (10 microM) prolonged the AP duration and reduced the contractile force (1 and 10 microM). Angiotensin II reduced the transient outward potassium current (I(to)) but increased the L-type calcium, delayed rectifier potassium (I(K)), transient inward (I(ti)), pacemaker, and Na(+)-Ca(2+) exchanger (NCX) currents in the PV cardiomyocytes. Losartan decreased the I(to), I(K), I(ti), and NCX currents. In conclusion, angiotensin II and AIIRB modulate the PV electrical activity, which may play a role in the pathophysiology of atrial fibrillation.

Inward rectifier potassium channels in the HL-1 cardiomyocyte-derived cell line.

PubMed

Goldoni, Dana; Zhao, YouYou; Green, Brian D; McDermott, Barbara J; Collins, Anthony

2010-11-01

HL-1 is a line of immortalized cells of cardiomyocyte origin that are a useful complement to native cardiomyocytes in studies of cardiac gene regulation. Several types of ion channel have been identified in these cells, but not the physiologically important inward rectifier K(+) channels. Our aim was to identify and characterize inward rectifier K(+) channels in HL-1 cells. External Ba(2+) (100 µM) inhibited 44 ± 0.05% (mean ± s.e.m., n = 11) of inward current in whole-cell patch-clamp recordings. The reversal potential of the Ba(2+)-sensitive current shifted with external [K(+)] as expected for K(+)-selective channels. The slope conductance of the inward Ba(2+)-sensitive current increased with external [K(+)]. The apparent Kd for Ba(2+) was voltage dependent, ranging from 15 µM at -150  mV to 148 µM at -75  mV in 120  mM external K(+). This current was insensitive to 10 µM glybenclamide. A component of whole-cell current was sensitive to 150 µM 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), although it did not correspond to the Ba(2+)-sensitive component. The effect of external 1 mM Cs(+) was similar to that of Ba(2+). Polymerase chain reaction using HL-1 cDNA as template and primers specific for the cardiac inward rectifier K(ir)2.1 produced a fragment of the expected size that was confirmed to be K(ir)2.1 by DNA sequencing. In conclusion, HL-1 cells express a current that is characteristic of cardiac inward rectifier K(+) channels, and express K(ir)2.1 mRNA. This cell line may have use as a system for studying inward rectifier gene regulation in a cardiomyocyte phenotype. © 2010 Wiley-Liss, Inc.

Kir2.1 encodes the inward rectifier potassium channel in rat arterial smooth muscle cells

PubMed Central

Bradley, Karri K; Jaggar, Jonathan H; Bonev, Adrian D; Heppner, Thomas J; Flynn, Elaine RM; Nelson, Mark T; Horowitz, Burton

1999-01-01

The molecular nature of the strong inward rectifier K+ channel in vascular smooth muscle was explored by using isolated cell RT-PCR, cDNA cloning and expression techniques.RT-PCR of RNA from single smooth muscle cells of rat cerebral (basilar), coronary and mesenteric arteries revealed transcripts for Kir2.1. Transcripts for Kir2.2 and Kir2.3 were not found.Quantitative PCR analysis revealed significant differences in transcript levels of Kir2.1 between the different vascular preparations (n = 3; P < 0.05). A two-fold difference was detected between Kir2.1 mRNA and β-actin mRNA in coronary arteries when compared with relative levels measured in mesenteric and basilar preparations.Kir2.1 was cloned from rat mesenteric vascular smooth muscle cells and expressed in Xenopus oocytes. Currents were strongly inwardly rectifying and selective for K+.The effect of extracellular Ba2+, Ca2+, Mg2+ and Cs2+ ions on cloned Kir2.1 channels expressed in Xenopus oocytes was examined. Ba2+ and Cs+ block were steeply voltage dependent, whereas block by external Ca2+ and Mg2+ exhibited little voltage dependence. The apparent half-block constants and voltage dependences for Ba2+, Cs+, Ca2+ and Mg2+ were very similar for inward rectifier K+ currents from native cells and cloned Kir2.1 channels expressed in oocytes.Molecular studies demonstrate that Kir2.1 is the only member of the Kir2 channel subfamily present in vascular arterial smooth muscle cells. Expression of cloned Kir2.1 in Xenopus oocytes resulted in inward rectifier K+ currents that strongly resemble those that are observed in native vascular arterial smooth muscle cells. We conclude that Kir2.1 encodes for inward rectifier K+ channels in arterial smooth muscle. PMID:10066894

Cocaine cues drive opposing context-dependent shifts in reward processing and emotional state.

PubMed

Wheeler, Robert A; Aragona, Brandon J; Fuhrmann, Katherine A; Jones, Joshua L; Day, Jeremy J; Cacciapaglia, Fabio; Wightman, R Mark; Carelli, Regina M

2011-06-01

Prominent neurobiological theories of addiction posit a central role for aberrant mesolimbic dopamine release but disagree as to whether repeated drug experience blunts or enhances this system. Although drug withdrawal diminishes dopamine release, drug sensitization augments mesolimbic function, and both processes have been linked to drug seeking. One possibility is that the dopamine system can rapidly switch from dampened to enhanced release depending on the specific drug-predictive environment. To test this, we examined dopamine release when cues signaled delayed cocaine delivery versus imminent cocaine self-administration. Fast-scan cyclic voltammetry was used to examine real-time dopamine release while simultaneously monitoring behavioral indexes of aversion as rats experienced a sweet taste cue that predicted delayed cocaine availability and during self-administration. Furthermore, the impact of cues signaling delayed drug availability on intracranial self-stimulation, a broad measure of reward function, was assessed. We observed decreased mesolimbic dopamine concentrations, decreased reward sensitivity, and negative affect in response to the cocaine-predictive taste cue that signaled delayed cocaine availability. Importantly, dopamine concentration rapidly switched to elevated levels to cues signaling imminent cocaine delivery in the subsequent self-administration session. These findings show rapid, bivalent contextual control over brain reward processing, affect, and motivated behavior and have implications for mechanisms mediating substance abuse. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

High voltage pulse generator

DOEpatents

Fasching, George E.

1977-03-08

An improved high-voltage pulse generator has been provided which is especially useful in ultrasonic testing of rock core samples. An N number of capacitors are charged in parallel to V volts and at the proper instance are coupled in series to produce a high-voltage pulse of N times V volts. Rapid switching of the capacitors from the paralleled charging configuration to the series discharging configuration is accomplished by using silicon-controlled rectifiers which are chain self-triggered following the initial triggering of a first one of the rectifiers connected between the first and second of the plurality of charging capacitors. A timing and triggering circuit is provided to properly synchronize triggering pulses to the first SCR at a time when the charging voltage is not being applied to the parallel-connected charging capacitors. Alternate circuits are provided for controlling the application of the charging voltage from a charging circuit to be applied to the parallel capacitors which provides a selection of at least two different intervals in which the charging voltage is turned "off" to allow the SCR's connecting the capacitors in series to turn "off" before recharging begins. The high-voltage pulse-generating circuit including the N capacitors and corresponding SCR's which connect the capacitors in series when triggered "on" further includes diodes and series-connected inductors between the parallel-connected charging capacitors which allow sufficiently fast charging of the capacitors for a high pulse repetition rate and yet allow considerable control of the decay time of the high-voltage pulses from the pulse-generating circuit.

Modeling, Development and Control of Multilevel Converters for Power System Application =

NASA Astrophysics Data System (ADS)

Vahedi, Hani

The main goal of this project is to develop a multilevel converter topology to be useful in power system applications. Although many topologies are introduced rapidly using a bunch of switches and isolated dc sources, having a single-dc-source multilevel inverter is still a matter of controversy. In fact, each isolated dc source means a bulky transformer and a rectifier that have their own losses and costs forcing the industries to avoid entering in this topic conveniently. On the other hand, multilevel inverters topologies with single-dc-source require associated controllers to regulate the dc capacitors voltages in order to have multilevel voltage waveform at the output. Thus, a complex controller would not interest investors properly. Consequently, developing a single-dc-source multilevel inverter topology along with a light and reliable voltage control is still a challenging topic to replace the 2-level inverters in the market effectively. The first effort in this project was devoted to the PUC7 inverter to design a simple and yet efficient controller. A new modelling is performed on the PUC7 inverter and it has been simplified to first order system. Afterwards, a nonlinear cascaded controller is designed and applied to regulate the capacitor voltage at 1/3 of the DC source amplitude and to generate 7 identical voltage levels at the output supplying different type of loads such as RL or rectifier harmonic ones. In next work, the PUC5 topology is proposed as a remedy to the PUC7 that requires a complicated controller to operate properly. The capacitor voltage is regulated at half of dc source amplitude to generate 5 voltage levels at the output. Although the 7-level voltage waveform is replaced by a 5-level one in PUC5 topology, it is shown that the PUC5 needs a very simple and reliable voltage balancing technique due to having some redundant switching states. Moreover, a sensor-less voltage balancing technique is designed and implemented on the PUC5 inverter successfully to work in both stand-alone and gridconnected mode of operation. Eventually, a modified configuration of the PUC5 topology is presented to work as a buck PFC rectifier. The internal performance of the rectifier is like a buck converter to generate stepped down DC voltages at the two output terminals while the grid sees a boost converter externally. As well, a decoupled voltage/current controller is designed and applied to balance the output voltages identically and synchronize the input current with grid voltage to have a PFC operation acceptably. A power balance analysis is done to show the load variation range limit. All the theoretical and simulation studies are validated by experimental results completely.

46 CFR 111.33-11 - Propulsion systems.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Propulsion systems. 111.33-11 Section 111.33-11 Shipping... REQUIREMENTS Power Semiconductor Rectifier Systems § 111.33-11 Propulsion systems. Each power semiconductor rectifier system in a propulsion system must meet sections 4-8-5/5.17.9 and 4-8-5/5.17.10 of ABS Steel...

46 CFR 111.33-11 - Propulsion systems.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 4 2013-10-01 2013-10-01 false Propulsion systems. 111.33-11 Section 111.33-11 Shipping... REQUIREMENTS Power Semiconductor Rectifier Systems § 111.33-11 Propulsion systems. Each power semiconductor rectifier system in a propulsion system must meet sections 4-8-5/5.17.9 and 4-8-5/5.17.10 of ABS Steel...

46 CFR 111.33-11 - Propulsion systems.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 4 2014-10-01 2014-10-01 false Propulsion systems. 111.33-11 Section 111.33-11 Shipping... REQUIREMENTS Power Semiconductor Rectifier Systems § 111.33-11 Propulsion systems. Each power semiconductor rectifier system in a propulsion system must meet sections 4-8-5/5.17.9 and 4-8-5/5.17.10 of ABS Steel...

46 CFR 111.33-11 - Propulsion systems.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 4 2012-10-01 2012-10-01 false Propulsion systems. 111.33-11 Section 111.33-11 Shipping... REQUIREMENTS Power Semiconductor Rectifier Systems § 111.33-11 Propulsion systems. Each power semiconductor rectifier system in a propulsion system must meet sections 4-8-5/5.17.9 and 4-8-5/5.17.10 of ABS Steel...

46 CFR 111.33-11 - Propulsion systems.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 4 2011-10-01 2011-10-01 false Propulsion systems. 111.33-11 Section 111.33-11 Shipping... REQUIREMENTS Power Semiconductor Rectifier Systems § 111.33-11 Propulsion systems. Each power semiconductor rectifier system in a propulsion system must meet sections 4-8-5/5.17.9 and 4-8-5/5.17.10 of ABS Steel...

Perceived Harm of Online Drug-Encouraging Messages: Third-Person Effect and Adolescents' Support for Rectifying Measures

ERIC Educational Resources Information Center

Leung, Wan Chi; Lo, Ven-Hwei

2015-01-01

This study examines third-person perceptions (TPP) of two types of online messages--antisocial messages that encourage drug abuse and prosocial messages in the youth anti-drug campaign--and their relationship with support for three types of rectifying measures: restrictive, corrective, and promotional. A survey of 778 secondary school students…

Operation of AC Adapters Visualized Using Light-Emitting Diodes

ERIC Educational Resources Information Center

Regester, Jeffrey

2016-01-01

A bridge rectifier is a diamond-shaped configuration of diodes that serves to convert alternating current(AC) into direct current (DC). In our world of AC outlets and DC electronics, they are ubiquitous. Of course, most bridge rectifiers are built with regular diodes, not the light-emitting variety, because LEDs have a number of disadvantages. For…

LSI logic for phase-control rectifiers

NASA Technical Reports Server (NTRS)

Dolland, C.

1980-01-01

Signals for controlling phase-controlled rectifier circuit are generated by combinatorial logic than can be implemented in large-scale integration (LSI). LSI circuit saves space, weight, and assembly time compared to previous controls that employ one-shot multivibrators, latches, and capacitors. LSI logic functions by sensing three phases of ac power source and by comparing actual currents with intended currents.

High performance ripple feedback for the buck unity-power-factor rectifier

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

Lo, Y.W.; King, R.J.

1995-03-01

The buck unity-power-factor rectifier has harmonic-free input current with complete load regulation down to zero output voltage. A new ``nonlinear ripple feedback`` is proposed which exactly cancels the spoiling effect of dc-side current ripple on the low-distortion ac line current waveforms, even for large amounts of ripple. This cancellation is independent of operating point and readily implemented with analog hardware, thereby permitting economies in the design of the dc filter while maintaining harmonic-free operation. Both large-signal and incremental analyses of the rectifier are given. Confirming experimental results from a 1-kW 48-V isolated battery charger operating with current-ripple levels ranging frommore » 50% to discontinuous-conduction-mode operation are given.« less

Time-resolved coherent Raman spectroscopy by high-speed pump-probe delay scanning.

PubMed

Domingue, S R; Winters, D G; Bartels, R A

2014-07-15

Using a spinning window pump-probe delay scanner, we demonstrate a means of acquiring time-resolved vibrational spectra at rates up to 700 Hz. The time-dependent phase shift accumulated by the probe pulse in the presence of a coherently vibrating sample gives rise to a Raman-induced frequency shifting readily detectable in a balanced detector. This rapid delay scanning system represents a 23-fold increase in averaging speed and is >10× faster than state-of-the-art voice coil delay lines. These advancements make pump-probe spectroscopy a more practical means of imaging complex media.

Intrinsic membrane hyperexcitability of amyotrophic lateral sclerosis patient-derived motor neurons.

PubMed

Wainger, Brian J; Kiskinis, Evangelos; Mellin, Cassidy; Wiskow, Ole; Han, Steve S W; Sandoe, Jackson; Perez, Numa P; Williams, Luis A; Lee, Seungkyu; Boulting, Gabriella; Berry, James D; Brown, Robert H; Cudkowicz, Merit E; Bean, Bruce P; Eggan, Kevin; Woolf, Clifford J

2014-04-10

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of the motor nervous system. We show using multielectrode array and patch-clamp recordings that hyperexcitability detected by clinical neurophysiological studies of ALS patients is recapitulated in induced pluripotent stem cell-derived motor neurons from ALS patients harboring superoxide dismutase 1 (SOD1), C9orf72, and fused-in-sarcoma mutations. Motor neurons produced from a genetically corrected but otherwise isogenic SOD1(+/+) stem cell line do not display the hyperexcitability phenotype. SOD1(A4V/+) ALS patient-derived motor neurons have reduced delayed-rectifier potassium current amplitudes relative to control-derived motor neurons, a deficit that may underlie their hyperexcitability. The Kv7 channel activator retigabine both blocks the hyperexcitability and improves motor neuron survival in vitro when tested in SOD1 mutant ALS cases. Therefore, electrophysiological characterization of human stem cell-derived neurons can reveal disease-related mechanisms and identify therapeutic candidates. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

The challenges of rescaling South African water resources management: Catchment Management Agencies and interbasin transfers

NASA Astrophysics Data System (ADS)

Bourblanc, Magalie; Blanchon, David

2014-11-01

The implementation of Catchment Management Agencies (CMAs) was supposed to be the cornerstone of the rescaling process of the South African water reform policy. Yet, less than 10 years after the adoption of the National Water Act, the process was suspended for 4 years and by 2012 only two CMAs had been established. Combining approaches in geography and political science, this paper investigates the reasons for the delays in CMAs' implementation in South Africa. It shows that the construction of interbasin transfers (IBTs) since the 1950s by the apartheid regime and nowadays the power struggles between CMAs and the Department of Water Affairs (DWA) are two of the main obstacles to the creation of CMAs planned by the 1998 National Water Act (NWA). Finally, the paper advocates taking the "hydrosocial cycle" as an analytical framework for designing new institutional arrangements that will include both rectifying the legacy of the past (the specific role of DWA) and acknowledging legitimate local interests.

Importance of nutrition in inflammatory bowel disease

PubMed Central

Lucendo, Alfredo José; De Rezende, Livia Cristina

2009-01-01

Inflammatory bowel disease (IBD) results from the interaction between an individual’s immune response and precipitant environmental factors, which generate an anomalous chronic inflammatory response in those who are genetically predisposed. Various feeding practices have been implicated in the origin of IBD based on epidemiological observations in developed countries, but we do not have solid evidence for the etiological role played by specific food types. IBD is associated with frequent nutritional deficiencies, the pattern and severity of which depends on the extent, duration and activity of the inflammation. Nutritional support allows these deficiencies in calories, macro- and micro-nutrients to be rectified. Enteral nutrition is also a primary therapy for IBD, especially for Crohn’s disease, as it allows the inflammatory activity to be controlled, kept in remission, and prevents or delays the need for surgery. Nutritional support is especially important in childhood IBD as an alternative to pharmacological treatment. This report discusses the complex relationship between diet and IBD. PMID:19418580

Osmotic forces and gap junctions in spreading depression: a computational model

NASA Technical Reports Server (NTRS)

Shapiro, B. E.

2001-01-01

In a computational model of spreading depression (SD), ionic movement through a neuronal syncytium of cells connected by gap junctions is described electrodiffusively. Simulations predict that SD will not occur unless cells are allowed to expand in response to osmotic pressure gradients and K+ is allowed to move through gap junctions. SD waves of [K+]out approximately 25 to approximately 60 mM moving at approximately 2 to approximately 18 mm/min are predicted over the range of parametric values reported in gray matter, with extracellular space decreasing up to approximately 50%. Predicted waveform shape is qualitatively similar to laboratory reports. The delayed-rectifier, NMDA, BK, and Na+ currents are predicted to facilitate SD, while SK and A-type K+ currents and glial activity impede SD. These predictions are consonant with recent findings that gap junction poisons block SD and support the theories that cytosolic diffusion via gap junctions and osmotic forces are important mechanisms underlying SD.

Temporal discounting and heart rate reactivity to stress.

PubMed

Diller, James W; Patros, Connor H G; Prentice, Paula R

2011-07-01

Temporal discounting is the reduction of the value of a reinforcer as a function of increasing delay to its presentation. Impulsive individuals discount delayed consequences more rapidly than self-controlled individuals, and impulsivity has been related to substance abuse, gambling, and other problem behaviors. A growing body of literature has identified biological correlates of impulsivity, though little research to date has examined relations between delay discounting and markers of poor health (e.g., cardiovascular reactivity to stress). We evaluated the relation between one aspect of impulsivity, measured using a computerized temporal discounting task, and heart rate reactivity, measured as a change in heart rate from rest during a serial subtraction task. A linear regression showed that individuals who were more reactive to stress responded more impulsively (i.e., discounted delayed reinforcers more rapidly). When results were stratified by gender, the effect was observed for females, but not for males. This finding supports previous research on gender differences in cardiovascular reactivity and suggests that this type of reactivity may be an important correlate of impulsive behavior. Copyright © 2011 Elsevier B.V. All rights reserved.

Brief Report: Impact of Early Antiretroviral Therapy on the Performance of HIV Rapid Tests and HIV Incidence Assays.

PubMed

Fogel, Jessica M; Piwowar-Manning, Estelle; Debevec, Barbara; Walsky, Tamara; Schlusser, Katherine; Laeyendecker, Oliver; Wilson, Ethan A; McCauley, Marybeth; Gamble, Theresa; Tegha, Gerald; Soko, Dean; Kumwenda, Johnstone; Hosseinipour, Mina C; Chen, Ying Q; Cohen, Myron S; Eshleman, Susan H

2017-08-01

Antiretroviral therapy (ART) can downregulate antibody responses to HIV infection. We evaluated the impact of early vs. delayed ART on the performance of HIV diagnostic and incidence assays. Samples were obtained from 207 participants in the HPTN 052 trial, who were stably suppressed on ART for ≥4 years [Malawi sites; pre-ART CD4 cell count 350-550 cells/mm (early ART arm, N = 180) or <250 cells/mm or an AIDS-defining illness (delayed ART arm, N = 27)]. Samples were tested with 2 HIV rapid tests and 2 HIV incidence assays; selected samples were also tested with two fourth-generation immunoassays and a Western blot (WB) assay. A pre-ART sample was analyzed if the follow-up sample had a false-negative or weakly-reactive rapid test result, or had an incidence assay result indicative of recent infection (false-recent result). Ten (4.8%) samples had a nonreactive or weakly-reactive rapid test result (7/180 early ART arm, 3/27 delayed ART arm, P = 0.13); one sample had nonreactive fourth-generation assay results and 3 had indeterminate WBs. Forty (18.9%) samples had a false-recent incidence assay result; 16 (7.8%) had false-recent results with both incidence assays. Baseline samples had stronger rapid test and WB bands, higher fourth-generation assay signal-to-cutoff values, and fewer HIV incidence assay results indicative of recent infection. False-negative/weakly-reactive HIV rapid tests and false-recent HIV incidence assay results were observed in virally-suppressed individuals, regardless of pre-ART CD4 cell count. Downregulation of the antibody response to HIV infection in the setting of ART may impact population-level surveys of HIV prevalence and incidence.

Rapid, generalized adaptation to asynchronous audiovisual speech

PubMed Central

Van der Burg, Erik; Goodbourn, Patrick T.

2015-01-01

The brain is adaptive. The speed of propagation through air, and of low-level sensory processing, differs markedly between auditory and visual stimuli; yet the brain can adapt to compensate for the resulting cross-modal delays. Studies investigating temporal recalibration to audiovisual speech have used prolonged adaptation procedures, suggesting that adaptation is sluggish. Here, we show that adaptation to asynchronous audiovisual speech occurs rapidly. Participants viewed a brief clip of an actor pronouncing a single syllable. The voice was either advanced or delayed relative to the corresponding lip movements, and participants were asked to make a synchrony judgement. Although we did not use an explicit adaptation procedure, we demonstrate rapid recalibration based on a single audiovisual event. We find that the point of subjective simultaneity on each trial is highly contingent upon the modality order of the preceding trial. We find compelling evidence that rapid recalibration generalizes across different stimuli, and different actors. Finally, we demonstrate that rapid recalibration occurs even when auditory and visual events clearly belong to different actors. These results suggest that rapid temporal recalibration to audiovisual speech is primarily mediated by basic temporal factors, rather than higher-order factors such as perceived simultaneity and source identity. PMID:25716790

Transformer-rectifier flux pump using inductive current transfer and thermally controlled Nb(3)Sn cryotrons.

PubMed

Atherton, D L; Davies, R

1979-10-01

Transformer-rectifier flux pumps using thermally switched Nb(3)Sn cryotrons are being investigated as a loss make-up device for the proposed isochorically operated (sealed) superconducting magnets for the Canadian Maglev vehicle. High currents (1000 A) were obtained in an experimental flux pump using inductive current transfer and operating at 2 Hz.

Amorphous silicon Schottky barrier solar cells incorporating a thin insulating layer and a thin doped layer

DOEpatents

Carlson, David E.

1980-01-01

Amorphous silicon Schottky barrier solar cells which incorporate a thin insulating layer and a thin doped layer adjacent to the junction forming metal layer exhibit increased open circuit voltages compared to standard rectifying junction metal devices, i.e., Schottky barrier devices, and rectifying junction metal insulating silicon devices, i.e., MIS devices.

Optical gas monitor

DOEpatents

Wu, Sheng; Deev, Andrei; Palm, Steve L.; Tang, Yongchun; Goddard, William A.

2010-11-30

A frequency modulated spectroscopy system, including a photo-detector, a band-pass filter to filter the output of the photo-detector, and a rectifier to demodulate. The band-pass filter has a relatively high Q factor. With the high Q factor band-pass filter and rectifier, a reference sinusoid is not required for demodulation, resulting in phase-insensitive spectroscopy. Other embodiments are described and claimed.

Influence of cavitation bubble growth by rectified diffusion on cavitation-enhanced HIFU

NASA Astrophysics Data System (ADS)

Okita, Kohei; Sugiyama, Kazuyasu; Takagi, Shu; Matsumoto, Yoichiro

2017-11-01

Cavitation is becoming increasingly important in therapeutic ultrasound applications such as diagnostic, tumor ablation and lithotripsy. Mass transfer through gas-liquid interface due to rectified diffusion is important role in an initial stage of cavitation bubble growth. In the present study, influences of the rectified diffusion on cavitation-enhanced high-intensity focused ultrasound (HIFU) was investigated numerically. Firstly, the mass transfer rate of gas from the surrounding medium to the bubble was examined as function of the initial bubble radius and the driving pressure amplitude. As the result, the pressure required to bubble growth was decreases with increasing the initial bubble radius. Next, the cavitation-enhanced HIFU, which generates cavitation bubbles by high-intensity burst and induces the localized heating owing to cavitation bubble oscillation by low-intensity continuous waves, was reproduced by the present simulation. The heating region obtained by the simulation is agree to the treatment region of an in vitro experiment. Additionally, the simulation result shows that the localized heating is enhanced by the increase of the equilibrium bubble size due to the rectified diffusion. This work was supported by JSPS KAKENHI Grant Numbers JP26420125,JP17K06170.

Three-dimensional crossbar arrays of self-rectifying Si/SiO 2/Si memristors

DOE PAGES

Li, Can; Han, Lili; Jiang, Hao; ...

2017-06-05

Memristors are promising building blocks for the next generation memory, unconventional computing systems and beyond. Currently common materials used to build memristors are not necessarily compatible with the silicon dominant complementary metal-oxide-semiconductor (CMOS) technology. Furthermore, external selector devices or circuits are usually required in order for large memristor arrays to function properly, resulting in increased circuit complexity. Here we demonstrate fully CMOS-compatible, all-silicon based and self-rectifying memristors that negate the need for external selectors in large arrays. It consists of p- and n-type doped single crystalline silicon electrodes and a thin chemically produced silicon oxide switching layer. The device exhibitsmore » repeatable resistance switching behavior with high rectifying ratio (10 5), high ON/OFF conductance ratio (10 4) and attractive retention at 300 °C. We further build a 5-layer 3-dimensional (3D) crossbar array of 100 nm memristors by stacking fluid supported silicon membranes. The CMOS compatibility and self-rectifying behavior open up opportunities for mass production of memristor arrays and 3D hybrid circuits on full-wafer scale silicon and flexible substrates without increasing circuit complexity.« less

Dual-bridge LLC-SRC with extended voltage range for deeply depleted PEV battery charging

NASA Astrophysics Data System (ADS)

Shahzad, M. Imran; Iqbal, Shahid; Taib, Soib

2017-11-01

This paper proposes a dual-bridge LLC series resonant converter with hybrid-rectifier for achieving extended charging voltage range of 50-420 V for on-board battery charger of plug-in electric vehicle for normal and deeply depleted battery charging. Depending upon the configuration of primary switching network and secondary rectifier, the proposed topology has three operating modes as half-bridge with bridge rectifier (HBBR), full-bridge with bridge rectifier (FBBR) and full-bridge with voltage doubler (FBVD). HBBR, FBBR and FBVD operating modes of converter achieve 50-125, 125-250 and 250-420 V voltage ranges, respectively. For voltage above 62 V, the converter operates below resonance frequency zero voltage switching region with narrow switching frequency range for soft commutation of secondary diodes and low turn-off current of MOSFETs to reduce switching losses. The proposed converter is simulated using MATLAB Simulink and a 1.5 kW laboratory prototype is also built to validate the operation of proposed topology. Simulation and experimental results show that the converter meets all the charging requirements for deeply depleted to fully charged battery using constant current-constant voltage charging method with fixed 400 V DC input and achieves 96.22% peak efficiency.

Prognostic value of a CCR5 defective allele in pediatric HIV-1 infection.

PubMed Central

Romiti, M. L.; Colognesi, C.; Cancrini, C.; Mas, A.; Berrino, M.; Salvatori, F.; Orlandi, P.; Jansson, M.; Palomba, E.; Plebani, A.; Bertran, J. M.; Hernandez, M.; de Martino, M.; Amoroso, A.; Tovo, P. A.; Rossi, P.; Espanol, T.; Scarlatti, G.

2000-01-01

BACKGROUND: A deletion of 32 base pairs in the CCR5 gene (delta32 CCR5) has been linked to resistance to HIV-1 infection in exposed adults and to the delay of disease progression in infected adults. MATERIALS AND METHODS: To determine the role of delta32 CCR5 in disease progression of HIV-1 infected children born to seropositive mothers, we studied a polymerase chain reaction in 301 HIV-1 infected, 262 HIV-1 exposed-uninfected and 47 HIV-1 unexposed-uninfected children of Spanish and Italian origin. Infected children were further divided into two groups according to their rate of HIV-1 disease progression: rapid progressors who developed severe clinical and/or immunological conditions within the second year of life, and delayed progressors with any other evolution of disease. Among the latter were the long-term, non-progressors (LTNP) who presented with mild or no symptoms of HIV-1 infection above 8 years of age. Viral phenotype was studied for 45 delayed progressors. RESULTS: No correlation was found between delta32 CCR5 and mother-to-child transmission of HIV-1. However, the frequency of the deletion was substantially higher in LTNP, compared with delayed (p = 0.019) and rapid progressors (p = 0.0003). In children carrying the delta32 CCRS mutation, the presence of MT-2 tropic virus isolate was associated with a severe immune suppression (p = 0.028); whereas, the presence of MT-2 negative viruses correlated with LTNP (p = 0.010). CONCLUSIONS: Given the rapidity and simplicity of the assay, the delta32 CCR5 mutation may be a useful predictive marker to identify children with delayed disease progression who, consequently, may not require immediate antiretroviral treatment. PMID:10803406

Prognostic value of a CCR5 defective allele in pediatric HIV-1 infection.

PubMed

Romiti, M L; Colognesi, C; Cancrini, C; Mas, A; Berrino, M; Salvatori, F; Orlandi, P; Jansson, M; Palomba, E; Plebani, A; Bertran, J M; Hernandez, M; de Martino, M; Amoroso, A; Tovo, P A; Rossi, P; Espanol, T; Scarlatti, G

2000-01-01

A deletion of 32 base pairs in the CCR5 gene (delta32 CCR5) has been linked to resistance to HIV-1 infection in exposed adults and to the delay of disease progression in infected adults. To determine the role of delta32 CCR5 in disease progression of HIV-1 infected children born to seropositive mothers, we studied a polymerase chain reaction in 301 HIV-1 infected, 262 HIV-1 exposed-uninfected and 47 HIV-1 unexposed-uninfected children of Spanish and Italian origin. Infected children were further divided into two groups according to their rate of HIV-1 disease progression: rapid progressors who developed severe clinical and/or immunological conditions within the second year of life, and delayed progressors with any other evolution of disease. Among the latter were the long-term, non-progressors (LTNP) who presented with mild or no symptoms of HIV-1 infection above 8 years of age. Viral phenotype was studied for 45 delayed progressors. No correlation was found between delta32 CCR5 and mother-to-child transmission of HIV-1. However, the frequency of the deletion was substantially higher in LTNP, compared with delayed (p = 0.019) and rapid progressors (p = 0.0003). In children carrying the delta32 CCRS mutation, the presence of MT-2 tropic virus isolate was associated with a severe immune suppression (p = 0.028); whereas, the presence of MT-2 negative viruses correlated with LTNP (p = 0.010). Given the rapidity and simplicity of the assay, the delta32 CCR5 mutation may be a useful predictive marker to identify children with delayed disease progression who, consequently, may not require immediate antiretroviral treatment.

Relating gastric scintigraphy and symptoms to motility capsule transit and pressure findings in suspected gastroparesis

PubMed Central

Hasler, W. L.; May, K. P.; Wilson, L. A.; Van Natta, M.; Parkman, H. P.; Pasricha, P. J.; Koch, K. L.; Abell, T. L.; McCallum, R. W.; Nguyen, L. A.; Snape, W. J.; Sarosiek, I.; Clarke, J. O.; Farrugia, G.; Calles-Escandon, J.; Grover, M.; Tonascia, J.; Lee, L. A.; Miriel, L.; Hamilton, F. A.

2018-01-01

Background Wireless motility capsule (WMC) findings are incompletely defined in suspected gastroparesis. We aimed to characterize regional WMC transit and contractility in relation to scintigraphy, etiology, and symptoms in patients undergoing gastric emptying testing. Methods A total of 209 patients with gastroparesis symptoms at NIDDK Gastroparesis Consortium centers underwent gastric scintigraphy and WMCs on separate days to measure regional transit and contractility. Validated questionnaires quantified symptoms. Key Results Solid scintigraphy and liquid scintigraphy were delayed in 68.8% and 34.8% of patients; WMC gastric emptying times (GET) were delayed in 40.3% and showed 52.8% agreement with scintigraphy; 15.5% and 33.5% had delayed small bowel (SBTT) and colon transit (CTT) times. Transit was delayed in ≥2 regions in 23.3%. Rapid transit was rarely observed. Diabetics had slower GET but more rapid SBTT versus idiopathics (P ≤ .02). GET delays related to greater scintigraphic retention, slower SBTT, and fewer gastric contractions (P ≤ .04). Overall gastroparesis symptoms and nausea/vomiting, early satiety/fullness, bloating/distention, and upper abdominal pain subscores showed no relation to WMC transit. Upper and lower abdominal pain scores (P ≤ .03) were greater with increased colon contractions. Constipation correlated with slower CTT and higher colon contractions (P = .03). Diarrhea scores were higher with delayed SBTT and CTT (P ≤ .04). Conclusions & Inferences Wireless motility capsules define gastric emptying delays similar but not identical to scintigraphy that are more severe in diabetics and relate to reduced gastric contractility. Extragastric transit delays occur in >40% with suspected gastroparesis. Gastroparesis symptoms show little association with WMC profiles, although lower symptoms relate to small bowel or colon abnormalities. PMID:28872760

The interaction evolution model of mass incidents with delay in a social network

NASA Astrophysics Data System (ADS)

Huo, Liang'an; Ma, Chenyang

2017-10-01

Recent years have witnessed rapid development of information technology. Today, modern media is widely used for the purpose of spreading information rapidly and widely. In particular, through micro-blog promotions, individuals tend to express their viewpoints and spread information on the internet, which could easily lead to public opinions. Moreover, government authorities also disseminate official information to guide public opinion and eliminate any incorrect conjecture. In this paper, a dynamical model with two delays is investigated to exhibit the interaction evolution between the public and official opinion fields in network mass incidents. Based on the theory of differential equations, the interaction mechanism between two public opinion fields in a micro-blog environment is analyzed. Two delays are proposed in the model to depict the response delays of public and official opinion fields. Some stable conditions are obtained, which shows that Hopf bifurcation can occur as delays cross critical values. Further, some numerical simulations are carried out to verify theoretical results. Our model indicates that there exists a golden time for government intervention, which should be emphasized given the impact of modern media and inaccurate rumors. If the government releases official information during the golden time, mass incidents on the internet can be controlled effectively.

Photoresponse in La0.9Hf0.1MnO3/0.05wt%Nb-doped SrTiO3 heteroepitaxial junctions

NASA Astrophysics Data System (ADS)

Qi, Yaping; Ni, Hao; Zheng, Ming; Zeng, Jiali; Jiang, Yucheng; Gao, Ju

2018-05-01

Excellent photo detectors need to have the rapid response and good repeatability from the requirement of industrial applications. In this paper, transport behavior and opto-response of heterostructures made with La0.9Hf0.1MnO3 and 0.05wt%Nb-doped SrTiO3 were investigated. The heterojunctions exhibited an excellent rectifying feature with very low leakage in a broad temperature region (from 40 to 300 K). These thin films presented persistent and stable photovoltages upon light illumination. Rapid shift between small and large voltages corresponding to "light OFF" and "light ON" states, respectively, was observed, demonstrating reliable photo detection behavior. A semiconductor laser with a wavelength of 650 nm was used as the light source. It is also noted that the observed photovoltages are strongly determined by light intensity. The injection of photoexcited charge carriers (electrons) could be responsible for the appearance of the observed opto-response. Such manipulative features by light irradiation exhibit great potential for light detectors for visible light.

Maternal Health Situation in India: A Case Study

PubMed Central

Mavalankar, Dileep V.; Ramani, K.V.; Upadhyaya, Mudita; Sharma, Bharati; Iyengar, Sharad; Gupta, Vikram; Iyengar, Kirti

2009-01-01

Since the beginning of the Safe Motherhood Initiative, India has accounted for at least a quarter of maternal deaths reported globally. India's goal is to lower maternal mortality to less than 100 per 100,000 livebirths but that is still far away despite its programmatic efforts and rapid economic progress over the past two decades. Geographical vastness and sociocultural diversity mean that maternal mortality varies across the states, and uniform implementation of health-sector reforms is not possible. The case study analyzes the trends in maternal mortality nationally, the maternal healthcare-delivery system at different levels, and the implementation of national maternal health programmes, including recent innovative strategies. It identifies the causes for limited success in improving maternal health and suggests measures to rectify them. It recommends better reporting of maternal deaths and implementation of evidence-based, focused strategies along with effective monitoring for rapid progress. It also stresses the need for regulation of the private sector and encourages further public-private partnerships and policies, along with a strong political will and improved management capacity for improving maternal health. PMID:19489415

The acoustic sensor for rapid analysis of bacterial cells in the conductive suspensions.

PubMed

Borodina, I A; Zaitsev, B D; Guliy, O; Teplykh, A A; Shikhabudinov, A M

2017-11-01

The possibility of using the acoustic sensor on the basis of a two-channel delay line for rapid analysis of bacterial cells in the conductive suspensions was investigated. The dependencies of change in phase and insertion loss of output signal of the sensor on conductivity of buffer solution with various concentrations of cells due to a specific interaction "bacterial cells - mini-antibodies" for electrically open and electrically shorted channels of delay line were measured. It has been found that these changes have the most values for the electrically open channel. It has been also shown that the sensor rapidly responds to the specific interaction and the time stabilization of the phase and insertion loss of output signal is less than 10min. Copyright © 2017 Elsevier B.V. All rights reserved.

p -n Junction Rectifying Characteristics of Purely n -Type GaN-Based Structures

NASA Astrophysics Data System (ADS)

Zuo, P.; Jiang, Y.; Ma, Z. G.; Wang, L.; Zhao, B.; Li, Y. F.; Yue, G.; Wu, H. Y.; Yan, H. J.; Jia, H. Q.; Wang, W. X.; Zhou, J. M.; Sun, Q.; Liu, W. M.; Ji, An-Chun; Chen, H.

2017-08-01

The GaN-based p -n junction rectifications are important in the development of high-power electronics. Here, we demonstrate that p -n junction rectifying characteristics can be realized with pure n -type structures by inserting an (In,Ga)N quantum well into the GaN /(Al ,Ga )N /GaN double heterostructures. Unlike the usual barriers, the insertion of an (In,Ga)N quantum well, which has an opposite polarization field to that of the (Al,Ga)N barrier, tailors significantly the energy bands of the system. The lifted energy level of the GaN spacer and the formation of the (In ,Ga )N /GaN interface barrier can improve the reverse threshold voltage and reduce the forward threshold voltage simultaneously, forming the p -n junction rectifying characteristics.

G-protein-coupled inwardly rectifying potassium channels are targets of alcohol action.

PubMed

Lewohl, J M; Wilson, W R; Mayfield, R D; Brozowski, S J; Morrisett, R A; Harris, R A

1999-12-01

G-protein-coupled inwardly rectifying potassium channels (GIRKs) are important for regulation of synaptic transmission and neuronal firing rates. Because of their key role in brain function, we asked if these potassium channels are targets of alcohol action. Ethanol enhanced function of cerebellar granule cell GIRKs coupled to GABAB receptors. Enhancement of GIRK function by ethanol was studied in detail using Xenopus oocytes expressing homomeric or heteromeric channels. Function of all GIRK channels was enhanced by intoxicating concentrations of ethanol, but other, related inwardly rectifying potassium channels were not affected. GIRK2/IRK1 chimeras and GIRK2 truncation mutants were used to identify a region of 43 amino acids in the carboxyl (C) terminus that is critical for the action of ethanol on these channels.

Power converter

NASA Technical Reports Server (NTRS)

Black, J. M. (Inventor)

1981-01-01

A dc-to-dc converter employs four transistor switches in a bridge to chop dc power from a source, and a voltage multiplying diode rectifying ladder network to rectify and filter the chopped dc power for delivery to a load. The bridge switches are cross coupled in order for diagonally opposite pairs to turn on and off together using RC networks for the cross coupling to achieve the mode of operation of a free running multivibrator, and the diode rectifying ladder is configured to operate in a push-pull mode driven from opposite sides of the multivibrator outputs of the ridge switches. The four transistor switches provide a square-wave output voltage which as a peak-to-peak amplitude that is twice the input dc voltage, and is thus useful as a dc-to-ac inverter.

ISGV Self-rectifying Turbine Design For Thermoacoustic Application

NASA Astrophysics Data System (ADS)

Sammak, Shervin; Asghary, Maryam; Ghorbanian, Kaveh

2014-11-01

Thermoacoustic engines produce the acoustic power from wasted heat and then electricity can be generated from acoustic power. Utilizing self-rectifying turbine after a thermoacoustic engine allows for deploying standard generators with high enough rotational speed that remarkably reduce abrasion, size and cost and significantly increase efficiency and controllability in comparison with linear alternators. In this paper, by evaluating all different type of self-rectifying turbine, impulse turbine with self-piched controlled (ISGV) is chosen as the most appropriate type for this application. This kind of turbine is designed in detail for a popular engine, thermoacoustic stirling heat engine (TASHE). In order to validate the design, a full scale size of designed turbine is modeled in ANSYS CFX. As a result, optimum power and efficiency gained based on numerical data.

Rectification induced in N2AA-doped armchair graphene nanoribbon device

NASA Astrophysics Data System (ADS)

Chen, Tong; Li, Xiao-Fei; Wang, Ling-Ling; Luo, Kai-Wu; Xu, Liang

2014-07-01

By using non-equilibrium Green function formalism in combination with density functional theory, we investigated the electronic transport properties of armchair graphene nanoribbon devices in which one lead is undoped and the other is N2AA-doped with two quasi-adjacent substitutional nitrogen atoms incorporating pairs of neighboring carbon atoms in the same sublattice A. Two kinds of N2AA-doped style are considered, for N dopants substitute the center or the edge carbon atoms. Our results show that the rectification behavior with a large rectifying ratio can be found in these devices and the rectifying characteristics can be modulated by changing the width of graphene nanoribbons or the position of the N2AA dopant. The mechanisms are revealed to explain the rectifying behaviors.

Design, fabrication, and characterization of 4H-silicon carbide rectifiers for power switching applications

NASA Astrophysics Data System (ADS)

Sheridan, David Charles

Silicon Carbide has received a substantial increase in research interest over the past few years as a base material system for high-frequency and high-power semiconductor devices. Of the over 1200 polytypes, 4H-SiC is the most attractive polytype for power devices due to its wide band gap (3.2eV), excellent thermal conductivity (4.9 W/cm·K), and high critical field strength (˜2 x 106 V/cm). Important for power devices, the 10x increase in critical field strength of SiC allows high voltage blocking layers to be fabricated significantly thinner than for comparable Si devices. For power rectifiers, this reduces device on-resistance, while maintaining the same high voltage blocking capability. In this work, 4H-SiC Schottky, pn, and junction barrier Schottky (JBS) rectifiers for use in high voltage switching applications have been designed, fabricated, and extensively characterized. First, a detailed review of 4H-SiC material parameters was performed and SiC models were implemented into a standard Si drift-diffusion numerical simulator. Using these models, a SiC simulation methodology was developed in order to enable predictive SiC device design. A wide variety of rectifier and edge termination designs were investigated and optimized with respect to breakdown efficiency, area consumption, resistance to interface charge, and fabrication practicality. Simulated termination methods include: field plates, floating guard rings, and a variety of junction termination extensions (JTE). Using the device simulation results, both Schottky and JBS rectifiers were fabricated with a novel self-aligned edge termination design, and fabricated with process elements developed at the Alabama Microelectronics Science and Technology Center facility. These rectifiers exhibited near-ideal forward characteristics and had blocking voltages in excess of 2.5kV. The SiC diodes were subjected to inductive switching tests, and were found to have superior reverse recovery characteristics compared to a similar Si diode. Finally, the performance of these SiC rectifiers were tested in inductive switching circuits and in high dose gamma radiation environments. In both cases, these devices were shown to be superior to their silicon counterparts. The details of this work was presented and published in the proceedings of the 45th International Meeting of the American Vacuum Society [1], the 1999 International Conference on Silicon Carbide and Related Materials [2, 3] and the 2000 European Conference on Silicon Carbide and Related Materials [4]. The expanded conference papers were published in the international journal. Solid-State Electronics [5, 6].

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

PubMed Central

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

2001-01-01

The aim of the study was to compare the properties of cloned Kir2 channels with the properties of native rectifier channels in guinea-pig (gp) cardiac muscle. The cDNAs of gpKir2.1, gpKir2.2, gpKir2.3 and gpKir2.4 were obtained by screening a cDNA library from guinea-pig cardiac ventricle. A partial genomic structure of all gpKir2 genes was deduced by comparison of the cDNAs with the nucleotide sequences derived from a guinea-pig genomic library. The cell-specific expression of Kir2 channel subunits was studied in isolated cardiomyocytes using a multi-cell RT-PCR approach. It was found that gpKir2.1, gpKir2.2 and gpKir2.3, but not gpKir2.4, are expressed in cardiomyocytes. Immunocytochemical analysis with polyclonal antibodies showed that expression of Kir2.4 is restricted to neuronal cells in the heart. After transfection in human embryonic kidney cells (HEK293) the mean single-channel conductance with symmetrical K+ was found to be 30.6 pS for gpKir2.1, 40.0 pS for gpKir2.2 and 14.2 pS for Kir2.3. Cell-attached measurements in isolated guinea-pig cardiomyocytes (n = 351) revealed three populations of inwardly rectifying K+ channels with mean conductances of 34.0, 23.8 and 10.7 pS. Expression of the gpKir2 subunits in Xenopus oocytes showed inwardly rectifying currents. The Ba2+ concentrations required for half-maximum block at -100 mV were 3.24 μm for gpKir2.1, 0.51 μm for gpKir2.2, 10.26 μm for gpKir2.3 and 235 μm for gpKir2.4. Ba2+ block of inward rectifier channels of cardiomyocytes was studied in cell-attached recordings. The concentration and voltage dependence of Ba2+ block of the large-conductance inward rectifier channels was virtually identical to that of gpKir2.2 expressed in Xenopus oocytes. Our results suggest that the large-conductance inward rectifier channels found in guinea-pig cardiomyocytes (34.0 pS) correspond to gpKir2.2. The intermediate-conductance (23.8 pS) and low-conductance (10.7 pS) channels described here may correspond to gpKir2.1 and gpKir2.3, respectively. PMID:11283229

Exchange protein directly activated by cAMP mediates slow delayed-rectifier current remodeling by sustained β-adrenergic activation in guinea pig hearts.

PubMed

Aflaki, Mona; Qi, Xiao-Yan; Xiao, Ling; Ordog, Balazs; Tadevosyan, Artavazd; Luo, Xiaobin; Maguy, Ange; Shi, Yanfen; Tardif, Jean-Claude; Nattel, Stanley

2014-03-14

β-Adrenoceptor activation contributes to sudden death risk in heart failure. Chronic β-adrenergic stimulation, as occurs in patients with heart failure, causes potentially arrhythmogenic reductions in slow delayed-rectifier K(+) current (IKs). To assess the molecular mechanisms of IKs downregulation caused by chronic β-adrenergic activation, particularly the role of exchange protein directly activated by cAMP (Epac). Isolated guinea pig left ventricular cardiomyocytes were incubated in primary culture and exposed to isoproterenol (1 μmol/L) or vehicle for 30 hours. Sustained isoproterenol exposure decreased IKs density (whole cell patch clamp) by 58% (P<0.0001), with corresponding decreases in potassium voltage-gated channel subfamily E member 1 (KCNE1) mRNA and membrane protein expression (by 45% and 51%, respectively). Potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) mRNA expression was unchanged. The β1-adrenoceptor antagonist 1-[2-((3-Carbamoyl-4-hydroxy)phenoxy)ethylamino]-3-[4-(1-methyl-4-trifluoromethyl-2-imidazolyl)phenoxy]-2-propanol dihydrochloride (CGP-20712A) prevented isoproterenol-induced IKs downregulation, whereas the β2-antagonist ICI-118551 had no effect. The selective Epac activator 8-pCPT-2'-O-Me-cAMP decreased IKs density to an extent similar to isoproterenol exposure, and adenoviral-mediated knockdown of Epac1 prevented isoproterenol-induced IKs/KCNE1 downregulation. In contrast, protein kinase A inhibition with a cell-permeable highly selective peptide blocker did not affect IKs downregulation. 1,2-Bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetate-AM acetoxymethyl ester (BAPTA-AM), cyclosporine, and inhibitor of nuclear factor of activated T cell (NFAT)-calcineurin association-6 (INCA6) prevented IKs reduction by isoproterenol and INCA6 suppressed isoproterenol-induced KCNE1 downregulation, consistent with signal-transduction via the Ca(2+)/calcineurin/NFAT pathway. Isoproterenol induced nuclear NFATc3/c4 translocation (immunofluorescence), which was suppressed by Epac1 knockdown. Chronic in vivo administration of isoproterenol to guinea pigs reduced IKs density and KCNE1 mRNA and protein expression while inducing cardiac dysfunction and action potential prolongation. Selective in vivo activation of Epac via sp-8-pCPT-2'-O-Me-cAMP infusion decreased IKs density and KCNE1 mRNA/protein expression. Prolonged β1-adrenoceptor stimulation suppresses IKs by downregulating KCNE1 mRNA and protein via Epac-mediated Ca(2+)/calcineurin/NFAT signaling. These results provide new insights into the molecular basis of K(+) channel remodeling under sustained adrenergic stimulation.

Phrenic Arterial Injury Presenting as Delayed Hemothorax Complicating Simple Rib Fracture.

PubMed

Ahn, Hong Joon; Lee, Jun Wan; Kim, Kun Dong; You, In Sool

2016-04-01

Delayed hemothorax after blunt torso injury is rare, but might be associated with significant morbidity and mortality. We present a case of delayed hemothorax bleeding from phrenic artery injury in a 24-year-old woman. The patient suffered from multiple rib fractures on the right side, a right hemopneumothorax, thoracic vertebral injury and a pelvic bone fracture after a fall from a fourth floor window. Delayed hemothorax associated with phrenic artery bleeding, caused by a stab injury from a fractured rib segment, was treated successfully by a minimally invasive thoracoscopic surgery. Here, we have shown that fracture of a lower rib or ribs might be accompanied by delayed massive hemothorax that can be rapidly identified and promptly managed by thoracoscopic means.

Phrenic Arterial Injury Presenting as Delayed Hemothorax Complicating Simple Rib Fracture

PubMed Central

2016-01-01

Delayed hemothorax after blunt torso injury is rare, but might be associated with significant morbidity and mortality. We present a case of delayed hemothorax bleeding from phrenic artery injury in a 24-year-old woman. The patient suffered from multiple rib fractures on the right side, a right hemopneumothorax, thoracic vertebral injury and a pelvic bone fracture after a fall from a fourth floor window. Delayed hemothorax associated with phrenic artery bleeding, caused by a stab injury from a fractured rib segment, was treated successfully by a minimally invasive thoracoscopic surgery. Here, we have shown that fracture of a lower rib or ribs might be accompanied by delayed massive hemothorax that can be rapidly identified and promptly managed by thoracoscopic means. PMID:27051252

Aging affects neural precision of speech encoding

PubMed Central

Anderson, Samira; Parbery-Clark, Alexandra; White-Schwoch, Travis; Kraus, Nina

2012-01-01

Older adults frequently report they can hear what is said but cannot understand the meaning, especially in noise. This difficulty may arise from the inability to process rapidly changing elements of speech. Aging is accompanied by a general slowing of neural processing and decreased neural inhibition, both of which likely interfere with temporal processing in auditory and other sensory domains. Age-related reductions in inhibitory neurotransmitter levels and delayed neural recovery can contribute to decreases in the auditory system’s temporal precision. Decreased precision may lead to neural timing delays, reductions in neural response magnitude, and a disadvantage in processing the rapid acoustic changes in speech. The auditory brainstem response (ABR), a scalp-recorded electrical potential, is known for its ability to capture precise neural synchrony within subcortical auditory nuclei; therefore, we hypothesized that a loss of temporal precision results in subcortical timing delays and decreases in response consistency and magnitude. To assess this hypothesis, we recorded ABRs to the speech syllable /da/ in normal hearing younger (ages 18 to 30) and older adult humans (60 to 67). Older adults had delayed ABRs, especially in response to the rapidly changing formant transition, and greater response variability. We also found that older adults had decreased phase locking and smaller response magnitudes than younger adults. Taken together, our results support the theory that older adults have a loss of temporal precision in subcortical encoding of sound, which may account, at least in part, for their difficulties with speech perception. PMID:23055485

Costs Climb on Materials for Schools: Construction Projects Delayed, Scrapped

ERIC Educational Resources Information Center

Sack, Joetta L.

2004-01-01

The rapidly rising cost of steel and other construction materials is forcing some districts that are building new schools to scramble for more money, delay work, or redesign projects. Nationwide, contractors and architects are finding it harder to give accurate estimates on projects, and some have even had to renegotiate contracts with districts.…

State and Federal project development procedures for bus rapid transit : managing differences and reducing implementation delays

DOT National Transportation Integrated Search

2011-08-01

This report documents an investigation into the transportation project development process in the : context of the implementation of bus rapid transit systems on the State Highway System as well as such : systems being part of the Federal New Starts ...

Creating Digital Environments for Multi-Agent Simulation

DTIC Science & Technology

2003-12-01

foliage on a polygon to represent a tree). Tile A spatial partition of a coverage that shares the same set of feature classes with the same... orthophoto datasets can be made from rectified grayscale aerial images. These datasets can support various weapon systems, Command, Control...Raster Product Format (RPF) Standard. This data consists of unclassified seamless orthophotos , made from rectified grayscale aerial images. DOI 10

37. VIEW OF SIX GAP ROTARY RECTIFIER FOR MAINTAINING CORONA ...

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

37. VIEW OF SIX GAP ROTARY RECTIFIER FOR MAINTAINING CORONA DISCHARGE IN THE COTTRELL ELECTROSTATIC GENERATORS. THE SYSTEM WAS CAPABLE OF PROVIDING 88,000 VOLTS TO THE ELECTRODES WITHIN THE PRECIPITATOR CHAMBER THE UNIT WAS LOCATED TO THE REAR OF BOILER 904 IN AN ENCLOSED ROOM. - New York, New Haven & Hartford Railroad, Cos Cob Power Plant, Sound Shore Drive, Greenwich, Fairfield County, CT

Laser Line Scan System for UXO Characterization

DTIC Science & Technology

2012-04-01

they geometrically rectified. The Year 2 survey collected LLSS images from seven passes over two separate calibration strings and six passes over two...Microsoft DOS-based software tool. According to the side- by-side comparisons shown in Figure 9, the morphometrics were relatively equal between...survey. Note: The imagery in this figure is not presented at full resolution nor geometrically rectified. LLSS Targets, Pass One 1. Danforth

Current management of penetrating torso trauma: nontherapeutic is not good enough anymore.

PubMed

Ball, Chad G

2014-04-01

A highly organized approach to the evaluation and treatment of penetrating torso injuries based on regional anatomy provides rapid diagnostic and therapeutic consistency. It also minimizes delays in diagnosis, missed injuries and nontherapeutic laparotomies. This review discusses an optimal sequence of structured rapid assessments that allow the clinician to rapidly proceed to gold standard therapies with a minimal risk of associated morbidity.

Inactivation of A currents and A channels on rat nodose neurons in culture

PubMed Central

1989-01-01

Cultured sensory neurons from nodose ganglia were investigated with whole-cell patch-clamp techniques and single-channel recordings to characterize the A current. Membrane depolarization from -40 mV holding potential activated the delayed rectifier current (IK) at potentials positive to -30 mV; this current had a sigmoidal time course and showed little or no inactivation. In most neurons, the A current was completely inactivated at the -40 mV holding potential and required hyperpolarization to remove the inactivation; the A current was isolated by subtracting the IK evoked by depolarizations from -40 mV from the total outward current evoked by depolarizations from -90 mV. The decay of the A current on several neurons had complex kinetics and was fit by the sum of three exponentials whose time constants were 10- 40 ms, 100-350 ms, and 1-3 s. At the single-channel level we found that one class of channel underlies the A current. The conductance of A channels varied with the square root of the external K concentration: it was 22 pS when exposed to 5.4 mM K externally, the increased to 40 pS when exposed to 140 mM K externally. A channels activated rapidly upon depolarization and the latency to first opening decreased with depolarization. The open time distributions followed a single exponential and the mean open time increased with depolarization. A channels inactivate in three different modes: some A channels inactivated with little reopening and gave rise to ensemble averages that decayed in 10-40 ms; other A channels opened and closed three to four times before inactivating and gave rise to ensemble averages that decayed in 100-350 ms; still other A channels opened and closed several hundred times and required seconds to inactivate. Channels gating in all three modes contributed to the macroscopic A current from the whole cell, but their relative contribution differed among neurons. In addition, A channels could go directly from the closed, or resting, state to the inactivated state without opening, and the probability for channels inactivating in this way was greater at less depolarized voltages. In addition, a few A channels appeared to go reversibly from a mode where inactivation occurred rapidly to a slow mode of inactivation. PMID:2592953

Local systematic differences in 2MASS positions

NASA Astrophysics Data System (ADS)

Bustos Fierro, I. H.; Calderón, J. H.

2018-01-01

We have found that positions in the 2MASS All-sky Catalog of Point Sources show local systematic differences with characteristic length-scales of ˜ 5 to ˜ 8 arcminutes when compared with several catalogs. We have observed that when 2MASS positions are used in the computation of proper motions, the mentioned systematic differences cause systematic errors in the resulting proper motions. We have developed a method to locally rectify 2MASS with respect to UCAC4 in order to diminish the systematic differences between these catalogs. The rectified 2MASS catalog with the proposed method can be regarded as an extension of UCAC4 for astrometry with accuracy ˜ 90 mas in its positions, with negligible systematic errors. Also we show that the use of these rectified positions removes the observed systematic pattern in proper motions derived from original 2MASS positions.

Rectification induced in N{sub 2}{sup AA}-doped armchair graphene nanoribbon device

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

Chen, Tong; Wang, Ling-Ling, E-mail: llwang@hnu.edu.cn; Luo, Kai-Wu

2014-07-07

By using non-equilibrium Green function formalism in combination with density functional theory, we investigated the electronic transport properties of armchair graphene nanoribbon devices in which one lead is undoped and the other is N{sub 2}{sup AA}-doped with two quasi-adjacent substitutional nitrogen atoms incorporating pairs of neighboring carbon atoms in the same sublattice A. Two kinds of N{sub 2}{sup AA}-doped style are considered, for N dopants substitute the center or the edge carbon atoms. Our results show that the rectification behavior with a large rectifying ratio can be found in these devices and the rectifying characteristics can be modulated by changingmore » the width of graphene nanoribbons or the position of the N{sub 2}{sup AA} dopant. The mechanisms are revealed to explain the rectifying behaviors.« less

Real-time multi-DSP control of three-phase current-source unity power factor PWM rectifier

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

Xiao Wang; Boon-Teck Ooi

1993-07-01

The design of a real-time multi-DSP controller for a high-quality six-valve three-phase current-source unity power factor PWM rectifier is discussed in this paper. With the decoupler preprocessor and the dynamic trilogic PWM trigger scheme, each of the three input currents can be controlled independently. Based on the a-b-c frame system model and the fast parallel computer control, the pole-placement control method is implemented successfully to achieve fast response in the ac currents. The low-frequency resonance in the ac filter L-C networks has been damped effectively. The experimental results are obtained from a 1-kVA bipolar transistor current-source PWM rectifier with amore » real-time controller using three TMS320C25 DSP's.« less

Apparatus and methods of measuring minority carrier lifetime using a liquid probe

DOEpatents

Li, Jian

2016-04-12

Methods and apparatus for measuring minority carrier lifetimes using liquid probes are provided. In one embodiment, a method of measuring the minority carrier lifetime of a semiconductor material comprises: providing a semiconductor material having a surface; forming a rectifying junction at a first location on the surface by temporarily contacting the surface with a conductive liquid probe; electrically coupling a second junction to the semiconductor material at a second location, wherein the first location and the second location are physically separated; applying a forward bias to the rectifying junction causing minority carrier injection in the semiconductor material; measuring a total capacitance as a function of frequency between the rectifying junction and the second junction; determining an inflection frequency of the total capacitance; and determining a minority lifetime of the semiconductor material from the inflection frequency.

Delays in Reducing Waterborne and Water-related Infectious Diseases in China under Climate Change

DOE PAGES

Hodges, Maggie; Belle, Jessica; Carlton, Elizabeth; ...

2014-11-02

Despite China’s rapid progress improving water, sanitation and hygiene (WSH) infrastructure and access, in 2011, 471 million people lacked access to improved sanitation, and 401 million people lacked access to household piped water. Infectious diseases are sensitive to changes in climate, particularly temperature, and WSH conditions. To explore possible impacts of climate change on these diseases in China in 2020 and 2030, we coupled estimates of the temperature sensitivity of diarrheal disease and three vector-borne diseases, temperature projections from global climate models using four emissions pathways, WSH-infrastructure development scenarios and projected demographic changes. By 2030, the projected impacts would delaymore » China’s historically rapid progress toward reducing the burden of WSH-attributable infectious disease by 8-85 months. This developmental delay provides a key summary measure of the impact of climate change in China, and in other societies undergoing rapid social, economic, and environmental change.« less

Delays in Reducing Waterborne and Water-related Infectious Diseases in China under Climate Change

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

Hodges, Maggie; Belle, Jessica; Carlton, Elizabeth

Despite China’s rapid progress improving water, sanitation and hygiene (WSH) infrastructure and access, in 2011, 471 million people lacked access to improved sanitation, and 401 million people lacked access to household piped water. Infectious diseases are sensitive to changes in climate, particularly temperature, and WSH conditions. To explore possible impacts of climate change on these diseases in China in 2020 and 2030, we coupled estimates of the temperature sensitivity of diarrheal disease and three vector-borne diseases, temperature projections from global climate models using four emissions pathways, WSH-infrastructure development scenarios and projected demographic changes. By 2030, the projected impacts would delaymore » China’s historically rapid progress toward reducing the burden of WSH-attributable infectious disease by 8-85 months. This developmental delay provides a key summary measure of the impact of climate change in China, and in other societies undergoing rapid social, economic, and environmental change.« less

SS Bootis - A totally eclipsing binary of the RS CVn type

NASA Technical Reports Server (NTRS)

Vaucher, C. A.; Africano, J. L.; Henry, G. W.; Hall, D. S.; Wilson, J. W.

1983-01-01

Photoelectric photometry gathered for SS Bootis over the 1976-1981 period shows a distortion wave amplitude variation from 0.05 to 0.20 mag, with no apparent pattern. From the rectified light curve, a new time of midprimary eclipse was found to be 2444332.0335 + or - 0.0005 days. Solutions of the primary eclipse data, rectified for star spots as well as for ellipticity and reflection, are presented.

Interleaved power converter

DOEpatents

Zhu, Lizhi

2007-11-13

A power converter architecture interleaves full bridge converters to alleviate thermal management problems in high current applications, and may, for example, double the output power capability while reducing parts count and costs. For example, one phase of a three phase inverter is shared between two transformers, which provide power to a rectifier such as a current doubler rectifier to provide two full bridge DC/DC converters with three rather than four high voltage inverter legs.

Teaching graphical simulations of Fourier series expansion of some periodic waves using spreadsheets

NASA Astrophysics Data System (ADS)

Singh, Iqbal; Kaur, Bikramjeet

2018-05-01

The present article demonstrates a way of programming using an Excel spreadsheet to teach Fourier series expansion in school/colleges without the knowledge of any typical programming language. By using this, a student learns to approximate partial sum of the n terms of Fourier series for some periodic signals such as square wave, saw tooth wave, half wave rectifier and full wave rectifier signals.

Children's understanding of equity in the context of inequality.

PubMed

Rizzo, Michael T; Killen, Melanie

2016-11-01

In the context of a pre-existing resource inequality, the concerns for strict equality (allocating the same number of resources to all recipients) conflict with the concerns for equity (allocating resources to rectify the inequality). This study demonstrated age-related changes in children's (3-8 years old, N = 133) ability to simultaneously weigh the concerns for equality and equity through the analysis of children's judgements, allocations, and reasoning in the context of a pre-existing inequality. Three- to 4-year-olds took equity into account in their judgements of allocations, but allocated resources equally in a behavioural task. In contrast, 5- to 6-year-olds rectified the inequality in their allocations, but judged both equitable and equal allocations to be fair. It was not until 7-8 years old that children focused on rectifying the inequality in their allocations and judgements, as well as judged equal allocations less positively than equitable allocations, thereby demonstrating a more complete understanding of the necessity of rectifying inequalities. The novel findings revealed age-related changes from 3 to 8 years old regarding how the concerns for equity and equality develop, and how children's judgements, allocations, and reasoning are coordinated when making allocation decisions. © 2016 The British Psychological Society.

Rectified motion in an asymmetrically structured channel due to induced-charge electrokinetic and thermo-kinetic phenomena

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

Sugioka, Hideyuki, E-mail: hsugioka@shinshu-u.ac.jp

2016-02-15

It would be advantageous to move fluid by the gradient of random thermal noises that are omnipresent in the natural world. To achieve this motion, we propose a rectifier that uses a thermal noise along with induced-charge electroosmosis and electrophoresis (ICEO and ICEP) around a metal post cylinder in an asymmetrically structured channel and numerically examine its rectification performance. By the boundary element method combined with the thin double layer approximation, we find that rectified motion occurs in the asymmetrically structured channel due to ICEO and ICEP. Further, by thermodynamical and equivalent circuit methods, we discuss a thermal voltage thatmore » drives a rectifier consisting of a fluidic channel of an electrolyte and an impedance as a noise source. Our calculations show that fluid can be moved in the asymmetrically structured channel by the fluctuation of electric fields due to a thermal noise only when there is a temperature difference. In addition, our simple noise argument provides a different perspective for the thermo-kinetic phenomena (around a metal post) which was predicted based on the electrolyte Seebeck effect in our previous paper [H. Sugioka, “Nonlinear thermokinetic phenomena due to the Seebeck effect,” Langmuir 30, 8621 (2014)].« less

Operational test report -- Project W-320 cathodic protection systems

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

Bowman, T.J.

1998-06-16

Washington Administrative Code (WAC) 173-303-640 specifies that corrosion protection must be designed into tank systems that treat or store dangerous wastes. Project W-320, Waste Retrieval Sluicing System (WRSS), utilizes underground encased waste transfer piping between tanks 241-C-106 and 241-AY-102. Corrosion protection is afforded to the encasements of the WRSS waste transfer piping through the application of earthen ionic currents onto the surface of the piping encasements. Cathodic protection is used in conjunction with the protective coatings that are applied upon the WRSS encasement piping. WRSS installed two new two rectifier systems (46 and 47) and modified one rectifier system (31).more » WAC 173-303-640 specifies that the proper operation of cathodic protection systems must be confirmed within six months after initial installation. The WRSS cathodic protection systems were energized to begin continuous operation on 5/5/98. Sixteen days after the initial steady-state start-up of the WRSS rectifier systems, the operational testing was accomplished with procedure OTP-320-006 Rev/Mod A-0. This operational test report documents the OTP-320-006 results and documents the results of configuration testing of integrated piping and rectifier systems associated with the W-320 cathodic protection systems.« less

Multi-service highly sensitive rectifier for enhanced RF energy scavenging.

PubMed

Shariati, Negin; Rowe, Wayne S T; Scott, James R; Ghorbani, Kamran

2015-05-07

Due to the growing implications of energy costs and carbon footprints, the need to adopt inexpensive, green energy harvesting strategies are of paramount importance for the long-term conservation of the environment and the global economy. To address this, the feasibility of harvesting low power density ambient RF energy simultaneously from multiple sources is examined. A high efficiency multi-resonant rectifier is proposed, which operates at two frequency bands (478-496 and 852-869 MHz) and exhibits favorable impedance matching over a broad input power range (-40 to -10 dBm). Simulation and experimental results of input reflection coefficient and rectified output power are in excellent agreement, demonstrating the usefulness of this innovative low-power rectification technique. Measurement results indicate an effective efficiency of 54.3%, and an output DC voltage of 772.8 mV is achieved for a multi-tone input power of -10 dBm. Furthermore, the measured output DC power from harvesting RF energy from multiple services concurrently exhibits a 3.14 and 7.24 fold increase over single frequency rectification at 490 and 860 MHz respectively. Therefore, the proposed multi-service highly sensitive rectifier is a promising technique for providing a sustainable energy source for low power applications in urban environments.

Ga2O3 Schottky rectifiers with 1 ampere forward current, 650 V reverse breakdown and 26.5 MW.cm-2 figure-of-merit

NASA Astrophysics Data System (ADS)

Yang, Jiancheng; Ren, F.; Tadjer, Marko; Pearton, S. J.; Kuramata, A.

2018-05-01

A key goal for Ga2O3 rectifiers is to achieve high forward currents and high reverse breakdown voltages. Field-plated β-Ga2O3 Schottky rectifiers with area 0.01 cm2, fabricated on 10 μm thick, lightly-doped drift regions (1.33 x 1016 cm-3) on heavily-doped (3.6 x 1018 cm-3) substrates, exhibited forward current density of 100A.cm-2 at 2.1 V, with absolute current of 1 A at this voltage and a reverse breakdown voltage (VB) of 650V. The on-resistance (RON) was 1.58 x 10-2 Ω.cm2, producing a figure of merit (VB2/RON) of 26.5 MW.cm-2. The Schottky barrier height of the Ni was 1.04 eV, with an ideality factor of 1.02. The on/off ratio was in the range 3.3 x 106 - 5.7 x 109 for reverse biases between 5 and 100V. The reverse recovery time was ˜30 ns for switching from +2V to -5V. The results show the capability of β-Ga2O3 rectifiers to achieve exceptional performance in both forward and reverse bias conditions.

Fabrication and characterization of magnetically tunable metal-semiconductor schottky diode using barium hexaferrite thin film on gold

NASA Astrophysics Data System (ADS)

Kaur, Jotinder; Sharma, Vinay; Sharma, Vipul; Veerakumar, V.; Kuanr, Bijoy K.

2016-05-01

Barium Hexaferrite (BaM) is an extensively studied magnetic material due to its potential device application. In this paper, we study Schottky junction diodes fabricated using gold and BaM and demonstrate the function of a spintronic device. Gold (50 nm)/silicon substrate was used to grow the BaM thin films (100-150 nm) using pulsed laser deposition. I-V characteristics were measured on the Au/BaM structure sweeping the voltage from ±5 volts. The forward and reverse bias current-voltage curves show diode like rectifying characteristics. The threshold voltage decreases while the output current increases with increase in the applied external magnetic field showing that the I-V characteristics of the BaM based Schottky junction diodes can be tuned by external magnetic field. It is also demonstrated that, the fabricated Schottky diode can be used as a half-wave rectifier, which could operate at high frequencies in the range of 1 MHz compared to the regular p-n junction diodes, which rectify below 10 kHz. In addition, it is found that above 1 MHz, Au/BaM diode can work as a rectifier as well as a capacitor filter, making the average (dc) voltage much larger.

UV/ozone assisted local graphene (p)/ZnO(n) heterojunctions as a nanodiode rectifier

NASA Astrophysics Data System (ADS)

Sahatiya, Parikshit; Badhulika, Sushmee

2016-07-01

Here we report the fabrication of a novel graphene/ZnO nanodiode by UV/ozone assisted oxidation of graphene and demonstrate its application as a half-wave rectifier to generate DC voltage. The method involves the use of electrospinning for one-step in situ synthesis and alignment of single Gr/ZnO nanocomposite across metal electrodes. On subsequent UV illumination, graphene oxidizes, which induces p type doping and ZnO being an n type semiconductor, thus resulting in the formation of a nanodiode. The as-fabricated device shows strong non-linear current-voltage characteristic similar to that of conventional semiconductor p-n junction diodes. Excellent rectifying behavior with a rectification ratio of ~103 was observed and the nanodiodes were found to exhibit long-term repeatability in their performance. Ideality factor and barrier height, as calculated by the thermionic emission model, were found to be 1.6 and 0.504 eV respectively. Due to the fact that diodes are the basic building blocks in the electronics and semiconductor industry, the successful fabrication of these nanodiodes based on UV assisted p type doping of graphene indicates that this approach can be used for developing highly scalable and efficient components for nanoelectronics, such as rectifiers and logic gates that find applications in numerous fields.

Multi-Service Highly Sensitive Rectifier for Enhanced RF Energy Scavenging

PubMed Central

Shariati, Negin; Rowe, Wayne S. T.; Scott, James R.; Ghorbani, Kamran

2015-01-01

Due to the growing implications of energy costs and carbon footprints, the need to adopt inexpensive, green energy harvesting strategies are of paramount importance for the long-term conservation of the environment and the global economy. To address this, the feasibility of harvesting low power density ambient RF energy simultaneously from multiple sources is examined. A high efficiency multi-resonant rectifier is proposed, which operates at two frequency bands (478–496 and 852–869 MHz) and exhibits favorable impedance matching over a broad input power range (−40 to −10 dBm). Simulation and experimental results of input reflection coefficient and rectified output power are in excellent agreement, demonstrating the usefulness of this innovative low-power rectification technique. Measurement results indicate an effective efficiency of 54.3%, and an output DC voltage of 772.8 mV is achieved for a multi-tone input power of −10 dBm. Furthermore, the measured output DC power from harvesting RF energy from multiple services concurrently exhibits a 3.14 and 7.24 fold increase over single frequency rectification at 490 and 860 MHz respectively. Therefore, the proposed multi-service highly sensitive rectifier is a promising technique for providing a sustainable energy source for low power applications in urban environments. PMID:25951137

Current management of penetrating torso trauma: nontherapeutic is not good enough anymore

PubMed Central

Ball, Chad G.

2014-01-01

A highly organized approach to the evaluation and treatment of penetrating torso injuries based on regional anatomy provides rapid diagnostic and therapeutic consistency. It also minimizes delays in diagnosis, missed injuries and nontherapeutic laparotomies. This review discusses an optimal sequence of structured rapid assessments that allow the clinician to rapidly proceed to gold standard therapies with a minimal risk of associated morbidity. PMID:24666458

Rapid Acquisition of Preference in Concurrent Chains: Effects of "d"-Amphetamine on Sensitivity to Reinforcement Delay

ERIC Educational Resources Information Center

Ta, Wei-Min; Pitts, Raymond C.; Hughes, Christine E.; McLean, Anthony P.; Grace, Randolph C.

2008-01-01

The purpose of this study was to examine effects of "d"-amphetamine on choice controlled by reinforcement delay. Eight pigeons responded under a concurrent-chains procedure in which one terminal-link schedule was always fixed- interval 8 s, and the other terminal-link schedule changed from session to session between fixed-interval 4 s and…

Delay Assessment Framework for Automated Question-Answering System: An Approach for eLearning Paradigm

ERIC Educational Resources Information Center

Iqbal, Muhammad Munwar; Saleem, Yasir

2017-01-01

Adoption of Electronic Learning (eLearning) for the dissemination of higher education is rapidly increasing day by day. A large number of universities offering hundreds of course and a large number of the students are taking advantage from this type of learning paradigm. The purpose of this study is to investigate the delay factor in answering the…

Temporal Lobe Epilepsy and the Selective Reminding Test: The Conventional 30-Minute Delay Suffices

ERIC Educational Resources Information Center

Bell, Brian D.; Fine, Jason; Dow, Christian; Seidenberg, Michael; Hermann, Bruce P.

2005-01-01

Conventional memory assessment may fail to identify memory dysfunction characterized by intact recall for a relatively brief period but rapid forgetting thereafter. This study assessed learning and retention after 30-min and 24-hr delays on auditory and visual selective reminding tests (SRTs) in right (n=20) and left (n=22) temporal lobe epilepsy…

Rapid, generalized adaptation to asynchronous audiovisual speech.

PubMed

Van der Burg, Erik; Goodbourn, Patrick T

2015-04-07

The brain is adaptive. The speed of propagation through air, and of low-level sensory processing, differs markedly between auditory and visual stimuli; yet the brain can adapt to compensate for the resulting cross-modal delays. Studies investigating temporal recalibration to audiovisual speech have used prolonged adaptation procedures, suggesting that adaptation is sluggish. Here, we show that adaptation to asynchronous audiovisual speech occurs rapidly. Participants viewed a brief clip of an actor pronouncing a single syllable. The voice was either advanced or delayed relative to the corresponding lip movements, and participants were asked to make a synchrony judgement. Although we did not use an explicit adaptation procedure, we demonstrate rapid recalibration based on a single audiovisual event. We find that the point of subjective simultaneity on each trial is highly contingent upon the modality order of the preceding trial. We find compelling evidence that rapid recalibration generalizes across different stimuli, and different actors. Finally, we demonstrate that rapid recalibration occurs even when auditory and visual events clearly belong to different actors. These results suggest that rapid temporal recalibration to audiovisual speech is primarily mediated by basic temporal factors, rather than higher-order factors such as perceived simultaneity and source identity. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Molecular characterization of genes encoding inward rectifier potassium (Kir) channels in the bed bug (Cimex lectularius).

PubMed

Mamidala, Praveen; Mittapelly, Priyanka; Jones, Susan C; Piermarini, Peter M; Mittapalli, Omprakash

2013-04-01

The molecular genetics of inward-rectifier potassium (Kir) channels in insects is poorly understood. To date, Kir channel genes have been characterized only from a few representative dipterans (i.e., fruit flies and mosquitoes). The goal of the present study was to characterize Kir channel cDNAs in a hemipteran, the bed bug (Cimex lectularius). Using our previously reported bed bug transcriptome (RNA-seq), we identified two cDNAs that encode putative Kir channels. One was a full-length cDNA that encodes a protein belonging to the insect 'Kir3' clade, which we designate as 'ClKir3'. The other was a partial cDNA that encodes a protein with similarity to both the insect 'Kir1' and 'Kir2' clades, which we designate as 'ClKir1/2'. Quantitative real-time PCR analysis revealed that ClKir1/2 and ClKir3 exhibited peak expression levels in late-instar nymphs and early-instar nymphs, respectively. Furthermore, ClKir3, but not ClKir1/2, showed tissue-specific expression in Malpighian tubules of adult bed bugs. Lastly, using an improved procedure for delivering double-stranded RNA (dsRNA) to male and female bed bugs (via the cervical membrane) we demonstrate rapid and systemic knockdown of ClKir3 transcripts. In conclusion, we demonstrate that the bed bug possesses at least two genes encoding Kir channels, and that RNAi is possible for at least Kir3, thereby offering a potential approach for elucidating the roles of Kir channel genes in bed bug physiology. Copyright © 2013 Elsevier Inc. All rights reserved.

On fundamental quality of fission chain reaction to oppose rapid runaways of nuclear reactors

NASA Astrophysics Data System (ADS)

Kulikov, G. G.; Shmelev, A. N.; Apse, V. A.; Kulikov, E. G.

2017-01-01

It has been shown that the in-hour equation characterizes the barriers and resistibility of fission chain reaction (FCR) against rapid runaways in nuclear reactors. Traditionally, nuclear reactors are characterized by the presence of barriers based on delayed and prompt neutrons. A new barrier based on the reflector neutrons that can occur when the fast reactor core is surrounded by a weakly absorbing neutron reflector with heavy atomic weight was proposed. It has been shown that the safety of this fast reactor is substantially improved, and considerable elongation of prompt neutron lifetime "devalues" the role of delayed neutron fraction as the maximum permissible reactivity for the reactor safety.

Heroin delay discounting: Modulation by pharmacological state, drug-use impulsivity, and intelligence.

PubMed

Stoltman, Jonathan J K; Woodcock, Eric A; Lister, Jamey J; Lundahl, Leslie H; Greenwald, Mark K

2015-12-01

Delay discounting (DD) refers to how rapidly an individual devalues goods based on delays to receipt. DD usually is considered a trait variable but can be state dependent, yet few studies have assessed commodity valuation at short, naturalistically relevant time intervals that might enable state-dependent analysis. This study aimed to determine whether drug-use impulsivity and intelligence influence heroin DD at short (ecologically relevant) delays during two pharmacological states (heroin satiation and withdrawal). Out-of-treatment, intensive heroin users (n = 170; 53.5% African American; 66.7% male) provided complete DD data during imagined heroin satiation and withdrawal. Delays were 3, 6, 12, 24, 48, 72, and 96 hours; maximum delayed heroin amount was thirty $10 bags. Indifference points were used to calculate area under the curve (AUC). We also assessed drug-use impulsivity (subscales from the Impulsive Relapse Questionnaire [IRQ]) and estimated intelligence (Shipley IQ) as predictors of DD. Heroin discounting was greater (smaller AUC) during withdrawal than satiation. In regression analyses, lower intelligence and IRQ Capacity for Delay as well as higher IRQ Speed (to return to drug use) predicted greater heroin discounting in the satiation condition. Lower intelligence and higher IRQ Speed predicted greater discounting in the withdrawal condition. Sex, race, substance use variables, and other IRQ subscales were not significantly related to the withdrawal or satiation DD behavior. In summary, heroin discounting was temporally rapid, pharmacologically state dependent, and predicted by drug-use impulsivity and estimated intelligence. These findings highlight a novel and sensitive measure of acute DD that is easy to administer. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

M-currents and other potassium currents in bullfrog sympathetic neurones

PubMed Central

Adams, P. R.; Brown, D. A.; Constanti, A.

1982-01-01

1. Bullfrog lumbar sympathetic neurones were voltage-clamped in vitro through twin micro-electrodes. Four different outward (K+) currents could be identified: (i) a large sustained voltage-sensitive delayed rectifier current (IK) activated at membrane potentials more positive than -25 mV; (ii) a calcium-dependent sustained outward current (IC) activated at similar positive potentials and peaking at +20 to +60 mV; (iii) a transient current (IA) activated at membrane potentials more positive than -60 mV after a hyperpolarizing pre-pulse, but which was rapidly and totally inactivated at all potentials within its activation range; and (iv) a new K+ current, the M-current (IM). 2. IM was detected as a non-inactivating current with a threshold at -60 mV. The underlying conductance GM showed a sigmoidal activation curve between -60 and -10 mV, with half-activation at -35 mV and a maximal value (ḠM) of 84±14 (S.E.M.) nS per neurone. The voltage sensitivity of GM could be expressed in terms of a simple Boltzmann distribution for a single multivalent gating particle. 3. IM activated and de-activated along an exponential time course with a time constant uniquely dependent upon voltage, maximizing at ≃ 150 ms at -35 mV at 22 °C. 4. Instantaneous current—voltage (I/V) curves were approximately linear in the presence of IM, suggesting that the M-channels do not show appreciable rectification. However, the time- and voltage-dependent opening of the M-channels induced considerable rectification in the steady-state I/V curves recorded under both voltage-clamp and current-clamp modes between -60 and -25 mV. Both time- and voltage-dependent rectification in the voltage responses to current injection over this range could be predicted from the kinetic properties of IM. 5. It is suggested that IM exerts a strong potential-clamping effect on the behaviour of these neurones at membrane potentials subthreshold to excitation. PMID:6294290