Dissection of K+ currents in Caenorhabditis elegans muscle cells by genetics and RNA interference

PubMed Central

Santi, C. M.; Yuan, A.; Fawcett, G.; Wang, Z.-W.; Butler, A.; Nonet, M. L.; Wei, A.; Rojas, P.; Salkoff, L.

2003-01-01

GFP-promoter experiments have previously shown that at least nine genes encoding potassium channel subunits are expressed in Caenorhabditis elegans muscle. By using genetic, RNA interference, and physiological techniques we revealed the molecular identity of the major components of the outward K+ currents in body wall muscle cells in culture. We found that under physiological conditions, outward current is dominated by the products of only two genes, Shaker (Kv1) and Shal (Kv4), both expressing voltage-dependent potassium channels. Other channels may be held in reserve to respond to particular circumstances. Because GFP-promoter experiments indicated that slo-2 expression is prominent, we created a deletion mutant to identify the SLO-2 current in vivo. In both whole-cell and single-channel modes, in vivo SLO-2 channels were active only when intracellular Ca2+ and Cl- were raised above normal physiological conditions, as occurs during hypoxia. Under such conditions, SLO-2 is the largest outward current, contributing up to 87% of the total current. Other channels are present in muscle, but our results suggest that they are unlikely to contribute a large outward component under physiological conditions. However, they, too, may contribute currents conditional on other factors. Hence, the picture that emerges is of a complex membrane with a small number of household conductances functioning under normal circumstances, but with additional conductances that are activated during unusual circumstances. PMID:14612577

Low-affinity spermine block mediating outward currents through Kir2.1 and Kir2.2 inward rectifier potassium channels

PubMed Central

Ishihara, Keiko; Yan, Ding-Hong

2007-01-01

The outward component of the strong inward rectifier K+ current (IKir) plays a pivotal role in polarizing the membranes of excitable and non-excitable cells and is regulated by voltage-dependent channel block by internal cations. Using the Kir2.1 channel, we previously showed that a small fraction of the conductance susceptible only to a low-affinity mode of block likely carries a large portion of the outward current. To further examine the relevance of the low-affinity block to outward IKir and to explore its molecular mechanism, we studied the block of the Kir2.1 and Kir2.2 channels by spermine, which is the principal Kir2 channel blocker. Current–voltage relations of outward Kir2.2 currents showed a peak, a plateau and two peaks in the presence of 10, 1 and 0.1 μm spermine, respectively, which was explained by the presence of two conductances that differ in their susceptibility to spermine block. When the current–voltage relations showed one peak, like those of native IKir, outward Kir2.2 currents were mediated mostly by the conductance susceptible to the low-affinity block. They also flowed in a narrower range than the corresponding Kir2.1 currents, because of 3- to 4-fold greater susceptibility to the low-affinity block than in Kir2.1. Reducing external [K+] shifted the voltage dependences of both the high- and low-affinity block of Kir2.1 in parallel with the shift in the reversal potential, confirming the importance of the low-affinity block in mediating outward IKir. When Kir2.1 mutants known to have reduced sensitivity to internal blockers were examined, the D172N mutation in the transmembrane pore region made almost all of the conductance susceptible only to low-affinity block, while the E224G mutation in the cytoplasmic pore region reduced the sensitivity to low-affinity block without markedly altering that to the high-affinity block or the high/low conductance ratio. The effects of these mutations support the hypothesis that Kir2 channels exist in two states having different susceptibilities to internal cationic blockers. PMID:17640933

Altered transient outward current in human atrial myocytes of patients with reduced left ventricular function.

PubMed

Schreieck, J; Wang, Y; Overbeck, M; Schömig, A; Schmitt, C

2000-02-01

Electrophysiologic remodeling is involved in the self-perpetuation of atrial fibrillation. To define whether differences in atrial electrophysiology already are present in patients with increased susceptibility for atrial fibrillation, we compared patients in sinus rhythm with and without heart failure. Atrial specimens were obtained from patients with reduced left ventricular ejection fraction (LVEF; n = 10) and normal LVEF (n = 16) who were undergoing aortocoronary bypass surgery and from donor hearts (n = 4). Enzymatically isolated atrial myocytes were investigated by whole cell, patch clamp techniques. Total outward current was significantly larger in myocytes of hearts with low LVEF than normal LVEF (19.4 +/- 1.3 vs 15.1 +/- 1.2 pA/pF at pulses to +60 mV, respectively). Analysis of inactivation time courses of different outward current components revealed that the observed current difference is due to the transient calcium-independent outward current I(to1) which is twice as large in the low LVEF group than in the normal LVEF group (9.4 +/- 0.9 vs 4.7 +/- 0.4 pA/pF at pulses to +60 mV, respectively). I(to1) recovery from inactivation was significantly more rapid in myocytes of hearts with low LVEF, and action potential plateau in these cells was significantly shorter. The results of I(to1) and action potential measurements in atrial myocytes of donor hearts were very similar to the results of patients with preserved heart function. I(to1) in human atrial myocytes of patients with reduced LVEF has an increased density and altered kinetics in sinus rhythm. These differences in outward current may explain the reduced plateau phase of action potentials.

Physiological basis of a steady endogenous current in rat lumbrical muscle

PubMed Central

1984-01-01

In an attempt to determine the mechanism by which rat skeletal muscle endplates generate a steady outward current, we measured the effects of several drugs (furosemide, bumetanide, 9-anthracene carboxylic acid [9- AC]) and changes in external ion concentration (Na+, K+, Cl-, Ba++) on resting membrane potential (Vm) and on the steady outward current. Each of the following treatments caused a 10-15-mV hyperpolarization of the membrane: replacement of extracellular Cl- with isethionate, addition of furosemide or bumetanide, and addition of 9-AC. These results suggest that Cl- is actively accumulated by the muscle fibers and that the equilibrium potential of Cl- is more positive than the membrane potential. Removal of external Na+ also caused a large hyperpolarization and is consistent with evidence in other tissues that active Cl- accumulation requires external Na+. The same treatments greatly reduced or abolished the steady outward current, with a time course that paralleled the changes in Vm. These results cannot be explained by a model in which the steady outward current is assumed to arise as a result of a nonuniform distribution of Na+ conductance, but they are consistent with models in which the steady current is produced by a nonuniform distribution of GCl or GK. Other treatments (Na+-free and K+-free solutions, and 50 microM BaCl2) caused a temporary reversal of the steady current. Parallel measurements of Vm suggested that in none of these cases did the electrochemical driving force for K+ change sign, which makes it unlikely that the steady current arises as a result of a nonuniform distribution of GK. All of the results, however, are consistent with a model in which the steady outward current arises as a result of a nonuniform distribution of Cl- conductance, with GCl lower near the endplate than in extrajunctional regions. PMID:6325581

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.

Properties of the late transient outward current in isolated intestinal smooth muscle cells of the guinea-pig.

PubMed

Zholos, A V; Baidan, L V; Shuba, M F

1991-11-01

1. Whole-cell membrane currents in voltage-clamped single isolated cells of longitudinal smooth muscle of guinea-pig ileum were studied at room temperature using patch pipettes filled with either high-K+ solution or high-Cs+ solution, to suppress K+ outward current, and containing 0.3 mM-EGTA. 2. In the presence of high-K+ solution in the pipette, membrane depolarization from the holding potential of -50 mV evoked an initial inward calcium current (ICa) followed by a large initial transient outward current and a sustained outward current with spontaneous oscillations superimposed. Prolonged depolarization above -20 mV produced a late transient outward current which reached a maximum (up to several nanoamps at +10 mV) within approximately 1 s and lasted several seconds. 3. The late outward current (ILTO) was voltage dependent and reversed at the EK (potassium equilibrium potential) in cells exposed to high-K+ external solution. It was blocked by TEA+ (tetraethylammonium) or Ba2+ applied externally (calculated Kd (dissociation constant) values were 0.67 and 4.43 mM, respectively) or by high-Cs+ solution perfusing the cell. The removal of extracellular Ca2+, application of Ca2+ channel blockers (3 mM-Co2+, 0.2 mM-Cd2+ or 1 microM-nifedipine) or perfusion of 5 mM-EGTA inside the cell also abolished the current. Thus, the current seems to be a Ca(2+)-activated K+ current. 4. There is a great discrepancy between the time course of the ICa and that of the late ILTO, which suggests that Ca2+ release from intracellular storage sites may contribute to the generation of the ILTO. 5. Bath application of caffeine (10 mM) during the development of ILTO enhanced the current. However, in the presence of caffeine ILTO was inhibited. Moderate inhibition of ICa by caffeine was also observed. 6. Ryanodine (5 microM) applied to the bathing solution completely inhibited ILTO within 3.5 min; however, it had no or little effect on the ICa. 7. Ruthenium Red (10 microM) completely blocked the ILTO and slightly and more slowly inhibited the ICa. 8. Increasing Mg2+ concentration in the pipette solution from 1 to 6 mM abolished the ILTO. 9. It was concluded that the ILTO was activated mainly by Ca2+ released from the intracellular storage sites following Ca2+ entry, presumably by a Ca(2+)-induced Ca2+ release mechanism.

Membrane currents underlying activity in frog sinus venosus

PubMed Central

Brown, Hilary F.; Giles, Wayne; Noble, Susan J.

1977-01-01

1. The spontaneous electrical activity of small strips of muscle from the sinus venosus region of the heart of Rana catesbeiana was investigated using the double sucrose gap technique. The voltage clamp was used to record the ionic currents underlying the pace-maker depolarization and the action potential. 2. The records of spontaneous electrical activity are very similar to those obtained from the sinus venosus using micro-electrodes. Moreover, the pace-maker activity is almost completely insensitive to tetrodotoxin (TTX) at 2·0 × 10-6 g/ml., which suggests that the pace-maker responses can be classified as primary, as opposed to follower pacing. 3. In response to short rectangular depolarizing voltage clamp pulses, only one inward current is activated. This current is almost completely insensitive to TTX but can be blocked by manganese ions. It appears, therefore, to be equivalent to the slow inward (Ca2+/Na+) current, Isi, of other cardiac tissues. The threshold for Isi is near to the maximum diastolic potential, indicating that it must be activated during the pace-maker depolarization. 4. Interruption of the normal pace-maker depolarization by rapid activation of the voltage clamp circuit reveals the time-dependent decay of outward current. This current reverses between -75 and -90 mV and, therefore, is probably carried mainly by potassium ions. 5. Outward current decay is not a simple exponential, and Hodgkin—Huxley analysis suggests that two distinct components of outward current may be present. One of these is activated in the potential range of the pace-maker depolarization and the other at more positive potentials. Both outward currents reach full, steady-state activation at about zero mV, i.e. within the `plateau' range of the sinus action potential. 6. These results are compared with other recently published voltage clamp data from the rabbit sino—atrial node. 7. A hypothesis for the generation of pace-maker activity is presented which involves (i) decay of outward current and (ii) activation of the slow inward current, Isi. PMID:303699

Novel KCNQ2 channel activators discovered using fluorescence-based and automated patch-clamp-based high-throughput screening techniques

PubMed Central

Yue, Jin-feng; Qiao, Guan-hua; Liu, Ni; Nan, Fa-jun; Gao, Zhao-bing

2016-01-01

Aim: To establish an improved, high-throughput screening techniques for identifying novel KCNQ2 channel activators. Methods: KCNQ2 channels were stably expressed in CHO cells (KCNQ2 cells). Thallium flux assay was used for primary screening, and 384-well automated patch-clamp IonWorks Barracuda was used for hit validation. Two validated activators were characterized using a conventional patch-clamp recording technique. Results: From a collection of 80 000 compounds, the primary screening revealed a total of 565 compounds that potentiated the fluorescence signals in thallium flux assay by more than 150%. When the 565 hits were examined in IonWorks Barracuda, 38 compounds significantly enhanced the outward currents recorded in KCNQ2 cells, and were confirmed as KCNQ2 activators. In the conventional patch-clamp recordings, two validated activators ZG1732 and ZG2083 enhanced KCNQ2 currents with EC50 values of 1.04±0.18 μmol/L and 1.37±0.06 μmol/L, respectively. Conclusion: The combination of thallium flux assay and IonWorks Barracuda assay is an efficient high-throughput screening (HTS) route for discovering KCNQ2 activators. PMID:26725738

Attenuation of hypoxic current by intracellular applications of ATP regenerating agents in hippocampal CA1 neurons of rat brain slices.

PubMed

Chung, I; Zhang, Y; Eubanks, J H; Zhang, L

1998-10-01

Hypoxia-induced outward currents (hyperpolarization) were examined in hippocampal CA1 neurons of rat brain slices, using the whole-cell recording technique. Hypoxic episodes were induced by perfusing slices with an artificial cerebrospinal fluid aerated with 5% CO2/95% N2 rather than 5% CO2/95% O2, for about 3 min. The hypoxic current was consistently and reproducibly induced in CA1 neurons dialysed with an ATP-free patch pipette solution. This current manifested as an outward shift in the holding current in association with increased conductance, and it reversed at -78 +/- 2.5 mV, with a linear I-V relation in the range of -100 to -40 mV. To provide extra energy resources to individual neurons recorded, agents were added to the patch pipette solution, including MgATP alone, MgATP + phosphocreatine + creatine kinase, or MgATP + creatine. In CA1 neurons dialysed with patch solutions including these agents, hypoxia produced small outward currents in comparison with those observed in CA1 neurons dialysed with the ATP-free solution. Among the above agents examined, whole-cell dialysis with MgATP + creatine was the most effective at decreasing the hypoxic outward currents. We suggest that the hypoxic hyperpolarization is closely related to energy metabolism in individual CA1 neurons, and that the energy supply provided by phosphocreatine metabolism may play a critical role during transient metabolic stress.

Potassium channels cloned from neuroblastoma cells display slowly inactivating outward currents in Xenopus oocytes.

PubMed

Ito, Y; Yokoyama, S; Higashida, H

1992-05-22

Messenger RNAs (mRNAs) specific for NGK1 and NGK2 potassium channels were synthesized from complementary DNAs (cDNAs) that had been cloned from mouse neuroblastoma x rat glioma hybrid NG108-15 cells. Outward pottasium currents were evoked by 5 s depolarizing voltage commands in Xenopus oocytes injected with NGK1- or NGK2-specific mRNAs. The NGK1 or NGK2 currents showed different activation and inactivation kinetics, and different pharmacological sensitivities. The threshold potential for activation of the NGK2 current (-14 mV) was more positive than that for the NGK1 (-36 mV). The NGK2 current showed faster inactivation during a 5 s depolarizing pulse than did the NGK1 current. Inactivation was best fit by time constants of 0.37, 1.5 and 19 s for the NGK2 current and 4.4 and 19 s for NGK1. Extracellularly applied tetraethylammonium chloride (TEA) was 1000 times more potent on the NGK2 current than the NGK1 current. Furthermore we examined outward current following co-injection of an equal amount of mRNAs for NGK1 and NGK2. The timecourse of inactivation differed from either alone or from a simple sum of the two individual currents. TEA sensitivity could not be explained by summation of the two homomultimeric channels. These findings suggest that both NGK1 and NGK2 proteins assemble to form heteromultimeric K+ channels in addition to homomultimeric K+ channels. NGK2 channels and the heteromultimeric channels may be responsible for the native transient outward current with slow inactivation in NG108-15 hybrid cells.

Two modes of polyamine block regulating the cardiac inward rectifier K+ current IK1 as revealed by a study of the Kir2.1 channel expressed in a human cell line.

PubMed

Ishihara, Keiko; Ehara, Tsuguhisa

2004-04-01

The strong inward rectifier K(+) current, I(K1), shows significant outward current amplitude in the voltage range near the reversal potential and thereby causes rapid repolarization at the final phase of cardiac action potentials. However, the mechanism that generates the outward I(K1) is not well understood. We recorded currents from the inside-out patches of HEK 293T cells that express the strong inward rectifier K(+) channel Kir2.1 and studied the blockage of the currents caused by cytoplasmic polyamines, namely, spermine and spermidine. The outward current-voltage (I-V) relationships of Kir2.1, obtained with 5-10 microm spermine or 10-100 microm spermidine, were similar to the steady-state outward I-V relationship of I(K1), showing a peak at a level that is approximately 20 mV more positive than the reversal potential, with a negative slope at more positive voltages. The relationships exhibited a plateau or a double-hump shape with 1 microm spermine/spermidine or 0.1 microm spermine, respectively. In the chord conductance-voltage relationships, there were extra conductances in the positive voltage range, which could not be described by the Boltzmann relations fitting the major part of the relationships. The extra conductances, which generated most of the outward currents in the presence of 5-10 microm spermine or 10-100 microm spermidine, were quantitatively explained by a model that considered two populations of Kir2.1 channels, which were blocked by polyamines in either a high-affinity mode (Mode 1 channel) or a low-affinity mode (Mode 2 channel). Analysis of the inward tail currents following test pulses indicated that the relief from the spermine block of Kir2.1 consisted of an exponential component and a virtually instantaneous component. The fractions of the two components nearly agreed with the fractions of the blockages in Mode 1 and Mode 2 calculated by the model. The estimated proportion of Mode 1 channels to total channels was 0.9 with 0.1-10 microm spermine, 0.75 with 1-100 microm spermidine, and between 0.75 and 0.9 when spermine and spermidine coexisted. An interaction of spermine/spermidine with the channel at an intracellular site appeared to modify the equilibrium of the two conformational channel states that allow different modes of blockage. Our results suggest that the outward I(K1) is primarily generated by channels with lower affinities for polyamines. Polyamines may regulate the amplitude of the outward I(K1), not only by blocking the channels but also by modifying the proportion of channels that show different sensitivities to the polyamine block.

Characterization of constitutive and acid-induced outwardly rectifying chloride currents in immortalized mouse distal tubular cells.

PubMed

Valinsky, William C; Touyz, Rhian M; Shrier, Alvin

2017-08-01

Thiazides block Na + reabsorption while enhancing Ca 2+ reabsorption in the kidney. As previously demonstrated in immortalized mouse distal convoluted tubule (MDCT) cells, chlorothiazide application induced a robust plasma membrane hyperpolarization, which increased Ca 2+ uptake. This essential thiazide-induced hyperpolarization was prevented by the Cl - channel inhibitor 5-Nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), implicating NPPB-sensitive Cl - channels, however the nature of these Cl - channels has been rarely described in the literature. Here we show that MDCT cells express a dominant, outwardly rectifying Cl - current at extracellular pH7.4. This constitutive Cl - current was more permeable to larger anions (Eisenman sequence I; I - >Br - ≥Cl - ) and was substantially inhibited by >100mM [Ca 2+ ] o , which distinguished it from ClC-K2/barttin. Moreover, the constitutive Cl - current was blocked by NPPB, along with other Cl - channel inhibitors (4,4'-diisothiocyanatostilbene-2,2'-disulfonate, DIDS; flufenamic acid, FFA). Subjecting the MDCT cells to an acidic extracellular solution (pH<5.5) induced a substantially larger outwardly rectifying NPPB-sensitive Cl - current. This acid-induced Cl - current was also anion permeable (I - >Br - >Cl - ), but was distinguished from the constitutive Cl - current by its rectification characteristics, ion sensitivities, and response to FFA. In addition, we have identified similar outwardly rectifying and acid-sensitive currents in immortalized cells from the inner medullary collecting duct (mIMCD-3 cells). Expression of an acid-induced Cl - current would be particularly relevant in the acidic IMCD (pH<5.5). To our knowledge, the properties of these Cl - currents are unique and provide the mechanisms to account for the Cl - efflux previously speculated to be present in MDCT cells. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Differential responses of rabbit ventricular and atrial transient outward current (Ito) to the Ito modulator NS5806.

PubMed

Cheng, Hongwei; Cannell, Mark B; Hancox, Jules C

2017-03-01

Transient outward potassium current (I to ) in the heart underlies phase 1 repolarization of cardiac action potentials and thereby affects excitation-contraction coupling. Small molecule activators of I to may therefore offer novel treatments for cardiac dysfunction, including heart failure and atrial fibrillation. NS5806 has been identified as a prototypic activator of canine I to This study investigated, for the first time, actions of NS5806 on rabbit atrial and ventricular I to Whole cell patch-clamp recordings of I to and action potentials were made at physiological temperature from rabbit ventricular and atrial myocytes. 10  μ mol/L NS5806 increased ventricular I to with a leftward shift in I to activation and accelerated restitution. At higher concentrations, stimulation of I to was followed by inhibition. The EC 50 for stimulation was 1.6  μ mol/L and inhibition had an IC 50 of 40.7  μ mol/L. NS5806 only inhibited atrial I to (IC 50 of 18  μ mol/L) and produced a modest leftward shifts in I to activation and inactivation, without an effect on restitution. 10  μ mol/L NS5806 shortened ventricular action potential duration (APD) at APD 20 -APD 90 but prolonged atrial APD NS5806 also reduced atrial AP upstroke and amplitude, consistent with an additional atrio-selective effect on Na + channels. In contrast to NS5806, flecainide, which discriminates between Kv1.4 and 4.x channels, produced similar levels of inhibition of ventricular and atrial I to NS5806 discriminates between rabbit ventricular and atrial I to, with mixed activator and inhibitor actions on the former and inhibitor actions against the later. NS5806 may be of significant value for pharmacological interrogation of regional differences in native cardiac I to . © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Properties of the calcium-activated chloride current in heart.

PubMed

Zygmunt, A C; Gibbons, W R

1992-03-01

We used the whole cell patch clamp technique to study transient outward currents of single rabbit atrial cells. A large transient current, IA, was blocked by 4-aminopyridine (4AP) and/or by depolarized holding potentials. After block of IA, a smaller transient current remained. It was completely blocked by nisoldipine, cadmium, ryanodine, or caffeine, which indicates that all of the 4AP-resistant current is activated by the calcium transient that causes contraction. Neither calcium-activated potassium current nor calcium-activated nonspecific cation current appeared to contribute to the 4AP-resistant transient current. The transient current disappeared when ECl was made equal to the pulse potential; it was present in potassium-free internal and external solutions. It was blocked by the anion transport blockers SITS and DIDS, and the reversal potential of instantaneous current-voltage relations varied with extracellular chloride as predicted for a chloride-selective conductance. We concluded that the 4AP-resistant transient outward current of atrial cells is produced by a calcium-activated chloride current like the current ICl(Ca) of ventricular cells (1991. Circulation Research. 68:424-437). ICl(Ca) in atrial cells demonstrated outward rectification, even when intracellular chloride concentration was higher than extracellular. When ICa was inactivated or allowed to recover from inactivation, amplitudes of ICl(Ca) and ICa were closely correlated. The results were consistent with the view that ICl(Ca) does not undergo independent inactivation. Tentatively, we propose that ICl(Ca) is transient because it is activated by an intracellular calcium transient. Lowering extracellular sodium increased the peak outward transient current. The current was insensitive to the choice of sodium substitute. Because a recently identified time-independent, adrenergically activated chloride current in heart is reduced in low sodium, these data suggest that the two chloride currents are produced by different populations of channels.

A unique alkaline pH-regulated and fatty acid-activated tandem pore domain potassium channel (K2P) from a marine sponge

PubMed Central

Wells, Gregory D.; Tang, Qiong-Yao; Heler, Robert; Tompkins-MacDonald, Gabrielle J.; Pritchard, Erica N.; Leys, Sally P.; Logothetis, Diomedes E.; Boland, Linda M.

2012-01-01

SUMMARY A cDNA encoding a potassium channel of the two-pore domain family (K2P, KCNK) of leak channels was cloned from the marine sponge Amphimedon queenslandica. Phylogenetic analysis indicated that AquK2P cannot be placed into any of the established functional groups of mammalian K2P channels. We used the Xenopus oocyte expression system, a two-electrode voltage clamp and inside-out patch clamp electrophysiology to determine the physiological properties of AquK2P. In whole cells, non-inactivating, voltage-independent, outwardly rectifying K+ currents were generated by external application of micromolar concentrations of arachidonic acid (AA; EC50 ∼30 μmol l–1), when applied in an alkaline solution (≥pH 8.0). Prior activation of channels facilitated the pH-regulated, AA-dependent activation of AquK2P but external pH changes alone did not activate the channels. Unlike certain mammalian fatty-acid-activated K2P channels, the sponge K2P channel was not activated by temperature and was insensitive to osmotically induced membrane distortion. In inside-out patch recordings, alkalinization of the internal pH (pKa 8.18) activated the AquK2P channels independently of AA and also facilitated activation by internally applied AA. The gating of the sponge K2P channel suggests that voltage-independent outward rectification and sensitivity to pH and AA are ancient and fundamental properties of animal K2P channels. In addition, the membrane potential of some poriferan cells may be dynamically regulated by pH and AA. PMID:22723483

A unique alkaline pH-regulated and fatty acid-activated tandem pore domain potassium channel (K₂P) from a marine sponge.

PubMed

Wells, Gregory D; Tang, Qiong-Yao; Heler, Robert; Tompkins-MacDonald, Gabrielle J; Pritchard, Erica N; Leys, Sally P; Logothetis, Diomedes E; Boland, Linda M

2012-07-15

A cDNA encoding a potassium channel of the two-pore domain family (K(2P), KCNK) of leak channels was cloned from the marine sponge Amphimedon queenslandica. Phylogenetic analysis indicated that AquK(2P) cannot be placed into any of the established functional groups of mammalian K(2P) channels. We used the Xenopus oocyte expression system, a two-electrode voltage clamp and inside-out patch clamp electrophysiology to determine the physiological properties of AquK(2P). In whole cells, non-inactivating, voltage-independent, outwardly rectifying K(+) currents were generated by external application of micromolar concentrations of arachidonic acid (AA; EC(50) ∼30 μmol l(-1)), when applied in an alkaline solution (≥pH 8.0). Prior activation of channels facilitated the pH-regulated, AA-dependent activation of AquK(2P) but external pH changes alone did not activate the channels. Unlike certain mammalian fatty-acid-activated K(2P) channels, the sponge K(2P) channel was not activated by temperature and was insensitive to osmotically induced membrane distortion. In inside-out patch recordings, alkalinization of the internal pH (pK(a) 8.18) activated the AquK(2P) channels independently of AA and also facilitated activation by internally applied AA. The gating of the sponge K(2P) channel suggests that voltage-independent outward rectification and sensitivity to pH and AA are ancient and fundamental properties of animal K(2P) channels. In addition, the membrane potential of some poriferan cells may be dynamically regulated by pH and AA.

Two modes of polyamine block regulating the cardiac inward rectifier K+ current IK1 as revealed by a study of the Kir2.1 channel expressed in a human cell line

PubMed Central

Ishihara, Keiko; Ehara, Tsuguhisa

2004-01-01

The strong inward rectifier K+ current, IK1, shows significant outward current amplitude in the voltage range near the reversal potential and thereby causes rapid repolarization at the final phase of cardiac action potentials. However, the mechanism that generates the outward IK1 is not well understood. We recorded currents from the inside-out patches of HEK 293T cells that express the strong inward rectifier K+ channel Kir2.1 and studied the blockage of the currents caused by cytoplasmic polyamines, namely, spermine and spermidine. The outward current–voltage (I–V) relationships of Kir2.1, obtained with 5–10μm spermine or 10–100μm spermidine, were similar to the steady-state outward I–V relationship of IK1, showing a peak at a level that is ∼20mV more positive than the reversal potential, with a negative slope at more positive voltages. The relationships exhibited a plateau or a double-hump shape with 1μm spermine/spermidine or 0.1μm spermine, respectively. In the chord conductance–voltage relationships, there were extra conductances in the positive voltage range, which could not be described by the Boltzmann relations fitting the major part of the relationships. The extra conductances, which generated most of the outward currents in the presence of 5–10μm spermine or 10–100μm spermidine, were quantitatively explained by a model that considered two populations of Kir2.1 channels, which were blocked by polyamines in either a high-affinity mode (Mode 1 channel) or a low-affinity mode (Mode 2 channel). Analysis of the inward tail currents following test pulses indicated that the relief from the spermine block of Kir2.1 consisted of an exponential component and a virtually instantaneous component. The fractions of the two components nearly agreed with the fractions of the blockages in Mode 1 and Mode 2 calculated by the model. The estimated proportion of Mode 1 channels to total channels was 0.9 with 0.1–10μm spermine, 0.75 with 1–100μm spermidine, and between 0.75 and 0.9 when spermine and spermidine coexisted. An interaction of spermine/spermidine with the channel at an intracellular site appeared to modify the equilibrium of the two conformational channel states that allow different modes of blockage. Our results suggest that the outward IK1 is primarily generated by channels with lower affinities for polyamines. Polyamines may regulate the amplitude of the outward IK1, not only by blocking the channels but also by modifying the proportion of channels that show different sensitivities to the polyamine block. PMID:14724206

Characteristics of action potentials and their underlying outward currents in rat taste receptor cells.

PubMed

Chen, Y; Sun, X D; Herness, S

1996-02-01

1. Taste receptor cells produce action potentials as a result of transduction mechanisms that occur when these cells are stimulated with tastants. These action potentials are thought to be key signaling events in relaying information to the central nervous system. We explored the ionic basis of action potentials from dissociated posterior rat taste cells using the patch-clamp recording technique in both voltage-clamp and current-clamp modes. 2. Action potentials were evoked by intracellular injection of depolarizing current pulses from a holding potential of -80 mV. The threshold potential for firing of action potentials was approximately -35 mV; the input resistance of these cells averaged 6.9 G omega. With long depolarizing pulses, two or three action potentials could be elicited with successive attenuation of the spike height. Afterhyperpolarizations were observed often. 3. Both sodium and calcium currents contribute to depolarizing phases of the action potential. Action potentials were blocked completely in the presence of the sodium channel blocker tetrodotoxin. Calcium contributions could be visualized as prolonged calcium plateaus when repolarizing potassium currents were blocked and barium was used as a charge carrier. 4. Outward currents were composed of sustained delayed rectifier current, transient potassium current, and calcium-activated potassium current. Transient and sustained potassium currents activated close to -30 mV and increased monotonically with further depolarization. Up to half the outward current inactivated with decay constants on the order of seconds. Sustained and transient currents displayed steep voltage dependence in conductance and inactivation curves. Half inactivation occurred at -20 +/- 3.1 mV (mean +/- SE) with a decrease of 11.2 +/- 0.5 mV per e-fold. Half maximal conductance occurred at 3.6 +/- 1.8 mV and increased 12.2 +/- 0.6 mV per e-fold. Calcium-activated potassium current was evidenced by application of apamin and the use of calcium-free bathing solution. It was most obvious at more depolarized holding potentials that inactivated much of the transient and sustained outward currents. 5. Potassium currents contribute to both the repolarization and afterhyperpolarization phases of the action potential. These currents were blocked by bath application of tetraethylammonium, which also substantially broadened the action potential. Application of 4-aminopyridine was able to selectively block transient potassium currents without affecting sustained currents. This also broadened the action potential as well as eliminated the afterhyperpolarization. 6. A second type of action potential was observed that differed in duration. These slow action potentials had t1/2 durations of 9.6 ms compared with 1.4 ms for fast action potentials. Input resistances of the two groups were indistinguishable. Approximately one-fourth of the cells eliciting action potentials were of the slow type. 7. Cells eliciting fast action potentials had large outward currents capable of producing a quick repolarization, whereas cells with slow action potentials had small outward currents by comparison. The average values of fast cells were 2,563 pA and 1.4 ms compared with 373 pA and 9.6 ms for slow cells. Current and duration values were related exponentially. No significant difference was noted for inward currents. 8. These results suggest that many taste receptor cells conduct action potentials, which may be classified broadly into two groups on the basis of action potential duration and potassium current magnitude. These groups may be related to cell turnover. The physiological role of action potentials remains to be elucidated but may be important for communication within the taste bud as well as to the afferent nerve.

Electronic cigarette use behaviors and motivations among smokers and non-smokers.

PubMed

Sussan, Thomas E; Shahzad, Fatima G; Tabassum, Eefa; Cohen, Joanna E; Wise, Robert A; Blaha, Michael J; Holbrook, Janet T; Biswal, Shyam

2017-09-08

The use of electronic cigarettes (EC) has risen exponentially over the past decade, including among never smokers, and ECs are now the most popular tobacco product among teenagers in the US. While, EC manufacturers utilize numerous marketing strategies to target both smokers and non-smokers, it is unclear how perceptions and behaviors differ between these two groups. We conducted a survey of 320 adults either via online surveys or in Baltimore vape shops to determine demographics, behaviors, perceptions, and motivations underlying use of ECs. Our survey respondents were predominantly young, Caucasian males, 74% of whom identified themselves as former smokers, while 20% identified as current smokers and 6% were never smokers. Former smokers reported a longer history of EC use and higher nicotine concentrations than current smokers. For former and current smokers, the primary motivation for EC use was assistance to quit smoking, and nearly half indicated that they plan to reduce their nicotine concentration and eventually quit using ECs. Among former smokers, self-reports on use and measures of dependence were consistent with nicotine replacement as their primary motivation. The majority of former and current smokers also reported that their respiratory health had improved as a result of EC use, although this effect was stronger for former smokers. Never smokers reported less frequent EC use and dependence compared to former and current smokers. Their motivations for use were more commonly for enjoyment and popularity, and they displayed a reduced desire to eventually quit using ECs. These responses provide insight into the underlying thoughts and behaviors of smoking and non-smoking EC users and also suggest that never smoking EC users are an emerging demographic with different motivations and perceptions than those of current and former smokers.

Transient compartment-like syndrome and normokalaemic periodic paralysis due to a Cav1.1 mutation

PubMed Central

Fan, Chunxiang; Lehmann-Horn, Frank; Weber, Marc-André; Bednarz, Marcin; Groome, James R.; Jonsson, Malin K. B.

2013-01-01

We studied a two-generation family presenting with conditions that included progressive permanent weakness, myopathic myopathy, exercise-induced contracture before normokalaemic periodic paralysis or, if localized to the tibial anterior muscle group, transient compartment-like syndrome (painful acute oedema with neuronal compression and drop foot). 23Na and 1H magnetic resonance imaging displayed myoplasmic sodium overload, and oedema. We identified a novel familial Cav1.1 calcium channel mutation, R1242G, localized to the third positive charge of the domain IV voltage sensor. Functional expression of R1242G in the muscular dysgenesis mouse cell line GLT revealed a 28% reduced central pore inward current and a −20 mV shift of the steady-state inactivation curve. Both changes may be at least partially explained by an outward omega (gating pore) current at positive potentials. Moreover, this outward omega current of 27.5 nS/nF may cause the reduction of the overshoot by 13 mV and slowing of the upstroke of action potentials by 36% that are associated with muscle hypoexcitability (permanent weakness and myopathic myopathy). In addition to the outward omega current, we identified an inward omega pore current of 95 nS/nF at negative membrane potentials after long depolarizing pulses that shifts the R1242G residue above the omega pore constriction. A simulation reveals that the inward current might depolarize the fibre sufficiently to trigger calcium release in the absence of an action potential and therefore cause an electrically silent depolarization-induced muscle contracture. Additionally, evidence of the inward current can be found in 23Na magnetic resonance imaging-detected sodium accumulation and 1H magnetic resonance imaging-detected oedema. We hypothesize that the episodes are normokalaemic because of depolarization-induced compensatory outward potassium flux through both delayed rectifiers and omega pore. We conclude that the position of the R1242G residue before elicitation of the omega current is decisive for its conductance: if the residue is located below the gating pore as in the resting state then outward currents are observed; if the residue is above the gating pore because of depolarization, as in the inactivated state, then inward currents are observed. This study shows for the first time that functional characterization of omega pore currents is possible using a cultured cell line expressing mutant Cav1.1 channels. Likewise, it is the first calcium channel mutation for complicated normokalaemic periodic paralysis. PMID:24240197

THE EFFECTS OF CURRENT FLOW ON BIOELECTRIC POTENTIAL

PubMed Central

Blinks, L. R.

1936-01-01

String galvanometer records show the effect of current flow upon the bioelectric potential of Nitella cells. Three classes of effects are distinguished. 1. Counter E.M.F'S, due either to static or polarization capacity, probably the latter. These account for the high effective resistance of the cells. They record as symmetrical charge and discharge curves, which are similar for currents passing inward or outward across the protoplasm, and increase in magnitude with increasing current density. The normal positive bioelectric potential may be increased by inward currents some 100 or 200 mv., or to a total of 300 to 400 mv. The regular decrease with outward current flow is much less (40 to 50 mv.) since larger outward currents produce the next characteristic effect. 2. Stimulation. This occurs with outward currents of a density which varies somewhat from cell to cell, but is often between 1 and 2 µa/cm.2 of cell surface. At this threshold a regular counter E.M.F. starts to develop but passes over with an inflection into a rapid decrease or even disappearance of positive P.D., in a sigmoid curve with a cusp near its apex. If the current is stopped early in the curve regular depolarization occurs, but if continued a little longer beyond the first inflection, stimulation goes on to completion even though the current is then stopped. This is the "action current" or negative variation which is self propagated down the cell. During the most profound depression of P.D. in stimulation, current flow produces little or no counter E.M.F., the resistance of the cell being purely ohmic and very low. Then as the P.D. begins to recover, after a second or two, counter E.M.F. also reappears, both becoming nearly normal in 10 or 15 seconds. The threshold for further stimulation remains enhanced for some time, successively larger current densities being needed to stimulate after each action current. The recovery process is also powerful enough to occur even though the original stimulating outward current continues to flow during the entire negative variation; recovery is slightly slower in this case however. Stimulation may be produced at the break of large inward currents, doubtless by discharge of the enhanced positive P.D. (polarization). 3. Restorative Effects.—The flow of inward current during a negative variation somewhat speeds up recovery. This effect is still more strikingly shown in cells exposed to KCl solutions, which may be regarded as causing "permanent stimulation" by inhibiting recovery from a negative variation. Small currents in either direction now produce no counter E.M.F., so that the effective resistance of the cells is very low. With inward currents at a threshold density of some 10 to 20 µa/cm.2, however, there is a counter E.M.F. produced, which builds up in a sigmoid curve to some 100 to 200 mv. positive P.D. This usually shows a marked cusp and then fluctuates irregularly during current flow, falling off abruptly when the current is stopped. Further increases of current density produce this P.D. more rapidly, while decreased densities again cease to be effective below a certain threshold. The effects in Nitella are compared with those in Valonia and Halicystis, which display many of the same phenomena under proper conditions. It is suggested that the regular counter E.M.F.'S (polarizations) are due to the presence of an intact surface film or other structure offering differential hindrance to ionic passage. Small currents do not affect this structure, but it is possibly altered or destroyed by large outward currents, restored by large inward currents. Mechanisms which might accomplish the destruction and restoration are discussed. These include changes of acidity by differential migration of H ion (membrane "electrolysis"); movement of inorganic ions such as potassium; movement of organic ions, (such as Osterhout's substance R), or the radicals (such as fatty acid) of the surface film itself. Although no decision can be yet made between these, much evidence indicates that inward currents increase acidity in some critical part of the protoplasm, while outward ones decrease acidity. PMID:19872991

Transient outward currents and changes of their gating properties after cell activation in thrombocytes of the newt.

PubMed Central

Kawa, K

1987-01-01

1. The electrical properties of the cell membrane of thrombocytes in the newt, Triturus pyrrhogaster, were studied using the whole-cell variation of the patch-electrode voltage-clamp technique. 2. In medium containing Ca2+ (1.8 mM), activated thrombocytes became round and then spread on the glass. Activation of thrombocytes was inhibited by the removal of external Ca2+ and addition of 1 w/v% albumin to the external media. 3. For thrombocytes kept in the resting state, depolarizations more positive than -30 mV evoked transient outward currents which decayed completely during the duration of the depolarization (150 ms). The half-decay time of the currents became smaller as the depolarizing pulse strengthened, reaching about 20 ms at +30 mV (20 degrees C). 4. The outward currents are identified as K+ currents, since (1) their reversal potential depended on extracellular K+ concentration and (2) the outward currents were suppressed either by external application of 4-aminopyridine (1 mM) or by internal application of Cs+ (120 mM). The monovalent cation selectivities of the K+ channels were evaluated from the reversal potential as Tl (1.68) greater than K(1.0) greater than Rb (0.89) greater than NH4 (0.13) greater than Na(less than 0.03). 5. When the thrombocytes had been activated, depolarization again evoked K+ currents. The currents, however, showed negligible or small decay during the duration of the depolarization (150 ms). The rate of recovery from preceding depolarization was also reduced to about one-sixth. 6. The sensitivity to 4-aminopyridine and the selectivity of the K+ channels were not changed by cell activation. 7. We conclude that during activation of thrombocytes the inactivation of the K+ channels is almost eliminated. Removal of inactivation of the K+ channels was also induced in resting thrombocytes by intracellular application of 4-bromoacetamide (50 microM). PMID:2443665

Effects of piperine, the pungent component of black pepper, at the human vanilloid receptor (TRPV1)

PubMed Central

McNamara, Fergal N; Randall, Andrew; Gunthorpe, Martin J

2005-01-01

We have characterised the effects of piperine, a pungent alkaloid found in black pepper, on the human vanilloid receptor TRPV1 using whole-cell patch-clamp electrophysiology. Piperine produced a clear agonist activity at the human TRPV1 receptor yielding rapidly activating whole-cell currents that were antagonised by the competitive TRPV1 antagonist capsazepine and the non-competitive TRPV1 blocker ruthenium red. The current–voltage relationship of piperine-activated currents showed pronounced outward rectification (25±4-fold between −70 and +70 mV) and a reversal potential of 0.0±0.4 mV, which was indistinguishable from that of the prototypical TRPV1 agonist capsaicin. Although piperine was a less potent agonist (EC50=37.9±1.9 μM) than capsaicin (EC50=0.29±0.05 μM), it demonstrated a much greater efficacy (approximately two-fold) at TRPV1. This difference in efficacy did not appear to be related to the proton-mediated regulation of the receptor since a similar degree of potentiation was observed for responses evoked by piperine (230±20%, n=11) or capsaicin (284±32%, n=8) upon acidification to pH 6.5. The effects of piperine upon receptor desensitisation were also unable to explain this effect since piperine resulted in more pronounced macroscopic desensitisation (t1/2=9.9±0.7 s) than capsaicin (t1/2>20 s) and also caused greater tachyphylaxis in response to repetitive agonist applications. Overall, our data suggest that the effects of piperine at human TRPV1 are similar to those of capsaicin except for its propensity to induce greater receptor desensitisation and, rather remarkably, exhibit a greater efficacy than capsaicin itself. These results may provide insight into the TRPV1-mediated effects of piperine on gastrointestinal function. PMID:15685214

Selectivity of externally facing ion-binding sites in the Na/K pump to alkali metals and organic cations

PubMed Central

Ratheal, Ian M.; Virgin, Gail K.; Yu, Haibo; Roux, Benoît; Gatto, Craig; Artigas, Pablo

2010-01-01

The Na/K pump is a P-type ATPase that exchanges three intracellular Na+ ions for two extracellular K+ ions through the plasmalemma of nearly all animal cells. The mechanisms involved in cation selection by the pump's ion-binding sites (site I and site II bind either Na+ or K+; site III binds only Na+) are poorly understood. We studied cation selectivity by outward-facing sites (high K+ affinity) of Na/K pumps expressed in Xenopus oocytes, under voltage clamp. Guanidinium+, methylguanidinium+, and aminoguanidinium+ produced two phenomena possibly reflecting actions at site III: (i) voltage-dependent inhibition (VDI) of outwardly directed pump current at saturating K+, and (ii) induction of pump-mediated, guanidinium-derivative–carried inward current at negative potentials without Na+ and K+. In contrast, formamidinium+ and acetamidinium+ induced K+-like outward currents. Measurement of ouabain-sensitive ATPase activity and radiolabeled cation uptake confirmed that these cations are external K+ congeners. Molecular dynamics simulations indicate that bound organic cations induce minor distortion of the binding sites. Among tested metals, only Li+ induced Na+-like VDI, whereas all metals tested except Na+ induced K+-like outward currents. Pump-mediated K+-like organic cation transport challenges the concept of rigid structural models in which ion specificity at site I and site II arises from a precise and unique arrangement of coordinating ligands. Furthermore, actions by guanidinium+ derivatives suggest that Na+ binds to site III in a hydrated form and that the inward current observed without external Na+ and K+ represents cation transport when normal occlusion at sites I and II is impaired. These results provide insights on external ion selectivity at the three binding sites. PMID:20937860

Synchronization modulation of Na/K pumps on Xenopus oocytes

NASA Astrophysics Data System (ADS)

Liang, Pengfei; Mast, Jason; Chen, Wei

We developed a new technique named synchronization modulation to electrically synchronize and modulate the Na/K pump molecules by a specially designed oscillating electric field. This technique is based on the theory of energy-trap in quantum physics as well as the concept of electronic synchrotron accelerator. As a result, the Na-transports are all entrapped into the positive half-cycle of the applied electric field and consequently, all of the K-transports are entrapped into the negative half cycle of the field. To demonstrate the process of the pump synchronization and modulation, we use Xenopus oocytes as a platform and introduce two-electrode whole-cell voltage clamp in measurement of pump current. Practically, we first synchronize the pump molecules running at the same pace (rate and phase) by a specially designed oscillation electric field. Then, we carefully maintain the pump synchronization status and gradually change the field frequency (decrease and increase) to modulate the pump molecules to newer pumping rate. The result shows a separation of the inward K current from the outward Na current, and about 10 time increase of the total (inward plus outward) pump current from the net outward current from the random paced pump molecules. Also, the ratio of the modulated total pump current with synchronized total pump current is consistent with the ratio of their field frequencies.

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

Tetrodotoxin-sensitive, voltage-dependent sodium currents in hair cells from the alligator cochlea.

PubMed

Evans, M G; Fuchs, P A

1987-10-01

We have used whole-cell patch clamp techniques to record from tall hair cells isolated from the apical half of the alligator cochlea. Some of these cells gave action potentials in response to depolarizing current injections. When the same cells were voltage clamped, large transient inward currents followed by smaller outward currents were seen in response to depolarizing steps. We studied the transient inward current after the outward current had been blocked by external tetraethylammonium (20 mM) or by replacing internal potassium with cesium. It was found to be a sodium current because it was abolished by either replacing external sodium with choline or by external application of tetrodotoxin (100 nM). The sodium current showed voltage-dependent activation and inactivation. Most of the spiking hair cells came from the apex of the cochlea, where they would be subject to low-frequency mechanical stimulation in vivo.

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.

Departure from corotation of the Io plasma torus - Local plasma production

NASA Technical Reports Server (NTRS)

Pontius, D. H., Jr.; Hill, T. W.

1982-01-01

The departure of the Jovian magnetosphere from rigid corotation is adequately explained by outward plasma transport at distances where L is greater than approximately 10. The departure of 5% observed in the Io plasma torus, however, is too large to be accounted for simply by plasma transport. Local plasma production is proposed as the main factor determining the corotation lag in the torus. The outward pick-up current provided by ionization of neutral atoms is calculated and related to the current produced in the ionosphere by the corotation lag. This leads to an expression giving the corotation lag of the torus as a function of radial distance. Charge transfer is found to be an important process, allowing the majority of the torus mass to be ejected from the magnetosphere in a neutral state. Thus, the mass loading rate is found to be several times that inferred from examination of the corotation lag associated with outward plasma transport.

Prolonged action potential duration in cardiac ablation of PDK1 mice.

PubMed

Han, Zhonglin; Jiang, Yu; Yang, Zhongzhou; Cao, Kejiang; Wang, Dao W

2015-01-01

The involvement of the AGC protein kinase family in regulating arrhythmia has drawn considerable attention, but the underlying mechanisms are still not clear. The aim of this study is to explore the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1), one of upstream protein kinases of the AGC protein kinase family, in the pathogenesis of dysregulated electrophysiological basis. PDK1(F/F) αMHC-Cre mice and PDK1(F/F) mice were divided into experiment group and control group. Using patch clamping technology, we explored action potential duration in both groups, and investigated the functions of transient outward potassium channel and L-type Ca(2+) channel to explain the abnormal action potential duration. Significant prolongation action potential duration was found in mice with PDK1 deletion. Further, the peak current of transient outward potassium current and L-type Ca(2+) current were decreased by 84% and 49% respectively. In addition, dysregulation of channel kinetics lead to action potential duration prolongation further. In conclusion, we have demonstrated that PDK1 participates in action potential prolongation in cardiac ablation of PDK1 mice. This effect is likely to be mediated largely through downregulation of transient outward potassium current. These findings indicate the modulation of the PDK1 pathway could provide a new mechanism for abnormal electrophysiological basis.

Nonselective Currents and Channels in Plasma Membranes of Protoplasts from Coats of Developing Seeds of Bean1

PubMed Central

Zhang, Wen-Hao; Skerrett, Martha; Walker, N. Alan; Patrick, John W.; Tyerman, Stephen D.

2002-01-01

In developing bean (Phaseolus vulgaris) seeds, phloem-imported nutrients move in the symplast from sieve elements to the ground parenchyma cells where they are transported across the plasma membrane into the seed apoplast. To study the mechanisms underlying this transport, channel currents in ground parenchyma protoplasts were characterized using patch clamp. A fast-activating outward current was found in all protoplasts, whereas a slowly activating outward current was observed in approximately 25% of protoplasts. The two currents had low selectivity for univalent cations, but the slow current was more selective for K+ over Cl− (PK:PCl = 3.6–4.2) than the fast current (PK:PCl = 1.8–2.5) and also displayed Ca2+ selectivity. The slow current was blocked by Ba2+, whereas both currents were blocked by Gd3+ and La3+. Efflux of K+ from seed coat halves was inhibited 25% by Gd3+ and La3+ but was stimulated by Ba2+ and Cs+, suggesting that only the fast current may be a component in the pathway for K+ release. An “instantaneous” inward current observed in all protoplasts exhibited similar pharmacology and permeability for univalent cations to the fast outward current. In outside-out patches, two classes of depolarization-activated cation-selective channels were observed: one slowly activating of low conductance (determined from nonstationary noise to be 2.4 pS) and another with conductances 10-fold higher. Both channels occurred at high density. The higher conductance channel in 10 mm KCl had PK:PCl = 2.8. Such nonselective channels in the seed coat ground parenchyma cell could function to allow some of the efflux of phloem-imported univalent ions into the seed apoplast. PMID:11842143

Relation of field-aligned currents measured by AMPERE project to solar wind and substorms

NASA Astrophysics Data System (ADS)

McPherron, R. L.; Anderson, B. J.; Chu, X.

2016-12-01

Magnetic perturbations measured in the Active Magnetosphere and Planetary Electrodynamics Response Experiment (AMPERE) by the Iridium constellation of spacecraft have been processed to obtain the time history of field-aligned currents (FAC) connecting the magnetosphere to the ionosphere. We find that the strength of these currents is closely related to the strength of the solar wind driver defined as a running average of the previous three hours of the optimum AL (auroral lower) coupling function. The relation is well represented by a saturation model I = A*S*Ss/(S+Ss) with I the current strength in mega Amps, S the driver strength in mV/m, Ss the saturation value of 7.78 mV/m, and A = 2.55 scales the relation to units of current. We also find that in general the upward current on the nightside increases with each substorm expansion onset defined by a combination of the SuperMag SML (SuperMag AL) and midlatitude positive bay (MPB) onset lists. A superposed epoch analysis using 700 onsets in 2010 shows the following: solar wind coupling peaks at expansion onset; dayside outward current starts to increase one hour before onset while nightside outward current starts suddenly at onset; nightside outward current reaches a peak at 28 minutes as do SML and MPB indices; FAC, SML, and MPB respectively take 1, 2, and 3 hours to decay to background. The data indicate that the substorm current wedge is superposed on a pre-existing field-aligned current system and that the location and properties of the current wedge can be studied with the AMPERE data.

Zonal variations in K+ currents in vestibular crista calyx terminals

PubMed Central

Meredith, Frances L.

2014-01-01

We developed a rodent crista slice to investigate regional variations in electrophysiological properties of vestibular afferent terminals. Thin transverse slices of the gerbil crista ampullaris were made and electrical properties of calyx terminals in central zones (CZ) and peripheral zones (PZ) compared with whole cell patch clamp. Spontaneous action potential firing was observed in 25% of current-clamp recordings and was either regular or irregular in both zones. Firing was abolished when extracellular choline replaced Na+ but persisted when hair cell mechanotransduction channels or calyx AMPA receptors were blocked. This suggests that ion channels intrinsic to the calyx can generate spontaneous firing. In response to depolarizing voltage steps, outward K+ currents were observed at potentials above −60 mV. K+ currents in PZ calyces showed significantly more inactivation than currents in CZ calyces. Underlying K+ channel populations contributing to these differences were investigated. The KCNQ channel blocker XE991 dihydrochloride blocked a slowly activating, sustained outward current in both PZ and CZ calyces, indicating the presence of KCNQ channels. Mean reduction was greatest in PZ calyces. XE991 also reduced action potential firing frequency in CZ and PZ calyces and broadened mean action potential width. The K+ channel blocker 4-aminopyridine (10–50 μM) blocked rapidly activating, moderately inactivating currents that were more prevalent in PZ calyces. α-Dendrotoxin, a selective blocker of KV1 channels, reduced outward currents in CZ calyces but not in PZ calyces. Regional variations in K+ conductances may contribute to different firing responses in calyx afferents. PMID:25343781

Zonal variations in K+ currents in vestibular crista calyx terminals.

PubMed

Meredith, Frances L; Rennie, Katherine J

2015-01-01

We developed a rodent crista slice to investigate regional variations in electrophysiological properties of vestibular afferent terminals. Thin transverse slices of the gerbil crista ampullaris were made and electrical properties of calyx terminals in central zones (CZ) and peripheral zones (PZ) compared with whole cell patch clamp. Spontaneous action potential firing was observed in 25% of current-clamp recordings and was either regular or irregular in both zones. Firing was abolished when extracellular choline replaced Na(+) but persisted when hair cell mechanotransduction channels or calyx AMPA receptors were blocked. This suggests that ion channels intrinsic to the calyx can generate spontaneous firing. In response to depolarizing voltage steps, outward K(+) currents were observed at potentials above -60 mV. K(+) currents in PZ calyces showed significantly more inactivation than currents in CZ calyces. Underlying K(+) channel populations contributing to these differences were investigated. The KCNQ channel blocker XE991 dihydrochloride blocked a slowly activating, sustained outward current in both PZ and CZ calyces, indicating the presence of KCNQ channels. Mean reduction was greatest in PZ calyces. XE991 also reduced action potential firing frequency in CZ and PZ calyces and broadened mean action potential width. The K(+) channel blocker 4-aminopyridine (10-50 μM) blocked rapidly activating, moderately inactivating currents that were more prevalent in PZ calyces. α-Dendrotoxin, a selective blocker of KV1 channels, reduced outward currents in CZ calyces but not in PZ calyces. Regional variations in K(+) conductances may contribute to different firing responses in calyx afferents. Copyright © 2015 the American Physiological Society.

Effects of female steroid hormones on A-type K+ currents in murine colon.

PubMed

Beckett, Elizabeth A H; McCloskey, Conor; O'Kane, Neil; Sanders, Kenton M; Koh, Sang Don

2006-06-01

Idiopathic constipation is higher in women of reproductive age than postmenopausal women or men, suggesting that female steroid hormones influence gastrointestinal motility. How female hormones affect motility is unclear. Colonic motility is regulated by ion channels in colonic myocytes. Voltage-dependent K(+) channels serve to set the excitability of colonic muscles. We investigated regulation of Kv 4.3 channel expression in response to acute or chronic changes in female hormones. Patch clamp experiments and quantitative PCR were used to compare outward currents and transcript expression in colonic myocytes from male, non-pregnant, pregnant and ovariectomized mice. Groups of ovariectomized mice received injections of oestrogen or progesterone to investigate the effects of hormone replacement. The capacitance of colonic myocytes from non-pregnant females was larger than in males. Net outward current density in male and ovariectomized mice was higher than in non-pregnant females and oestrogen-treated ovariectomized mice. Current densities in late pregnancy were lower than in female controls. Progesterone had no effect on outward currents. A-type currents were decreased in non-pregnant females compared with ovariectomized mice, and were further decreased by pregnancy or oestrogen replacement. Kv 4.3 transcripts did not differ significantly between groups; however, expression of the potassium channel interacting protein KChIP1 was elevated in ovariectomized mice compared with female controls and oestrogen-treated ovariectomized mice. Delayed rectifier currents were not affected by oestrogen. In the mouse colon, oestrogen suppresses A-type currents, which are important for regulating excitability. These observations suggest a possible link between female hormones and altered colonic motility associated with menses, pregnancy and menopause.

Vape and Aviate: Electronic-Cigarette Use and Misuse in Naval Aviation.

PubMed

Hall, Matthew T; Austin, Ryan P; Do, Tai A; McGlynn, Andrea

2018-03-01

Electronic cigarettes (EC) are an emerging form of nicotine replacement that has had a discernible increase in prevalence in the general population. Little is known regarding EC use among different military demographic groups or the extent of influence that social determinants of health may have on the behavior. The purpose of this study was to assess the prevalence and correlates of EC use in a select population of active duty U.S. Naval personnel. This study is unique in that it allows for EC behavior comparison between a traditionally healthy demographic (aviators, a subset of aircrew) and a representative general military population sample. Cross-sectional survey data were collected anonymously and analyzed in 2015-2016. Active duty Naval personnel (n = 977) were asked about ever trying ECs, frequency of use, and when was the last time an EC was used. Participants were assessed similarly regarding cigarette use. Descriptive and inferential statistics as well as multinomial logistic regression analyses were conducted using categorical and ordinal variables assigned to usage and demographic factors. This protocol was approved by the Institutional Review Board at Naval Hospital Portsmouth located in Portsmouth, Virginia. Within the study population, 31.4% have tried ECs, 9.3% were current users, and only 3.8% were dual (EC and cigarettes) users. EC use was significantly associated with paygrade (enlisted), primary job duty (non-aircrew), and education (less than a bachelor degree, p < 0.001, p < 0.01, and p < 0.001, respectively). ECs were used at some point as a smoking cessation tool for 43.6% of current EC users (p < 0.001), 21.6% of current smokers, and only 5.6% of former smokers. Continued EC use after ever trying ECs (30.0%) was only slightly more prevalent as continued cigarette use after ever trying cigarettes (27.3%). Smokers were nearly five times more likely to currently use ECs compared with non-smokers. Trying cigarettes was associated with nearly 12 times the risk for trying ECs compared with those who never tried cigarettes. No significant misuse of ECs was noted; however, several cases of drinking, tasting, and touching EC fluid were reported. This study is unique in that it examines the use of electronic cigarettes among selected healthy and baseline groups within the active duty U.S. Navy population. The current prevalence of EC use among active duty personnel is much higher than previously thought. Continued use of ECs after ever trying them appears to exceed that of cigarettes even among healthy populations such as aircrew. The findings of increased risk of EC use among those with lower income and less than a bachelor's degree suggest social determinants of health implications. This study sheds new light on EC use, characteristics of use, addiction implications, and highlights concerns for a growing health risk behavior.

Microglial K+ Channel Expression in Young Adult and Aged Mice

PubMed Central

Schilling, Tom; Eder, Claudia

2015-01-01

The K+ channel expression pattern of microglia strongly depends on the cells' microenvironment and has been recognized as a sensitive marker of the cells' functional state. While numerous studies have been performed on microglia in vitro, our knowledge about microglial K+ channels and their regulation in vivo is limited. Here, we have investigated K+ currents of microglia in striatum, neocortex and entorhinal cortex of young adult and aged mice. Although almost all microglial cells exhibited inward rectifier K+ currents upon membrane hyperpolarization, their mean current density was significantly enhanced in aged mice compared with that determined in young adult mice. Some microglial cells additionally exhibited outward rectifier K+ currents in response to depolarizing voltage pulses. In aged mice, microglial outward rectifier K+ current density was significantly larger than in young adult mice due to the increased number of aged microglial cells expressing these channels. Aged dystrophic microglia exhibited outward rectifier K+ currents more frequently than aged ramified microglia. The majority of microglial cells expressed functional BK-type, but not IK- or SK-type, Ca2+-activated K+ channels, while no differences were found in their expression levels between microglia of young adult and aged mice. Neither microglial K+ channel pattern nor K+ channel expression levels differed markedly between the three brain regions investigated. It is concluded that age-related changes in microglial phenotype are accompanied by changes in the expression of microglial voltage-activated, but not Ca2+-activated, K+ channels. PMID:25472417

External K+ dependence of strong inward rectifier K+ channel conductance is caused not by K+ but by competitive pore blockade by external Na.

PubMed

Ishihara, Keiko

2018-06-15

Strong inward rectifier K + (sKir) channels determine the membrane potentials of many types of excitable and nonexcitable cells, most notably the resting potentials of cardiac myocytes. They show little outward current during membrane depolarization (i.e., strong inward rectification) because of the channel blockade by cytoplasmic polyamines, which depends on the deviation of the membrane potential from the K + equilibrium potential ( V - E K ) when the extracellular K + concentration ([K + ] out ) is changed. Because their open - channel conductance is apparently proportional to the "square root" of [K + ] out , increases/decreases in [K + ] out enhance/diminish outward currents through sKir channels at membrane potentials near their reversal potential, which also affects, for example, the repolarization and action-potential duration of cardiac myocytes. Despite its importance, however, the mechanism underlying the [K + ] out dependence of the open sKir channel conductance has remained elusive. By studying Kir2.1, the canonical member of the sKir channel family, we first show that the outward currents of Kir2.1 are observed under the external K + -free condition when its inward rectification is reduced and that the complete inhibition of the currents at 0 [K + ] out results solely from pore blockade caused by the polyamines. Moreover, the noted square-root proportionality of the open sKir channel conductance to [K + ] out is mediated by the pore blockade by the external Na + , which is competitive with the external K + Our results show that external K + itself does not activate or facilitate K + permeation through the open sKir channel to mediate the apparent external K + dependence of its open channel conductance. The paradoxical increase/decrease in outward sKir channel currents during alternations in [K + ] out , which is physiologically relevant, is caused by competition from impermeant extracellular Na . © 2018 Ishihara.

High wall shear stress and spatial gradients in vascular pathology: a review.

PubMed

Dolan, Jennifer M; Kolega, John; Meng, Hui

2013-07-01

Cardiovascular pathologies such as intracranial aneurysms (IAs) and atherosclerosis preferentially localize to bifurcations and curvatures where hemodynamics are complex. While extensive knowledge about low wall shear stress (WSS) has been generated in the past, due to its strong relevance to atherogenesis, high WSS (typically >3 Pa) has emerged as a key regulator of vascular biology and pathology as well, receiving renewed interests. As reviewed here, chronic high WSS not only stimulates adaptive outward remodeling, but also contributes to saccular IA formation (at bifurcation apices or outer curves) and atherosclerotic plaque destabilization (in stenosed vessels). Recent advances in understanding IA pathogenesis have shed new light on the role of high WSS in pathological vascular remodeling. In complex geometries, high WSS can couple with significant spatial WSS gradient (WSSG). A combination of high WSS and positive WSSG has been shown to trigger aneurysm initiation. Since endothelial cells (ECs) are sensors of WSS, we have begun to elucidate EC responses to high WSS alone and in combination with WSSG. Understanding such responses will provide insight into not only aneurysm formation, but also plaque destabilization and other vascular pathologies and potentially lead to improved strategies for disease management and novel targets for pharmacological intervention.

Relationship between Hard X-Ray Footpoint Sources and Photospheric Electric Currents in Solar Flares: a Statistical Study

NASA Astrophysics Data System (ADS)

Zimovets, I. V.; Sharykin, I. N.; Wang, R.; Liu, Y. D.; Kosovichev, A. G.

2017-12-01

It is believed that solar flares are a result of release of free magnetic energy contained in electric currents (ECs) flowing in active regions (ARs). However, there are still debates whether the primary energy release and acceleration of electrons take place in coronal current sheets or in chromospheric footpoints of current-carrying magnetic flux tubes (loops). We present results of an observational statistical study of spatial relationship between hard X-ray (HXR; EHXR≥50keV) footpoint sources detected by RHESSI and vertical photospheric ECs calculated using vector magnetograms obtained from the SDO/HMI data. We found that for a sample of 47 flares (from C3.0 to X3.1 class) observed on the solar disk by both instruments in 2010-2016, at least one HXR source was in a region of strong (within 20% of the maximum EC density in the corresponding ARs) vertical ECs having the form of a ribbon (79%) or an island (21%). The total vertical ECs in such HXR sources are in the range of 1010-1013 A. The EC density is in the range of 0.01-1.0 A/m2. We found no correlation between intensity of the HXR sources and the EC density. By comparing pre-flare and post-flare EC maps we did not find evidences of significant dissipation of vertical ECs in the regions corresponding to the HXR sources. In some cases, we found amplification of ECs during flares. We discuss effects of sensitivity and angular resolution of RHESSI and SDO/HMI. In general, the results indicate that there is a link between the flare HXR footpoint sources and enhanced vertical ECs in the photosphere. However, the results do not support a concept of electron acceleration by the electric field excited in footpoints of current-carrying loops due to some (e.g. Rayleigh-Taylor) instabilities (Zaitsev et al., 2016), since strong correlation between the HXR intensity and the EC density is expected in such concept.

State-changes in the swimmeret system: a neural circuit that drives locomotion

PubMed Central

Tschuluun, N.; Hall, W. M.; Mulloney, B.

2009-01-01

Summary The crayfish swimmeret system undergoes transitions between a silent state and an active state. In the silent state, no patterned firing occurs in swimmeret motor neurons. In the active state, bursts of spikes in power stroke motor neurons alternate periodically with bursts of spikes in return stroke motor neurons. In preparations of the isolated crayfish central nervous system (CNS), the temporal structures of motor patterns expressed in the active state are similar to those expressed by the intact animal. These transitions can occur spontaneously, in response to stimulation of command neurons, or in response to application of neuromodulators and transmitter analogues. We used single-electrode voltage clamp of power-stroke exciter and return-stroke exciter motor neurons to study changes in membrane currents during spontaneous transitions and during transitions caused by bath-application of carbachol or octopamine (OA). Spontaneous transitions from silence to activity were marked by the appearance of a standing inward current and periodic outward currents in both types of motor neurons. Bath-application of carbachol also led to the development of these currents and activation of the system. Using low Ca2+–high Mg2+ saline to block synaptic transmission, we found that the carbachol-induced inward current included a direct response by the motor neuron and an indirect component. Spontaneous transitions from activity to silence were marked by disappearance of the standing inward current and the periodic outward currents. Bath-application of OA led promptly to the disappearance of both currents, and silenced the system. OA also acted directly on both types of motor neurons to cause a hyperpolarizing outward current that would contribute to silencing the system. PMID:19880720

State-changes in the swimmeret system: a neural circuit that drives locomotion.

PubMed

Tschuluun, N; Hall, W M; Mulloney, B

2009-11-01

The crayfish swimmeret system undergoes transitions between a silent state and an active state. In the silent state, no patterned firing occurs in swimmeret motor neurons. In the active state, bursts of spikes in power stroke motor neurons alternate periodically with bursts of spikes in return stroke motor neurons. In preparations of the isolated crayfish central nervous system (CNS), the temporal structures of motor patterns expressed in the active state are similar to those expressed by the intact animal. These transitions can occur spontaneously, in response to stimulation of command neurons, or in response to application of neuromodulators and transmitter analogues. We used single-electrode voltage clamp of power-stroke exciter and return-stroke exciter motor neurons to study changes in membrane currents during spontaneous transitions and during transitions caused by bath-application of carbachol or octopamine (OA). Spontaneous transitions from silence to activity were marked by the appearance of a standing inward current and periodic outward currents in both types of motor neurons. Bath-application of carbachol also led to the development of these currents and activation of the system. Using low Ca(2+)-high Mg(2+) saline to block synaptic transmission, we found that the carbachol-induced inward current included a direct response by the motor neuron and an indirect component. Spontaneous transitions from activity to silence were marked by disappearance of the standing inward current and the periodic outward currents. Bath-application of OA led promptly to the disappearance of both currents, and silenced the system. OA also acted directly on both types of motor neurons to cause a hyperpolarizing outward current that would contribute to silencing the system.

Contribution of delayed rectifier potassium currents to the electrical activity of murine colonic smooth muscle

PubMed Central

Koh, S D; Ward, S M; Dick, G M; Epperson, A; Bonner, H P; Sanders, K M; Horowitz, B; Kenyon, J L

1999-01-01

We used intracellular microelectrodes to record the membrane potential (Vm) of intact murine colonic smooth muscle. Electrical activity consisted of spike complexes separated by quiescent periods (Vm≈−60 mV). The spike complexes consisted of about a dozen action potentials of approximately 30 mV amplitude. Tetraethylammonium (TEA, 1–10 mM) had little effect on the quiescent periods but increased the amplitude of the action potential spikes. 4-Aminopyridine (4-AP, ⋧ 5 mM) caused continuous spiking.Voltage clamp of isolated myocytes identified delayed rectifier K+ currents that activated rapidly (time to half-maximum current, 11.5 ms at 0 mV) and inactivated in two phases (τf = 96 ms, τs = 1.5 s at 0 mV). The half-activation voltage of the permeability was −27 mV, with significant activation at −50 mV.TEA (10 mM) reduced the outward current at potentials positive to 0 mV. 4-AP (5 mM) reduced the early current but increased outward current at later times (100–500 ms) consistent with block of resting channels relieved by depolarization. 4-AP inhibited outward current at potentials negative to −20 mV, potentials where TEA had no effect.Qualitative PCR amplification of mRNA identified transcripts encoding delayed rectifier K+ channel subunits Kv1.6, Kv4.1, Kv4.2, Kv4.3 and the Kvβ1.1 subunit in murine colon myocytes. mRNA encoding Kv 1.4 was not detected.We find that TEA-sensitive delayed rectifier currents are important determinants of action potential amplitude but not rhythmicity. Delayed rectifier currents sensitive to 4-AP are important determinants of rhythmicity but not action potential amplitude. PMID:10050014

Treatment of leachate by electrocoagulation using aluminum and iron electrodes.

PubMed

Ilhan, Fatih; Kurt, Ugur; Apaydin, Omer; Gonullu, M Talha

2008-06-15

In this paper, treatment of leachate by electrocoagulation (EC) has been investigated in a batch process. The sample of leachate was supplied from Odayeri Landfill Site in Istanbul. Firstly, EC was compared with classical chemical coagulation (CC) process via COD removal. The first comparison results with 348 A/m2 current density showed that EC process has higher treatment performance than CC process. Secondly, effects of process variables such as electrode material, current density (from 348 to 631 A/m2), pH, treatment cost, and operating time for EC process are investigated on COD and NH4-N removal efficiencies. The appropriate electrode type search for EC provided that aluminum supplies more COD removal (56%) than iron electrode (35%) at the end of the 30 min operating time. Finally, EC experiments were also continued to determine the efficiency of ammonia removal, and the effects of current density, mixing, and aeration. All the findings of the study revealed that treatment of leachate by EC can be used as a step of a joint treatment.

Cardiomyocyte dysfunction during the chronic phase of Chagas disease.

PubMed

Roman-Campos, Danilo; Sales-Júnior, Policarpo; Duarte, Hugo Leonardo; Gomes, Eneas Ricardo; Guatimosim, Silvia; Ropert, Catherine; Gazzinelli, Ricardo Tostes; Cruz, Jader Santos

2013-04-01

Chagas disease, which is caused by the parasite Trypanosoma cruzi, is an important cause of heart failure. We investigated modifications in the cellular electrophysiological and calcium-handling characteristics of an infected mouse heart during the chronic phase of the disease. The patch-clamp technique was used to record action potentials (APs) and L-type Ca2+ and transient outward K+ currents. [Ca2+]i changes were determined using confocal microscopy. Infected ventricular cells showed prolonged APs, reduced transient outward K+ and L-type Ca2+ currents and reduced Ca2+ release from the sarcoplasmic reticulum. Thus, the chronic phase of Chagas disease is characterised by cardiomyocyte dysfunction, which could lead to heart failure.

Cardiomyocyte dysfunction during the chronic phase of Chagas disease

PubMed Central

Roman-Campos, Danilo; Sales-Júnior, Policarpo; Duarte, Hugo Leonardo; Gomes, Eneas Ricardo; Guatimosim, Silvia; Ropert, Catherine; Gazzinelli, Ricardo Tostes; Cruz, Jader Santos

2013-01-01

Chagas disease, which is caused by the parasite Trypanosoma cruzi, is an important cause of heart failure. We investigated modifications in the cellular electrophysiological and calcium-handling characteristics of an infected mouse heart during the chronic phase of the disease. The patch-clamp technique was used to record action potentials (APs) and L-type Ca2+ and transient outward K+ currents. [Ca2+]i changes were determined using confocal microscopy. Infected ventricular cells showed prolonged APs, reduced transient outward K+ and L-type Ca2+ currents and reduced Ca2+ release from the sarcoplasmic reticulum. Thus, the chronic phase of Chagas disease is characterised by cardiomyocyte dysfunction, which could lead to heart failure. PMID:23579807

Three dimensional instabilities of an electron scale current sheet in collisionless magnetic reconnection

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

Jain, Neeraj; Büchner, Jörg; Max Planck Institute for Solar System Research, Justus-Von-Liebig-Weg-3, Göttingen

In collisionless magnetic reconnection, electron current sheets (ECS) with thickness of the order of an electron inertial length form embedded inside ion current sheets with thickness of the order of an ion inertial length. These ECS's are susceptible to a variety of instabilities which have the potential to affect the reconnection rate and/or the structure of reconnection. We carry out a three dimensional linear eigen mode stability analysis of electron shear flow driven instabilities of an electron scale current sheet using an electron-magnetohydrodynamic plasma model. The linear growth rate of the fastest unstable mode was found to drop with themore » thickness of the ECS. We show how the nature of the instability depends on the thickness of the ECS. As long as the half-thickness of the ECS is close to the electron inertial length, the fastest instability is that of a translational symmetric two-dimensional (no variations along flow direction) tearing mode. For an ECS half thickness sufficiently larger or smaller than the electron inertial length, the fastest mode is not a tearing mode any more and may have finite variations along the flow direction. Therefore, the generation of plasmoids in a nonlinear evolution of ECS is likely only when the half-thickness is close to an electron inertial length.« less

Voltage-gated currents in identified rat olfactory receptor neurons.

PubMed

Trombley, P Q; Westbrook, G L

1991-02-01

Whole-cell recording techniques were used to characterize voltage-gated membrane currents in neonatal rat olfactory receptor neurons (ORNs) in cell culture. Mature ORNs were identified in culture by their characteristic bipolar morphology, by retrograde labeling techniques, and by olfactory marker protein (OMP) immunoreactivity. ORNs did not have spontaneous activity, but fired action potentials to depolarizing current pulses. Action potentials were blocked by tetrodotoxin (TTX), which contrasts with the TTX-resistant action potentials in salamander olfactory receptor cells (e.g., Firestein and Werblin, 1987). Prolonged, suprathreshold current pulses evoked only a single action potential; however, repetitive firing up to 35 Hz could be elicited by a series of brief depolarizing pulses. Under voltage clamp, the TTX-sensitive sodium current had activation and inactivation properties similar to other excitable cells. In TTX and 20 mM barium, sustained inward current were evoked by voltage steps positive to -30 mV. This current was blocked by Cd (100 microM) and by nifedipine (IC50 = 368 nM) consistent with L-type calcium channels in other neurons. No T-type calcium current was observed. Voltage steps positive to -20 mV also evoked an outward current that did not inactivate during 100-msec depolarizations. Tail current analysis of this current was consistent with a selective potassium conductance. The outward current was blocked by external tetraethylammonium but was unaffected by Cd or 4-aminopyridine (4-AP) or by removal of external calcium. A transient outward current was not observed. The 3 voltage-dependent conductances in cultured rat ORNs appear to be sufficient for 2 essential functions: action potential generation and transmitter release. As a single odorant-activated channel can trigger an action potential (e.g., Lynch and Barry, 1989), the repetitive firing seen with brief depolarizing pulses suggests that ORNs do not integrate sensory input, but rather act as high-fidelity relays such that each opening of an odorant-activated channel reaches the olfactory bulb glomeruli as an action potential.

Transient outwardly rectifying A currents are involved in the firing rate response to altered CO2 in chemosensitive locus coeruleus neurons from neonatal rats

PubMed Central

Li, Ke-Yong

2013-01-01

The effect of hypercapnia on outwardly rectifying currents was examined in locus coeruleus (LC) neurons in slices from neonatal rats [postnatal day 3 (P3)–P15]. Two outwardly rectifying currents [4-aminopyridine (4-AP)-sensitive transient current and tetraethyl ammonium (TEA)-sensitive sustained current] were found in LC neurons. 4-AP induced a membrane depolarization of 3.6 ± 0.6 mV (n = 4), while TEA induced a smaller membrane depolarization of 1.2 ± 0.3 mV (n = 4). Hypercapnic acidosis (HA) inhibited both currents. The maximal amplitude of the TEA-sensitive current was reduced by 52.1 ± 4.5% (n = 5) in 15% CO2 [extracellular pH (pHo) 7.00, intracellular pH (pHi) 6.96]. The maximal amplitude of the 4-AP-sensitive current was reduced by 34.5 ± 3.0% (n = 6) in 15% CO2 (pHo 7.00, pHi 6.96), by 29.4 ± 6.8% (n = 6) in 10% CO2 (pHo 7.15, pHi 7.14), and increased by 29.0 ± 6.4% (n = 6) in 2.5% CO2 (pHo 7.75, pHi 7.35). 4-AP completely blocked hypercapnia-induced increased firing rate, but TEA did not affect it. When LC neurons were exposed to HA with either pHo or pHi constant, the 4-AP-sensitive current was inhibited. The data show that the 4-AP-sensitive current (likely an A current) is inhibited by decreases in either pHo or pHi. The change of the A current by various levels of CO2 is correlated with the change in firing rate induced by CO2, implicating the 4-AP-sensitive current in chemosensitive signaling in LC neurons. PMID:23948777

BmP02 Atypically Delays Kv4.2 Inactivation: Implication for a Unique Interaction between Scorpion Toxin and Potassium Channel

PubMed Central

Wu, Bin; Zhu, Yan; Shi, Jian; Tao, Jie; Ji, Yonghua

2016-01-01

BmP02, a short-chain peptide with 28 residues from the venom of Chinese scorpion Buthus martensi Karsch, has been reported to inhibit the transient outward potassium currents (Ito) in rat ventricular muscle cells. However, it remains unclear whether BmP02 modulates the Kv4.2 channel, one of the main contributors to Ito. The present study investigated the effects of BmP02 on Kv4.2 kinetics and its underlying molecular mechanism. The electrophysiological recordings showed that the inactivation of Kv4.2 expressed in HEK293T cells was significantly delayed by BmP02 in a dose-response manner with EC50 of ~850 nM while the peak current, activation and voltage-dependent inactivation of Kv4.2 were not affected. Meanwhile, the recovery from inactivation of Kv4.2 was accelerated and the deactivation was slowed after the application of BmP02. The site-directed mutagenesis combined with computational modelling identified that K347 and K353, located in the turret motif of the Kv4.2, and E4/E5, D20/D21 in BmP02 are key residues to interact with BmP02 through electrostatic force. These findings not only reveal a novel interaction between Kv4.2 channel and its peptidyl modulator, but also provide valuable information for design of highly-selective Kv4.2 modulators. PMID:27690098

Supply-demand balance in outward-directed networks and Kleiber's law

PubMed Central

Painter, Page R

2005-01-01

Background Recent theories have attempted to derive the value of the exponent α in the allometric formula for scaling of basal metabolic rate from the properties of distribution network models for arteries and capillaries. It has recently been stated that a basic theorem relating the sum of nutrient currents to the specific nutrient uptake rate, together with a relationship claimed to be required in order to match nutrient supply to nutrient demand in 3-dimensional outward-directed networks, leads to Kleiber's law (b = 3/4). Methods The validity of the supply-demand matching principle and the assumptions required to prove the basic theorem are assessed. The supply-demand principle is evaluated by examining the supply term and the demand term in outward-directed lattice models of nutrient and water distribution systems and by applying the principle to fractal-like models of mammalian arterial systems. Results Application of the supply-demand principle to bifurcating fractal-like networks that are outward-directed does not predict 3/4-power scaling, and evaluation of water distribution system models shows that the matching principle does not match supply to demand in such systems. Furthermore, proof of the basic theorem is shown to require that the covariance of nutrient uptake and current path length is 0, an assumption unlikely to be true in mammalian arterial systems. Conclusion The supply-demand matching principle does not lead to a satisfactory explanation for the approximately 3/4-power scaling of mammalian basal metabolic rate. PMID:16283939

Supply-demand balance in outward-directed networks and Kleiber's law.

PubMed

Painter, Page R

2005-11-10

Recent theories have attempted to derive the value of the exponent alpha in the allometric formula for scaling of basal metabolic rate from the properties of distribution network models for arteries and capillaries. It has recently been stated that a basic theorem relating the sum of nutrient currents to the specific nutrient uptake rate, together with a relationship claimed to be required in order to match nutrient supply to nutrient demand in 3-dimensional outward-directed networks, leads to Kleiber's law (b = 3/4). The validity of the supply-demand matching principle and the assumptions required to prove the basic theorem are assessed. The supply-demand principle is evaluated by examining the supply term and the demand term in outward-directed lattice models of nutrient and water distribution systems and by applying the principle to fractal-like models of mammalian arterial systems. Application of the supply-demand principle to bifurcating fractal-like networks that are outward-directed does not predict 3/4-power scaling, and evaluation of water distribution system models shows that the matching principle does not match supply to demand in such systems. Furthermore, proof of the basic theorem is shown to require that the covariance of nutrient uptake and current path length is 0, an assumption unlikely to be true in mammalian arterial systems. The supply-demand matching principle does not lead to a satisfactory explanation for the approximately 3/4-power scaling of mammalian basal metabolic rate.

Electrogenic properties of the Na+/K+ ATPase control transitions between normal and pathological brain states

PubMed Central

Krishnan, Giri P.; Filatov, Gregory; Shilnikov, Andrey

2015-01-01

Ionic concentrations fluctuate significantly during epileptic seizures. In this study, using a combination of in vitro electrophysiology, computer modeling, and dynamical systems analysis, we demonstrate that changes in the potassium and sodium intra- and extracellular ion concentrations ([K+] and [Na+], respectively) during seizure affect the neuron dynamics by modulating the outward Na+/K+ pump current. First, we show that an increase of the outward Na+/K+ pump current mediates termination of seizures when there is a progressive increase in the intracellular [Na+]. Second, we show that the Na+/K+ pump current is crucial in maintaining the stability of the physiological network state; a reduction of this current leads to the onset of seizures via a positive-feedback loop. We then present a novel dynamical mechanism for bursting in neurons with a reduced Na+/K+ pump. Overall, our study demonstrates the profound role of the current mediated by Na+/K+ ATPase on the stability of neuronal dynamics that was previously unknown. PMID:25589588

Moderate hypoxia influences excitability and blocks dendrotoxin sensitive K+ currents in rat primary sensory neurones

PubMed Central

Gruss, Marco; Ettorre, Giovanni; Stehr, Annette Jana; Henrich, Michael; Hempelmann, Gunter; Scholz, Andreas

2006-01-01

Hypoxia alters neuronal function and can lead to neuronal injury or death especially in the central nervous system. But little is known about the effects of hypoxia in neurones of the peripheral nervous system (PNS), which survive longer hypoxic periods. Additionally, people have experienced unpleasant sensations during ischemia which are dedicated to changes in conduction properties or changes in excitability in the PNS. However, the underlying ionic conductances in dorsal root ganglion (DRG) neurones have not been investigated in detail. Therefore we investigated the influence of moderate hypoxia (27.0 ± 1.5 mmHg) on action potentials, excitability and ionic conductances of small neurones in a slice preparation of DRGs of young rats. The neurones responded within a few minutes non-uniformly to moderate hypoxia: changes of excitability could be assigned to decreased outward currents in most of the neurones (77%) whereas a smaller group (23%) displayed increased outward currents in Ringer solution. We were able to attribute most of the reduction in outward-current to a voltage-gated K+ current which activated at potentials positive to -50 mV and was sensitive to 50 nM α-dendrotoxin (DTX). Other toxins that inhibit subtypes of voltage gated K+ channels, such as margatoxin (MgTX), dendrotoxin-K (DTX-K), r-tityustoxin Kα (TsTX-K) and r-agitoxin (AgTX-2) failed to prevent the hypoxia induced reduction. Therefore we could not assign the hypoxia sensitive K+ current to one homomeric KV channel type in sensory neurones. Functionally this K+ current blockade might underlie the increased action potential (AP) duration in these neurones. Altogether these results, might explain the functional impairment of peripheral neurones under moderate hypoxia. PMID:16579848

Homing in humans: A different look.

PubMed

Bovet, J

1994-08-01

A current model holds that the long-distance homing abilities of free-ranging mammals rest primarily on a strategy of course reversal, based on outward journey information. In this study, I measured the ability to orient toward home in humans displaced under conditions that promote the use of this strategy, namely along an outward route that was direct, and the main bearing of which could be extrapolated by reference to a pre-existant mental map and by visual backup during the outward journey. Even though the individual course estimates obtained did show a certain amount of dispersion and/or error, they were more accurate and less dispersed than in experiments by other authors, where subjects could not use this strategy, because they were displaced blindfolded and/or along circuitous routes. Copyright © 1994. Published by Elsevier B.V.

Association between Electronic Cigarette Use and Asthma among High School Students in South Korea

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

Cho, Jun Ho; Paik, Samuel Y.

Little is known about health outcomes related to electronic cigarette (EC) use, despite its growing popularity. The aim of this study is to investigate the association between EC use and asthma. The study design is a cross-sectional study. A total of 35,904 high school students were included as the final study population. The presence of asthma was based on a student’s self-reported doctor diagnosis of asthma in the past 12 months. Results showed prevalence rates of asthmatics in ‘current EC users’ (n = 2,513), ‘former EC users’ (n = 2,078), and ‘never EC users’ (n = 31,313), were 3.9% (nmore » = 98), 2.2% (n = 46) and 1.7% (n = 530), respectively. Comparing ‘current EC’ users with ‘never EC’ users, the unadjusted OR for asthma was 2.36 (95% CI: 1.89–2.94). In order to control for the effect of conventional cigarette (CC) smoking, after stratifying the subjects by the three CC smoking categories (never CC, former CC, and current CC), within the ‘never CC’ category, the unadjusted OR for asthma for ‘current EC’ users was 3.41 (95% CI: 1.79–6.49), and the adjusted OR was 2.74 (95% CI: 1.30–5.78). Severe asthma was reflected by the number of days absent from school due to asthma symptoms; current EC users had the highest adjusted OR for severe asthma compared to ‘never EC’ users. In conclusion, when compared to a reference population of high school students in South Korea, EC users have an increased association with asthma and are more likely to have had days absent from school due to severe asthma symptoms. In conclusion, the results indicate that EC use may be a risk factor for asthma. The results may be useful in developing a scientific basis for the evaluation of a potential health hazard by EC.« less

Association between Electronic Cigarette Use and Asthma among High School Students in South Korea

DOE PAGES

Cho, Jun Ho; Paik, Samuel Y.

2016-03-04

Little is known about health outcomes related to electronic cigarette (EC) use, despite its growing popularity. The aim of this study is to investigate the association between EC use and asthma. The study design is a cross-sectional study. A total of 35,904 high school students were included as the final study population. The presence of asthma was based on a student’s self-reported doctor diagnosis of asthma in the past 12 months. Results showed prevalence rates of asthmatics in ‘current EC users’ (n = 2,513), ‘former EC users’ (n = 2,078), and ‘never EC users’ (n = 31,313), were 3.9% (nmore » = 98), 2.2% (n = 46) and 1.7% (n = 530), respectively. Comparing ‘current EC’ users with ‘never EC’ users, the unadjusted OR for asthma was 2.36 (95% CI: 1.89–2.94). In order to control for the effect of conventional cigarette (CC) smoking, after stratifying the subjects by the three CC smoking categories (never CC, former CC, and current CC), within the ‘never CC’ category, the unadjusted OR for asthma for ‘current EC’ users was 3.41 (95% CI: 1.79–6.49), and the adjusted OR was 2.74 (95% CI: 1.30–5.78). Severe asthma was reflected by the number of days absent from school due to asthma symptoms; current EC users had the highest adjusted OR for severe asthma compared to ‘never EC’ users. In conclusion, when compared to a reference population of high school students in South Korea, EC users have an increased association with asthma and are more likely to have had days absent from school due to severe asthma symptoms. In conclusion, the results indicate that EC use may be a risk factor for asthma. The results may be useful in developing a scientific basis for the evaluation of a potential health hazard by EC.« less

Fully non-inductive second harmonic electron cyclotron plasma ramp-up in the QUEST spherical tokamak

NASA Astrophysics Data System (ADS)

Idei, H.; Kariya, T.; Imai, T.; Mishra, K.; Onchi, T.; Watanabe, O.; Zushi, H.; Hanada, K.; Qian, J.; Ejiri, A.; Alam, M. M.; Nakamura, K.; Fujisawa, A.; Nagashima, Y.; Hasegawa, M.; Matsuoka, K.; Fukuyama, A.; Kubo, S.; Shimozuma, T.; Yoshikawa, M.; Sakamoto, M.; Kawasaki, S.; Nakashima, H.; Higashijima, A.; Ide, S.; Maekawa, T.; Takase, Y.; Toi, K.

2017-12-01

Fully non-inductive second (2nd) harmonic electron cyclotron (EC) plasma current ramp-up was demonstrated with a newlly developed 28 GHz system in the QUEST spherical tokamak. A high plasma current of 54 kA was non-inductively ramped up and sustained stably for 0.9 s with a 270 kW 28 GHz wave. A higher plasma current of 66 kA was also non-inductively achieved with a slow ramp-up of the vertical field. We have achieved a significantly higher plasma current than those achieved previously with the 2nd harmonic EC waves. This fully non-inductive 2nd harmonic EC plasma ramp-up method might be useful for future burning plasma devices and fusion reactors, in particular for operations at half magnetic field with the same EC heating equipment.

A Randomized Trial Comparing the Effect of Nicotine Versus Placebo Electronic Cigarettes on Smoking Reduction Among Young Adult Smokers.

PubMed

Tseng, Tuo-Yen; Ostroff, Jamie S; Campo, Alena; Gerard, Meghan; Kirchner, Thomas; Rotrosen, John; Shelley, Donna

2016-10-01

Electronic cigarette (EC) use is growing dramatically with use highest among young adults and current smokers. One of the most common reasons for using ECs is interest in quitting or reducing cigarettes per day (CPD); however there are few randomized controlled trials (RCT) on the effect of ECs on smoking abstinence and reduction. We conducted a two-arm; double-blind RCT. Subjects were randomized to receive 3-weeks of either disposable 4.5% nicotine EC (intervention) or placebo EC. The primary outcome was self-reported reduction of at least 50% in the number of CPDs smoked at week 3 (end of treatment) compared to baseline. Study subjects (n = 99) were young adult (21-35), current smokers (smoked ≥ 10 CPDs) living in NYC. Compared with baseline, a significant reduction in CPDs was observed at both study time periods (1 and 3 weeks) for intervention (P < .001) and placebo (P < .001) groups. Between-group analyses showed significantly fewer CPDs in the intervention group compared to the placebo group at week 3 (P = .03), but not at any other follow-up periods. The logistic regression analysis showed that using a greater number of ECs, treatment condition and higher baseline readiness to quit were significantly associated with achieving at least 50% reduction in CPDs at the end of treatment. A diverse young adult sample of current everyday smokers, who were not ready to quit, was able to reduce smoking with the help of ECs. Further study is needed to establish the role of both placebo and nicotine containing ECs in increasing both reduction and subsequent cessation. Despite the critical need for well-designed clinical trials on the effect of ECs on cessation and cigarette reduction, the majority of studies have been observational or noncomparative intervention designs. Only three RCTs studying ECs as a cessation or reduction intervention have been published, and none were conducted in the United States. The current study adds knowledge to current literature on the feasibility of using ECs to aid smoking reduction among young smokers in US urban populations. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Electrophysiological responses of dissociated type I cells of the rabbit carotid body to cyanide.

PubMed Central

Biscoe, T J; Duchen, M R

1989-01-01

1. The carotid body is the major peripheral sensor of arterial PO2 in the mammal and is excited by cyanide (CN-). Type I cells, the presumed sites for transduction, were freshly dissociated from the carotid body of the adult rabbit and studied with the whole-cell patch clamp technique. 2. Type I cells were hyperpolarized by CN-, the action potential was shortened, and there was an increased after-hyperpolarization. 3. Under voltage clamp control, CN- increased a voltage-dependent outward current, which showed pronounced outward rectification. Tail currents increased by CN- reversed close to the predicted EK, the reversal potential of the CN--induced current depended on extracellular [K+], and the current was blocked by intracellular TEA+ and Cs+. 4. The i-V relation of the CN--induced conductance strongly mirrored that of voltage-gated Ca2+ entry, and the response was abolished by removal of extracellular Ca2+. We conclude that the increased gK is Ca2+ -dependent (gK(Ca]. 5. The Ca2+ current was attenuated by CN-, and showed an increased rate of inactivation. Thus, the increased gK(Ca) must result from an alteration in Ca2+ homeostasis independent of the Ca2+ current, and not an increased Ca2+ entry through voltage-activated channels. 6. Carbachol also hyperpolarized cells and increased a K+ conductance. 7. At depolarized holding potentials a steady-state outward current was increased by CN-. The current reversed close to EK, and was associated with increased current fluctuations. Noise analysis showed that a channel conductance of 3 pS carries the current. 8. The response to CN- was not impaired by the inclusion of 5 mM-MgATP in the patch pipette. 9. If signals to the CNS are initiated by the calcium-dependent release of transmitters from type I cells, transduction would appear to be the direct consequence of the energy dependence of Ca2+ homeostasis. PMID:2557439

Chloride channel blockers activate an endogenous cationic current in oocytes of Bufo arenarum.

PubMed

Cavarra, M S; del Mónaco, S M; Kotsias, B A

2004-07-01

A two-electrode, voltage-clamp technique was used to measure the effect of the Cl(-) channel blockers, 9-anthracene carboxylic acid and niflumic acid, upon the ionic currents of oocytes of the South American toad Bufo arenarum. The main results were: (1) both blockers produced a reversible increase of the outward currents on a dose-dependent manner; (2) the activated outward current was voltage dependent; (3) the 9-anthracene carboxylic acid-sensitive current was blocked with barium; and (4) the effect of 9-anthracene carboxylic acid was more pronounced in a zero-K(+) solution than in standard (2 mmol l(-1)) or high (20 mmol l(-1)) K(+) solutions, indicating that a K(+) conductance is activated. The effect of the Cl(-) channel blockers could be due to a direct interaction with endogenous cationic channels. Another possible explanation is that Cl(-) that enter the cell during depolarizing steps in control solution inhibit this cationic conductance; thus, the blockade of Cl(-) channels by 9-anthracene carboxylic acid and niflumic acid would remove this inhibition, allowing the cationic current to flow freely.

Trends in E-Cigarette Awareness, Trial, and Use Under the Different Regulatory Environments of Australia and the United Kingdom.

PubMed

Yong, Hua-Hie; Borland, Ron; Balmford, James; McNeill, Ann; Hitchman, Sara; Driezen, Pete; Thompson, Mary E; Fong, Geoffrey T; Cummings, K Michael

2015-10-01

E-cigarettes (ECs) have gained significant attention in recent years. They have been introduced in jurisdictions with divergent existing laws that affect their legality. This provides the opportunity for natural experiments to assess effects of such laws in some cases independent of any formulated government policy. We compare patterns of EC awareness and use over a 3 year period in Australia where laws severely restrict EC availability, with awareness and use in the United Kingdom where ECs are readily available. Data analyzed come from Waves 8 and 9 (collected in 2010 and 2013, respectively) of the International Tobacco Control surveys in Australia and the United Kingdom (approximately 1,500 respondents per wave per country). Across both waves, EC awareness, trial, and use among current and former smokers were significantly greater in the United Kingdom than in Australia, but all 3 of these measures increased significantly between 2010 and 2013 in both countries, and the rate of increase was equivalent between countries. Seventy-three percent of U.K. respondents reported that their current brands contained nicotine as did 43% in Australia even though sale, possession and/or use of nicotine-containing ECs without a permit are illegal in Australia. EC use was greater among smokers in both countries, at least in part due to less uptake by ex-smokers. EC awareness and use have risen rapidly between 2010 and 2013 among current and former smokers in both Australia and the United Kingdom despite different EC regulatory environments. Substantial numbers in both countries are using ECs that contain nicotine. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Modeling the light-induced electric potential difference ΔΨ across the thylakoid membrane based on the transition state rate theory.

PubMed

Lyu, Hui; Lazár, Dušan

2017-03-01

In photosynthesis, electron transport-coupled proton movement initiates the formation of the light-induced electric potential difference, ΔΨ, across the thylakoid membrane (TM). Ions are transported across the TM to counterbalance the charge of protons accumulated in the lumen. The objective of this work is to construct range of mathematical models for simulation of ΔΨ, using the transition state rate theory (TSRT) for description of movement of ions through the channels. The TSRT considers either single-ion (TSRT-SI) or multi-ion occupancy (TSRT-MI) in the channels. Movement of ions through the channel pore is described by means of energy barriers and binding sites; ions move in and out of vacant sites with rate constants that depend on the barrier heights and well depths, as well as on the interionic repulsion in TSRT-MI model. Three energy motifs are used to describe the TSRT-SI model: two-barrier one-site (2B1S), three-barrier two-site (3B2S), and four-barrier three-site (4B3S). The 3B2S energy motif is used for the TSRT-MI model. The accumulation of cations due to the TM surface negative fixed charges is also taken into account. A model employing the electro-diffusion theory instead of the TSRT is constructed for comparison. The dual wavelength transmittance signal (ΔA515-560nm) measuring the electrochromic shift (ECS) provides a proxy for experimental light-induced ΔΨ. The simulated ΔΨ traces qualitatively agree with the measured ECS traces. The models can simulate different channel conducting regimes and assess their impact on ΔΨ. The ionic flux coupling in the TSRT-MI model suggests that an increase in the internal or external K + concentration may block the outward or the inward Mg 2+ current, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

Esophageal cancer in Kenya

PubMed Central

Odera, Joab Otieno; Odera, Elizabeth; Githang’a, Jessie; Walong, Edwin Oloo; Li, Fang; Xiong, Zhaohui; Chen, Xiaoxin Luke

2017-01-01

Kenya belongs to a high incidence region known as Africa’s esophageal cancer (EC) corridor. It has one of the highest incidence rates of EC worldwide, but research on EC in Kenya has gone highly unnoticed. EC in Kenya is unique in its high percentage of young cases (< 30 years of age). In this review, we show the current status of EC in the country. We mainly focus on significant risk factors such as alcohol drinking, genetic factors, malnutrition and hot food/drink. Future directions in the study and prevention of EC in Kenya are also discussed. PMID:29082268

Sodium-bicarbonate cotransport in retinal Müller (glial) cells of the salamander.

PubMed

Newman, E A

1991-12-01

An electrogenic Na+/HCO3- cotransport system was studied in freshly dissociated Müller cells of the salamander retina. Cotransporter currents were recorded from isolated cells using the whole-cell, voltage-clamp technique following the block of K+ conductance with external Ba2+ and internal Cs+. At constant pHo, an outward current was evoked when extracellular HCO3- concentration was raised by pressure ejecting a HCO3(-)-buffered solution onto the surface of cells bathed in nominally HCO3(-)-free solution. The HCO3(-)-evoked outward current was reduced to 4.4% of control by 0.5 mM DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonate), to 28.8% of control by 2 mM DNDS (4,4'-dinitrostilbene-2,2'-disulfonate), and to 28.4% of control by 2 mM harmaline. Substitution of choline for Na+ in bath and ejection solutions reduced the response to 1.3% of control. Bicarbonate-evoked currents of normal magnitude were recorded when methane sulfonate was substituted for Cl- in bath, ejection, and intracellular solutions. Similarly, an outward current was evoked when extracellular Na+ concentration was raised in the presence of HCO3-. The Na(+)-evoked response was reduced to 16.2% of control by 2 mM DNDS and was abolished by removal of HCO3- from bath and ejection solutions. Taken together, these results (block by stilbenes and harmaline, HCO3- and Na+ dependence, Cl- independence) indicate that salamander Müller cells possess an electrogenic Na+/HCO3- cotransport system. Na+/HCO3- cotransporter sites were localized primarily at the endfoot region of Müller cells. Ejection of HCO3- onto the endfoot evoked outward currents 10 times larger than currents evoked by ejections onto the opposite (distal) end of the cell. The reversal potential of the cotransporter was determined by DNDS block of cotransport current. In the absence of a transmembrane HCO3- gradient, the reversal potential varied systematically as a function of the transmembrane Na+ gradient. The reversal potential was -0.1 mV for a [Na+]o:[Na+]i ratio of 1:1 and -25.2 mV for a Na+ gradient ratio of 7.4:1. Based on these values, the estimated stoichiometry of the cotransporter was 2.80 +/- 0.13:1 (HCO3-:Na+). Possible functions of the glial cell Na+/HCO3- cotransporter, including the regulation of CO2 in the retina and the regulation of cerebral blood flow, are discussed.

On the Emergent Constraints of Climate Sensitivity [On proposed emergent constraints of climate sensitivity

DOE PAGES

Qu, Xin; Hall, Alex; DeAngelis, Anthony M.; ...

2018-01-11

Differences among climate models in equilibrium climate sensitivity (ECS; the equilibrium surface temperature response to a doubling of atmospheric CO2) remain a significant barrier to the accurate assessment of societally important impacts of climate change. Relationships between ECS and observable metrics of the current climate in model ensembles, so-called emergent constraints, have been used to constrain ECS. Here a statistical method (including a backward selection process) is employed to achieve a better statistical understanding of the connections between four recently proposed emergent constraint metrics and individual feedbacks influencing ECS. The relationship between each metric and ECS is largely attributable tomore » a statistical connection with shortwave low cloud feedback, the leading cause of intermodel ECS spread. This result bolsters confidence in some of the metrics, which had assumed such a connection in the first place. Additional analysis is conducted with a few thousand artificial metrics that are randomly generated but are well correlated with ECS. The relationships between the contrived metrics and ECS can also be linked statistically to shortwave cloud feedback. Thus, any proposed or forthcoming ECS constraint based on the current generation of climate models should be viewed as a potential constraint on shortwave cloud feedback, and physical links with that feedback should be investigated to verify that the constraint is real. Additionally, any proposed ECS constraint should not be taken at face value since other factors influencing ECS besides shortwave cloud feedback could be systematically biased in the models.« less

On the Emergent Constraints of Climate Sensitivity [On proposed emergent constraints of climate sensitivity

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

Qu, Xin; Hall, Alex; DeAngelis, Anthony M.

Differences among climate models in equilibrium climate sensitivity (ECS; the equilibrium surface temperature response to a doubling of atmospheric CO2) remain a significant barrier to the accurate assessment of societally important impacts of climate change. Relationships between ECS and observable metrics of the current climate in model ensembles, so-called emergent constraints, have been used to constrain ECS. Here a statistical method (including a backward selection process) is employed to achieve a better statistical understanding of the connections between four recently proposed emergent constraint metrics and individual feedbacks influencing ECS. The relationship between each metric and ECS is largely attributable tomore » a statistical connection with shortwave low cloud feedback, the leading cause of intermodel ECS spread. This result bolsters confidence in some of the metrics, which had assumed such a connection in the first place. Additional analysis is conducted with a few thousand artificial metrics that are randomly generated but are well correlated with ECS. The relationships between the contrived metrics and ECS can also be linked statistically to shortwave cloud feedback. Thus, any proposed or forthcoming ECS constraint based on the current generation of climate models should be viewed as a potential constraint on shortwave cloud feedback, and physical links with that feedback should be investigated to verify that the constraint is real. Additionally, any proposed ECS constraint should not be taken at face value since other factors influencing ECS besides shortwave cloud feedback could be systematically biased in the models.« less

Selective activation of heteromeric SK channels contributes to action potential repolarization in mouse atrial myocytes.

PubMed

Hancock, Jane M; Weatherall, Kate L; Choisy, Stéphanie C; James, Andrew F; Hancox, Jules C; Marrion, Neil V

2015-05-01

Activation of small conductance calcium-activated potassium (SK) channels is proposed to contribute to repolarization of the action potential in atrial myocytes. This role is controversial, as these cardiac SK channels appear to exhibit an uncharacteristic pharmacology. The objectives of this study were to resolve whether activation of SK channels contributes to atrial action potential repolarization and to determine the likely subunit composition of the channel. The effect of 2 SK channel inhibitors was assessed on outward current evoked in voltage clamp and on action potential duration in perforated patch and whole-cell current clamp recording from acutely isolated mouse atrial myocytes. The presence of SK channel subunits was assessed using immunocytochemistry. A significant component of outward current was reduced by the SK channel blockers apamin and UCL1684. Block by apamin displayed a sensitivity indicating that this current was carried by homomeric SK2 channels. Action potential duration was significantly prolonged by UCL1684, but not by apamin. This effect was accompanied by an increase in beat-to-beat variability and action potential triangulation. This pharmacology was matched by that of expressed heteromeric SK2-SK3 channels in HEK293 cells. Immunocytochemistry showed that atrial myocytes express both SK2 and SK3 channels with an overlapping expression pattern. Only proposed heteromeric SK2-SK3 channels are physiologically activated to contribute to action potential repolarization, which is indicated by the difference in pharmacology of evoked outward current and prolongation of atrial action potential duration. The effect of blocking this channel on the action potential suggests that SK channel inhibition during cardiac function has the potential to be proarrhythmic. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Endothelial cell metabolism: A novel player in atherosclerosis? Basic principles and therapeutic opportunities.

PubMed

Pircher, Andreas; Treps, Lucas; Bodrug, Natalia; Carmeliet, Peter

2016-10-01

Atherosclerosis is a leading cause of morbidity and mortality in Western society. Despite improved insight into disease pathogenesis and therapeutic options, additional treatment strategies are required. Emerging evidence highlights the relevance of endothelial cell (EC) metabolism for angiogenesis, and indicates that EC metabolism is perturbed when ECs become dysfunctional to promote atherogenesis. In this review, we overview the latest insights on EC metabolism and discuss current knowledge on how atherosclerosis deregulates EC metabolism, and how maladaptation of deregulated EC metabolism can contribute to atherosclerosis progression. We will also highlight possible therapeutic avenues, based on targeting EC metabolism. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Impact of flavour variability on electronic cigarette use experience: an internet survey.

PubMed

Farsalinos, Konstantinos E; Romagna, Giorgio; Tsiapras, Dimitris; Kyrzopoulos, Stamatis; Spyrou, Alketa; Voudris, Vassilis

2013-12-17

A major characteristic of the electronic cigarette (EC) market is the availability of a large number of different flavours. This has been criticised by the public health authorities, some of whom believe that diverse flavours will attract young users and that ECs are a gateway to smoking. At the same time, several reports in the news media mention that the main purpose of flavour marketing is to attract youngsters. The importance of flavourings and their patterns of use by EC consumers have not been adequately evaluated, therefore, the purpose of this survey was to examine and understand the impact of flavourings in the EC experience of dedicated users. A questionnaire was prepared and uploaded in an online survey tool. EC users were asked to participate irrespective of their current smoking status. Participants were divided according to their smoking status at the time of participation in two subgroups: former smokers and current smokers. In total, 4,618 participants were included in the analysis, with 4,515 reporting current smoking status. The vast majority (91.1%) were former smokers, while current smokers had reduced smoking consumption from 20 to 4 cigarettes per day. Both subgroups had a median smoking history of 22 years and had been using ECs for 12 months. On average they were using three different types of liquid flavours on a regular basis, with former smokers switching between flavours more frequently compared to current smokers; 69.2% of the former subgroup reported doing so on a daily basis or within the day. Fruit flavours were more popular at the time of participation, while tobacco flavours were more popular at initiation of EC use. On a scale from 1 (not at all important) to 5 (extremely important) participants answered that variability of flavours was "very important" (score = 4) in their effort to reduce or quit smoking. The majority reported that restricting variability will make ECs less enjoyable and more boring, while 48.5% mentioned that it would increase craving for cigarettes and 39.7% said that it would have been less likely for them to reduce or quit smoking. The number of flavours used was independently associated with smoking cessation. The results of this survey of dedicated users indicate that flavours are marketed in order to satisfy vapers' demand. They appear to contribute to both perceived pleasure and the effort to reduce cigarette consumption or quit smoking. Due to the fact that adoption of ECs by youngsters is currently minimal, it seems that implementing regulatory restrictions to flavours could cause harm to current vapers while no public health benefits would be observed in youngsters. Therefore, flavours variability should be maintained; any potential future risk for youngsters being attracted to ECs can be sufficiently minimized by strictly prohibiting EC sales in this population group.

The Cannabinoid System and Pain

PubMed Central

Woodhams, Stephen G.; Chapman, Victoria; Finn, David P.; Hohmann, Andrea G.; Neugebauer, Volker

2018-01-01

Chronic pain states are highly prevalent and yet poorly controlled by currently available analgesics, representing an enormous clinical, societal, and economic burden. Existing pain medications have significant limitations and adverse effects including tolerance, dependence, gastrointestinal dysfunction, cognitive impairment, and a narrow therapeutic window, making the search for novel analgesics ever more important. In this article, we review the role of an important endogenous pain control system, the endocannabinoid (EC) system, in the sensory, emotional, and cognitive aspects of pain. Herein, we briefly cover the discovery of the EC system and its role in pain processing pathways, before concentrating on three areas of current major interest in EC pain research; 1. Pharmacological enhancement of endocannabinoid activity (via blockade of EC metabolism or allosteric modulation of CB1 receptors); 2. The EC System and stress-induced modulation of pain; and 3. The EC system & medial prefrontal cortex (mPFC) dysfunction in pain states. Whilst we focus predominantly on the preclinical data, we also include extensive discussion of recent clinical failures of endocannabinoid-related therapies, the future potential of these approaches, and important directions for future research on the EC system and pain. PMID:28625720

Differential Expression of Inward and Outward Potassium Currents in the Macrophage-like Cell Line J774.1

DTIC Science & Technology

1985-04-02

skeletal muscle (Adrian, Hodgkin & Chandler, 1970), and nerve (Goldman & Schauf , 1973; Thompson, 1977). The general mathematical formalism describes the...594-609. Goldman, L. & Schauf , C. L. (1973) Quantitative description of sodium and potassium currents and computed action potentials in Myxicola giant

Emergency Contraception.

PubMed

Batur, Pelin; Kransdorf, Lisa N; Casey, Petra M

2016-06-01

Emergency contraception (EC) may help prevent pregnancy in various circumstances, such as contraceptive method failure, unprotected sexual intercourse, or sexual assault, yet it remains underused. There are 4 approved EC options in the United States. Although ulipristal acetate requires a provider's prescription, oral levonorgestrel (LNG) is available over the counter for women of all ages. The most effective method of EC is the copper intrauterine device, which can be left in place for up to 10 years for efficacious, cost-effective, hormone-free, and convenient long-term primary contraception. Ulipristal acetate tends to be more efficacious in pregnancy prevention than is LNG, especially when taken later than 72 hours postcoitus. The mechanism of action of oral EC is delay of ovulation, and current evidence reveals that it is ineffective postovulation. Women who weigh more than 75 kg or have a body mass index greater than 25 kg/m(2) may have a higher risk of unintended pregnancy when using oral LNG EC; therefore, ulipristal acetate or copper intrauterine devices are preferable in this setting. Providers are often unaware of the range of EC options or are unsure of how to counsel patients regarding the access and use of EC. This article critically reviews current EC literature, summarizes recommendations, and provides guidance for counseling women about EC. Useful tips for health care providers are provided, with a focus on special populations, including breast-feeding women and those transitioning to long-term contraception after EC use. When treating women of reproductive age, clinicians should be prepared to counsel them about EC options, provide EC appropriately, and, if needed, refer for EC in a timely manner. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

ToxCast HTS Assay Development and Retrofitting: Strategies ...

EPA Pesticide Factsheets

A presentation to EC JRC partners on new ToxCast HTS assay methods and strategies to address current limitations to HTS methods Slide presentation to EC JRC partners on new ToxCast HTS assay methods and strategies to address current limitations to HTS methods.

Volume-dependent ATP-conductive large-conductance anion channel as a pathway for swelling-induced ATP release.

PubMed

Sabirov, R Z; Dutta, A K; Okada, Y

2001-09-01

In mouse mammary C127i cells, during whole-cell clamp, osmotic cell swelling activated an anion channel current, when the phloretin-sensitive, volume-activated outwardly rectifying Cl(-) channel was eliminated. This current exhibited time-dependent inactivation at positive and negative voltages greater than around +/-25 mV. The whole-cell current was selective for anions and sensitive to Gd(3)+. In on-cell patches, single-channel events appeared with a lag period of approximately 15 min after a hypotonic challenge. Under isotonic conditions, cell-attached patches were silent, but patch excision led to activation of currents that consisted of multiple large-conductance unitary steps. The current displayed voltage- and time-dependent inactivation similar to that of whole-cell current. Voltage-dependent activation profile was bell-shaped with the maximum open probability at -20 to 0 mV. The channel in inside-out patches had the unitary conductance of approximately 400 pS, a linear current-voltage relationship, and anion selectivity. The outward (but not inward) single-channel conductance was suppressed by extracellular ATP with an IC(50) of 12.3 mM and an electric distance (delta) of 0.47, whereas the inward (but not outward) conductance was inhibited by intracellular ATP with an IC(50) of 12.9 mM and delta of 0.40. Despite the open channel block by ATP, the channel was ATP-conductive with P(ATP)/P(Cl) of 0.09. The single-channel activity was sensitive to Gd(3)+, SITS, and NPPB, but insensitive to phloretin, niflumic acid, and glibenclamide. The same pharmacological pattern was found in swelling-induced ATP release. Thus, it is concluded that the volume- and voltage-dependent ATP-conductive large-conductance anion channel serves as a conductive pathway for the swelling-induced ATP release in C127i cells.

Intrinsic spontaneous activity and subthreshold oscillations in neurones of the rat dorsal column nuclei in culture

PubMed Central

Reboreda, Antonio; Sánchez, Estela; Romero, Marcos; Lamas, J Antonio

2003-01-01

The basis of rhythmic activity observed at the dorsal column nuclei (DCN) is still open to debate. This study has investigated the electrophysiological properties of isolated DCN neurones deprived of any synaptic influence, using the perforated-patch technique. About half of the DCN neurones (64/130) were spontaneously active. More than half of the spontaneous neurones (36/64) showed a low threshold membrane oscillation (LTO) with a mean frequency of 11.4 Hz (range: 4.3–22.1 Hz, n = 20; I = 0). Cells showing LTOs also invariably showed a rhythmic 1.2 Hz clustering activity (groups of 2–5 action potentials separated by silent LTO periods). Also, more than one-third of the silent neurones presented clustering activity, always accompanied by LTOs, when slightly depolarised. The frequency of LTOs was voltage dependent and could be abolished by TTX (0.5 μM) and riluzole (30 μM), suggesting the participation of a sodium current. LTOs were also abolished by TEA (15 mM), which transformed clustering into tonic activity. In voltage clamp, most DCN neurones (85 %) showed a TTX-/riluzole-sensitive persistent sodium current (INa,p), which activated at about -60 mV and had a half-maximum activation at −49.8 mV. An M-like, non-inactivating outward current was present in 95 % of DCN neurones, and TEA (15 mM) inhibited this current by 73.7 %. The non-inactivating outward current was also inhibited by barium (1 mM) and linopirdine (10 μM), which suggests its M-like nature; both drugs failed to block the LTOs, but induced a reduction in their frequency by 56 and 20 %, respectively. These results demonstrate for the first time that DCN neurones have a complex and intrinsically driven clustering discharge pattern, accompanied by subthreshold membrane oscillations. Subthreshold oscillations rely on the interplay of a persistent sodium current and a non-inactivating TEA-sensitive outward current. PMID:12844503

Effects of Xinjining extract on inward rectifier potassium current in ventricular myocytes of guinea pig.

PubMed

Zhu, Ming-jun; Wang, Guo-juan; Wang, Yong-xia; Pu, Jie-lin; Liu, Hong-jun; Yu, Hai-bin

2010-02-01

To study the effect of Xinjining extract (, XJN) on inward rectifier potassium current (I(K1)) in ventricular myocyte (VMC) of guinea pigs and its anti-arrhythmic mechanism on ion channel level. Single VMC was enzymatically isolated by zymolisis, and whole-cell patch clamp recording technique was used to record the I(k1) in VMC irrigated with XJN of different concentrations (1.25, 2.50, 5.00 g/L; six samples for each). The stable current and conductance of the inward component of I(K1) as well as the outward component of peak I(K1) and conductance of it accordingly was recorded when the test voltage was set on -110 mV. The suppressive rate of XJN on the inward component of I(K1) was 9.54% + or - 5.81%, 34.82% + or - 15.03%, and 59.52% + or - 25.58% with a concentration of 1.25, 2.50, and 5.00 g/L, respectively, and that for the outward component of peak I(K1) was 23.94% + or - 7.45%, 52.98% + or - 19.62%, and 71.42% + or - 23.01%, respectively (all P<0.05). Moreover, different concentrations of XJN also showed effects for reducing I(K1) conductance. XJN has inhibitory effect on I(K1) in guinea pig's VMC, and that of the same concentration shows stronger inhibition on outward component than on inward component, which may be one of the mechanisms of its anti-arrhythmic effect.

Kv4.2 Knockout Mice Have Hippocampal-Dependent Learning and Memory Deficits

ERIC Educational Resources Information Center

Lugo, Joaquin N.; Brewster, Amy L.; Spencer, Corinne M.; Anderson, Anne E.

2012-01-01

Kv4.2 channels contribute to the transient, outward K[superscript +] current (A-type current) in hippocampal dendrites, and modulation of this current substantially alters dendritic excitability. Using Kv4.2 knockout (KO) mice, we examined the role of Kv4.2 in hippocampal-dependent learning and memory. We found that Kv4.2 KO mice showed a deficit…

Status of Europe's contribution to the ITER EC system

NASA Astrophysics Data System (ADS)

Albajar, F.; Aiello, G.; Alberti, S.; Arnold, F.; Avramidis, K.; Bader, M.; Batista, R.; Bertizzolo, R.; Bonicelli, T.; Braunmueller, F.; Brescan, C.; Bruschi, A.; von Burg, B.; Camino, K.; Carannante, G.; Casarin, V.; Castillo, A.; Cauvard, F.; Cavalieri, C.; Cavinato, M.; Chavan, R.; Chelis, J.; Cismondi, F.; Combescure, D.; Darbos, C.; Farina, D.; Fasel, D.; Figini, L.; Gagliardi, M.; Gandini, F.; Gantenbein, G.; Gassmann, T.; Gessner, R.; Goodman, T. P.; Gracia, V.; Grossetti, G.; Heemskerk, C.; Henderson, M.; Hermann, V.; Hogge, J. P.; Illy, S.; Ioannidis, Z.; Jelonnek, J.; Jin, J.; Kasparek, W.; Koning, J.; Krause, A. S.; Landis, J. D.; Latsas, G.; Li, F.; Mazzocchi, F.; Meier, A.; Moro, A.; Nousiainen, R.; Purohit, D.; Nowak, S.; Omori, T.; van Oosterhout, J.; Pacheco, J.; Pagonakis, I.; Platania, P.; Poli, E.; Preis, A. K.; Ronden, D.; Rozier, Y.; Rzesnicki, T.; Saibene, G.; Sanchez, F.; Sartori, F.; Sauter, O.; Scherer, T.; Schlatter, C.; Schreck, S.; Serikov, A.; Siravo, U.; Sozzi, C.; Spaeh, P.; Spichiger, A.; Strauss, D.; Takahashi, K.; Thumm, M.; Tigelis, I.; Vaccaro, A.; Vomvoridis, J.; Tran, M. Q.; Weinhorst, B.

2015-03-01

The electron cyclotron (EC) system of ITER for the initial configuration is designed to provide 20MW of RF power into the plasma during 3600s and a duty cycle of up to 25% for heating and (co and counter) non-inductive current drive, also used to control the MHD plasma instabilities. The EC system is being procured by 5 domestic agencies plus the ITER Organization (IO). F4E has the largest fraction of the EC procurements, which includes 8 high voltage power supplies (HVPS), 6 gyrotrons, the ex-vessel waveguides (includes isolation valves and diamond windows) for all launchers, 4 upper launchers and the main control system. F4E is working with IO to improve the overall design of the EC system by integrating consolidated technological advances, simplifying the interfaces, and doing global engineering analysis and assessments of EC heating and current drive physics and technology capabilities. Examples are the optimization of the HVPS and gyrotron requirements and performance relative to power modulation for MHD control, common qualification programs for diamond window procurements, assessment of the EC grounding system, and the optimization of the launcher steering angles for improved EC access. Here we provide an update on the status of Europe's contribution to the ITER EC system, and a summary of the global activities underway by F4E in collaboration with IO for the optimization of the subsystems.

Access to Emergency Contraception in the Over-the-Counter Era

PubMed Central

Cleland, Kelly; Bass, Jamie; Doci, Florida; Foster, Angel M.

2016-01-01

Introduction After years of complex regulatory changes, levonorgestrel emergency contraception (LNG EC) is now approved for unrestricted sale in the US. Timely access to EC pills is critical because they are more likely to work the sooner they are taken. This study assesses whether LNG EC is sold in accordance with current Food and Drug Administration regulations. Methods We distributed an online questionnaire through an EC-focused listserv for reproductive health professionals, asking data collectors to visit local stores and document product names, price, over-the-counter (OTC) shelf availability, and misinformation about age restrictions. We used Chi-square analysis to assess bivariate associations and t-tests and Wilcoxon rank-sum tests to determine differences in means. Results We collected information about 220 stores. The majority (65%) stocked EC on OTC shelves, although only 22% of these displayed it without a locked security enclosure. Chain pharmacies were more likely to shelf-stock EC than independent pharmacies (77% vs 5%; p=0.000), but variation existed among stores within the same chain. Among stores that were asked, 40% incorrectly reported an age restriction for non-prescription purchase of LNG EC, while 95% correctly reported that men can buy LNG EC. The average price of branded and generic LNG EC was $49.64 and $40.05, respectively. Conclusion Changes in the regulatory status of LNG EC have resulted in widespread confusion about how EC can be sold, and its high price contributes to access barriers. Retailers should ensure that consumers can access LNG EC quickly and easily by stocking the product on OTC shelves and educating staff about current regulations. PMID:27682018

An Electronic Commerce Course for Undergraduate I.S. Majors: A Review of Current EC Courses and a Course Outline.

ERIC Educational Resources Information Center

Dutt, James S.

Although electronic commerce (EC) has been a reality for more than two decades, interest in EC has exploded within the past three years due to the increased business use of the Internet and the World Wide Web. While companies are increasingly looking for individuals with knowledge of and/or a background in EC, they are finding that most…

Reconstruction of the action potential of ventricular myocardial fibres

PubMed Central

Beeler, G. W.; Reuter, H.

1977-01-01

1. A mathematical model of membrane action potentials of mammalian ventricular myocardial fibres is described. The reconstruction model is based as closely as possible on ionic currents which have been measured by the voltage-clamp method. 2. Four individual components of ionic current were formulated mathematically in terms of Hodgkin—Huxley type equations. The model incorporates two voltage- and time-dependent inward currents, the excitatory inward sodium current, iNa, and a secondary or slow inward current, is, primarily carried by calcium ions. A time-independent outward potassium current, iK1, exhibiting inward-going rectification, and a voltage- and time-dependent outward current, ix1, primarily carried by potassium ions, are further elements of the model. 3. The iNa is primarily responsible for the rapid upstroke of the action potential, while the other current components determine the configuration of the plateau of the action potential and the re-polarization phase. The relative importance of inactivation of is and of activation of ix1 for termination of the plateau is evaluated by the model. 4. Experimental phenomena like slow recovery of the sodium system from inactivation, frequency dependence of the action potential duration, all-or-nothing re-polarization, membrane oscillations are adequately described by the model. 5. Possible inadequacies and shortcomings of the model are discussed. PMID:874889

Removal of malachite green from aqueous solutions by electrocoagulation/peanut shell adsorption coupling in a batch system.

PubMed

Wang, Xiansheng; Ni, Jiaheng; Pang, Shuo; Li, Ying

2017-04-01

A electrocoagulation (EC)/peanut shell (PS) adsorption coupling technique was studied for the removal of malachite green (MG) in our present work. The addition of an appropriate PS dosage (5 g/L) resulted in remarkable increase in the removal efficiency of MG at lower current density and shorter operating time compared with the conventional EC process. The effect of current density, pH of MG solution, dosage of PS and initial concentration of MG were also investigated. The maximum removal efficiency of MG was 98% under optimum conditions in 5 min. And it was 23% higher than that in EC process. Furthermore, the unit energy demand (UED) and the unit electrode material demand (UEMD) were calculated and discussed. The results demonstrated that the EC/PS adsorption coupling method achieved a reduction of 94% UED and UEMD compared with EC process.

Nonlinear evolution of three-dimensional instabilities of thin and thick electron scale current sheets: Plasmoid formation and current filamentation

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

Jain, Neeraj; Büchner, Jörg; Max Planck Institute for Solar System Research, Justus-Von-Liebig-Weg-3, Göttingen

Nonlinear evolution of three dimensional electron shear flow instabilities of an electron current sheet (ECS) is studied using electron-magnetohydrodynamic simulations. The dependence of the evolution on current sheet thickness is examined. For thin current sheets (half thickness =d{sub e}=c/ω{sub pe}), tearing mode instability dominates. In its nonlinear evolution, it leads to the formation of oblique current channels. Magnetic field lines form 3-D magnetic spirals. Even in the absence of initial guide field, the out-of-reconnection-plane magnetic field generated by the tearing instability itself may play the role of guide field in the growth of secondary finite-guide-field instabilities. For thicker current sheetsmore » (half thickness ∼5 d{sub e}), both tearing and non-tearing modes grow. Due to the non-tearing mode, current sheet becomes corrugated in the beginning of the evolution. In this case, tearing mode lets the magnetic field reconnect in the corrugated ECS. Later thick ECS develops filamentary structures and turbulence in which reconnection occurs. This evolution of thick ECS provides an example of reconnection in self-generated turbulence. The power spectra for both the thin and thick current sheets are anisotropic with respect to the electron flow direction. The cascade towards shorter scales occurs preferentially in the direction perpendicular to the electron flow.« less

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.

Activation of muscarinic M3 receptors inhibits large-conductance voltage- and Ca2+-activated K+ channels in rat urinary bladder smooth muscle cells

PubMed Central

Parajuli, Shankar P.

2013-01-01

Large conductance voltage- and Ca2+-activated K+ (BK) channels are key regulators of detrusor smooth muscle (DSM) contraction and relaxation during urine voiding and storage. Here, we explored whether BK channels are regulated by muscarinic receptors (M-Rs) in native freshly isolated rat DSM cells under physiological conditions using the perforated whole cell patch-clamp technique and pharmacological inhibitors. M-R activation with carbachol (1 μM) initially evoked large transient outward BK currents, followed by inhibition of the spontaneous transient outward BK currents (STBKCs) in DSM cells. Carbachol (1 μM) also inhibited the amplitude and frequency of spontaneous transient hyperpolarizations (STHs) and depolarized the DSM cell membrane potential. Selective inhibition of the muscarinic M3 receptors (M3-Rs) with 4-diphenylacetoxy-N-methylpiperidine (4-DAMP; 0.1 μM), but not muscarinic M2 receptors with methoctramine (1 μM), blocked the carbachol inhibitory effects on STBKCs. Furthermore, blocking the inositol 1,4,5-triphosphate (IP3) receptors with xestospongin-C (1 μM) inhibited the carbachol-induced large transient outward BK currents without affecting carbachol inhibitory effects on STBKCs. Upon pharmacological inhibition of all known cellular sources of Ca2+ for BK channel activation, carbachol (1 μM) did not affect the voltage-step-induced steady-state BK currents, suggesting that the muscarinic effects in DSM cells are mediated by mobilization of intracellular Ca2+. In conclusion, our findings provide strong evidence that activation of M3-Rs leads to inhibition of the STBKCs, STHs, and depolarization of DSM cells. Collectively, the data suggest the existence of functional interactions between BK channels and M3-Rs at a cellular level in DSM. PMID:23703523

Proteomic identification of dysferlin-interacting protein complexes in human vascular endothelium

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

Leung, Cleo; Utokaparch, Soraya; Sharma, Arpeeta

2011-11-18

Highlights: Black-Right-Pointing-Pointer Bi-directional (inward and outward) movement of GFP-dysferlin in COS-7 cells. Black-Right-Pointing-Pointer Dysferlin interacts with key signaling proteins for transcytosis in EC. Black-Right-Pointing-Pointer Dysferlin mediates trafficking of vesicles carrying protein cargos in EC. -- Abstract: Dysferlin is a membrane-anchored protein known to facilitate membrane repair in skeletal muscles following mechanical injury. Mutations of dysferlin gene impair sarcolemma integrity, a hallmark of certain forms of muscular dystrophy in patients. Dysferlin contains seven calcium-dependent C2 binding domains, which are required to promote fusion of intracellular membrane vesicles. Emerging evidence reveal the unexpected expression of dysferlin in non-muscle, non-mechanically active tissues, suchmore » as endothelial cells, which cast doubts over the belief that ferlin proteins act exclusively as membrane repair proteins. We and others have shown that deficient trafficking of membrane bound proteins in dysferlin-deficient cells, suggesting that dysferlin might mediate trafficking of client proteins. Herein, we describe the intracellular trafficking and movement of GFP-dysferlin positive vesicles in unfixed reconstituted cells using live microscopy. By performing GST pull-down assays followed by mass spectrometry, we identified dysferlin binding protein complexes in human vascular endothelial cells. Together, our data further support the claims that dysferlin not only mediates membrane repair but also trafficking of client proteins, ultimately, help bridging dysferlinopathies to aberrant membrane signaling.« less

Effect of Ionic Diffusion on Extracellular Potentials in Neural Tissue

PubMed Central

Halnes, Geir; Mäki-Marttunen, Tuomo; Keller, Daniel; Pettersen, Klas H.; Andreassen, Ole A.

2016-01-01

Recorded potentials in the extracellular space (ECS) of the brain is a standard measure of population activity in neural tissue. Computational models that simulate the relationship between the ECS potential and its underlying neurophysiological processes are commonly used in the interpretation of such measurements. Standard methods, such as volume-conductor theory and current-source density theory, assume that diffusion has a negligible effect on the ECS potential, at least in the range of frequencies picked up by most recording systems. This assumption remains to be verified. We here present a hybrid simulation framework that accounts for diffusive effects on the ECS potential. The framework uses (1) the NEURON simulator to compute the activity and ionic output currents from multicompartmental neuron models, and (2) the electrodiffusive Kirchhoff-Nernst-Planck framework to simulate the resulting dynamics of the potential and ion concentrations in the ECS, accounting for the effect of electrical migration as well as diffusion. Using this framework, we explore the effect that ECS diffusion has on the electrical potential surrounding a small population of 10 pyramidal neurons. The neural model was tuned so that simulations over ∼100 seconds of biological time led to shifts in ECS concentrations by a few millimolars, similar to what has been seen in experiments. By comparing simulations where ECS diffusion was absent with simulations where ECS diffusion was included, we made the following key findings: (i) ECS diffusion shifted the local potential by up to ∼0.2 mV. (ii) The power spectral density (PSD) of the diffusion-evoked potential shifts followed a 1/f2 power law. (iii) Diffusion effects dominated the PSD of the ECS potential for frequencies up to several hertz. In scenarios with large, but physiologically realistic ECS concentration gradients, diffusion was thus found to affect the ECS potential well within the frequency range picked up in experimental recordings. PMID:27820827

Effect of Ionic Diffusion on Extracellular Potentials in Neural Tissue.

PubMed

Halnes, Geir; Mäki-Marttunen, Tuomo; Keller, Daniel; Pettersen, Klas H; Andreassen, Ole A; Einevoll, Gaute T

2016-11-01

Recorded potentials in the extracellular space (ECS) of the brain is a standard measure of population activity in neural tissue. Computational models that simulate the relationship between the ECS potential and its underlying neurophysiological processes are commonly used in the interpretation of such measurements. Standard methods, such as volume-conductor theory and current-source density theory, assume that diffusion has a negligible effect on the ECS potential, at least in the range of frequencies picked up by most recording systems. This assumption remains to be verified. We here present a hybrid simulation framework that accounts for diffusive effects on the ECS potential. The framework uses (1) the NEURON simulator to compute the activity and ionic output currents from multicompartmental neuron models, and (2) the electrodiffusive Kirchhoff-Nernst-Planck framework to simulate the resulting dynamics of the potential and ion concentrations in the ECS, accounting for the effect of electrical migration as well as diffusion. Using this framework, we explore the effect that ECS diffusion has on the electrical potential surrounding a small population of 10 pyramidal neurons. The neural model was tuned so that simulations over ∼100 seconds of biological time led to shifts in ECS concentrations by a few millimolars, similar to what has been seen in experiments. By comparing simulations where ECS diffusion was absent with simulations where ECS diffusion was included, we made the following key findings: (i) ECS diffusion shifted the local potential by up to ∼0.2 mV. (ii) The power spectral density (PSD) of the diffusion-evoked potential shifts followed a 1/f2 power law. (iii) Diffusion effects dominated the PSD of the ECS potential for frequencies up to several hertz. In scenarios with large, but physiologically realistic ECS concentration gradients, diffusion was thus found to affect the ECS potential well within the frequency range picked up in experimental recordings.

New concepts for an old problem: the diagnosis of endometrial hyperplasia

PubMed Central

Sanderson, Peter A.; Critchley, Hilary O.D.; Williams, Alistair R.W.; Arends, Mark J.; Saunders, Philippa T.K.

2017-01-01

Abstract BACKGROUND Endometrial hyperplasia (EH) is a uterine pathology representing a spectrum of morphological endometrial alterations. It is predominantly characterized by an increase in the endometrial gland-to-stroma ratio when compared to normal proliferative endometrium. The clinical significance of EH lies in the associated risk of progression to endometrioid endometrial cancer (EC) and ‘atypical’ forms of EH are regarded as premalignant lesions. Traditional histopathological classification systems for EH exhibit wide and varying degrees of diagnostic reproducibility and, as a consequence, standardized patient management can be challenging. OBJECTIVE AND RATIONALE EC is the most common gynaecological malignancy in developed countries. The incidence of EC is rising, with alarming increases described in the 40–44-year-old age group. This review appraises the current EH classification systems used to stratify women at risk of malignant progression to EC. In addition, we summarize the evidence base regarding the use of immunohistochemical biomarkers for EH and discuss an emerging role for genomic analysis. SEARCH METHODS PubMed, Medline and the Cochrane Database were searched for original peer-reviewed primary and review articles, from January 2000 to January 2016. The following search terms were used: ‘endometrial hyperplasia’, ‘endometrial intraepithelial neoplasia’, ‘atypical hyperplasia’, ‘complex atypical hyperplasia’, ‘biomarker’, ‘immunohistochemistry’, ‘progression’, ‘genomic’, ‘classification’ and ‘stratification’. OUTCOMES Recent changes to EH classification reflect our current understanding of the genesis of endometrioid ECs. The concept of endometrial intraepithelial neoplasia (EIN) as a mutationally activated, monoclonal pre-malignancy represents a fundamental shift from the previously held notion that unopposed oestrogenic stimulation causes ever-increasing hyperplastic proliferation, with accumulating cytological atypia that imperceptibly leads to the development of endometrioid EC. Our review highlights several key biomarker candidates that have been described as both diagnostic tools for EH and markers of progression to EC. We propose that, moving forwards, a ‘panel’ approach of combinations of the immunohistochemical biomarkers described in this review may be more informative since no single candidate can currently fill the entire role. WIDER IMPLICATIONS EC has historically been considered a predominantly postmenopausal disease. Owing in part to the current unprecedented rates of obesity, we are starting to see signs of a shift towards a rising incidence of EC amongst pre- and peri-menopausal woman. This creates unique challenges both diagnostically and therapeutically. Furthering our understanding of the premalignant stages of EC development will allow us to pursue earlier diagnosis and facilitate appropriate stratification of women at risk of developing EC, permitting timely and appropriate therapeutic interventions. PMID:27920066

New concepts for an old problem: the diagnosis of endometrial hyperplasia.

PubMed

Sanderson, Peter A; Critchley, Hilary O D; Williams, Alistair R W; Arends, Mark J; Saunders, Philippa T K

2017-03-01

Endometrial hyperplasia (EH) is a uterine pathology representing a spectrum of morphological endometrial alterations. It is predominantly characterized by an increase in the endometrial gland-to-stroma ratio when compared to normal proliferative endometrium. The clinical significance of EH lies in the associated risk of progression to endometrioid endometrial cancer (EC) and 'atypical' forms of EH are regarded as premalignant lesions. Traditional histopathological classification systems for EH exhibit wide and varying degrees of diagnostic reproducibility and, as a consequence, standardized patient management can be challenging. EC is the most common gynaecological malignancy in developed countries. The incidence of EC is rising, with alarming increases described in the 40-44-year-old age group. This review appraises the current EH classification systems used to stratify women at risk of malignant progression to EC. In addition, we summarize the evidence base regarding the use of immunohistochemical biomarkers for EH and discuss an emerging role for genomic analysis. PubMed, Medline and the Cochrane Database were searched for original peer-reviewed primary and review articles, from January 2000 to January 2016. The following search terms were used: 'endometrial hyperplasia', 'endometrial intraepithelial neoplasia', 'atypical hyperplasia', 'complex atypical hyperplasia', 'biomarker', 'immunohistochemistry', 'progression', 'genomic', 'classification' and 'stratification'. Recent changes to EH classification reflect our current understanding of the genesis of endometrioid ECs. The concept of endometrial intraepithelial neoplasia (EIN) as a mutationally activated, monoclonal pre-malignancy represents a fundamental shift from the previously held notion that unopposed oestrogenic stimulation causes ever-increasing hyperplastic proliferation, with accumulating cytological atypia that imperceptibly leads to the development of endometrioid EC. Our review highlights several key biomarker candidates that have been described as both diagnostic tools for EH and markers of progression to EC. We propose that, moving forwards, a 'panel' approach of combinations of the immunohistochemical biomarkers described in this review may be more informative since no single candidate can currently fill the entire role. EC has historically been considered a predominantly postmenopausal disease. Owing in part to the current unprecedented rates of obesity, we are starting to see signs of a shift towards a rising incidence of EC amongst pre- and peri-menopausal woman. This creates unique challenges both diagnostically and therapeutically. Furthering our understanding of the premalignant stages of EC development will allow us to pursue earlier diagnosis and facilitate appropriate stratification of women at risk of developing EC, permitting timely and appropriate therapeutic interventions. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

Fluid flow plate for decreased density of fuel cell assembly

DOEpatents

Vitale, Nicholas G.

1999-01-01

A fluid flow plate includes first and second outward faces. Each of the outward faces has a flow channel thereon for carrying respective fluid. At least one of the fluids serves as reactant fluid for a fuel cell of a fuel cell assembly. One or more pockets are formed between the first and second outward faces for decreasing density of the fluid flow plate. A given flow channel can include one or more end sections and an intermediate section. An interposed member can be positioned between the outward faces at an interface between an intermediate section, of one of the outward faces, and an end section, of that outward face. The interposed member can serve to isolate the reactant fluid from the opposing outward face. The intermediate section(s) of flow channel(s) on an outward face are preferably formed as a folded expanse.

Evaluation of eddy current and magnetic techniques for inspecting rebars in bridge barrier rails

NASA Astrophysics Data System (ADS)

Lo, C. C. H.; Nakagawa, N.

2013-01-01

This paper reports on a feasibility study of using eddy current (EC) and magnetic flux leakage (MFL) methods to detect corrosion damage in rebars that anchor concrete barrier rails to the road deck of bridge structures. EC and MFL measurements were carried out on standalone rebars with and without artificial defects of 25% and 50% material loss, using a commercial EC-based rebar locator and a MFL system that was developed using giant magnetoresistance sensors to detect leakage fluxes from the defects. Both techniques can readily detect the defects at a distance of 2.5″ (63.5 mm). The amplitudes of the EC and MFL signals vary monotonically with the amount of material loss, indicating the potential of using the techniques to quantify material loss of standalone rebars.

ERP Correlates of Effortful Control in Children with Varying Levels of ADHD Symptoms

ERIC Educational Resources Information Center

Wiersema, Jan R.; Roeyers, Herbert

2009-01-01

As effortful control (EC), the self-regulation aspect of temperament, has been argued to play a key role in the normal and psychopathological course of development, research adding to the construct validity of EC is needed. In the current study, interrelations between the temperament construct of EC and the efficiency of the executive attention…

The fate of pharmaceuticals and personal care products (PPCPs), endocrine disrupting contaminants (EDCs), metabolites and illicit drugs in a WWTW and environmental waters.

PubMed

Archer, Edward; Petrie, Bruce; Kasprzyk-Hordern, Barbara; Wolfaardt, Gideon M

2017-05-01

A large number of emerging contaminants (ECs) are known to persist in surface waters, and create pressure on wastewater treatment works (WWTW) for their effective removal. Although a large database for the levels of these pollutants in water systems exist globally, there is still a lack in the correlation of the levels of these pollutants with possible long-term adverse health effects in wildlife and humans, such as endocrine disruption. The current study detected a total of 55 ECs in WWTW influent surface water, 41 ECs in effluent, and 40 ECs in environmental waters located upstream and downstream of the plant. A list of ECs persisted through the WWTW process, with 28% of all detected ECs removed by less than 50%, and 18% of all ECs were removed by less than 25%. Negative mass balances of some pharmaceuticals and metabolites were observed within the WWTW, suggesting possible back-transformation of ECs during wastewater treatment. Three parental illicit drug compounds were detected within the influent of the WWTW, with concentrations ranging between 27.6 and 147.0 ng L -1 for cocaine, 35.6-120.6 ng L -1 for mephedrone, and 270.9-450.2 ng L -1 for methamphetamine. The related environmental risks are also discussed for some ECs, with particular reference to their ability to disrupt endocrine systems. The current study propose the potential of the pharmaceuticals carbamazepine, naproxen, diclofenac and ibuprofen to be regarded as priority ECs for environmental monitoring due to their regular detection and persistence in environmental waters and their possible contribution towards adverse health effects in humans and wildlife. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Present developments in theory of the solar wind

NASA Technical Reports Server (NTRS)

Parker, E. N.

1972-01-01

Current problems and developments in the theory of the large-scale expansion of the solar corona are reviewed. The outstanding question is whether the energy supply to the quiet corona is mainly thermal conduction outward from a region of active heating at its base, or mainly wave propagation outward from the base. It is suggested that the question can be settled only when the properties of the wind can be sampled over a wide range of radial distance from the sun, from far inside the orbit of earth to well beyond. It was suggested that hydromagnetic waves may drive the expansion of the active corona by direct transfer of momentum as well as energy.

Inward rectifier potassium (Kir2.1) channels as end-stage boosters of endothelium-dependent vasodilators.

PubMed

Sonkusare, Swapnil K; Dalsgaard, Thomas; Bonev, Adrian D; Nelson, Mark T

2016-06-15

Increase in endothelial cell (EC) calcium activates calcium-sensitive intermediate and small conductance potassium (IK and SK) channels, thereby causing hyperpolarization and endothelium-dependent vasodilatation. Endothelial cells express inward rectifier potassium (Kir) channels, but their role in endothelium-dependent vasodilatation is not clear. In the mesenteric arteries, only ECs, but not smooth muscle cells, displayed Kir currents that were predominantly mediated by the Kir2.1 isoform. Endothelium-dependent vasodilatations in response to muscarinic receptor, TRPV4 (transient receptor potential vanilloid 4) channel and IK/SK channel agonists were highly attenuated by Kir channel inhibitors and by Kir2.1 channel knockdown. These results point to EC Kir channels as amplifiers of vasodilatation in response to increases in EC calcium and IK/SK channel activation and suggest that EC Kir channels could be targeted to treat endothelial dysfunction, which is a hallmark of vascular disorders. Endothelium-dependent vasodilators, such as acetylcholine, increase intracellular Ca(2+) through activation of transient receptor potential vanilloid 4 (TRPV4) channels in the plasma membrane and inositol trisphosphate receptors in the endoplasmic reticulum, leading to stimulation of Ca(2+) -sensitive intermediate and small conductance K(+) (IK and SK, respectively) channels. Although strong inward rectifier K(+) (Kir) channels have been reported in the native endothelial cells (ECs) their role in EC-dependent vasodilatation is not clear. Here, we test the idea that Kir channels boost the EC-dependent vasodilatation of resistance-sized arteries. We show that ECs, but not smooth muscle cells, of small mesenteric arteries have Kir currents, which are substantially reduced in EC-specific Kir2.1 knockdown (EC-Kir2.1(-/-) ) mice. Elevation of extracellular K(+) to 14 mm caused vasodilatation of pressurized arteries, which was prevented by endothelial denudation and Kir channel inhibitors (Ba(2+) , ML-133) or in the arteries from EC-Kir2.1(-/-) mice. Potassium-induced dilatations were unaffected by inhibitors of TRPV4, IK and SK channels. The Kir channel blocker, Ba(2+) , did not affect currents through TRPV4, IK or SK channels. Endothelial cell-dependent vasodilatations in response to activation of muscarinic receptors, TRPV4 channels or IK/SK channels were reduced, but not eliminated, by Kir channel inhibitors or EC-Kir2.1(-/-) . In angiotensin II-induced hypertension, the Kir channel function was not altered, although the endothelium-dependent vasodilatation was severely impaired. Our results support the concept that EC Kir2 channels boost vasodilatory signals that are generated by Ca(2+) -dependent activation of IK and SK channels. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Mechanisms of leukotriene D4-induced constriction in human small bronchioles

PubMed Central

Snetkov, V A; Hapgood, K J; McVicker, C G; Lee, T H; Ward, J P T

2001-01-01

We examined the mechanisms underlying leukotriene D4- (LTD4) induced constriction of human small (300 – 500 μm i.d.) bronchioles, and the effect of LTD4 on ion currents and Ca2+ transients in smooth muscle cells (SMC) isolated from these bronchioles. LTD4 caused a concentration-dependent bronchoconstriction with an EC50=0.58±0.05 nM (n=7) which was not easily reversible upon washout. This bronchoconstriction was entirely dependent on extracellular Ca2+. Blockade of L-type Ca2+ channels with nifedipine (10 μM) reduced LTD4 response by 39±2% (n=8), whilst La3+, Gd3+ and SK&F 96,365 abolished LTD4-induced bronchoconstriction completely and reversibly, suggesting the majority of Ca2+ entry was via non-selective cation channels. Antagonists of PI-PLC (U73,122 and ET-18-OCH3), PLD (propranolol) and PKC (cheleretrine and Ro31-8220) were without any effect on LTD4-induced bronchoconstriction, whilst the PC-PLC inhibitor D609 caused complete relaxation. Inhibition of protein tyrosine kinase with tyrphostin A23 (100 μM) caused about 50% relaxation, although the inactive analogue tyrphostin A1 was without effect. In freshly isolated SMC from human small bronchioles LTD4 caused a slow increase of intracellular Ca2+ concentration, with a consequent rise of the activity of large conductance Ca2+-dependent K+ channels and the amplitude of depolarization-induced outward whole-cell current. Again, no effect of LTD4 could be observed in the absence of extracellular Ca2+. We conclude that LTD4 causes constriction of these small bronchioles primarily by activating Ca2+ entry via non-voltage gated channels, possibly by a PC-PLC mediated pathway. PMID:11350860

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.

Experimental and analytical study on vibration control effects of eddy-current tuned mass dampers under seismic excitations

NASA Astrophysics Data System (ADS)

Lu, Zheng; Huang, Biao; Zhang, Qi; Lu, Xilin

2018-05-01

Eddy-current tuned mass dampers (EC-TMDs) are non-contacting passive control devices and are developed on the basis of conventional tuned mass dampers. They comprise a solid mass, a stiffness element, and a damping element, wherein the damping mechanism originates from eddy currents. By relative motion between a non-magnetic conductive metal and a permanent magnet in a dynamic system, a time-varying magnetic field is induced in the conductor, thereby generating eddy currents. The eddy currents induce a magnetic field with opposite polarity, causing repulsive forces, i.e., damping forces. This technology can overcome the drawbacks of conventional tuned mass dampers, such as limited service life, deterioration of mechanical properties, and undesired additional stiffness. The experimental and analytical study of this system installed on a multi-degree-of-freedom structure is presented in this paper. A series of shaking table tests were conducted on a five-story steel-frame model with/without an EC-TMD to evaluate the effectiveness and performance of the EC-TMD in suppressing the vibration of the model under seismic excitations. The experimental results show that the EC-TMD can effectively reduce the displacement response, acceleration response, interstory drift ratio, and maximum strain of the columns under different earthquake excitations. Moreover, an analytical method was proposed on the basis of electromagnetic and structural dynamic theories. A comparison between the test and simulation results shows that the simulation method can be used to estimate the response of structures with an EC-TMD under earthquake excitations with acceptable accuracy.

Lightning Channel Corona Formation Treated as a Large System of Streamers

NASA Astrophysics Data System (ADS)

Carlson, B.; Lehtinen, N. G.; Kochkin, P.

2017-12-01

Transfer of charge along a lightning channel leads to strong electric fields that drive such charge outward. This charge flow is nonuniform, breaking up into millimeter-scale discharge structures called streamers. The motion of such streamers can carry charge many meters outward from the channel, but each individual streamer only carries a small amount of charge. Transfer of macroscopic charge outward thus requires a large population of streamers that are expected to interact and exhibit interesting collective behaviors. We attempt to simulate such collective behaviors by approximating the behavior of each streamer but retaining streamer interactions and overall electrodynamic effects and apply this simulation to a few key scenarios. For the case of flow of charge off a lightning channel, we simulate a continually growing population of streamers injected near a charged conducting channel. Further, motivated by lightning initiation, we simulate the growth of a population of streamers from a single seed streamer as might initiate from a hydrometeor. For all cases considered, we characterize the charges and currents involved, compare to observations where possible, and characterize the collective effects including spatial and temporal non-uniformity.

Physiological roles of Kv2 channels in entorhinal cortex layer II stellate cells revealed by Guangxitoxin‐1E

PubMed Central

Hönigsperger, Christoph; Nigro, Maximiliano J.

2016-01-01

Key points Kv2 channels underlie delayed‐rectifier potassium currents in various neurons, although their physiological roles often remain elusive. Almost nothing is known about Kv2 channel functions in medial entorhinal cortex (mEC) neurons, which are involved in representing space, memory formation, epilepsy and dementia.Stellate cells in layer II of the mEC project to the hippocampus and are considered to be space‐representing grid cells. We used the new Kv2 blocker Guangxitoxin‐1E (GTx) to study Kv2 functions in these neurons.Voltage clamp recordings from mEC stellate cells in rat brain slices showed that GTx inhibited delayed‐rectifier K+ current but not transient A‐type current.In current clamp, GTx had multiple effects: (i) increasing excitability and bursting at moderate spike rates but reducing firing at high rates; (ii) enhancing after‐depolarizations; (iii) reducing the fast and medium after‐hyperpolarizations; (iv) broadening action potentials; and (v) reducing spike clustering.GTx is a useful tool for studying Kv2 channels and their functions in neurons. Abstract The medial entorhinal cortex (mEC) is strongly involved in spatial navigation, memory, dementia and epilepsy. Although potassium channels shape neuronal activity, their roles in mEC are largely unknown. We used the new Kv2 blocker Guangxitoxin‐1E (GTx; 10–100 nm) in rat brain slices to investigate Kv2 channel functions in mEC layer II stellate cells (SCs). These neurons project to the hippocampus and are considered to be grid cells representing space. Voltage clamp recordings from SCs nucleated patches showed that GTx inhibited a delayed rectifier K+ current activating beyond –30 mV but not transient A‐type current. In current clamp, GTx (i) had almost no effect on the first action potential but markedly slowed repolarization of late spikes during repetitive firing; (ii) enhanced the after‐depolarization (ADP); (iii) reduced fast and medium after‐hyperpolarizations (AHPs); (iv) strongly enhanced burst firing and increased excitability at moderate spike rates but reduced spiking at high rates; and (v) reduced spike clustering and rebound potentials. The changes in bursting and excitability were related to the altered ADPs and AHPs. Kv2 channels strongly shape the activity of mEC SCs by affecting spike repolarization, after‐potentials, excitability and spike patterns. GTx is a useful tool and may serve to further clarify Kv2 channel functions in neurons. We conclude that Kv2 channels in mEC SCs are important determinants of intrinsic properties that allow these neurons to produce spatial representation. The results of the present study may also be important for the accurate modelling of grid cells. PMID:27562026

Control of Current Profile and Instability by Radiofrequency Wave Injection in JT-60U and Its Applicability in JT-60SA

NASA Astrophysics Data System (ADS)

Isayama, A.; Suzuki, T.; Hayashi, N.; Ide, S.; Hamamatsu, K.; Fujita, T.; Hosoyama, H.; Kamada, Y.; Nagasaki, K.; Oyama, N.; Ozeki, T.; Sakata, S.; Seki, M.; Sueoka, M.; Takechi, M.; Urano, H.

2007-09-01

Recent results of control of current profile and instability using radiofrequency wave in JT-60U and prediction analysis in JT-60SA are descried. In JT-60U, control of current profile in high-beta regime was demonstrated by using a real-time system, where the motional Stark effect diagnostic and lower hybrid wave were used as a detector and actuator, respectively. The minimum value of the safety factor was raised from 1.3 to 1.7 so as to follow the commanded value. Complete stabilization of a neoclassical tearing mode (NTM) with the poloidal mode number m = 2 and the toroidal mode number n = 1 was demonstrated using electron cyclotron (EC) current drive. By scanning the location of EC current drive in detail, strong stabilization effect was found for misalignment less than about half of the full island width. In addition, destabilization of the 2/1 NTM was observed for misalignment comparable to the full island width. Simulation of NTM stabilization in JT-60SA was performed by using the TOPICS code combined with the modified Rutherford equation. The TOPICS simulation showed that complete stabilization can be achieved more effectively by optimizing the EC wave injection angle and modulating the EC wave.

Control of Current Profile and Instability by Radiofrequency Wave Injection in JT-60U and Its Applicability in JT-60SA

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

Isayama, A.; Suzuki, T.; Hayashi, N.

2007-09-28

Recent results of control of current profile and instability using radiofrequency wave in JT-60U and prediction analysis in JT-60SA are descried. In JT-60U, control of current profile in high-beta regime was demonstrated by using a real-time system, where the motional Stark effect diagnostic and lower hybrid wave were used as a detector and actuator, respectively. The minimum value of the safety factor was raised from 1.3 to 1.7 so as to follow the commanded value. Complete stabilization of a neoclassical tearing mode (NTM) with the poloidal mode number m = 2 and the toroidal mode number n = 1 wasmore » demonstrated using electron cyclotron (EC) current drive. By scanning the location of EC current drive in detail, strong stabilization effect was found for misalignment less than about half of the full island width. In addition, destabilization of the 2/1 NTM was observed for misalignment comparable to the full island width. Simulation of NTM stabilization in JT-60SA was performed by using the TOPICS code combined with the modified Rutherford equation. The TOPICS simulation showed that complete stabilization can be achieved more effectively by optimizing the EC wave injection angle and modulating the EC wave.« less

Intrusion Pattern of the Offshore Kuroshio Branch Current and Its Effects on Nutrient Contributions in the East China Sea

NASA Astrophysics Data System (ADS)

Wang, Wentao; Yu, Zhiming; Song, Xiuxian; Yuan, Yongquan; Wu, Zaixing; Zhou, Peng; Cao, Xihua

2018-03-01

During the autumn season of 2014 (October-November), nutrient samples and nitrogen and oxygen isotope samples from the East China Sea (ECS) were collected and analyzed, and auxiliary physical parameters were determined. Distinctive high-salinity water column conditions with significant haloclines and pycnoclines similar to those observed during the spring were detected at the bottom of the ECS during the autumn. These water column conditions were attributed to the intrusion of the Kuroshio Subsurface Water (KSSW), which then separated into two currents, including the Offshore Kuroshio Branch Current (OKBC). Compared with spring, this intrusion transported higher phosphorus (P) concentrations onto the ECS continental shelf in autumn. However, according to multiple analyses, biogeochemical nitrogen processes are unable to explain the variations in the P concentrations (increase) while assuming that each distinctive water column is consistent. Identifying the water columns by their salinities and P concentrations revealed that the northern ECS water column was similar to the deep KSSW while the southern ECS water column was similar to the shallow KSSW. Therefore, we speculate that the distinctions among the seasonal variations of P-enriched water masses were attributable to the different intrusion positions of the Kuroshio. The shift of the KSSW intrusion location moved toward the northeast during the autumn relative to the spring. This shift, which was proved by the oceanic vortex data, caused the deeper KSSW water upwelled to the ECS and formed the OKBC, thereby supplying additional P during the autumn.

AGU Student and Early Career Leadership

NASA Astrophysics Data System (ADS)

Dolan, A. M.; Tamalavage, A.; Crumsey, J.; Klima, K.; Lechner, H. N.; LLera, K.; Oaida, C.; Okoro, M. H.; Riker, J.; van Emmerik, T. H. M.; Enderlein, C.

2017-12-01

The American Geophysical Union (AGU) is the largest single organization dedicated to the advancement of geophysics in order to promote discovery in Earth and space science for the benefit of humanity. AGU unites scientists across disciplines by promoting collaborative advances in Earth, atmospheric, oceanic, hydrologic, space, and planetary sciences. One critical strand of AGU is the volunteer leaders who work together with AGU staff to ensure that the voice of the AGU membership is heard in all forms of decision making within the organization. Volunteer leaders include the president and president elect of individual Section and Focus groups, and importantly Student and Early Career (S/EC) representatives from across the AGU landscape. Here, we will describe the roles of past and current AGU S/EC leaders and how these roles have evolved from the onset of student and early career scientist representation on the AGU Council. We will also discuss current plans for solidifying the relationship between S/EC leaders and other S/EC volunteers within AGU (e.g. those who sit on the executive committees of Section or Focus groups). We will describe the process for becoming an AGU S/EC leader and the roles that current S/EC leaders fulfill on the AGU Council, the Board, the Council Leadership Team, and on various committees that enable decision making and progress within AGU (e.g. the Governance Committee, the Centennial Committee, and the Ethics Committee). Including S/EC volunteers within AGU leadership ensures that the organization indeed progresses forward to achieve the vision of AGU: to galvanize a community of Earth and space scientists that collaboratively advances and communicates science and its power to ensure a sustainable future.

Optimization of the ITER electron cyclotron equatorial launcher for improved heating and current drive functional capabilities

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

Farina, D.; Figini, L.; Henderson, M.

2014-06-15

The design of the ITER Electron Cyclotron Heating and Current Drive (EC H and CD) system has evolved in the last years both in goals and functionalities by considering an expanded range of applications. A large effort has been devoted to a better integration of the equatorial and the upper launchers, both from the point of view of the performance and of the design impact on the engineering constraints. However, from the analysis of the ECCD performance in two references H-mode scenarios at burn (the inductive H-mode and the advanced non-inductive scenario), it was clear that the EC power depositionmore » was not optimal for steady-state applications in the plasma region around mid radius. An optimization study of the equatorial launcher is presented here aiming at removing this limitation of the EC system capabilities. Changing the steering of the equatorial launcher from toroidal to poloidal ensures EC power deposition out to the normalized toroidal radius ρ ≈ 0.6, and nearly doubles the EC driven current around mid radius, without significant performance degradation in the core plasma region. In addition to the improved performance, the proposed design change is able to relax some engineering design constraints on both launchers.« less

ECRH System For ITER

NASA Astrophysics Data System (ADS)

Darbos, C.; Henderson, M.; Albajar, F.; Bigelow, T.; Bomcelli, T.; Chavan, R.; Denisov, G.; Farina, D.; Gandini, F.; Heidinger, R.; Goodman, T.; Hogge, J. P.; Kajiwara, K.; Kasugai, A.; Kern, S.; Kobayashi, N.; Oda, Y.; Ramponi, G.; Rao, S. L.; Rasmussen, D.; Rzesnicki, T.; Saibene, G.; Sakamoto, K.; Sauter, O.; Scherer, T.; Strauss, D.; Takahashi, K.; Zohm, H.

2009-11-01

A 26 MW Electron Cyclotron Heating and Current Drive (EC H&CD) system is to be installed for ITER. The main objectives are to provide, start-up assist, central H&CD and control of MHD activity. These are achieved by a combination of two types of launchers, one located in an equatorial port and the second type in four upper ports. The physics applications are partitioned between the two launchers, based on the deposition location and driven current profiles. The equatorial launcher (EL) will access from the plasma axis to mid radius with a relatively broad profile useful for central heating and current drive applications, while the upper launchers (ULs) will access roughly the outer half of the plasma radius with a very narrow peaked profile for the control of the Neoclassical Tearing Modes (NTM) and sawtooth oscillations. The EC power can be switched between launchers on a time scale as needed by the immediate physics requirements. A revision of all injection angles of all launchers is under consideration for increased EC physics capabilities while relaxing the engineering constraints of both the EL and ULs. A series of design reviews are being planned with the five parties (EU, IN, JA, RF, US) procuring the EC system, the EC community and ITER Organization (IO). The review meetings qualify the design and provide an environment for enhancing performances while reducing costs, simplifying interfaces, predicting technology upgrades and commercial availability. In parallel, the test programs for critical components are being supported by IO and performed by the Domestic Agencies (DAs) for minimizing risks. The wide participation of the DAs provides a broad representation from the EC community, with the aim of collecting all expertise in guiding the EC system optimization. Still a strong relationship between IO and the DA is essential for optimizing the design of the EC system and for the installation and commissioning of all ex-vessel components when several teams from several DAs will be involved together in the tests on the ITER site.

Electric and hybrid vehicle environmental control subsystem study

NASA Technical Reports Server (NTRS)

Heitner, K. L.

1980-01-01

An environmental control subsystem (ECS) in electric and hybrid vehicles is studied. A combination of a combustion heater and gasoline engine (Otto cycle) driven vapor compression air conditioner is selected. The combustion heater, the small gasoline engine, and the vapor compression air conditioner are commercially available. These technologies have good cost and performance characteristics. The cost for this ECS is relatively close to the cost of current ECS's. Its effect on the vehicle's propulsion battery is minimal and the ECS size and weight do not have significant impact on the vehicle's range.

ECS Resignations Raise Questions of Fiscal Health: Leader of State Policy Group Says Problems Can Be Fixed

ERIC Educational Resources Information Center

Hoff, David J.

2006-01-01

Kathy Christie, senior vice president at the Education Commission of the States (ECS), resigned on May 1, 2006, saying that the Denver-based group faces a financial crisis, and that she doubts the current ECS president can fix it. By the end of the week, the accounting manager had also resigned, expressing similar concerns, and two policy analysts…

Performance evaluation of multi-material electronic cleansing for ultra-low-dose dual-energy CT colonography

NASA Astrophysics Data System (ADS)

Tachibana, Rie; Kohlhase, Naja; Näppi, Janne J.; Hironaka, Toru; Ota, Junko; Ishida, Takayuki; Regge, Daniele; Yoshida, Hiroyuki

2016-03-01

Accurate electronic cleansing (EC) for CT colonography (CTC) enables the visualization of the entire colonic surface without residual materials. In this study, we evaluated the accuracy of a novel multi-material electronic cleansing (MUMA-EC) scheme for non-cathartic ultra-low-dose dual-energy CTC (DE-CTC). The MUMA-EC performs a wateriodine material decomposition of the DE-CTC images and calculates virtual monochromatic images at multiple energies, after which a random forest classifier is used to label the images into the regions of lumen air, soft tissue, fecal tagging, and two types of partial-volume boundaries based on image-based features. After the labeling, materials other than soft tissue are subtracted from the CTC images. For pilot evaluation, 384 volumes of interest (VOIs), which represented sources of subtraction artifacts observed in current EC schemes, were sampled from 32 ultra-low-dose DE-CTC scans. The voxels in the VOIs were labeled manually to serve as a reference standard. The metric for EC accuracy was the mean overlap ratio between the labels of the reference standard and the labels generated by the MUMA-EC, a dualenergy EC (DE-EC), and a single-energy EC (SE-EC) scheme. Statistically significant differences were observed between the performance of the MUMA/DE-EC and the SE-EC methods (p<0.001). Visual assessment confirmed that the MUMA-EC generated less subtraction artifacts than did DE-EC and SE-EC. Our MUMA-EC scheme yielded superior performance over conventional SE-EC scheme in identifying and minimizing subtraction artifacts on noncathartic ultra-low-dose DE-CTC images.

Ionic mechanisms of action of prion protein fragment PrP(106-126) in rat basal forebrain neurons.

PubMed

Alier, Kwai; Li, Zongming; Mactavish, David; Westaway, David; Jhamandas, Jack H

2010-08-01

Prion diseases are neurodegenerative disorders that are characterized by the presence of the misfolded prion protein (PrP). Neurotoxicity in these diseases may result from prion-induced modulation of ion channel function, changes in neuronal excitability, and consequent disruption of cellular homeostasis. We therefore examined PrP effects on a suite of potassium (K(+)) conductances that govern excitability of basal forebrain neurons. Our study examined the effects of a PrP fragment [PrP(106-126), 50 nM] on rat neurons using the patch clamp technique. In this paradigm, PrP(106-126) peptide, but not the "scrambled" sequence of PrP(106-126), evoked a reduction of whole-cell outward currents in a voltage range between -30 and +30 mV. Reduction of whole-cell outward currents was significantly attenuated in Ca(2+)-free external media and also in the presence of iberiotoxin, a blocker of calcium-activated potassium conductance. PrP(106-126) application also evoked a depression of the delayed rectifier (I(K)) and transient outward (I(A)) potassium currents. By using single cell RT-PCR, we identified the presence of two neuronal chemical phenotypes, GABAergic and cholinergic, in cells from which we recorded. Furthermore, cholinergic and GABAergic neurons were shown to express K(v)4.2 channels. Our data establish that the central region of PrP, defined by the PrP(106-126) peptide used at nanomolar concentrations, induces a reduction of specific K(+) channel conductances in basal forebrain neurons. These findings suggest novel links between PrP signalling partners inferred from genetic experiments, K(+) channels, and PrP-mediated neurotoxicity.

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.

Early diagnostic potential of APC hypermethylation in esophageal cancer.

PubMed

Wang, Bujiang; Song, Haojun; Jiang, Haizhong; Fu, Yangbo; Ding, Xiaoyun; Zhou, Chongchang

2018-01-01

The hypermethylation of APC gene is observed in various cancers, including esophageal cancer (EC). However, the association between APC methylation and the initiation and progression of EC is poorly understood. The current study systematically reviewed studies on abnormal methylation of APC in EC and quantitatively synthesized 18 studies by meta-analysis involving 1008 ECs, 570 Barrett's esophagus (BE), and 782 controls. Our results showed higher methylation of APC in EC (OR = 23.33, P < 0.001) and BE (OR = 9.34, P < 0.001) than in normal controls. Whereas APC methylation in EC was similar to that in BE ( P = 0.052), it was not associated with tumor stage ( P = 0.204). Additionally, APC methylation was not significantly associated with overall survival (OS) and relapse-free survival (RFS) in patients with EC. The performance of APC methylation for the detection of EC and BE achieved areas under the receiver operating characteristic curves of 0.94 and 0.88, respectively. Our results imply that APC methylation detection is a potential diagnostic biomarker for EC and BE.

Population patch-clamp electrophysiology analysis of recombinant GABAA alpha1beta3gamma2 channels expressed in HEK-293 cells.

PubMed

Hollands, Emma C; Dale, Tim J; Baxter, Andrew W; Meadows, Helen J; Powell, Andrew J; Clare, Jeff J; Trezise, Derek J

2009-08-01

Gamma-amino butyric acid (GABA)-activated Cl- channels are critical mediators of inhibitory postsynaptic potentials in the CNS. To date, rational design efforts to identify potent and selective GABA(A) subtype ligands have been hampered by the absence of suitable high-throughput screening approaches. The authors describe 384-well population patch-clamp (PPC) planar array electrophysiology methods for the study of GABA(A) receptor pharmacology. In HEK293 cells stably expressing human alpha1beta3gamma2 GABA(A) channels, GABA evoked outward currents at 0 mV of 1.05 +/- 0.08 nA, measured 8 s post GABA addition. The I(GABA) was linear and reversed close to the theoretical E(Cl) (-56 mV). Concentration-response curve analysis yielded a mean pEC(50) value of 5.4 and Hill slope of 1.5, and for a series of agonists, the rank order of potency was muscimol > GABA > isoguvacine. A range of known positive modulators, including diazepam and pentobarbital, produced concentration-dependent augmentation of the GABA EC( 20) response (1 microM). The competitive antagonists bicuculline and gabazine produced concentration-dependent, parallel, rightward displacement of GABA curves with pA(2) and slope values of 5.7 and 1.0 and 6.7 and 1.0, respectively. In contrast, picrotoxin (0.2-150 microM) depressed the maximal GABA response, implying a non-competitive antagonism. Overall, the pharmacology of human alpha1beta3gamma2 GABA(A) determined by PPC was highly similar to that obtained by conventional patch-clamp methods. In small-scale single-shot screens, Z' values of >0.5 were obtained in agonist, modulator, and antagonist formats with hit rates of 0% to 3%. The authors conclude that despite the inability of the method to resolve the peak agonist responses, PPC can rapidly and usefully quantify pharmacology for the alpha1beta3gamma2 GABA(A) isoform. These data suggest that PPC may be a valuable approach for a focused set and secondary screening of GABA(A) receptors and other slow ligand-gated ion channels.

Experiences of using an Environmental Control System (ECS) for persons with high cervical spinal cord injury: the interplay between hassle and engagement.

PubMed

Verdonck, Michèle; Steggles, Elizabeth; Nolan, Maeve; Chard, Gill

2014-01-01

Environmental Control Systems (ECS) have many benefits; however studies of personal experience of ECS use are scarce. This qualitative study explored the insiders' experience of using an ECS. An ECS starter-pack was compiled and trialled for an eight-week period with six persons with high spinal cord injuries (SCI) living in Ireland. Semi-structured interviews were subsequently completed with each person and analysed using Interpretative Phenomenological Analysis (IPA). Two major themes emerged: "Taking back a little of what has been lost", and "Getting used to ECS" which is the focus of the current paper. This theme captured a dynamic interplay between the experience of "hassle" and "engagement" for new users of ECS. "Hassle" resulted from technological frustrations and the challenge of breaking familiar habits, while "Engagement" resulted from feeling good, having fun and being surprised. The complex interweaving of hassle and engagement experienced by new ECS users reflects the clinical experience of rehabilitation providers. The importance of overcoming initial hassle needs to be understood by clinicians and users in order to maximise the potential benefit of ECS. Non-use must be considered one reasonable outcome if based on realistic ECS trials.

Activation of TRPC channels contributes to OA-NO2-induced responses in guinea-pig dorsal root ganglion neurons

PubMed Central

Zhang, Xiulin; Beckel, Jonathan M; Daugherty, Stephanie L; Wang, Ting; Woodcock, Stephen R; Freeman, Bruce A; de Groat, William C

2014-01-01

Effects of nitro-oleic acid (OA-NO2) on TRP channels were examined in guinea-pig dissociated dorsal root ganglia (DRG) neurons using calcium imaging and patch clamp techniques. OA-NO2 increased intracellular Ca2+ in 60–80% DRG neurons. 1-Oleoyl-2acetyl-sn-glycerol (OAG), a TRPC agonist, elicited responses in 36% of OA-NO2-sensitive neurons while capsaicin (TRPV1 agonist) or allyl-isothiocyanate (AITC, TRPA1 agonist) elicited responses in only 16% and 10%, respectively, of these neurons. A TRPV1 antagonist (diarylpiperazine, 5 μm) in combination with a TRPA1 antagonist (HC-030031, 30 μm) did not change the amplitude of the Ca2+ transients or percentage of neurons responding to OA-NO2; however, a reducing agent DTT (50 mm) or La3+ (50 μm) completely abolished OA-NO2 responses. OA-NO2 also induced a transient inward current associated with a membrane depolarization followed by a prolonged outward current and hyperpolarization in 80% of neurons. The reversal potentials of inward and outward currents were approximately −20 mV and −60 mV, respectively. Inward current was reduced when extracellular Na+ was absent, but unchanged by niflumic acid (100 μm), a Cl− channel blocker. Outward current was abolished in the absence of extracellular Ca2+ or a combination of two Ca2+-activated K+ channel blockers (iberiotoxin, 100 nm and apamin, 1 μm). BTP2 (1 or 10 μm), a broad spectrum TRPC antagonist, or La3+ (50 μm) completely abolished OA-NO2 currents. RT-PCR performed on mRNA extracted from DRGs revealed the expression of all seven subtypes of TRPC channels. These results support the hypothesis that OA-NO2 activates TRPC channels other than the TRPV1 and TRPA1 channels already known to be targets in rat and mouse sensory neurons and challenge the prevailing view that electrophilic compounds act specifically on TRPA1 or TRPV1 channels. The modulation of sensory neuron excitability via actions on multiple TRP channels can contribute to the anti-inflammatory effect of OA-NO2. PMID:25128576

Plasma circulation in Jupiter's magnetosphere

NASA Astrophysics Data System (ADS)

Chané, E.

2017-12-01

We are using our three-dimensional global MHD model of Jupiter's magnetosphere to study the plasma circulation in the magnetodisk. We show that the Iogenic plasma does not travel outward axisymmetrically but rather forms a long spiral arm of high density corotating with the planet. This leads to periodic phenomena in the magnetodisk: for instance, every rotation period, a region of high density is rapidly moving outward on the pre-noon sector. This leads to shearing motions that generate field aligned currents and periodically affect the main oval in this sector.We will also show how the interplanetary magnetic field influences the position of the magnetodisk in our simulations, displacing the current sheet above and below the equatorial plan. We will discuss how this is affecting the depleted flux-tubes returning from the night-side after unloading most of their plasma in the magnetotail (Vasyliunas cycle) and see how they can then move above or below the magnetodisk when arriving at dawn and then reconnect with the interplanetary magnetic field on the day-side.

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

Ahedo, Eduardo; Merino, Mario

A previous axisymmetric model of the supersonic expansion of a collisionless, hot plasma in a divergent magnetic nozzle is extended here in order to include electron-inertia effects. Up to dominant order on all components of the electron velocity, electron momentum equations still reduce to three conservation laws. Electron inertia leads to outward electron separation from the magnetic streamtubes. The progressive plasma filling of the adjacent vacuum region is consistent with electron-inertia being part of finite electron Larmor radius effects, which increase downstream and eventually demagnetize the plasma. Current ambipolarity is not fulfilled and ion separation can be either outwards ormore » inwards of magnetic streamtubes, depending on their magnetization. Electron separation penalizes slightly the plume efficiency and is larger for plasma beams injected with large pressure gradients. An alternative nonzero electron-inertia model [E. Hooper, J. Propul. Power 9, 757 (1993)] based on cold plasmas and current ambipolarity, which predicts inwards electron separation, is discussed critically. A possible competition of the gyroviscous force with electron-inertia effects is commented briefly.« less

Effect of early childhood malnutrition on tooth eruption in Haitian adolescents.

PubMed

Psoter, W; Gebrian, B; Prophete, S; Reid, B; Katz, R

2008-04-01

The objective of this retrospective cohort study was to determine the effects of early childhood protein-energy malnutrition (EC-PEM) and current nutritional status as defined by anthropomorphic measures on the exfoliation and eruption patterns of teeth among adolescents. Oral clinical examinations were conducted in 2005 using World Health Organization (WHO) diagnostic criteria on 498 11- to 13-year-old Haitians for whom early childhood malnutrition data were available. Anthropomorphic records (weight-for-age) from the Haitian Health Foundation computerized database on children from birth through 5-years old were utilized. Current heights and weights were ascertained. Both sets of data were converted to z-scores based on the National Center for Health Statistics (NCHS) referent database. Based upon these z-scores, EC-PEM and current malnutrition categories were developed for this study. The analyses separately regressed the number of primary and permanent teeth on age, gender, EC-PEM status and current nutritional status. Both a delayed exfoliation of primary teeth and a delayed eruption of permanent teeth were associated with EC-PEM and current stunting in adolescence. The observed associations were either direct and statistically significant or indirectly demonstrated by presenting evidence of confounding. The overall interpretation of the models is that malnutrition beginning in the earliest years and extending throughout childhood influences the exfoliation and eruption of teeth. These findings present evidence of an association between tooth exfoliation/eruption patterns and both EC-PEM and nutritional insufficiency (stunting) throughout childhood. This observed delay in the exfoliation of the primary dentition and in the eruption of the permanent dentition has practical significance in interpreting age-specific dental caries data from populations with different malnutrition experiences.

Efficiency analysis of the electrocoagulation and electroflotation treatment of poultry slaughterhouse wastewater using aluminum and graphite anodes.

PubMed

Paulista, Larissa Oliveira; Presumido, Pedro Henrique; Theodoro, Joseane Debora Peruço; Pinheiro, Alexei Lorenzetti Novaes

2018-05-08

The application of electrocoagulation (EC) and electroflotation (EF) was investigated for the treatment of poultry slaughterhouse wastewater in a bench scale unit cell electrolyzer with different EC-to-EF ratios at current densities of 3, 9, and 15 mA cm -2 . The EC-to-EF ratio was controlled by current reversal using aluminum and graphite electrodes. The electrochemical treatment showed satisfactory removal efficiencies for Al coagulant loads greater than 51.8 mg L -1 . The 4/5 EC to EF ratio (69.1 mg L -1 Al and 32.2 NmL L -1 additional EF gas) and 3/5 (51.8 mg L -1 Al/64 NmL L -1 additional EF gas) presented the best results for the removal of COD (76-85%), color (93-99%), and turbidity (95-99%), with the additional benefit of reducing the electrode consumption and sludge disposal costs proportionally to the EC-to-EF ratio. The effects of the EC-to-EF ratio and the current density on efficiency of the electrochemical treatment for the removal of COD, apparent color, turbidity, TSS, TSD, and NH 3 -N were discussed in the light of the physicochemical and electrochemical processes underlying the removal mechanism for each parameter. In particular, the blow-off mechanism seems to play an important role in the NH 3 -N removal, whereas indirect electrooxidation mechanism accounts for a fraction of the soluble COD removal for the electrodes configuration used in the treatment.

[Electrophysiological study on rat conduit pulmonary artery smooth muscle cells under normoxia and acute hypoxia].

PubMed

Hu, Ying; Zou, Fei; Cai, Chun-Qing; Wu, Hang-Yu; Yun, Hai-Xia; Chen, Yun-Tian; Jin, Guo-En; Ge, Ri-Li

2006-10-25

The present study was designed to investigate the electrophysiological characteristics of rat conduit pulmonary artery smooth muscle cells (PASMCs) and the response to acute hypoxia. PASMCs of the 1st to 2nd order branches in the conduit pulmonary arteries were obtained by enzymatic isolation. The PASMCs were divided into acute hypoxia preconditioned group and normoxia group. Hypoxia solutions were achieved by bubbling with 5% CO2 plus 95% N2 for at least 30 min before cell perfusion. Potassium currents were compared between these two groups using whole-cell patch clamp technique. The total outward current of PASMCs was measured under normoxia condition when iBTX [specific blocking agent of large conductance Ca-activated K(+) (BK(Ca)) channel] and 4-AP [specific blocking agent of delayed rectifier K(+) (K(DR)) channel] were added consequently into bath solution. PASMCs were classified into three types according to their size, shape and electrophysiological characteristics. Type I cells are the smallest with spindle shape, smooth surface and discrete perinuclear bulge. Type II cells show the biggest size with banana-like appearance. Type III cells have the similar size with type I, and present intermediary shape between type I and type II. iBTX had little effect on the total outward current in type I cells, while 4-AP almost completely blocked it. Most of the total outward current in type II cells was inhibited by iBTX, and the remaining was sensitive to 4-AP. In type III cells, the total outward current was sensitive to both iBTX and 4-AP. Acute hypoxia reduced the current in all three types of cells: (1614.8+/-62.5) pA to (892.4+/-33.6) pA for type I cells (P<0.01); (438.3+/-42.8) pA to (277.5+/-44.7) pA for type II cells (P<0.01); (1 042.0+/-37.2) pA to (613.6+/-23.8) pA for type III (P<0.01), and raised the resting membrane potentials (E(m)) in all these three types of cells: (-41.6+/-1.6) mV to (-18.6+/-1.5) mV (P<0.01), (-42.3+/-3.8) mV to (-30.6+/-3.0) mV (P<0.01), (-43.3+/-1.6) mV to (-28.4+/-1.4) mV (P<0.01), for type I, II, III cells, respectively. These results suggest that acute hypoxia suppresses the potassium current and improves the E(m) in PASMCs. These effects may be involved in the modulation of constriction/relaxation of conduit artery under acute hypoxia. Different distribution of K(DR) and BK(Ca) channels in these three types of PASMCs might account for their different constriction/relaxation response to acute hypoxia.

Eating competence of college students in an introductory nutrition course.

PubMed

Brown, Lora Beth; Larsen, Katrina J; Nyland, Nora K; Eggett, Dennis L

2013-01-01

Describe eating competence, a positive and flexible way of conceptualizing eating attitudes and behaviors, in students enrolled in an introductory nutrition course. Online completion of the Satter Eating Competence Inventory (ecSI) and self-assessment of eating disorder status by 557 students (343 ages 18-20 years and 180 ages 21-26 years; 377 females) at the beginning of 1 semester. Analysis of variance and post hoc Tukey adjusted tests were used. The mean ecSI score was 30.7 ± 0.29; 47.4% were classified as eating competent, or ecSI ≥ 32. Mean ecSI was higher for males than females (29.4 ± 0.95 vs 27.4 ± 0.77; P < .001). Mean ecSI was higher for students who never had an eating disorder, compared with those reporting current (32.0 ± 0.43 vs 22.9 ± 1.91; P < .001) or past (28.8 ± 0.93; P < .01) eating disorders. Students had limited eating competence, but a majority of males were eating competent. Students who had never had an eating disorder had higher eating competence than students with current or past disorders. Examining nutrition courses as currently taught may reveal ways courses could contribute to eating competence. Copyright © 2013 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

Data Sharing and Scientific Impact in Eddy Covariance Research

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

Bond-Lamberty, B.

Do the benefits of data sharing outweigh its perceived costs? This is a critical question, and one with the potential to change culture and behavior. Dai et al. (2018) examine how data sharing is related to scientific impact in the field of eddy covariance (EC), and find that data sharers are disproportionately high-impact researchers, and vice versa; they also note strong regional differences in EC data sharing norms. The current policies and restrictions of EC journals and repositories are highly uneven. Incentivizing data sharing and enhancing computational reproducibility are critical next steps for EC, ecology, and science more broadly.

Multispacecraft observations of the electron current sheet, neighboring magnetic islands, and electron acceleration during magnetotail reconnection

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

Chen Lijen; Bessho, Naoki; Bhattacharjee, Amitava

Open questions concerning structures and dynamics of diffusion regions and electron acceleration in collisionless magnetic reconnection are addressed based on data from the four-spacecraft mission Cluster and particle-in-cell simulations. Using time series of electron distribution functions measured by the four spacecraft, distinct electron regions around a reconnection layer are mapped out to set the framework for studying diffusion regions. A spatially extended electron current sheet (ecs), a series of magnetic islands, and bursts of energetic electrons within islands are identified during magnetotail reconnection with no appreciable guide field. The ecs is collocated with a layer of electron-scale electric fields normalmore » to the ecs and pointing toward the ecs center plane. Both the observed electron and ion densities vary by more than a factor of 2 within one ion skin depth north and south of the ecs, and from the ecs into magnetic islands. Within each of the identified islands, there is a burst of suprathermal electrons whose fluxes peak at density compression sites [L.-J. Chen et al., Nat. Phys. 4, 19 (2008)] and whose energy spectra exhibit power laws with indices ranging from 6 to 7.3. These results indicate that the in-plane electric field normal to the ecs can be of the electron scale at certain phases of reconnection, electrons and ions are highly compressible within the ion diffusion region, and for reconnection involving magnetic islands, primary electron acceleration occurs within the islands.« less

A New Approach to Look at the Electrical Conductivity of Streamflow: Decomposing a Bulk Signal to Recover Individual Solute Concentrations at High-Frequency

NASA Astrophysics Data System (ADS)

Benettin, P.; Van Breukelen, B. M.

2017-12-01

The ability to evaluate stream hydrochemistry is often constrained by the capacity to sample streamwater at an adequate frequency. While technology is no longer a limiting factor, economic and management efforts can still be a barrier to high-resolution water quality instrumentation. We propose a new framework to investigate the electrical conductivity (EC) of streamwater, which can be measured continuously through inexpensive sensors. We show that EC embeds information on ion content which can be isolated to retrieve solute concentrations at high resolution. The approach can already be applied to a number of datasets worldwide where water quality campaigns are conducted, provided continuous EC measurements can be collected. The essence of the approach is the decomposition of the EC signal into its "harmonics", i.e. the specific contributions of the major ions which conduct current in water. The ion contribution is used to explore water quality patterns and to develop algorithms that reconstruct solute concentrations during periods where solute measurements are not available. The approach is validated on a hydrochemical dataset from Plynlimon, Wales. Results show that the decomposition of EC is feasible and for at least two major elements the methodology provided improved estimates of high-frequency solute dynamics. Our results support the installation of EC probes to complement water quality campaigns and suggest that the potential of EC measurements in rivers is currently far from being fully exploited.

Emerging Contaminants Identification, Concerns, Actions

EPA Science Inventory

This presentation serves as a background introduction to a current EPA/ORD study on the characterization and treatment of emerging contaminants (ECs ) in wet-weather flows. It briefly discusses other ongoing work relating to ECs and provides the foundation for prioritizing the c...

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.

Effects of tetraethylammonium on potassium currents in a molluscan neurons

PubMed Central

1981-01-01

The effects of tetraethylammonium (TEA) on the delayed K+ current and on the Ca2+-activated K+ current of the Aplysia pacemaker neurons R-15 and L-6 were studied. The delayed outward K+ current was measured in Ca2+-free ASW containing tetrodotoxin (TTX), using brief depolarizing clamp pulses. External TEA blocks the delayed K+ current reversibly in a dose-dependent manner. The experimental results are well fitted with a Michaelis-Menten expression, assuming a one-to-one reaction between TEA and a receptor site, with an apparent dissociation constant of 6.0 mM. The block depends on membrane voltage and is reduced at positive membrane potentials. The Ca2+-activated K+ current was measured in Ca2+- free artificial seawater (ASW) containing TTX, using internal Ca2+ ion injection to directly activate the K+ conductance. External TEA and a number of other quaternary ammonium ions block the Ca2+-activated K+ current reversibly in a dose-dependent manner. TEA is the most effective blocker, with an apparent dissociation constant, for a one-to- one reaction with a receptor site, of 0.4 mM. The block decreases with depolarization. The Ca2+-activated K+ current was also measured after intracellular iontophoretic TEA injection. Internal TEA blocks the Ca2+- activated K+ current (but the block is only apparent at positive membrane potentials), is increased by depolarization, and is irreversible. The effects of external and internal TEA can be seen in measurements of the total outward K+ current at different membrane potentials in normal ASW. PMID:6265594

Electroconvection in one-dimensional liquid crystal cells

NASA Astrophysics Data System (ADS)

Huh, Jong-Hoon

2018-04-01

We investigate the alternating current (ac) -driven electroconvection (EC) in one-dimensional cells (1DCs) under the in-plane switching mode. In 1DCs, defect-free EC can be realized. In the presence and absence of external multiplicative noise, the features of traveling waves (TWs), such as their Hopf frequency fH and velocity, are examined in comparison with those of conventional two-dimensional cells (2DCs) accompanying defects of EC rolls. In particular, we show that the defects significantly contribute to the features of the TWs. Additionally, owing to the defect-free EC in the 1DCs, the effects of the ac and noise fields on the TW are clarified. The ac field linearly increases fH, independent of the ac frequency f . The noise increases fH monotonically, but fH does not vary below a characteristic noise intensity VN*. In addition, soliton-like waves and unfamiliar oscillation of EC vortices in 1DCs are observed, in contrast to the localized EC (called worms) and the oscillation of EC rolls in 2DCs.

Research Trends in Emerging Contaminants on the Aquatic Environments of Tanzania

PubMed Central

Miraji, H.; Othman, O. C.; Ngassapa, F. N.; Mureithi, E. W.

2016-01-01

The continuity for discovery and production of new chemicals, allied products, and uses has currently resulted into generation of recent form of contaminants known as Emerging Contaminants (ECs). Once in the aquatic environment ECs are carcinogenic and cause other threats to both human's and animals' health. Due to their effects this study was aimed at investigating research trends of ECs in Tanzania. Findings revealed that USA and EU countries were leading in ECs researches, little followed by Asia, South Africa, and then Zambia. Only few guidelines from USA-EPA, WHO, Canada, and Australia existed. Neither published guidelines nor regulations for ECs existed in Tanzania; rather only the occurrence of some disinfection by-products and antibiotics was, respectively, reported in Arusha and Dar es Salaam, Tanzania. As these reports had a limited coverage of ECs, henceforth, these findings constitute the first-line reference materials for ECs research in Tanzania which shall be useful for future monitoring and regulation planning. PMID:26998381

Emerging contaminants in surface waters in China—a short review

NASA Astrophysics Data System (ADS)

Yang, Guang; Fan, Maohong; Zhang, Guangming

2014-07-01

Emerging contaminants (ECs) have drawn attention to many countries due to their persistent input and potential threat to human health and the environment. This article reviews the current contamination sources and their status for surface waters in China. The contamination levels of ECs in surface waters are in the range ng L-1 to μg L-1 in China, apparently about the same as the situation in other countries. ECs enter surface water via runoff, drainage, rainfall, and wastewater treatment effluent. The frequency of occurrence of ECs increased rapidly from 2006 to 2011; a significant reason is the production and consumption of pharmaceuticals and personal care products. As for the distribution of EC pollution in China, the frequency of occurrence of ECs in eastern regions is higher than in western regions. A majority of EC studies have focused on surface waters of the Haihe River and Pearl River watersheds due to their highly developed industries and intense human activity. Legislative and administrative regulation of ECs is lacking in China. To remove ECs, a number of technologies, such as absorption by activated carbon, membrane filtration technology, and advanced oxidation processes, have been researched.

A Contact-Based Method for Differentiation of Human Mesenchymal Stem Cells into an Endothelial Cell-Phenotype.

PubMed

Joddar, Binata; Kumar, Shweta Anil; Kumar, Alok

2018-06-01

Adult stem cells such as mesenchymal stem cells (MSC) are known to possess the ability to augment neovascularization processes and are thus widely popular as an autologous source of progenitor cells. However there is a huge gap in our current knowledge of mechanisms involved in differentiating MSC into endothelial cells (EC), essential for lining engineered blood vessels. To fill up this gap, we attempted to differentiate human MSC into EC, by culturing the former onto chemically fixed layers of EC or its ECM, respectively. We expected direct contact of MSC when cultured atop fixed EC or its ECM, would coax the former to differentiate into EC. Results showed that human MSC cultured atop chemically fixed EC or its ECM using EC-medium showed enhanced expression of CD31, a marker for EC, compared to other cases. Further in all human MSC cultured using EC-medium, typically characteristic cobble stone shaped morphologies were noted in comparison to cells cultured using MSC medium, implying that the differentiated cells were sensitive to soluble VEGF supplementation present in the EC-medium. Results will enhance and affect therapies utilizing autologous MSC as a cell source for generating vascular cells to be used in a variety of tissue engineering applications.

In vitro pharmacologic characterization of a cholinergic receptor on outer hair cells.

PubMed

Erostegui, C; Norris, C H; Bobbin, R P

1994-04-01

Acetylcholine (ACh) is the major neurotransmitter released from the efferent fibers in the cochlea onto the outer hair cells (OHCs). The type of ACh receptor on OHCs and the events subsequent to receptor activation are unclear. Therefore we studied the effect of agonists and antagonists of the ACh receptor on isolated OHCs from the guinea pig. OHCs were recorded from in whole cell voltage and current clamp configuration. ACh induced an increase in outward K+ current (IACh) which hyperpolarized the OHCs. No desensitization to ACh application was observed. Cs+ replaced K+ in carrying the IACh. The IACh is Ca(2+)-dependent, time and voltage sensitive, and different from the IKCa induced by depolarization of the membrane potential. When tested at 100 microM, several agonists also induced outward current responses (acetylcholine > suberyldicholine > or = carbachol > DMPP) whereas nicotine, cytisine and muscarine did not. The IACh response to 10 microM ACh was blocked by low concentrations of traditional and non-traditional-nicotinic antagonists (strychnine > curare > bicuculline > alpha-bungarotoxin > thimethaphan) and by higher concentrations of muscarinic antagonists (atropine > 4-DAMP > AF-DX 116 > pirenzepine). Pharmacologically, the ACh receptor on OHCs is nicotinic.

[Analysis of electrically evoked response (EER) in relation to the central visual pathway of the cat (1). Wave shape of the cat EER].

PubMed

Fukatsu, Y; Miyake, Y; Sugita, S; Saito, A; Watanabe, S

1990-11-01

To analyze the Electrically evoked response (EER) in relation to the central visual pathway, the authors studied the properties of wave patterns and peak latencies of EER in 35 anesthetized adult cats. The cat EER showed two early positive waves on outward current (cornea cathode) stimulus and three or four early positive waves on inward current (cornea anode) stimulus. These waves were recorded within 50 ms after stimulus onset, and were the most consistent components in cat EER. The stimulus threshold for EER showed a less individual variation than amplitude. The difference of stimulus threshold between outward and inward current stimulus was also essentially negligible. The stimulus threshold was higher in early components than in late components. The peak latency of EER became shorter and the amplitude became higher, as the stimulus intensity was increased. However, this tendency was reversed and some wavelets started to appear when the stimulus was extremely strong. The recording using short stimulus duration and bipolar electrodes enabled us to reduce the electrical artifact of EER. These results obtained from cats were compared with those of humans and rabbits.

Electrocoagulation in Water Treatment

NASA Astrophysics Data System (ADS)

Liu, Huijuan; Zhao, Xu; Qu, Jiuhui

Electrocoagulation (EC) is an electrochemical method of treating polluted water where sacrificial anodes corrode to release active coagulant precursors (usually aluminum or iron cations) into solution. At the cathode, gas evolves (usually as hydrogen bubbles) accompanying electrolytic reactions. EC needs simple equipments and is designable for virtually any size. It is cost effective and easily operable. Specially, the recent technical improvements combined with a growing need for small-scale water treatment facilities have led to a revaluation of EC. In this chapter, the basic principle of EC was introduced first. Following that, reactions at the electrodes and electrode assignment were reviewed; electrode passivation process and activation method were presented; comparison between electrocoagulation and chemical coagulation was performed; typical design of the EC reactors was also described; and factors affecting electrocoagulation including current density, effect of conductivity, temperature, and pH were introduced in details. Finally, application of EC in water treatment was given in details.

Combined electrocoagulation and electro-oxidation of industrial textile wastewater treatment in a continuous multi-stage reactor.

PubMed

GilPavas, Edison; Arbeláez-Castaño, Paula; Medina, José; Acosta, Diego A

2017-11-01

A combined electrocoagulation (EC) and electrochemical oxidation (EO) industrial textile wastewater treatment potential is evaluated in this work. A fractional factorial design of experiment showed that EC current density, followed by pH, were the most significant factors. Conductivity and number of electrooxidation cells did not affect chemical oxygen demand degradation (DCOD). Aluminum and iron anodes performed similarly as sacrificial anodes. Current density, pH and conductivity were chosen for a Box-Behnken design of experiment to determine optimal conditions to achieve a high DCOD minimizing operating cost (OC). The optimum to achieve a 70% DCOD with an OC of USD 1.47/m 3 was: pH of 4, a conductivity of 3.7 mS/cm and a current density of 4.1 mA/cm 2 . This study also shows the applicability of a combined EC/EO treatment process of a real complex industrial wastewater.

Iron Polymerization and Arsenic Removal During In-Situ Iron Electrocoagulation in Synthetic Bangladeshi Groundwater

NASA Astrophysics Data System (ADS)

van Genuchten, C. M.; Pena, J.; Addy, S.; Gadgil, A.

2010-12-01

Millions of people worldwide are exposed to arsenic-contamination in groundwater drinking supplies. The majority of affected people live in rural Bangladesh. Electrocoagulation (EC) using iron electrodes is a promising arsenic removal strategy that is based on the generation of iron precipitates with a high affinity for arsenic through the electrochemical dissolution of a sacrificial iron anode. Many studies of iron hydrolysis in the presence of co-occurring ions in groundwater such as PO43-, SiO44-, and AsO43- suggest that these ions influence the polymerization and formation of iron oxide phases. However, the combined impact of these ions on precipitates generated by EC is not well understood. X-ray absorption spectroscopy (XAS) was used to examine EC precipitates generated in synthetic Bangladeshi groundwater (SBGW). The iron oxide structure and arsenic binding geometry were investigated as a function of EC operating conditions. As and Fe k-edge spectra were similar between samples regardless of the large range of current density (0.02, 1.1, 5.0, 100 mA/cm2) used during sample generation. This result suggests that current density does not play a large role in the formation EC precipitates in SBGW. Shell-by-shell fits of Fe K-edge data revealed the presence of a single Fe-Fe interatomic distance at approximately 3.06 Å. The absence of longer ranged Fe-Fe correlations suggests that EC precipitates consist of nano-scale chains (polymers) of FeO6 octahedra sharing equatorial edges. Shell-by-shell fits of As K-edge spectra show arsenic bound in primarily bidentate, binuclear corner sharing complexes. In this coordination geometry, arsenic prevents the formation of FeO6 corner-sharing linkages, which are necessary for 3-dimensional crystal growth. The individual and combined effects of other anions, such as PO43- and SiO44- present in SBGW are currently being investigated to determine the role of these ions in stunting crystal growth. The results provided by this study are useful in explaining the large adsorption capacity of EC precipitates. This study will also lead to better predictions of arsenic removal efficiency during EC and a better understanding of the long-term stability of arsenic-laden EC sludge.

Mechanism of block by tedisamil of transient outward current in human ventricular subepicardial myocytes

PubMed Central

Wettwer, Erich; Himmel, Herbert M; Amos, Gregory J; Li, Qi; Metzger, Franz; Ravens, Ursula

1998-01-01

Tedisamil is a new antiarrhythmic drug with predominant class III action. The aim of the present study was to investigate the blocking pattern of the compound on the transient outward current (Ito) in human subepicardial myocytes isolated from explanted left ventricles. Using the single electrode whole cell voltage clamp technique, Ito was analysed after appropriate voltage inactivation of sodium current and block of calcium current.Tedisamil reduced the amplitude of peak Ito, but did not affect the amplitude of non-inactivating outward current. The drug accelerated the apparent rate of Ito inactivation. The reduction in time constant of Ito inactivation depended on drug concentration, the apparent IC50 value was 4.4 μM.Tedisamil affected Ito amplitude in a use-dependent manner. After 2 min at −80 mV, maximum block of Ito was reached after 4–5 clamp steps either at the frequency of 0.2 or 2 Hz, indicating that the block was not frequency-dependent in an experimentally relevant range. Recovery from block was very slow and proceeded with a time constant of 12.1±1.8 s. Also in the presence of drug, a fraction of channels recovered from inactivation with a similar time constant as in control myocytes (i.e. 81±40 ms and 51±8 ms, respectively, n.s.).From the onset of fractional block of Ito by tedisamil during the initial 60 ms of a clamp step, we calculated k1=9×106 mol−1 s−1 for the association rate constant, and k2=23 s−1 for the dissociation rate constant. The resulting apparent KD was 2.6 μM and is similar to the IC50 value.The effects of tedisamil on Ito could be simulated by assuming a four state channel model where the drug binds to the channel in an open (activated) conformation. It is concluded that in human subepicardial myocytes tedisamil is an open channel blocker of Ito and that this effect probably contributes to the antiarrhythmic potential of this drug. PMID:9831899

Extracellular matrix of collagen modulates arrhythmogenic activity of pulmonary veins through p38 MAPK activation.

PubMed

Lu, Yen-Yu; Chen, Yao-Chang; Kao, Yu-Hsun; Chen, Shih-Ann; Chen, Yi-Jen

2013-06-01

Atrial fibrillation (AF) is the most common sustained arrhythmia. Cardiac fibrosis with enhanced extracellular collagen plays a critical role in the pathophysiology of AF through structural and electrical remodeling. Pulmonary veins (PVs) are important foci for AF genesis. The purpose of this study was to evaluate whether collagen can directly modulate PV arrhythmogenesis. Action potentials and ionic currents were investigated in isolated male New Zealand rabbit PV cardiomyocytes with and without collagen incubation (10μg/ml, 5-7h) using the whole-cell patch-clamp technique. Compared to control PV cardiomyocytes (n=25), collagen-treated PV cardiomyocytes (n=22) had a faster beating rate (3.2±04 vs. 1.9±0.2Hz, p<0.005) and a larger amplitude of delayed afterdepolarization (16±2 vs. 10±1mV, p<0.01). Moreover, collagen-treated PV cardiomyocytes showed a larger transient outward potassium current, small-conductance Ca(2+)-activated K(+) current, inward rectifier potassium current, pacemaker current, and late sodium current than control PV cardiomyocytes, but amplitudes of the sodium current, sustained outward potassium current, and L-type calcium current were similar. Collagen increased the p38 MAPK phosphorylation in PV cardiomyocytes as compared to control. The change of the spontaneous activity and action potential morphology were ameliorated by SB203580 (the p38 MAPK catalytic activity inhibitor), indicating that collagen can directly increase PV cardiomyocyte arrhythmogenesis through p38 MAPK activation, which may contribute to the pathogenesis of AF. Copyright © 2013 Elsevier Ltd. All rights reserved.

Catalysts for Lightweight Solar Fuels Generation

DTIC Science & Technology

2017-03-10

single bandgap solar cells to OER catalysts could lead to very high solar -to-fuel efficiencies. Figure 3 illustrates a PV -EC utilizing a PV , an...3- or 4 -single junction c-Si solar cells connected in series. Considering a PV -EC device based on commercially available single junction-Si solar ...30.8%) with open circuit voltage and short circuit current density ; total plot area is scaled to incident solar power (100 mW cm–2). The PV -EC

A finite element analysis modeling tool for solid oxide fuel cell development: coupled electrochemistry, thermal and flow analysis in MARC®

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

Khaleel, Mohammad A.; Lin, Zijing; Singh, Prabhakar

2004-05-03

A 3D simulation tool for modeling solid oxide fuel cells is described. The tool combines the versatility and efficiency of a commercial finite element analysis code, MARC{reg_sign}, with an in-house developed robust and flexible electrochemical (EC) module. Based upon characteristic parameters obtained experimentally and assigned by the user, the EC module calculates the current density distribution, heat generation, and fuel and oxidant species concentration, taking the temperature profile provided by MARC{reg_sign} and operating conditions such as the fuel and oxidant flow rate and the total stack output voltage or current as the input. MARC{reg_sign} performs flow and thermal analyses basedmore » on the initial and boundary thermal and flow conditions and the heat generation calculated by the EC module. The main coupling between MARC{reg_sign} and EC is for MARC{reg_sign} to supply the temperature field to EC and for EC to give the heat generation profile to MARC{reg_sign}. The loosely coupled, iterative scheme is advantageous in terms of memory requirement, numerical stability and computational efficiency. The coupling is iterated to self-consistency for a steady-state solution. Sample results for steady states as well as the startup process for stacks with different flow designs are presented to illustrate the modeling capability and numerical performance characteristic of the simulation tool.« less

Eddy current loss analysis of open-slot fault-tolerant permanent-magnet machines based on conformal mapping method

NASA Astrophysics Data System (ADS)

Ji, Jinghua; Luo, Jianhua; Lei, Qian; Bian, Fangfang

2017-05-01

This paper proposed an analytical method, based on conformal mapping (CM) method, for the accurate evaluation of magnetic field and eddy current (EC) loss in fault-tolerant permanent-magnet (FTPM) machines. The aim of modulation function, applied in CM method, is to change the open-slot structure into fully closed-slot structure, whose air-gap flux density is easy to calculate analytically. Therefore, with the help of Matlab Schwarz-Christoffel (SC) Toolbox, both the magnetic flux density and EC density of FTPM machine are obtained accurately. Finally, time-stepped transient finite-element method (FEM) is used to verify the theoretical analysis, showing that the proposed method is able to predict the magnetic flux density and EC loss precisely.

Multiplexed HTS rf SQUID magnetometer array for eddy current testing of aircraft rivet joints

NASA Astrophysics Data System (ADS)

Gärtner, S.; Krause, H.-J.; Wolters, N.; Lomparski, D.; Wolf, W.; Schubert, J.; Kreutzbruck, M. v.; Allweins, K.

2002-05-01

Using three rf SQUID magnetometers, a multiplexed SQUID array was implemented. The SQUIDs are positioned in line with 7 mm spacing and operated using one feedback electronics with sequential read out demodulation at different radio frequencies (rf). The cross-talk between SQUID channels was determined to be negligible. To show the performance of the SQUID array, eddy current (EC) measurements of aluminum aircraft samples in conjunction with a differential (double-D) EC excitation and lock-in readout were carried out. With computer-controlled continuous switching of the SQUIDs during the scan, three EC signal traces of the sample are obtained simultaneously. We performed measurements with an EC excitation frequency of 135 Hz to localize an artificial crack (sawcut flaw) of 20 mm length in an aluminum sheet with 0.6 mm thickness. The flaw was still detected when covered with aluminum of up to 10 mm thickness. In addition, measurements with varying angles between scanning direction and flaw orientation are presented.

Precise on-machine extraction of the surface normal vector using an eddy current sensor array

NASA Astrophysics Data System (ADS)

Wang, Yongqing; Lian, Meng; Liu, Haibo; Ying, Yangwei; Sheng, Xianjun

2016-11-01

To satisfy the requirements of on-machine measurement of the surface normal during complex surface manufacturing, a highly robust normal vector extraction method using an Eddy current (EC) displacement sensor array is developed, the output of which is almost unaffected by surface brightness, machining coolant and environmental noise. A precise normal vector extraction model based on a triangular-distributed EC sensor array is first established. Calibration of the effects of object surface inclination and coupling interference on measurement results, and the relative position of EC sensors, is involved. A novel apparatus employing three EC sensors and a force transducer was designed, which can be easily integrated into the computer numerical control (CNC) machine tool spindle and/or robot terminal execution. Finally, to test the validity and practicability of the proposed method, typical experiments were conducted with specified testing pieces using the developed approach and system, such as an inclined plane and cylindrical and spherical surfaces.

Knowledge, attitudes and prescribing pattern of emergency contraceptives by health care workers in Kampala, Uganda.

PubMed

Byamugisha, Josaphat K; Mirembe, Florence M; Faxelid, Elisabeth; Gemzell-Danielsson, Kristina

2007-01-01

Health care workers (HCWs) play an important role in making emergency contraceptives (ECs) available to clients. They can influence accessibility positively through counselling, prescribing or advocating the use of ECs. However, in some settings, HCWs have been blamed for unfavourable attitudes and lack of accurate information. Objective. To assess the knowledge, attitudes and prescribing pattern of EC by HCWs in Kampala district, Uganda. The total number of health units at different levels of health care delivery in Kampala (894) was obtained. Probability proportional to size (PPS) technique of sampling was applied. Some 247 HCWs completed a self-administered questionnaire on their knowledge about EC, including methods, mechanism of action, prescription of EC, sources of information, attitudes towards EC, and if and how it should be made available. Of the HCWs, 80% had knowledge of ECs. However, 1 in every 4 was not sure about the time limit within which EC is effective. A total of 50% of the participants had obtained information from a physician (26.4%) or from a training school (24%). The Yuzpe regimen was the most commonly mentioned and prescribed method of EC. The HCWs attitudes to EC were generally positive, and it was suggested that the community should be informed and sensitised about EC. There was a significant difference between having had a family planning educational update or not in the last year and knowledge of EC (p=0.005). Most HCWs were aware of EC, but some lacked important knowledge on its use or available methods. HCWs should have regular (annual) in-service training in reproductive health issues, such as counselling on EC. This will enable them to keep up to date with the current evidence-based recommendations in the field of contraceptive technology.

Electronic cigarettes: Review of use, content, safety, effects on smokers, and potential for harm and benefit

PubMed Central

Hajek, Peter; Etter, Jean-François; Benowitz, Neal; Eissenberg, Thomas; McRobbie, Hayden

2015-01-01

Aims We reviewed available research on the use, content and safety of electronic cigarettes (EC) and on their effects on users, to assess their potential for harm or benefit and to extract evidence that can guide future policy. Methods Studies were identified by systematic database searches and screening references to February 2014. Results EC aerosol can contain some of the toxicants present in tobacco smoke, but at levels which are much lower. Long-term health effects of EC use are unknown but compared with cigarettes, EC are likely to be much less, if at all, harmful to users or bystanders. EC are increasingly popular among smokers, but to date there is no evidence of regular use by never-smokers or by non-smoking children. EC enable some users to reduce or quit smoking. Conclusions Allowing EC to compete with cigarettes in the marketplace might decrease smoking-related morbidity and mortality. Regulating EC as strictly as cigarettes, or even more strictly as some regulators propose, is not warranted on current evidence. Health professionals may consider advising smokers unable or unwilling to quit through other routes to switch to EC as a safer alternative to smoking and a possible pathway to complete cessation of nicotine use. PMID:25078252

Histopathological features of endometrial carcinomas associated with POLE mutations: implications for decisions about adjuvant therapy.

PubMed

Bakhsh, Salwa; Kinloch, Mary; Hoang, Lien N; Soslow, Robert A; Köbel, Martin; Lee, Cheng-Han; McAlpine, Jessica N; McConechy, Melissa K; Gilks, C Blake

2016-05-01

To characterize the histomorphological features of endometrial carcinomas (ECs) harbouring polymerase ε (POLE) mutations. Forty-three ECs with POLE mutations were compared with a cohort of 202 ECs. Most POLE-mutated ECs were endometrioid [34/43 (79%)]; the remaining tumours were mixed [6/43 (14%)], serous [2/43 (5%)], and clear cell [1/43 (2%)]. The endometrioid carcinomas were predominantly International Federation of Gynecology and Obstetrics grade 3 (27/43, 63%). The histotype distribution did not differ from that of control ECs (P = 0.69), but the grade of the EC was higher (P < 0.0005). Both nuclear grade and mitotic index were significantly higher in POLE-mutated ECs than in the comparison cohort. POLE-mutated ECs were associated with peritumoral lymphocytes and numerous tumour-infiltrating lymphocytes. Lymphovascular invasion was present in 20 of 43 tumours. Adjuvant radiotherapy and adjuvant chemotherapy would be offered in up to 80% and 40% of patients, respectively, on the basis of stage, grade, lymphovascular invasion, and histotype. POLE-mutated ECs are typically of high grade, with prominent lymphocytic infiltration, but they are not sufficiently distinctive to allow accurate diagnosis based on routine haematoxylin and eosin staining. Even though POLE-mutated tumours are associated with an excellent prognosis, current guidelines for giving adjuvant treatment for EC result in most patients receiving adjuvant therapy. © 2015 John Wiley & Sons Ltd.

Is evaluative conditioning really uncontrollable? A comparative test of three emotion-focused strategies to prevent the acquisition of conditioned preferences.

PubMed

Gawronski, Bertram; Mitchell, Derek G V; Balas, Robert

2015-10-01

Evaluative conditioning (EC) is defined as the change in the evaluation of a conditioned stimulus (CS) because of its pairing with a valenced unconditioned stimulus (US). Counter to views that EC is the product of automatic learning processes, recent research has revealed various characteristics of nonautomatic processing in EC. The current research investigated the controllability of EC by testing the effectiveness of 3 emotion-focused strategies in preventing the acquisition of conditioned preferences: (a) suppression of emotional reactions to the US, (b) reappraisal of the valence of the US, and (c) facial blocking of emotional responses. Although all 3 strategies reduced EC effects on self-reported evaluations by impairing recollective memory for CS-US pairings, they were ineffective in reducing EC effects on an evaluative priming measure. Regardless of the measure, effective control did not depend on the level of arousal elicited by the US. The results suggest that the 3 strategies can influence deliberate CS evaluations through memory-related processes, but they are ineffective in reducing EC effects on spontaneous evaluative responses. Implications for mental process theories of EC are discussed. (c) 2015 APA, all rights reserved).

Interactions of Human Endothelial and Multipotent Mesenchymal Stem Cells in Cocultures

PubMed Central

Ern, Christina; Krump-Konvalinkova, Vera; Docheva, Denitsa; Schindler, Stefanie; Rossmann, Oliver; Böcker, Wolfgang; Mutschler, Wolf; Schieker, Matthias

2010-01-01

Current strategies for tissue engineering of bone rely on the implantation of scaffolds, colonized with human mesenchymal stem cells (hMSC), into a recipient. A major limitation is the lack of blood vessels. One approach to enhance the scaffold vascularisation is to supply the scaffolds with endothelial cells (EC). The main goal of this study was to establish a coculture system of hMSC and EC for the purposes of bone tissue engineering. Therefore, the cell behaviour, proliferation and differentiation capacity in various cell culture media as well as cell interactions in the cocultures were evaluated. The differentiation capacity of hMSC along osteogenic, chondrogenic, and adipogenic lineage was impaired in EC medium while in a mixed EC and hMSC media, hMSC maintained osteogenic differentiation. In order to identify and trace EC in the cocultures, EC were transduced with eGFP. Using time-lapse imaging, we observed that hMSC and EC actively migrated towards cells of their own type and formed separate clusters in long term cocultures. The scarcity of hMSC and EC contacts in the cocultures suggest the influence of growth factor-mediated cell interactions and points to the necessity of further optimization of the coculture conditions. PMID:21625373

On the respective contributions of awareness of unconditioned stimulus valence and unconditioned stimulus identity in attitude formation through evaluative conditioning.

PubMed

Stahl, Christoph; Unkelbach, Christian; Corneille, Olivier

2009-09-01

Evaluative conditioning (EC) is a central mechanism for both classic and current theories of attitude formation. In contrast to Pavlovian conditioning, it is often conceptualized as a form of evaluative learning that occurs without awareness of the conditioned stimulus-unconditioned stimulus (CS-US) contingencies. In the present research, the authors directly address this point by assessing the respective roles of US valence awareness and US identity awareness in attitude formation through EC. Across 4 experiments, EC was assessed with evaluative ratings as well as evaluative priming measures, and the impact of valence and identity awareness on EC was evaluated. EC effects on priming and rating measures occurred only for CSs for which participants could report the associated US valence, and US identity awareness did not further contribute to EC. This finding was obtained both for semantically meaningless (i.e., nonword letter sequences) and meaningful (i.e., consumer products) CSs. These results provide further support for the critical role of contingency awareness in EC, albeit valence awareness, not identity awareness. (c) 2009 APA, all rights reserved).

Temporal and spatial variations of sea surface temperature in the East China Sea

NASA Astrophysics Data System (ADS)

Tseng, Chente; Lin, Chiyuan; Chen, Shihchin; Shyu, Chungzen

2000-03-01

Sea surface temperature of the East China Sea (ECS) were analyzed using the NOAA/AVHRR SST images. These satellite images reveal surface features of ECS including mainly the Kuroshio Current, Kuroshio Branch Current, Taiwan Warm Current, China coastal water, Changjiang diluted water and Yellow Sea mixed cold water. The SST of ECS ranges from 27 to 29°C in summer; some cold eddies were found off northeast Taiwan and to the south of Changjiang mouth. SST anomalies at the center of these eddies were about 2-5°C. The strongest front usually occurs in May each year and its temperature gradient is about 5-6°C over a cross-shelf distance of 30 nautical miles. The Yellow Sea mixed cold water also provides a contrast from China Coastal waters shoreward of the 50 m isobath; cross-shore temperature gradient is about 6-8°C over 30 nautical miles. The Kuroshio intrudes into ECS preferably at two locations. The first is off northeast Taiwan; the subsurface water of Kuroshio is upwelled onto the shelf while the main current is deflected seaward. The second site is located at 31°N and 128°E, which is generally considered as the origin of the Tsushima Warm Current. More quantitatively, a 2-year time series of monthly SST images is examined using EOF analysis to determine the spatial and temporal variations in the northwestern portion of ECS. The first spatial EOF mode accounts for 47.4% of total spatial variance and reveals the Changjiang plume and coastal cold waters off China. The second and third EOF modes account for 16.4 and 9.6% of total variance, respectively, and their eigenvector images show the intrusion of Yellow Sea mixed cold waters and the China coastal water. The fourth EOF mode accounts for 5.4% of total variance and reveals cold eddies around Chusan Islands. The temporal variance EOF analysis is less revealing in this study area.

The Year Abroad: Understanding the Employability Skills of the Global Graduate

ERIC Educational Resources Information Center

López-Moreno, Cristina

2017-01-01

This chapter will examine the employability profile of outwardly mobile British graduates and the ways in which their international skillset fits the UK labour market. It will draw upon several recent reports to highlight the current shortage of professionals with such global skills. In this context, the chapter will demonstrate that…

Northwest Outward Bound Instructor's Manual.

ERIC Educational Resources Information Center

Northwest Outward Bound School, Portland, OR.

Instructor responsibilities, procedures for completing activities safely, and instructional methods and techniques are outlined to assist instructors in the Northwest Outward Bound School (Portland, Oregon) as they strive for teaching excellence. Information is organized into six chapters addressing: history and philosophy of Outward Bound; course…

Relations of Positive and Negative Expressivity and Effortful Control to Kindergarteners’ Student-Teacher Relationship, Academic Engagement, and Externalizing Problems at School

PubMed Central

Diaz, Anjolii; Eisenberg, Nancy; Valiente, Carlos; VanSchyndel, Sarah; Spinrad, Tracy L.; Berger, Rebecca; Hernandez, Maciel M.; Silva, Kassondra M.; Southworth, Jody

2015-01-01

The current study examined the role of naturally-occurring negative and positive emotion expressivity in kindergarten and children’s effortful control (EC) on their relationships with teachers, academic engagement, and problems behaviors in school. Further, the potential moderating role of EC on these important school outcomes was assessed. Emotion and engagement were observed at school. EC was assessed by multiple methods. Teachers reported on their student–teacher relationships and student’s externalizing behaviors. Children’s emotion expressivity and EC were related to engagement and relationships with teachers as well as behavioral problems at school. Children low in EC may be particularly vulnerable to the poor outcomes associated with relatively intense emotion expressivity as they struggle to manage their emotions and behaviors in the classroom. PMID:28584388

Simultaneous preparation of naturally abundant and rare catechins by tannase-mediated biotransformation combining high speed counter current chromatography.

PubMed

Xia, Guobin; Hong, Shan; Liu, Songbai

2014-05-15

Simultaneous preparation of naturally rare catechins, EGC and EC, has been realized by tannase-mediated biotransformation combining high speed counter current chromatography. In addition, simultaneous preparation of the four catechins, EGCG, ECG, EGC, and EC in green tea extract has also been achieved by HSCCC under the normal phase and the reversed phase modes. The identity of the catechins was determined by HPLC-DAD-ESI-MS and quantification of the catechins was performed by HPLC-DAD. In a typical HSCCC separation, 27.2 mg 98.8% EGCG, 14.1 mg 94.7% EGC, and 9.3 mg 97.5% EC were obtained. This new method is efficient, time-saving and valuable for biological studies. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Advance in study of vascular endothelial cell and smooth muscle cell co-culture system].

PubMed

Li, Yujie; Yang, Qing; Weng, Xiaogang; Chen, Ying; Ruan, Congxiao; Li, Dan; Zhu, Xiaoxing

2012-02-01

The interactions between endothelial cells (EC) and smooth muscle cells (SMC) contribute to vascular physiological functions and also cause the occurrence and development of different kinds of diseases. Currently, EC-SMC co-culture model is the best way to study the interactions between the two kinds of cells. This article summarizes existing EC-SMC co-culture models and their effects on the structure and functions of the two kinds of cells. Microscopically speaking, it provides a basis for in-depth studies on their interactions as well as a reference for the establishment of in vitro EC-SMC co-culture system that is closer to organic physiology or pathology state.

Single-mode, narrow-linewidth external cavity quantum cascade laser through optical feedback from a partial-reflector.

PubMed

Cendejas, Richard A; Phillips, Mark C; Myers, Tanya L; Taubman, Matthew S

2010-12-06

An external-cavity (EC) quantum cascade (QC) laser using optical feedback from a partial-reflector is reported. With this configuration, the otherwise multi-mode emission of a Fabry-Perot QC laser was made single-mode with optical output powers exceeding 40 mW. A mode-hop free tuning range of 2.46 cm(-1) was achieved by synchronously tuning the EC length and QC laser current. The linewidth of the partial-reflector EC-QC laser was measured for integration times from 100 μs to 4 seconds, and compared to a distributed feedback QC laser. Linewidths as small as 480 kHz were recorded for the EC-QC laser.

Prevalence and predictors of mental disorders in intentionally and unintentionally injured emergency centre patients

PubMed Central

van der Westhuizen, Claire; Wyatt, Gail; Williams, John K.; Stein, Dan J.; Sorsdahl, Katherine

2014-01-01

Little is known about the prevalence and predictors of mental disorders amongst injured emergency centre (EC) patients in low- and middle-income countries. Patients presenting with either an intentional or unintentional injury were recruited (n=200). Mental health, injury and psychological trauma histories were assessed. Descriptive statistics and logistic regressions were conducted and predictors for current mental disorder were identified. Diagnostic criteria for a current mental disorder, including substance use disorders, were met by 59.5% of participants. Compared to those with an unintentional injury, intentionally injured participants were more likely to be diagnosed with a current mental disorder (66.9% vs 48.8%; p=0.01). High frequencies of previous intentional injuries predicted for current mental disorder (OR = 1.460, 95% CI 1.08-1.98), while male gender and witnessed community violence predicted substance use disorder diagnoses. Findings indicate that injured EC patients, particularly those with intentional injuries, are at risk for mental disorders. Psychosocial interventions in the EC context can potentially make an important contribution in reducing the burden of mental disorders and injuries in low- and middle-income countries. PMID:25126754

Modeling human endothelial cell transformation in vascular neoplasias

PubMed Central

Wen, Victoria W.; MacKenzie, Karen L.

2013-01-01

Endothelial cell (EC)-derived neoplasias range from benign hemangioma to aggressive metastatic angiosarcoma, which responds poorly to current treatments and has a very high mortality rate. The development of treatments that are more effective for these disorders will be expedited by insight into the processes that promote abnormal proliferation and malignant transformation of human ECs. The study of primary endothelial malignancy has been limited by the rarity of the disease; however, there is potential for carefully characterized EC lines and animal models to play a central role in the discovery, development and testing of molecular targeted therapies for vascular neoplasias. This review describes molecular alterations that have been identified in EC-derived neoplasias, as well as the processes that underpin the immortalization and tumorigenic conversion of ECs. Human EC lines, established through the introduction of defined genetic elements or by culture of primary tumor tissue, are catalogued and discussed in relation to their relevance as models of vascular neoplasia. PMID:24046386

Don't Worry, Be Happy: Endocannabinoids and Cannabis at the Intersection of Stress and Reward.

PubMed

Volkow, Nora D; Hampson, Aidan J; Baler, Ruben D

2017-01-06

Cannabis enables and enhances the subjective sense of well-being by stimulating the endocannabinoid system (ECS), which plays a key role in modulating the response to stress, reward, and their interactions. However, over time, repeated activation of the ECS by cannabis can trigger neuroadaptations that may impair the sensitivity to stress and reward. This effect, in vulnerable individuals, can lead to addiction and other adverse consequences. The recent shift toward legalization of medical or recreational cannabis has renewed interest in investigating the physiological role of the ECS as well as the potential health effects, both adverse and beneficial, of cannabis. Here we review our current understanding of the ECS and its complex physiological roles. We discuss the implications of this understanding vis-á-vis the ECS's modulation of stress and reward and its relevance to mental disorders in which these processes are disrupted (i.e., addiction, depression, posttraumatic stress disorder, schizophrenia), along with the therapeutic potential of strategies to manipulate the ECS for these conditions.

Nitrogen removal from the saline sludge liquor by electrochemical denitrification.

PubMed

Xie, Z M; Li, X Y; Chan, K Y

2006-01-01

Sludge liquor from the sludge dewatering process has a high ammonia content. In the present study, a lab-scale electrochemical (EC) system with a pair of Ti electrode plates was used for treating the sludge centrate liquor of digested wastewater sludge with a NH4(+) - N content of around 500 mg/L. The sludge liquor had a high salinity due to seawater being used for toilet flushing in Hong Kong. The results show that the EC process is highly effective for denitrification of the saline sludge liquor. Complete nitrogen removal could be achieved within 1 hr or so. The rate of EC denitrification increased with the current intensity applied. The best current efficiency for nitrogen removal was obtained for a gap distance between the electrodes at 8 mm. Electro-chlorination was considered to be the major mechanism of EC denitrification. The formation of chlorination by-products (CBPs) appeared to be minimal with the total trihalomethanes (THM) detected at a level of 300 microg/L or lower. The power consumption for EC denitrification was around 23 kWh/kg N. Additional electro-flocculation with a pair of iron needle electrodes could enhance the flocculation and subsequent sedimentation of colloidal organics in the sludge liquor, increasing the organic removal from less than 30% to more than 70%. Therefore, the EC process including both electro-denitrification and electro-flocculation can be developed as the most cost-effective method for treatment of the saline sludge liquor.

Status of the ITER Electron Cyclotron Heating and Current Drive System

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

Darbos, Caroline; Albajar, Ferran; Bonicelli, Tullio

2015-10-07

We present that the electron cyclotron (EC) heating and current drive (H&CD) system developed for the ITER is made of 12 sets of high-voltage power supplies feeding 24 gyrotrons connected through 24 transmission lines (TL), to five launchers, four located in upper ports and one at the equatorial level. Nearly all procurements are in-kind, following general ITER philosophy, and will come from Europe, India, Japan, Russia and the USA. The full system is designed to couple to the plasma 20 MW among the 24 MW generated power, at the frequency of 170 GHz, for various physics applications such as plasmamore » start-up, central H&CD and magnetohydrodynamic (MHD) activity control. The design takes present day technology and extends toward high-power continuous operation, which represents a large step forward as compared to the present state of the art. The ITER EC system will be a stepping stone to future EC systems for DEMO and beyond.The development of the EC system is facing significant challenges, which includes not only an advanced microwave system but also compliance with stringent requirements associated with nuclear safety as ITER became the first fusion device licensed as basic nuclear installations as of 9 November 2012. Finally, since the conceptual design of the EC system was established in 2007, the EC system has progressed to a preliminary design stage in 2012 and is now moving forward toward a final design.« less

Parasitic momentum flux in the tokamak core

DOE PAGES

Stoltzfus-Dueck, T.

2017-03-06

A geometrical correction to the E × B drift causes an outward flux of co-current momentum whenever electrostatic potential energy is transferred to ion parallel flows. The robust, fully nonlinear symmetry breaking follows from the free-energy flow in phase space and does not depend on any assumed linear eigenmode structure. The resulting rotation peaking is counter-current and scales as temperature over plasma current. Lastly, this peaking mechanism can only act when fluctuations are low-frequency enough to excite ion parallel flows, which may explain some recent experimental observations related to rotation reversals.

Influences of operational parameters on phosphorus removal in batch and continuous electrocoagulation process performance.

PubMed

Nguyen, Dinh Duc; Yoon, Yong Soo; Bui, Xuan Thanh; Kim, Sung Su; Chang, Soon Woong; Guo, Wenshan; Ngo, Huu Hao

2017-11-01

Performance of an electrocoagulation (EC) process in batch and continuous operating modes was thoroughly investigated and evaluated for enhancing wastewater phosphorus removal under various operating conditions, individually or combined with initial phosphorus concentration, wastewater conductivity, current density, and electrolysis times. The results revealed excellent phosphorus removal (72.7-100%) for both processes within 3-6 min of electrolysis, with relatively low energy requirements, i.e., less than 0.5 kWh/m 3 for treated wastewater. However, the removal efficiency of phosphorus in the continuous EC operation mode was better than that in batch mode within the scope of the study. Additionally, the rate and efficiency of phosphorus removal strongly depended on operational parameters, including wastewater conductivity, initial phosphorus concentration, current density, and electrolysis time. Based on experimental data, statistical model verification of the response surface methodology (RSM) (multiple factor optimization) was also established to provide further insights and accurately describe the interactive relationship between the process variables, thus optimizing the EC process performance. The EC process using iron electrodes is promising for improving wastewater phosphorus removal efficiency, and RSM can be a sustainable tool for predicting the performance of the EC process and explaining the influence of the process variables.

Prospective and retrospective high order eddy current mitigation for diffusion weighted echo planar imaging.

PubMed

Xu, Dan; Maier, Joseph K; King, Kevin F; Collick, Bruce D; Wu, Gaohong; Peters, Robert D; Hinks, R Scott

2013-11-01

The proposed method is aimed at reducing eddy current (EC) induced distortion in diffusion weighted echo planar imaging, without the need to perform further image coregistration between diffusion weighted and T2 images. These ECs typically have significant high order spatial components that cannot be compensated by preemphasis. High order ECs are first calibrated at the system level in a protocol independent fashion. The resulting amplitudes and time constants of high order ECs can then be used to calculate imaging protocol specific corrections. A combined prospective and retrospective approach is proposed to apply correction during data acquisition and image reconstruction. Various phantom, brain, body, and whole body diffusion weighted images with and without the proposed method are acquired. Significantly reduced image distortion and misregistration are consistently seen in images with the proposed method compared with images without. The proposed method is a powerful (e.g., effective at 48 cm field of view and 30 cm slice coverage) and flexible (e.g., compatible with other image enhancements and arbitrary scan plane) technique to correct high order ECs induced distortion and misregistration for various diffusion weighted echo planar imaging applications, without the need for further image post processing, protocol dependent prescan, or sacrifice in signal-to-noise ratio. Copyright © 2013 Wiley Periodicals, Inc.

An optimized design to reduce eddy current sensitivity in velocity-selective arterial spin labeling using symmetric BIR-8 pulses.

PubMed

Guo, Jia; Meakin, James A; Jezzard, Peter; Wong, Eric C

2015-03-01

Velocity-selective arterial spin labeling (VSASL) tags arterial blood on a velocity-selective (VS) basis and eliminates the tagging/imaging gap and associated transit delay sensitivity observed in other ASL tagging methods. However, the flow-weighting gradient pulses in VS tag preparation can generate eddy currents (ECs), which may erroneously tag the static tissue and create artificial perfusion signal, compromising the accuracy of perfusion quantification. A novel VS preparation design is presented using an eight-segment B1 insensitive rotation with symmetric radio frequency and gradient layouts (sym-BIR-8), combined with delays after gradient pulses to optimally reduce ECs of a wide range of time constants while maintaining B0 and B1 insensitivity. Bloch simulation, phantom, and in vivo experiments were carried out to determine robustness of the new and existing pulse designs to ECs, B0 , and B1 inhomogeneity. VSASL with reduced EC sensitivity across a wide range of EC time constants was achieved with the proposed sym-BIR-8 design, and the accuracy of cerebral blood flow measurement was improved. The sym-BIR-8 design performed the most robustly among the existing VS tagging designs, and should benefit studies using VS preparation with improved accuracy and reliability. © 2014 Wiley Periodicals, Inc.

Outward-dipping ring-fault structure at rabaul caldera as shown by earthquake locations.

PubMed

Mori, J; McKee, C

1987-01-09

The locations of a large number of earthquakes recorded at Rabaul caldera in Papua New Guinea from late 1983 to mid-1985 have produced a picture of this active caldera's structural boundary. The earthquake epicenters form an elliptical annulus about 10 kilometers long by 4 kilometers wide, centered in the southern part of the Rabaul volcanic complex. A set of events with well-constrained depth determinations shows a ring-fault structure that extends from the surface to a depth of about 4 kilometers and slopes steeply outward from the center of the caldera. This is the first geophysical data set that clearly outlines the orientation of an active caldera's bounding faults. This orientation, however, conflicts with the configuration of many other calderas and is not in keeping with currently preferred models of caldera formation.

Characterization of Arctic elemental carbon in Barrow, AK using radiocarbon source apportionment

NASA Astrophysics Data System (ADS)

Barrett, T. E.; Usenko, S.; Robinson, E. M.; Sheesley, R. J.

2013-12-01

Currently, the Arctic is one of the fastest warming regions on earth with surface temperatures increasing at a rate nearly double the global mean over recent decades. Despite the fact that atmospheric concentrations of elemental carbon (EC) are lower in the Arctic than in lower latitudes, deposition of EC on snow and ice may exacerbate regional warming by simultaneously decreasing albedo and increasing melt rates. Due to the intensifying Arctic oil exploration in areas such as the Beaufort and Chukchi seas, the impact of new emission sources such as heavy fuel and heavy diesel combustion on regional carbon needs to be assessed. The first step in developing mitigation strategies for reducing current and future EC emissions in the Arctic is to determine emission source contributions. This study aims to determine the relative contributions of fossil fuel and biomass combustion and to identify major source regions of EC to the Arctic. Radiocarbon analysis of both total organic carbon (TOC) and EC combined with organic tracer and back trajectory analysis has been applied to a set of wintertime coarse particulate matter (PM10) samples from Barrow, AK. Preliminary apportionment for January 2013 indicates roughly half of TOC is from biogenic/biomass burning emissions and one third of EC is due to biomass burning emissions. The radiocarbon results will be combined with organic tracer analysis (polycyclic aromatic hydrocarbons, petroleum biomarkers and normal alkanes), increasing the specificity of the relative contribution of both the fossil and modern (biogenic/biomass burning) carbon emission sources. This research represents the first reported radiocarbon values for Arctic EC, providing highly conclusive source apportionment prior to the influence of increased drilling operations and ship traffic in the Beaufort and Chukchi seas.

Gradual Streamer Expansions and the Relationship between Blobs and Inflows

NASA Astrophysics Data System (ADS)

Wang, Y.-M.; Hess, P.

2018-06-01

Coronal helmet streamers show a continual tendency to expand outward and pinch off, giving rise to flux ropes that are observed in white light as “blobs” propagating outward along the heliospheric current/plasma sheet. The blobs form within the r ∼ 2–6 R ⊙ heliocentric range of the Large Angle and Spectrometric Coronagraph (LASCO) C2 instrument, but the expected inward-moving counterparts are often not detected. Here we show that the height of blob formation varies as a function of the underlying photospheric field, with the helmet streamer loops expanding to greater heights when active regions (ARs) emerge underneath them. When the pinch-offs occur at r ∼ 3–4 R ⊙, diverging inward/outward tracks sometimes appear in height–time maps constructed from LASCO C2 running-difference images. When the underlying photospheric field is weak, the blobs form closer to the inner edge of the C2 field of view and only the outward tracks are clearly visible. Conversely, when the emergence of large ARs leads to a strengthening of the outer coronal field and an increase in the total white-light radiance (as during late 2014), the expanding helmet-streamer loops pinch off beyond r ∼ 4 R ⊙, triggering strong inflow streams whose outgoing counterparts are usually very faint. We deduce that the visibility of the blobs and inflows depends on the amount of material that the diverging components sweep up within the 2–6 R ⊙ field of view. We also note that the rate of blob production tends to increase when a helmet streamer is “activated” by underlying flux emergence.

Organic pollutant removal from edible oil process wastewater using electrocoagulation

NASA Astrophysics Data System (ADS)

Sharma, S.; Can, O. T.; Hammed, M.; Nawarathna, D.; Simsek, H.

2018-03-01

Wastewaters generated from vegetable oil industries contain a high concentration of organic pollutants that are detrimental to the aquatic ecosystem. Electrochemical processes are gaining importance in the treatment of inorganic and resistant organic pollutants in wastewaters. In this study, electrocoagulation (EC) was applied to remove organic pollutants and oil and grease from canola oil wastewater using aluminum (Al) and iron (Fe) electrodes. The application of EC in the wastewater achieved more than 80% removal of organic carbon and nearly 100% removal of suspended solids (SS). The effectiveness of EC is influenced mainly by current density, pH, electrolyte (NaCl), electrode contact time and electrode type. It was observed that Al electrode combination yielded better removal at a lesser time compared to that of Fe electrodes. However, varying current densities had its significance in terms of coagulation time only. Increase in current density achieved decrease in coagulation time. Both Al and Fe could remove between 52-59% of oil and grease from canola oil wastewater

Culture methods impact recovery of antibiotic-resistant Enterococci including Enterococcus cecorum from pre- and postharvest chicken.

PubMed

Suyemoto, M M; Barnes, H J; Borst, L B

2017-03-01

Pathogenic strains of Enterococcus cecorum (EC) expressing multidrug resistance have emerged. In National Antimicrobial Resistance Monitoring System (NARMS) data, EC is rarely recovered from chickens. Two NARMS methodologies (FDA and USDA) were compared with standard culture (SC) techniques for recovery of EC. NARMS methods failed to detect EC in 58 caecal samples, 20 chicken breast or six whole broiler samples. EC was recovered from 1 of 38 (2·6%) and 2 of 38 (5·2%) preharvest spinal lesions (USDA and FDA method, respectively). In contrast, using the SC method, EC was recovered from 44 of 53 (83%) caecal samples, all 38 (100%) spinal lesions, 14 of 20 (70%) chicken breast samples, and all three spinal lesions identified in whole carcasses. Compared with other Enterococcus spp., EC isolates had a higher prevalence of resistance to macrolides. The NARMS methods significantly affected recovery of enterococcal species other than EC. When the postharvest FDA method was applied to preharvest caecal samples, isolates of Enterococcus faecium were preferentially recovered. All 11 E. faecium isolates were multidrug resistant, including resistance to penicillin, daptomycin and linezolid. These findings confirm that current methodologies may not accurately identify the amount and range of antimicrobial resistance of enterococci from chicken sources. Enterococci are an important reservoir for antimicrobial resistance. This study demonstrates how current culture methods underreport resistance to macrolides in enterococci by selecting against strains of Enterococcus cecorum in pre- and postharvest chicken. Further, the application of postharvest surveillance methods to preharvest samples resulted in selective recovery of Enterococcus faecium over Enterococcus faecalis. Isolates of E. faecium recovered exhibited multidrug resistance including penicillin, daptomycin and linezolid resistance. These findings suggest that culture methodology significantly impacts the range and amount of antimicrobial resistance detected in enterococci isolated from chicken. © 2016 The Society for Applied Microbiology.

Laboratory experiment on the 3D tide-induced Lagrangian residual current using the PIV technique

NASA Astrophysics Data System (ADS)

Chen, Yang; Jiang, Wensheng; Chen, Xu; Wang, Tao; Bian, Changwei

2017-12-01

The 3D structure of the tide-induced Lagrangian residual current was studied using the particle image velocimetry (PIV) technique in a long shallow narrow tank in the laboratory. At the mouth of the tank, a wave generator was used to make periodic wave which represents the tide movement, and at the head of the tank, a laterally sloping topography with the length of one fifth of the water tank was installed, above which the tide-induced Lagrangian residual current was studied. Under the weakly nonlinear condition in the present experiment setup, the results show that the Lagrangian residual velocity (LRV) field has a three-layer structure. The residual current flows inwards (towards the head) in the bottom layer and flows outwards in the middle layer, while in the surface layer, it flows inwards along the shallow side of the sloping topography and outwards along the deep side. The depth-averaged and breadth-averaged LRV are also analyzed based on the 3D LRV observations. Our results are in good agreement with the previous experiment studies, the analytical solutions with similar conditions and the observational results in real bays. Moreover, the volume flux comparison between the Lagrangian and Eulerian residual currents shows that the Eulerian residual velocity violates the mass conservation law while the LRV truly represents the inter-tidal water transport. This work enriches the laboratory studies of the LRV and offers valuable references for the LRV studies in real bays.

Mechanisms of the palmitoylcarnitine-induced response in vascular endothelial cells.

PubMed

Taki, H; Muraki, K; Imaizumi, Y; Watanabe, M

1999-09-01

The mechanisms of Ca2+ mobilization induced by palmitoylcarnitine (Palcar) in rabbit aortic endothelial cells (ETCs) were examined using electrophysiological techniques. The results obtained were compared with those induced by acetylcholine (ACh). When a rabbit aortic muscle preparation with an intact endothelium was treated with 10 microM Palcar, the ACh-induced relaxation was markedly attenuated, whereas endothelium-independent relaxation caused by sodium nitroprusside was not affected. Under perforated-patch whole-cell-clamp conditions, the application of Palcar over the concentration range 0.3 and 10 microM elicited a slowly activating outward current (IPalcar-out), whereas ACh induced a rapidly activating outward current (IACh). A potassium channel blocker, 4-aminopyridine, significantly inhibited both IPalcar-out and IACh. Removal of external Ca2+ almost abolished IPalcar-out. Under the same conditions, however, IACh remained transient. Addition of cation channel blockers SK&F96365 and La3+ inhibited IPalcar-out more effectively than IACh. Application of staurosporine, an inhibitor of protein kinase C, affected neither IACh nor IPalcar-out. In contrast, treatment of ETCs with pertussis toxin (PTX) reduced IACh and almost abolished IPalcar-out. These findings demonstrate that, in ETCs, Palcar induces Ca2+ influx via the activation of PTX-sensitive GTP-binding protein, leading to the activation of Ca(2+)-dependent K+ current and hyperpolarization of the cell.

Substorms At Jupiter: Galileo Observations of Transient Reconnection in The Near Tail

NASA Technical Reports Server (NTRS)

Russell, C. T.; Khurana, K. K.; Kivelson, M. G.; Huddleston, D. E.

2000-01-01

The magnetic flux content of the Jovian magnetosphere is set by the internal dynamo, but those magnetic field lines are constantly being loaded by heavy ions at the orbit of lo and dragged inexorably outward by the centrifugal force. Vasyliunas has proposed a steady state reconnecting magnetospheric model that sheds plasma islands of zero net magnetic flux and returns nearly empty flux tubes to the inner magnetosphere. The Galileo observations indicate that beyond 40 Rj the current sheet begins to tear and beyond 50 Rj on the nightside explosively reconnects as the tearing site reaches the low density lobe region above and below the current sheet. Small events occur irregularly but on average about every 4 hours and large events about once a day. The magnetic flux reconnected in such events amounts up to about 70,000 Webers/sec and is sufficient to return the outwardly convected magnetic flux to the inner magnetosphere. Since this process releases plasmoids into the jovian tail, as do terrestrial substorms; since this process involves explosive reconnection across the current sheet on the nightside of the planet, as do terrestrial substorms; and since the process is a key in closing the circulation pattern of the magnetic and plasma flux, as it is in terrestrial substorms; we refer to these events as jovian substorms.

A systematic analysis of online marketing materials used by providers of expanded carrier screening.

PubMed

Chokoshvili, Davit; Borry, Pascal; Vears, Danya F

2017-12-14

PurposeExpanded carrier screening (ECS) for a large number of recessive disorders is available to prospective parents through commercial providers. This study aimed to analyze the content of marketing materials on ECS providers' websites.MethodsTo identify providers of ECS tests, we undertook a comprehensive online search, reviewed recent academic literature on commercial carrier screening, and consulted with colleagues familiar with the current ECS landscape. The identified websites were archived in April 2017, and inductive content analysis was performed on website text, brochures and educational materials, and video transcripts.ResultsWe identified 18 ECS providers, including 16 commercial genetic testing companies. Providers typically described ECS as an important family planning tool. The content differed in both the tone used to promote ECS and the accuracy and completeness of the test information provided. We found that most providers offered complimentary genetic counseling to their consumers, although this was often optional, limited to the posttest context, and, in some cases, appeared to be available only to test-positive individuals.ConclusionThe quality of ECS providers' websites could be improved by offering more complete and accurate information about ECS and their tests. Providers should also ensure that all carrier couples receive posttest genetic counseling to inform their subsequent reproductive decision making.Genet Med advance online publication, 14 December 2017; doi:10.1038/gim.2017.222.

Removal of metals in leachate from sewage sludge using electrochemical technology.

PubMed

Meunier, N; Drogui, P; Gourvenec, C; Mercier, G; Hausler, R; Blais, J F

2004-02-01

Heavy metals in acidic leachates from sewage sludge are usually removed by chemical precipitation, which often requires high concentration of chemicals and induces high metallic sludge production. Electrochemical technique has been explored as an alternative method in a laboratory pilot scale reactor for heavy metals (Cu and Zn) removal from sludge leachate. Three electrolytic cell arrangements using different electrodes materials were tested: mild steel or aluminium bipolar electrode (EC cell), Graphite/stainless steel monopolar electrodes (ER cell) and iron-monopolar electrodes (EC-ER cell). Results showed that the best performances of metal removal were obtained with EC and EC-ER cells using mild steel electrodes operated respectively at current intensities of 0.8 and 2.0 A through 30 and 60 min of treatment. The yields of Cu and Zn removal from leachate varied respectively from 92.4 to 98.9% and from 69.8 to 76.6%. The amounts of 55 and 44 kg tds(-1) of metallic sludge were respectively produced using EC and EC-ER cells. EC and EC-ER systems involved respectively a total cost of 21.2 and 13.1 CAN dollars per ton of dry sludge treated including only energy consumption and metallic sludge disposal. The treatment using EC-ER system was found to be effective and more economical than the traditional metal precipitation using either Ca(OH)2 and/or NaOH.

AKT inhibition mitigates GRP78 (glucose-regulated protein) expression and contribution to chemoresistance in endometrial cancers.

PubMed

Gray, Michael J; Mhawech-Fauceglia, Paulette; Yoo, Eunjeong; Yang, Wangrong; Wu, Eijean; Lee, Amy S; Lin, Yvonne G

2013-07-01

Overexpression of the unfolded protein response master regulator GRP78 is associated with poor prognosis and therapeutic resistance in numerous human cancers, yet its role in endometrial cancers (EC) is undefined. To better understand the contribution of GRP78 to EC, we examined its expression levels in EC patient samples and EC cell lines. We demonstrate that GRP78 overexpression occurs more frequently in EC tissues compared with that found in normal endometrium, and that GRP78 expression occurs in most EC cell lines examined. Functional analysis demonstrated that GRP78 is inducible by cisplatin in EC cells, and siRNA knockdown of GRP78 augments chemotherapy-mediated cell death. Examination of AKT and GRP78 expression demonstrated that inhibition of AKT activity by MK2206 blocks GRP78 expression in EC cells. SiRNA studies also revealed that knockdown of GRP78 reduces but does not abrogate AKT activity, demonstrating that GRP78 is required for optimal AKT activity. In the presence of MK2206, siRNA knockdown of GRP78 does not augment AKT mediated survival in response to cisplatin treatment, suggesting that GRP78's antiapoptosis functions are part of the AKT survival pathway. Targeted therapies that reduce GRP78 expression or activity in cancers may serve to increase the effectiveness of current therapies for EC patients. Copyright © 2012 UICC.

Emergency Contraception in Mexico: Trends in Knowledge and Ever-Use 2006-2014.

PubMed

Han, Leo; Saavedra-Avendano, Biani; Lambert, William; Fu, Rongwei; Rodriguez, Maria I; Edelman, Alison; Darney, Blair

2017-11-01

Objectives A package of interventions to introduce emergency contraception (EC) to Mexico was implemented, resulting in the addition of EC to the national family planning guidelines in 2004. We describe EC knowledge and use among women in Mexico over time. Methods We used the 2006, 2009, and 2014 of waves of a nationally representative demographic survey (ENADID). We assessed EC knowledge and usage in women ages 15-29 who are not using permanent methods and tested whether EC knowledge and use is changing over time after controlling for socio-demographic characteristics using logistic regression. Results Our sample included n = 99,223 (population N = 40,234,355) women ages 15-29. Overall, knowledge of EC increased over time: 62% in 2006 to 79% in 2009 to 83% in 2014 (p < 0.001). Among young women who have used contraception (n = 42,883; N = 16,816,701), the proportion that reported EC use increased from 3 to 11% to 29% (p < 0.001). Compared to non-users, women who had ever used EC were more likely to be using no method of contraception (44 vs. 35%) or barrier method (22 vs. 17%). Demographic factors including lower wealth, lower education, indigenous status and rural living are significantly associated with less EC knowledge and use. Stratified multivariate analysis found that demographic disadvantages magnify lower EC use among rural residents compared to non-rural residents. Conclusions for Practice Knowledge and use of EC are growing rapidly in Mexico, but disparities persist in demographically disadvantaged women, particularly those living in rural areas. Women who use EC appear to be at higher risk of unintended pregnancy based on current contraceptive use.

Outward Bound--An Adjunctive Psychiatric Therapy: Preliminary Research Findings.

ERIC Educational Resources Information Center

Stich, Thomas F.; Sussman, Lewis R.

According to a small study, Outward Bound can enhance the treatment of hospitalized psychiatric patients. Researchers measured the effect of a therapeutic Outward Bound program of prescribed physical and social tasks on the contentment and self-esteem of seven patients undergoing short-term treatment at the Veterans Administration Hospital in…

Innovative Adolescent Chemical Dependency Treatment and Its Outcome: A Model Based on Outward Bound Programming.

ERIC Educational Resources Information Center

McPeake, John D.; And Others

1991-01-01

Describes adolescent chemical dependency treatment model developed at Beech Hill Hospital (New Hampshire) which integrated Twelve Step-oriented alcohol and drug rehabilitation program with experiential education school, Hurricane Island Outward Bound School. Describes Beech Hill Hurricane Island Outward Bound School Adolescent Chemical Dependency…

The Business of Childcare in Europe

ERIC Educational Resources Information Center

Penn, Helen

2014-01-01

This article is based on work undertaken for the European Commission (EC) as part of a wider project on what is termed "social services of general interest". The EC is currently engaged in considering what kind of legislative and quality assurance mechanisms might be promoted for those social services, which have been opened up to…

On the Intentional Control of Conditioned Evaluative Responses

ERIC Educational Resources Information Center

Balas, Robert; Gawronski, Bertram

2012-01-01

The evaluative conditioning (EC) effect is defined as a change in the evaluation of a conditioned stimulus (CS) due to its pairing with a valenced unconditioned stimulus (US). The current research investigated the controllability of EC effects by asking participants to either promote or prevent the influence of CS-US pairings before they provided…

Detection of Anomalous Machining Damages in Inconel 718 and TI 6-4 by Eddy Current Techniques

NASA Astrophysics Data System (ADS)

Lo, C. C. H.; Shimon, M.; Nakagawa, N.

2010-02-01

This paper reports on an eddy current (EC) study aimed at detecting anomalous machining damages in Inconel 718 and Ti 6-4 samples, including (i) surface discontinuities such as re-depositing of chips onto the machined surface, and (ii) microstructural damages manifested as a white surface layer and a subsurface layer of distorted grains, typically tens of microns thick. A series of pristine and machine-damaged coupons were studied by EC scans using a differential probe operated at 2 MHz to detect discontinuous surface anomalies, and by swept high frequency EC (SHFEC) measurements from 0.5 MHz to 65.5 MHz using proprietary detection coils to detect surface microstructural damages. In general, the EC c-scan data from machine-damaged surfaces show spatial variations with larger standard deviations than those from the undamaged surfaces. In some cases, the c-scan images exhibit characteristic bipolar indications in good spatial correlation with surface anomalies revealed by optical microscopy and laser profilometry. Results of the SHFEC measurements indicate a reduced near-surface conductivity of the damaged surfaces compared to the undamaged surfaces.

EDITORIAL: ECRH physics and technology in ITER

NASA Astrophysics Data System (ADS)

Luce, T. C.

2008-05-01

It is a great pleasure to introduce you to this special issue containing papers from the 4th IAEA Technical Meeting on ECRH Physics and Technology in ITER, which was held 6-8 June 2007 at the IAEA Headquarters in Vienna, Austria. The meeting was attended by more than 40 ECRH experts representing 13 countries and the IAEA. Presentations given at the meeting were placed into five separate categories EC wave physics: current understanding and extrapolation to ITER Application of EC waves to confinement and stability studies, including active control techniques for ITER Transmission systems/launchers: state of the art and ITER relevant techniques Gyrotron development towards ITER needs System integration and optimisation for ITER. It is notable that the participants took seriously the focal point of ITER, rather than simply contributing presentations on general EC physics and technology. The application of EC waves to ITER presents new challenges not faced in the current generation of experiments from both the physics and technology viewpoints. High electron temperatures and the nuclear environment have a significant impact on the application of EC waves. The needs of ITER have also strongly motivated source and launcher development. Finally, the demonstrated ability for precision control of instabilities or non-inductive current drive in addition to bulk heating to fusion burn has secured a key role for EC wave systems in ITER. All of the participants were encouraged to submit their contributions to this special issue, subject to the normal publication and technical merit standards of Nuclear Fusion. Almost half of the participants chose to do so; many of the others had been published in other publications and therefore could not be included in this special issue. The papers included here are a representative sample of the meeting. The International Advisory Committee also asked the three summary speakers from the meeting to supply brief written summaries (O. Sauter: EC wave physics and applications, M. Thumm: Source and transmission line development, and S. Cirant: ITER specific system designs). These summaries are included in this issue to give a more complete view of the technical meeting. Finally, it is appropriate to mention the future of this meeting series. With the ratification of the ITER agreement and the formation of the ITER International Organization, it was recognized that meetings conducted by outside agencies with an exclusive focus on ITER would be somewhat unusual. However, the participants at this meeting felt that the gathering of international experts with diverse specialities within EC wave physics and technology to focus on using EC waves in future fusion devices like ITER was extremely valuable. It was therefore recommended that this series of meetings continue, but with the broader focus on the application of EC waves to steady-state and burning plasma experiments including demonstration power plants. As the papers in this special issue show, the EC community is already taking seriously the challenges of applying EC waves to fusion devices with high neutron fluence and continuous operation at high reliability.

The Role of Endothelial Cells in Myofiber Differentiation and the Vascularization and Innervation of Bioengineered Muscle Tissue in vivo

DTIC Science & Technology

2012-10-08

differentiation of co- cultured cells in vivo and in vitro. We first utilized a co- culture of fluorescently labeled endothelial cells (ECs) and muscle...of 10T1/2 cells as pericytes (PCs) to the culture of MPCs and ECs can result in the stabilization of bioengineered vessels [10]. In the current study...Burlingame, CA). 2.2. Cell culture 2.2.1. MPC, EC, PC isolation and culture Green fluorescent protein (GFP)-labeled muscle progenitor cells (GFPþ MPCs

Pharmacy-based interventions for initiating effective contraception following the use of emergency contraception: a pilot study.

PubMed

Michie, L; Cameron, S T; Glasier, A; Larke, N; Muir, A; Lorimer, A

2014-10-01

In Scotland most women get emergency contraception (EC) from pharmacies. Pharmacists currently cannot provide effective ongoing contraception after EC. In this pilot study, we aimed to determine the feasibility of a larger study designed to ascertain if pharmacy-based interventions can increase the uptake of effective contraception after EC. This is a pilot study of women presenting for levonorgestrel EC to community pharmacies in Edinburgh, UK, in 2012. Pharmacies were cluster randomized to provide either standard care or one of two interventions: (a) one packet of progestogen-only pills (POPs), giving women 1 month to arrange ongoing contraception; (b) invitation to present the empty EC packet to a family planning clinic (FPC) for contraceptive advice (rapid access). One hundred sixty-eight women were recruited from 11 pharmacies to POP (n=56), rapid access (n=58) and standard care (N=54) groups, respectively. Telephone follow-up was conducted successfully in 102 women (61%) 6-8 weeks later to determine current contraceptive use. In the POP arm, 35/39 (90%) women used the pills provided, and 9/28 women (32%) in the rapid access arm attended the FPC. The proportion of women using effective contraception at follow-up was significantly greater in both POP [56% (22/39), p=<0.001] and rapid access [52% (13/25), p=0.006] groups compared to standard care [16% (5/31)]. The relative probability of a woman using an effective method of contraception versus barrier/no method, after use of EC, was 3.13 [95% confidence interval (CI), 1.90-5.13] in the POP group and 2.57 (95% CI, 1.55-4.27) in the rapid access group. This promising pilot study suggests that simple pharmacy-based interventions may increase the uptake of effective contraception after EC. A larger study is required to provide further validation of these findings. For women obtaining EC from a pharmacy, simple interventions such as supplying 1 month of a POP, or offering rapid access to a FPC, hold promise as strategies to increase the uptake of effective contraception after EC. Copyright © 2014 Elsevier Inc. All rights reserved.

Closed Classrooms, High Mountains and Strange Lands: An Inquiry into Culture and Caring.

ERIC Educational Resources Information Center

Kraft, Richard J.

1992-01-01

The current closed classroom system of education is not sufficient in preparing students for real world life. Proposes that the wilderness, cross-cultural, and international settings are a very powerful learning environment in which life-changing experiences can and do occur. Presents the Outward Bound process and Adler's stage theory of…

Changes in left ventricular repolarization and ion channel currents following a transient rate increase superimposed on bradycardia in anesthetized dogs.

PubMed

Rubart, M; Lopshire, J C; Fineberg, N S; Zipes, D P

2000-06-01

We previously demonstrated in dogs that a transient rate increase superimposed on bradycardia causes prolongation of ventricular refractoriness that persists for hours after resumption of bradycardia. In this study, we examined changes in membrane currents that are associated with this phenomenon. The whole cell, patch clamp technique was used to record transmembrane voltages and currents, respectively, in single mid-myocardial left ventricular myocytes from dogs with 1 week of complete AV block; dogs either underwent 1 hour of left ventricular pacing at 120 beats/min or did not undergo pacing. Pacing significantly heightened mean phase 1 and peak plateau amplitudes by approximately 6 and approximately 3 mV, respectively (P < 0.02), and prolonged action potential duration at 90% repolarization from 235+/-8 msec to 278+/-8 msec (1 Hz; P = 0.02). Rapid pacing-induced changes in transmembrane ionic currents included (1) a more pronounced cumulative inactivation of the 4-aminopyridine-sensitive transient outward K+ current, Ito, over the range of physiologic frequencies, resulting from a approximately 30% decrease in the population of quickly reactivating channels; (2) increases in peak density of L-type Ca2+ currents, I(Ca.L), by 15% to 35 % between +10 and +60 mV; and (3) increases in peak density of the Ca2+-activated chloride current, I(Cl.Ca), by 30% to 120% between +30 and +50 mV. Frequency-dependent reduction in Ito combined with enhanced I(Ca.L) causes an increase in net inward current that may be responsible for the observed changes in ventricular repolarization. This augmentation of net cation influx is partially antagonized by an increase in outward I(Ca.Cl).

Ca2+ current of frog vestibular hair cells is modulated by intracellular ATP but not by long-lasting depolarisation.

PubMed

Martini, Marta; Farinelli, Federica; Rossi, Maria Lisa; Rispoli, Giorgio

2007-09-01

Some aspects of Ca(2+) channel modulation in hair cells isolated from semicircular canals of the frog (Rana esculenta) have been investigated using the whole-cell technique and intra and extracellular solutions designed to modify the basic properties of the Ca(2+) macrocurrent. With 1 mM ATP in the pipette solution, about 60% of the recorded cells displayed a Ca(2+) current constituted by a mix of an L and a drug-resistant (R2) component; the remaining 40% exhibited an additional drug-resistant fraction (R1), which inactivated in a Ca-dependent manner. If the pipette ATP was raised to 10 mM, cells exhibiting the R1 current fraction displayed an increase of both the R1 and L components by approximately 280 and approximately 70%, respectively, while cells initially lacking R1 showed a similar increase in the L component with R1 becoming apparent and raising up to a mean amplitude of approximately 44 pA. In both cell types the R2 current fraction was negligibly affect by ATP. The current run-up was unaffected by cyclic nucleotides, and was not triggered by 10 mM ATPgammaS, ADP, AMP or GTP. Long-lasting depolarisations (>5 s) produced a progressive, reversible decay in the inward current despite the presence of intracellular ATP. Ca(2+) channel blockade by Cd(2+) unmasked a slowly activating outward Cs(+) current flowing through a non-Ca(2+) channel type, which became progressively unblocked by prolonged depolarisation even though Cs(+) and TEA(+) were present on both sides of the channel. The outward current waveform could be erroneously ascribed to a Ca- and/or voltage dependence of the Ca(2+) macrocurrent.

Calcium Homeostasis Modulator 1-Like Currents in Rat Fungiform Taste Cells Expressing Amiloride-Sensitive Sodium Currents.

PubMed

Bigiani, Albertino

2017-05-01

Salt reception by taste cells is still the less understood transduction process occurring in taste buds, the peripheral sensory organs for the detection of food chemicals. Although there is evidence suggesting that the epithelial sodium channel (ENaC) works as sodium receptor, yet it is not clear how salt-detecting cells signal the relevant information to nerve endings. Taste cells responding to sweet, bitter, and umami substances release ATP as neurotransmitter through a nonvesicular mechanism. Three different channel proteins have been proposed as conduit for ATP secretion: pannexin channels, connexin hemichannels, and calcium homeostasis modulator 1 (CALHM1) channels. In heterologous expression systems, these channels mediate outwardly rectifying membrane currents with distinct biophysical and pharmacological properties. I therefore tested whether also salt-detecting taste cells were endowed with these currents. To this aim, I applied the patch-clamp techniques to single cells in isolated taste buds from rat fungiform papillae. Salt-detecting cells were functionally identified by exploiting the effect of amiloride, which induces a current response by shutting down ENaCs. I looked for the presence of outwardly rectifying currents by using appropriate voltage-clamp protocols and specific pharmacological tools. I found that indeed salt-detecting cells possessed these currents with properties consistent with the presence, at least in part, of CALHM1 channels. Unexpectedly, CALHM1-like currents in taste cells were potentiated by known blockers of pannexin, suggesting a possible inhibitory action of this protein on CALMH1. These findings indicate that communication between salt-detecting cells and nerve endings might involve ATP release by CALMH1 channels. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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.

Electrical properties associated with wide intercellular clefts in rabbit Purkinje fibres.

PubMed Central

Colatsky, T J; Tsien, R W

1979-01-01

1. Rabbit Purkinje fibres were studied using micro-electrode recordings of electrical activity or a two-micro-electrode voltage clamp. Previous morphological work had suggested that these preparations offer structural advantages for the analysis of ionic permeability mechanisms. 2. Viable preparations could be obtained consistently by exposure to a K glutamate Tyrode solution during excision and recovery. In NaCl Tyrode solution, the action potential showed a large overshoot and fully developed plateau, but no pacemaker depolarization at negative potentials. 3. The passive electrical properties were consistent with morphological evidence for the accessibility of cleft membranes within the cell bundle. Electrotonic responses to intracellular current steps showed the behaviour expected for a simple leaky capacitative cable. Capacitative current transients under voltage clamp were changed very little by an eightfold reduction in the external solution conductivity. 4. Slow current changes attributable to K depletion were small compared to those found in other cardiac preparations. The amount of depletion was close to that predicted by a cleft model which assumed free K diffusion in 1 micron clefts. 5. Step depolarizations over the plateau range of potentials evoked a slow inward current which was resistant to tetrodotoxin but blocked by D600. 6. Strong depolarizations to potentials near 0 mV elicited a transient outward current and a slowly activating late outward current. Both components resembled currents found in sheep or calf Purkinje fibres. 7. These experiments support previous interpretations of slow plateau currents in terms of genuine permeability changes. The rabbit Purkinje fibre may allow various ionic channels to be studied with relatively little interference from radial non-uniformities in membrane potential or ion concentration. Images Fig. 7 PMID:469754

Biophysical mechanism of spike threshold dependence on the rate of rise of the membrane potential by sodium channel inactivation or subthreshold axonal potassium current

PubMed Central

Wester, Jason C.

2013-01-01

Spike threshold filters incoming inputs and thus gates activity flow through neuronal networks. Threshold is variable, and in many types of neurons there is a relationship between the threshold voltage and the rate of rise of the membrane potential (dVm/dt) leading to the spike. In primary sensory cortex this relationship enhances the sensitivity of neurons to a particular stimulus feature. While Na+ channel inactivation may contribute to this relationship, recent evidence indicates that K+ currents located in the spike initiation zone are crucial. Here we used a simple Hodgkin-Huxley biophysical model to systematically investigate the role of K+ and Na+ current parameters (activation voltages and kinetics) in regulating spike threshold as a function of dVm/dt. Threshold was determined empirically and not estimated from the shape of the Vm prior to a spike. This allowed us to investigate intrinsic currents and values of gating variables at the precise voltage threshold. We found that Na+ inactivation is sufficient to produce the relationship provided it occurs at hyperpolarized voltages combined with slow kinetics. Alternatively, hyperpolarization of the K+ current activation voltage, even in the absence of Na+ inactivation, is also sufficient to produce the relationship. This hyperpolarized shift of K+ activation allows an outward current prior to spike initiation to antagonize the Na+ inward current such that it becomes self-sustaining at a more depolarized voltage. Our simulations demonstrate parameter constraints on Na+ inactivation and the biophysical mechanism by which an outward current regulates spike threshold as a function of dVm/dt. PMID:23344915

Subliminal influence on preferences? A test of evaluative conditioning for brief visual conditioned stimuli using auditory unconditioned stimuli

PubMed Central

2017-01-01

In the field of evaluative conditioning (EC), two opposing theories—propositional single-process theory versus dual-process theory—are currently being discussed in the literature. The present set of experiments test a crucial prediction to adjudicate between these two theories: Dual-process theory postulates that evaluative conditioning can occur without awareness of the contingency between conditioned stimulus (CS) and unconditioned stimulus (US); in contrast, single-process propositional theory postulates that EC requires CS-US contingency awareness. In a set of three studies, we experimentally manipulate contingency awareness by presenting the CSs very briefly, thereby rendering it unlikely to be processed consciously. We address potential issues with previous studies on EC with subliminal or near-threshold CSs that limited their interpretation. Across two experiments, we consistently found an EC effect for CSs presented for 1000 ms and consistently failed to find an EC effect for briefly presented CSs. In a third pre-registered experiment, we again found evidence for an EC effect with CSs presented for 1000 ms, and we found some indication for an EC effect for CSs presented for 20 ms. PMID:28989730

Subliminal influence on preferences? A test of evaluative conditioning for brief visual conditioned stimuli using auditory unconditioned stimuli.

PubMed

Heycke, Tobias; Aust, Frederik; Stahl, Christoph

2017-09-01

In the field of evaluative conditioning (EC), two opposing theories-propositional single-process theory versus dual-process theory-are currently being discussed in the literature. The present set of experiments test a crucial prediction to adjudicate between these two theories: Dual-process theory postulates that evaluative conditioning can occur without awareness of the contingency between conditioned stimulus (CS) and unconditioned stimulus (US); in contrast, single-process propositional theory postulates that EC requires CS-US contingency awareness. In a set of three studies, we experimentally manipulate contingency awareness by presenting the CSs very briefly, thereby rendering it unlikely to be processed consciously. We address potential issues with previous studies on EC with subliminal or near-threshold CSs that limited their interpretation. Across two experiments, we consistently found an EC effect for CSs presented for 1000 ms and consistently failed to find an EC effect for briefly presented CSs. In a third pre-registered experiment, we again found evidence for an EC effect with CSs presented for 1000 ms, and we found some indication for an EC effect for CSs presented for 20 ms.

Expression of Finger Millet EcDehydrin7 in Transgenic Tobacco Confers Tolerance to Drought Stress.

PubMed

Singh, Rajiv Kumar; Singh, Vivek Kumar; Raghavendrarao, Sanagala; Phanindra, Mullapudi Lakshmi Venkata; Venkat Raman, K; Solanke, Amolkumar U; Kumar, Polumetla Ananda; Sharma, Tilak Raj

2015-09-01

One of the critical alarming constraints for agriculture is water scarcity. In the current scenario, global warming due to climate change and unpredictable rainfall, drought is going to be a master player and possess a big threat to stagnating gene pool of staple food crops. So it is necessary to understand the mechanisms that enable the plants to cope with drought stress. In this study, effort was made to prospect the role of EcDehydrin7 protein from normalized cDNA library of drought tolerance finger millet in transgenic tobacco. Biochemical and molecular analyses of T0 transgenic plants were done for stress tolerance. Leaf disc assay, seed germination test, dehydration assay, and chlorophyll estimation showed EcDehydrin7 protein directly link to drought tolerance. Northern and qRT PCR analyses shows relatively high expression of EcDehydrin7 protein compare to wild type. T0 transgenic lines EcDehydrin7(11) and EcDehydrin7(15) shows superior expression among all lines under study. In summary, all results suggest that EcDehydrin7 protein has a remarkable role in drought tolerance and may be used for sustainable crop breeding program in other food crops.

Activation of K+ channels by lanthanum contributes to the block of transmitter release in chick and rat sympathetic neurons.

PubMed

Przywara, D A; Bhave, S V; Bhave, A; Chowdhury, P S; Wakade, T D; Wakade, A R

1992-01-01

We studied the effects of lanthanum (La3+) on the release of 3H-norepinephrine (3H-NE), intracellular Ca2+ concentration, and voltage clamped Ca2+ and K+ currents in cultured sympathetic neurons. La3+ (0.1 to 10 microM) produced concentration-dependent inhibition of depolarization induced Ca2+ influx and 3H-NE release. La3+ was more potent and more efficacious in blocking 3H-NE release than the Ca(2+)-channel blockers cadmium and verapamil, which never blocked more than 70% of the release. At 3 microM, La3+ produced a complete block of the electrically stimulated rise in intracellular free Ca2+ ([Ca2+]i) in the cell body and the growth cone. The stimulation-evoked release of 3H-NE was also completely blocked by 3 microM La3+. However, 3 microM La3+ produced only a partial block of voltage clamped Ca2+ current (ICa). Following La3+ (10 microM) treatment 3H-NE release could be evoked by high K+ stimulation of neurons which were refractory to electrical stimulation. La3+ (1 microM) increased the hyperpolarization activated, 4-aminopyridine (4-AP) sensitive, transient K+ current (IA) with little effect on the late outward current elicited from depolarized holding potentials. We conclude that the effective block of electrically stimulated 3H-NE release is a result of the unique ability of La3+ to activate a stabilizing, outward K+ current at the same concentration that it blocks inward Ca2+ current.

Role of Nrf2 in preventing oxidative stress induced chloride current alteration in human lung cells.

PubMed

Canella, Rita; Benedusi, Mascia; Martini, Marta; Cervellati, Franco; Cavicchio, Carlotta; Valacchi, Giuseppe

2018-08-01

The lung tissue is one of the main targets of oxidative stress due to external sources and respiratory activity. In our previous work, we have demonstrated in that O 3 exposure alters the Cl - current-voltage relationship, with the appearance of a large outward rectifier component mainly sustained by outward rectifier chloride channels (ORCCs) in human lung epithelial cells (A549 line). In the present study, we have performed patch clamp experiments, in order to identify which one of the O 3 byproducts (4hydroxynonenal (HNE) and/or H 2 O 2 ) was responsible for chloride current change. While 4HNE exposition (up to 25 μM for 30' before electrophysiological analysis) did not reproduce O 3 effect, H 2 O 2 produced by glucose oxidase 10 mU for 24 hr before electrophysiological analysis mimicked O 3 response. This result was confirmed treating the cell with catalase (CAT) before O 3 exposure (1,000 U/ml for 2 hr): CAT was able to rescue Cl - current alteration. Since CAT is regulated by Nrf2 transcription factor, we pre-treated the cells with the Nrf2 activators, resveratrol and tBHQ. Immunochemical and immunocytochemical results showed Nrf2 activation with both substances that lead to prevent OS effect on Cl - current. These data bring new insights into the mechanisms involved in OS-induced lung tissue damage, pointing out the role of H 2 O 2 in chloride current alteration and the ability of Nfr2 activation in preventing this effect. © 2017 Wiley Periodicals, Inc.

Airway epithelial wounds in rhesus monkey generate ionic currents that guide cell migration to promote healing

PubMed Central

Sun, Yao-Hui; Reid, Brian; Fontaine, Justin H.; Miller, Lisa A.; Hyde, Dallas M.; Mogilner, Alex

2011-01-01

Damage to the respiratory epithelium is one of the most critical steps to many life-threatening diseases, such as acute respiratory distress syndrome and chronic obstructive pulmonary disease. The mechanisms underlying repair of the damaged epithelium have not yet been fully elucidated. Here we provide experimental evidence suggesting a novel mechanism for wound repair: endogenous electric currents. It is known that the airway epithelium maintains a voltage difference referred to as the transepithelial potential. Using a noninvasive vibrating probe, we demonstrate that wounds in the epithelium of trachea from rhesus monkeys generate significant outward electric currents. A small slit wound produced an outward current (1.59 μA/cm2), which could be enhanced (nearly doubled) by the ion transport stimulator aminophylline. In addition, inhibiting cystic fibrosis transmembrane conductance regulator (CFTR) with CFTR(Inh)-172 significantly reduced wound currents (0.17 μA/cm2), implicating an important role of ion transporters in wound induced electric potentials. Time-lapse video microscopy showed that applied electric fields (EFs) induced robust directional migration of primary tracheobronchial epithelial cells from rhesus monkeys, towards the cathode, with a threshold of <23 mV/mm. Reversal of the field polarity induced cell migration towards the new cathode. We further demonstrate that application of an EF promoted wound healing in a monolayer wound healing assay. Our results suggest that endogenous electric currents at sites of tracheal epithelial injury may direct cell migration, which could benefit restitution of damaged airway mucosa. Manipulation of ion transport may lead to novel therapeutic approaches to repair damaged respiratory epithelium. PMID:21719726

Effect of electrical coupling on ionic current and synaptic potential measurements.

PubMed

Rabbah, Pascale; Golowasch, Jorge; Nadim, Farzan

2005-07-01

Recent studies have found electrical coupling to be more ubiquitous than previously thought, and coupling through gap junctions is known to play a crucial role in neuronal function and network output. In particular, current spread through gap junctions may affect the activation of voltage-dependent conductances as well as chemical synaptic release. Using voltage-clamp recordings of two strongly electrically coupled neurons of the lobster stomatogastric ganglion and conductance-based models of these neurons, we identified effects of electrical coupling on the measurement of leak and voltage-gated outward currents, as well as synaptic potentials. Experimental measurements showed that both leak and voltage-gated outward currents are recruited by gap junctions from neurons coupled to the clamped cell. Nevertheless, in spite of the strong coupling between these neurons, the errors made in estimating voltage-gated conductance parameters were relatively minor (<10%). Thus in many cases isolation of coupled neurons may not be required if a small degree of measurement error of the voltage-gated currents or the synaptic potentials is acceptable. Modeling results show, however, that such errors may be as high as 20% if the gap-junction position is near the recording site or as high as 90% when measuring smaller voltage-gated ionic currents. Paradoxically, improved space clamp increases the errors arising from electrical coupling because voltage control across gap junctions is poor for even the highest realistic coupling conductances. Furthermore, the common procedure of leak subtraction can add an extra error to the conductance measurement, the sign of which depends on the maximal conductance.

Reduced Sodium Current in the Lateral Ventricular Wall Induces Inferolateral J-Waves.

PubMed

Meijborg, Veronique M F; Potse, Mark; Conrath, Chantal E; Belterman, Charly N W; De Bakker, Jacques M T; Coronel, Ruben

2016-01-01

J-waves in inferolateral leads are associated with a higher risk for idiopathic ventricular fibrillation. We aimed to test potential mechanisms (depolarization or repolarization dependent) responsible for inferolateral J-waves. We hypothesized that inferolateral J-waves can be caused by regional delayed activation of myocardium that is activated late during normal conditions. Computer simulations were performed to evaluate how J-point elevation is influenced by reducing sodium current conductivity (GNa), increasing transient outward current conductivity (Gto), or cellular uncoupling in three predefined ventricular regions (lateral, anterior, or septal). Two pig hearts were Langendorff-perfused with selective perfusion with a sodium channel blocker of lateral or anterior/septal regions. Volume-conducted pseudo-electrocardiograms (ECG) were recorded to detect the presence of J-waves. Epicardial unipolar electrograms were simultaneously recorded to obtain activation times (AT). Simulation data showed that conduction slowing, caused by reduced sodium current, in lateral, but not in other regions induced inferolateral J-waves. An increase in transient outward potassium current or cellular uncoupling in the lateral zone elicited slight J-point elevations which did not meet J-wave criteria. Additional conduction slowing in the entire heart attenuated J-waves and J-point elevations on the ECG, because of masking by the QRS. Experimental data confirmed that conduction slowing attributed to sodium channel blockade in the left lateral but not in the anterior/septal ventricular region induced inferolateral J-waves. J-waves coincided with the delayed activation. Reduced sodium current in the left lateral ventricular myocardium can cause inferolateral J-waves on the ECG.

Outward Bound Outcome Model Validation and Multilevel Modeling

ERIC Educational Resources Information Center

Luo, Yuan-Chun

2011-01-01

This study was intended to measure construct validity for the Outward Bound Outcomes Instrument (OBOI) and to predict outcome achievement from individual characteristics and course attributes using multilevel modeling. A sample of 2,340 participants was collected by Outward Bound USA between May and September 2009 using the OBOI. Two phases of…

Outward Bound Giwaykiwin: Connecting to Land and Culture through Indigenous Outdoor Education

ERIC Educational Resources Information Center

Lowan, Greg

2007-01-01

Outward Bound Canada's (OBC) Giwaykiwin Program was founded in 1985 in response to a recognized need for programming specific to students from Indigenous backgrounds. The Giwaykiwin program aims to integrate Outward Bound (OB) and Indigenous philosophies and traditions. Giwaykiwin means "coming home" in Ojibwa and signifies the program's…

Helical unwinding and side-chain unlocking unravel the outward open conformation of the melibiose transporter

NASA Astrophysics Data System (ADS)

Wang, Li-Ying; Ravi, Vidhya M.; Leblanc, Gérard; Padrós, Esteve; Cladera, Josep; Perálvarez-Marín, Alex

2016-09-01

Molecular dynamics simulations have been used to study the alternate access mechanism of the melibiose transporter from Escherichia coli. Starting from the outward-facing partially occluded form, 2 out of 12 simulations produced an outward full open form and one partially open, whereas the rest yielded fully or partially occluded forms. The shape of the outward-open form resembles other outward-open conformations of secondary transporters. During the transporter opening, conformational changes in some loops are followed by changes in the periplasm region of transmembrane helix 7. Helical curvature relaxation and unlocking of hydrophobic and ionic locks promote the outward opening of the transporter making accessible the substrate binding site. In particular, FRET studies on mutants of conserved aromatic residues of extracellular loop 4 showed lack of substrate binding, emphasizing the importance of this loop for making crucial interactions that control the opening of the periplasmic side. This study indicates that the alternate access mechanism for the melibiose transporter fits better into a flexible gating mechanism rather than the archetypical helical rigid-body rocker-switch mechanism.

E-cigarettes and Urologic Health: A Collaborative Review of Toxicology, Epidemiology, and Potential Risks.

PubMed

Bourke, Liam; Bauld, Linda; Bullen, Christopher; Cumberbatch, Marcus; Giovannucci, Edward; Islami, Farhad; McRobbie, Hayden; Silverman, Debra T; Catto, James W F

2017-06-01

Use of electronic cigarettes (ECs) is on the rise in most high-income countries. Smoking conventional cigarettes is a known risk factor for urologic malignancy incidence, progression, and mortality, as well as for other urologic health indicators. The potential impact of EC use on urologic health is therefore of clinical interest to the urology community. To review the available data on current EC use, including potential benefits in urologic patients, potential issues linked to toxicology of EC constituents, and how this might translate into urologic health risks. A Medline search was carried out in August 2016 for studies reporting urologic health outcomes and EC use. Snowballing techniques were also used to identify relevant studies from recent systematic reviews. A narrative synthesis of data around EC health outcomes, toxicology, and potential use in smoking cessation and health policy was carried out. We found no studies to date that have been specifically designed to prospectively assess urologic health risks, even in an observational setting. Generating such data would be an important contribution to the debate on the role of ECs in public health and clinical practice. There is evidence from a recent Cochrane review of RCTs that ECs can support smoking cessation. There are emerging data indicating that potentially harmful components of ECs such as tobacco-specific nitrosamines, polyaromatic hydrocarbons, and heavy metals could be linked to possible urologic health risks. ECs might be a useful tool to encourage cessation of conventional cigarette smoking. However, data collection around the specific impact of ECs on urologic health is needed to clarify the possible patient benefits, outcomes, and adverse events. While electronic cigarettes might help some people to stop smoking, their overall impact on urologic health is not clear. Copyright © 2017 European Association of Urology. All rights reserved.

Relations of emotion-related temperamental characteristics to attentional biases and social functioning.

PubMed

Nozadi, Sara S; Spinrad, Tracy L; Johnson, Scott P; Eisenberg, Nancy

2018-06-01

The current study examined whether an important temperamental characteristic, effortful control (EC), moderates the associations between dispositional anger and sadness, attention biases, and social functioning in a group of preschool-aged children (N = 77). Preschoolers' attentional biases toward angry and sad facial expressions were assessed using eye-tracking, and we obtained teachers' reports of children's temperament and social functioning. Associations of dispositional anger and sadness with time looking at relevant negative emotional stimuli were moderated by children's EC, but relations between time looking at emotional faces and indicators of social functioning, for the most part, were direct and not moderated by EC. In particular, time looking at angry faces (and low EC) predicted high levels of aggressive behaviors, whereas longer time looking at sad faces (and high EC) predicted higher social competence. Finally, latency to detect angry faces predicted aggressive behavior under conditions of average and low levels of EC. Findings are discussed in terms of the importance of differentiating between components of attention biases toward distinct negative emotions, and implications for attention training. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Soft drink wastewater treatment by electrocoagulation-electrooxidation processes.

PubMed

Linares Hernández, Ivonne; Barrera Díaz, Carlos; Valdés Cerecero, Mario; Almazán Sánchez, Perla Tatiana; Castañeda Juárez, Monserrat; Lugo Lugo, Violeta

2017-02-01

The aim of this work was to implement a coupled system, a monopolar Electrocoagulation (EC)-Electrooxidation (EO) processes, for the treatment of soft drink wastewater. For the EC test, Cu-Cu, anode-cathode were used at current densities of 17, 51 and 68 mA cm -2 . Only 37.67% of chemical oxygen demand (COD) and 27% of total organic carbon (TOC) were removed at 20 min with an optimum pH of 8, this low efficiency can be associated with the high concentration of inorganic ions which inhibit the oxidation of organic matter due to their complexation with copper ions. Later EO treatment was performed with boron-doped diamond-Cu electrodes and a current density of 30 Am -2 . The coupled EC-EO system was efficient to reduce organic pollutants from initial values of 1875 mg L -1 TOC and 4300 mg L -1 COD, the removal efficiencies were 75% and 85%, respectively. Electric energy consumption to degrade a kilogram of a pollutant in the soft drink wastewater using EC was 3.19 kWh kg -1 TOC and 6.66 kWh kg -1 COD. It was concluded that the coupled system EC-EO was effective for the soft drink wastewater treatment, reducing operating costs and residence time, and allowing its reuse in indirect contact with humans, thus contributing to the sustainable reuse as an effluent of industrial wastewater.

TRANSP: status and planning

NASA Astrophysics Data System (ADS)

Andre, R.; Carlsson, J.; Gorelenkova, M.; Jardin, S.; Kaye, S.; Poli, F.; Yuan, X.

2016-10-01

TRANSP is an integrated interpretive and predictive transport analysis tool that incorporates state of the art heating/current drive sources and transport models. The treatments and transport solvers are becoming increasingly sophisticated and comprehensive. For instance, the ISOLVER component provides a free boundary equilibrium solution, while the PT- SOLVER transport solver is especially suited for stiff transport models such as TGLF. TRANSP incorporates high fidelity heating and current drive source models, such as NUBEAM for neutral beam injection, the beam tracing code TORBEAM for EC, TORIC for ICRF, the ray tracing TORAY and GENRAY for EC. The implementation of selected components makes efficient use of MPI for speed up of code calculations. Recently the GENRAY-CQL3D solver for modeling of LH heating and current drive has been implemented and currently being extended to multiple antennas, to allow modeling of EAST discharges. Also, GENRAY+CQL3D is being extended to the use of EC/EBW and of HHFW for NSTX-U. This poster will describe present uses of the code worldwide, as well as plans for upgrading the physics modules and code framework. Work supported by the US Department of Energy under DE-AC02-CH0911466.

Treatment of Ni-EDTA containing wastewater by electrocoagulation using iron scraps packed-bed anode.

PubMed

Ye, Xiaokun; Zhang, Junya; Zhang, Yan; Lv, Yuancai; Dou, Rongni; Wen, Shulong; Li, Lianghao; Chen, Yuancai; Hu, YongYou

2016-12-01

The unique electrocoagulator proposed in this study is highly efficient at removing Ni-EDTA, providing a potential remediation option for wastewater containing lower concentrations of Ni-EDTA (Ni ≤ 10 mg L -1 ). In the electrocoagulation (EC) system, cylindrical graphite was used as a cathode, and a packed-bed formed from iron scraps was used as an anode. The results showed that the removal of Ni-EDTA increased with the application of current and favoured acidic conditions. We also found that the iron scrap packed-bed anode was superior in its treatment ability and specific energy consumption (SECS) compared with the iron rod anode. In addition, the packed density and temperature had a large influence on the energy consumption (ECS). Over 94.3% of Ni and 95.8% of TOC were removed when conducting the EC treatment at an applied current of 0.5 A, initial pH of 3, air-purged rate 0.2 L min -1 , anode packed density of 400 kg m -3 temperature of 313 K and time of 30 min. SEM analysis of the iron scraps indicated that the specific area of the anode increased after the EC. The XRD analysis of flocs produced during EC revealed that hematite (α-Fe 2 O 3 ) and magnetite (Fe 3 O 4 ) were the main by-products under aerobic and anoxic conditions, respectively. A kinetic study demonstrated that the removal of Ni-EDTA followed a first-order model with the current parameters. Moreover, the removal efficiency of real wastewater was essentially consistent with that of synthetic wastewater. Copyright © 2016 Elsevier Ltd. All rights reserved.

Removal of suspended solids and turbidity from marble processing wastewaters by electrocoagulation: comparison of electrode materials and electrode connection systems.

PubMed

Solak, Murat; Kiliç, Mehmet; Hüseyin, Yazici; Sencan, Aziz

2009-12-15

In this study, removal of suspended solids (SS) and turbidity from marble processing wastewaters by electrocoagulation (EC) process were investigated by using aluminium (Al) and iron (Fe) electrodes which were run in serial and parallel connection systems. To remove these pollutants from the marble processing wastewater, an EC reactor including monopolar electrodes (Al/Fe) in parallel and serial connection system, was utilized. Optimization of differential operation parameters such as pH, current density, and electrolysis time on SS and turbidity removal were determined in this way. EC process with monopolar Al electrodes in parallel and serial connections carried out at the optimum conditions where the pH value was 9, current density was approximately 15 A/m(2), and electrolysis time was 2 min resulted in 100% SS removal. Removal efficiencies of EC process for SS with monopolar Fe electrodes in parallel and serial connection were found to be 99.86% and 99.94%, respectively. Optimum parameters for monopolar Fe electrodes in both of the connection types were found to be for pH value as 8, for electrolysis time as 2 min. The optimum current density value for Fe electrodes used in serial and parallel connections was also obtained at 10 and 20 A/m(2), respectively. Based on the results obtained, it was found that EC process running with each type of the electrodes and the connections was highly effective for the removal of SS and turbidity from marble processing wastewaters, and that operating costs with monopolar Al electrodes in parallel connection were the cheapest than that of the serial connection and all the configurations for Fe electrode.

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.

Advanced Communications Technology Satellite high burst rate link evaluation terminal experiment control and monitor software maintenance manual, version 1.0

NASA Technical Reports Server (NTRS)

Reinhart, Richard C.

1992-01-01

The Experiment Control and Monitor (EC&M) software was developed at NASA Lewis Research Center to support the Advanced Communications Technology Satellite (ACTS) High Burst Rate Link Evaluation Terminal (HBR-LET). The HBR-LET is an experimenter's terminal to communicate with the ACTS for various investigations by government agencies, universities, and industry. The EC&M software is one segment of the Control and Performance Monitoring (C&PM) software system of the HBR-LET. The EC&M software allows users to initialize, control, and monitor the instrumentation within the HBR-LET using a predefined sequence of commands. Besides instrument control, the C&PM software system is also responsible for computer communication between the HBR-LET and the ACTS NASA Ground Station and for uplink power control of the HBR-LET to demonstrate power augmentation during rain fade events. The EC&M Software User's Guide, Version 1.0 (NASA-CR-189160) outlines the commands required to install and operate the EC&M software. Input and output file descriptions, operator commands, and error recovery procedures are discussed in the document. The EC&M Software Maintenance Manual, Version 1.0 (NASA-CR-189161) is a programmer's guide that describes current implementation of the EC&M software from a technical perspective. An overview of the EC&M software, computer algorithms, format representation, and computer hardware configuration are included in the manual.

Structures and Evolutions of Explosive Cyclones over the Northwestern and Northeastern Pacific

NASA Astrophysics Data System (ADS)

Zhang, Shuqin; Fu, Gang

2018-06-01

In this study, the structures and evolutions of moderate (MO) explosive cyclones (ECs) over the Northwestern Pacific (NWP) and Northeastern Pacific (NEP) are investigated and compared using composite analysis with cyclone-relative coordinates. Final Operational Global Analysis data gathered during the cold seasons (October-April) of the 15 years from 2000 to 2015 are used. The results indicate that MO NWP ECs have strong baroclinicity and abundant latent heat release at low levels and strong upper-level forcing, which favors explosive cyclogenesis. The rapid development of MO NEP ECs results from their interaction with a northern cyclone and a large middle-level advection of cyclonic vorticity. The structural differences between MO NWP ECs and MO NEP ECs are significant. This results from their specific large-scale atmospheric and oceanic environments. MO NWP ECs usually develop rapidly in the east and southeast of the Japan Islands; the intrusion of cold dry air from the East Asian continent leads to strong baroclinicity, and the Kuroshio/Kuroshio Extension provides abundant latent heat release at low levels. The East Asian subtropical westerly jet stream supplies strong upper-level forcing. While MO NEP ECs mainly occur over the NEP, the low-level baroclinicity, upper-level jet stream, and warm ocean currents are relatively weaker. The merged cyclone associated with a strong middle-level trough transports large cyclonic vorticity to MO NEP ECs, which favors their rapid development.

Status of the ITER Electron Cyclotron Heating and Current Drive System

NASA Astrophysics Data System (ADS)

Darbos, Caroline; Albajar, Ferran; Bonicelli, Tullio; Carannante, Giuseppe; Cavinato, Mario; Cismondi, Fabio; Denisov, Grigory; Farina, Daniela; Gagliardi, Mario; Gandini, Franco; Gassmann, Thibault; Goodman, Timothy; Hanson, Gregory; Henderson, Mark A.; Kajiwara, Ken; McElhaney, Karen; Nousiainen, Risto; Oda, Yasuhisa; Omori, Toshimichi; Oustinov, Alexander; Parmar, Darshankumar; Popov, Vladimir L.; Purohit, Dharmesh; Rao, Shambhu Laxmikanth; Rasmussen, David; Rathod, Vipal; Ronden, Dennis M. S.; Saibene, Gabriella; Sakamoto, Keishi; Sartori, Filippo; Scherer, Theo; Singh, Narinder Pal; Strauß, Dirk; Takahashi, Koji

2016-01-01

The electron cyclotron (EC) heating and current drive (H&CD) system developed for the ITER is made of 12 sets of high-voltage power supplies feeding 24 gyrotrons connected through 24 transmission lines (TL), to five launchers, four located in upper ports and one at the equatorial level. Nearly all procurements are in-kind, following general ITER philosophy, and will come from Europe, India, Japan, Russia and the USA. The full system is designed to couple to the plasma 20 MW among the 24 MW generated power, at the frequency of 170 GHz, for various physics applications such as plasma start-up, central H&CD and magnetohydrodynamic (MHD) activity control. The design takes present day technology and extends toward high-power continuous operation, which represents a large step forward as compared to the present state of the art. The ITER EC system will be a stepping stone to future EC systems for DEMO and beyond.

Measurement of the depth of narrow slotted sections in eddy current reference standards

NASA Astrophysics Data System (ADS)

Kim, Young-Joo; Kim, Young-gil; Ahn, Bongyoung; Yoon, Dong-Jin

2007-02-01

The dimensions of the slots in eddy current (EC) reference standards are too narrow to be measured by general depth measurement methods such as the optical (laser) or stylus methods. However, measurement of the dimensions of the machined slots is a prerequisite to using the blocks as references. The present paper suggests a measurement method for the slotted section using an ultrasonic test. The width and depth of the slots measured in our study are roughly 0.1 mm and 0.5 mm, respectively. The time of flight (TOF) of the ultrasonic wave was measured precisely. The ultrasonic velocity in the material of the EC reference standard was calculated with the measured values of the TOF and its thickness. Reflected waves from the tip of the slot and the bottom surface of the EC standard were successfully classified. Using this method we have successfully determined the depth of the slotted section.

Rectification of Acetylcholine-Elicited Currents in PC12 Pheochromocytoma Cells

NASA Astrophysics Data System (ADS)

Ifune, C. K.; Steinbach, J. H.

1990-06-01

The current-voltage (I-V) relationship for acetylcholine-elicited currents in the rat pheochromocytoma cell line PC12 is nonlinear. Two voltage-dependent processes that could account for the whole-cell current rectification were examined, receptor channel gating and single receptor channel permeation. We found that both factors are involved in the rectification of the whole-cell currents. The voltage dependence of channel gating determines the shape of the I-V curve at negative potentials. The single-channel I-V relationship is inwardly rectifying and largely responsible for the characteristic shape of the whole-cell I-V curve at positive potentials. The rectification of the single-channel currents is produced by the voltage-dependent block of outward currents by intracellular Mg2+ ions.

A Means-End Investigation of Outcomes Associated with Outward Bound and NOLS Programs

ERIC Educational Resources Information Center

Goldenberg, Marni; Pronsolino, Dan

2008-01-01

This study compares outcomes associated with participation in Outward Bound (OB) and National Outdoor Leadership Schools (NOLS) courses in the United States. OB and NOLS (two of the largest providers of outdoor adventure education [OAE] courses) combined saw more than 30,000 students in 2006 (NOLS, n.d.; Outward Bound, n.d.). Comparing these two…

Studies on impact of electron cyclotron wave injection on the internal transport barriers in JT-60U weak shear plasmas

NASA Astrophysics Data System (ADS)

Ide, S.; Takenaga, H.; Isayama, A.; Sakamoto, Y.; Yoshida, M.; Gormezano, C.

2007-11-01

Impact of the electron cyclotron range of frequency wave (ECRF) on the internal transport barriers (ITBs) in a weak shear (WS) plasma has been investigated in JT-60U. The fundamental O-mode ECRF of 110 GHz injected obliquely (co-current drive) from the low field side is used. It is observed that the ion temperature (Ti) ITB in a WS plasma can be degraded by ECRF. It is clarified for the first time that the degradation depends increasingly on the EC power (PEC) but decreasingly on the plasma current (Ip). Moreover it is confirmed that ECRF affects the toroidal rotation (Vt) indirectly and results in the flattening of Vt(ρ) and therefore the radial electric field (Er) profiles regardless of the direction of the target Vt(ρ), peaking co or counter direction (relative to the Ip direction). Furthermore, it is recently found that Ti and Vt in the whole ITB region are affected with almost no delay from the EC onset even with off-axis EC deposition. These results indicate that EC injection unveiled a semi-global structure that characterizes Ti ITB in a WS plasma.

Current advances in esophageal cancer proteomics.

PubMed

Uemura, Norihisa; Kondo, Tadashi

2015-06-01

We review the current status of proteomics for esophageal cancer (EC) from a clinician's viewpoint. The ultimate goal of cancer proteomics is the improvement of clinical outcome. The proteome as a functional translation of the genome is a straightforward representation of genomic mechanisms that trigger carcinogenesis. Cancer proteomics has identified the mechanisms of carcinogenesis and tumor progression, detected biomarker candidates for early diagnosis, and provided novel therapeutic targets for personalized treatments. Our review focuses on three major topics in EC proteomics: diagnostics, treatment, and molecular mechanisms. We discuss the major histological differences between EC types, i.e., esophageal squamous cell carcinoma and adenocarcinoma, and evaluate the clinical significance of published proteomics studies, including promising diagnostic biomarkers and novel therapeutic targets, which should be further validated prior to launching clinical trials. Multi-disciplinary collaborations between basic scientists, clinicians, and pathologists should be established for inter-institutional validation. In conclusion, EC proteomics has provided significant results, which after thorough validation, should lead to the development of novel clinical tools and improvement of the clinical outcome for esophageal cancer patients. This article is part of a Special Issue entitled: Medical Proteomics. Copyright © 2014 Elsevier B.V. All rights reserved.

Adsorption treatment of oxide chemical mechanical polishing wastewater from a semiconductor manufacturing plant by electrocoagulation.

PubMed

Chou, Wei-Lung; Wang, Chih-Ta; Chang, Wen-Chun; Chang, Shih-Yu

2010-08-15

In this study, metal hydroxides generated during electrocoagulation (EC) were used to remove the chemical oxygen demand (COD) of oxide chemical mechanical polishing (oxide-CMP) wastewater from a semiconductor manufacturing plant by EC. Adsorption studies were conducted in a batch system for various current densities and temperatures. The COD concentration in the oxide-CMP wastewater was effectively removed and decreased by more than 90%, resulting in a final wastewater COD concentration that was below the Taiwan discharge standard (100 mg L(-1)). Since the processed wastewater quality exceeded the direct discharge standard, the effluent could be considered for reuse. The adsorption kinetic studies showed that the EC process was best described using the pseudo-second-order kinetic model at the various current densities and temperatures. The experimental data were also tested against different adsorption isotherm models to describe the EC process. The Freundlich adsorption isotherm model predictions matched satisfactorily with the experimental observations. Thermodynamic parameters, including the Gibbs free energy, enthalpy, and entropy, indicated that the COD adsorption of oxide-CMP wastewater on metal hydroxides was feasible, spontaneous and endothermic in the temperature range of 288-318 K. Copyright 2010 Elsevier B.V. All rights reserved.

Removal of nitrate and sulphate from biologically treated municipal wastewater by electrocoagulation

NASA Astrophysics Data System (ADS)

Sharma, Arun Kumar; Chopra, A. K.

2017-06-01

The present investigation observed the effect of current density ( j), electrocoagulation (EC) time, inter electrode distance, electrode area, initial pH and settling time on the removal of nitrate (NO3 -) and sulphate (SO4 2-) from biologically treated municipal wastewater (BTMW), and optimization of the operating conditions of the EC process. A glass chamber of two-liter volume was used for the experiments with DC power supply using two electrode plates of aluminum (Al-Al). The maximum removal of NO3 - (63.21 %) and SO4 2- (79.98 %) of BTMW was found with the optimum operating conditions: current density: 2.65 A/m2, EC time: 40 min, inter electrode distance: 0.5 cm, electrode area: 160 cm2, initial pH: 7.5 and settling time: 60 min. The EC brought down the concentration of NO3 - within desirable limit of the Bureau of Indian Standard (BIS)/WHO for drinking water. Under optimal operating conditions, the operating cost was found to be 1.01/m3 of water in terms of the electrode consumption (23.71 × 10-5 kg Al/m3) and energy consumption (101.76 kWh/m3).

Amplitude-independent flaw length determination using differential eddy current

NASA Astrophysics Data System (ADS)

Shell, E.

2013-01-01

Military engine component manufacturers typically specify the eddy current (EC) inspection requirements as a crack length or depth with the assumption that the cracks in both the test specimens and inspected component are of a similar fixed aspect ratio. However, differential EC response amplitude is dependent on the area of the crack face, not the length or depth. Additionally, due to complex stresses, in-service cracks do not always grow in the assumed manner. It would be advantageous to use more of the information contained in the EC data to better determine the full profile of cracks independent of the fixed aspect ratio amplitude response curve. A specimen with narrow width notches is used to mimic cracks of varying aspect ratios in a controllable manner. The specimen notches have aspect ratios that vary from 1:1 to 10:1. Analysis routines have been developed using the shape of the EC response signals that can determine the length of a surface flaw of common orientations without use of the amplitude of the signal or any supporting traditional probability of detection basis. Combined with the relationship between signal amplitude and area, the depth of the flaw can also be calculated.

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.

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

An overview of carbon materials for flexible electrochemical capacitors.

PubMed

He, Yongmin; Chen, Wanjun; Gao, Caitian; Zhou, Jinyuan; Li, Xiaodong; Xie, Erqing

2013-10-07

Under the background of the quick development of lightweight, flexible, and wearable electronic devices in our society, a flexible and highly efficient energy management strategy is needed for their counterpart energy-storage systems. Among them, flexible electrochemical capacitors (ECs) have been considered as one of the most promising candidates because of their significant advantages in power and energy densities, and unique properties of being flexible, lightweight, low-cost, and environmentally friendly compared with current energy storage devices. In a common EC, carbon materials play an irreplaceable and principal role in its energy-storage performance. Up till now, most progress towards flexible ECs technologies has mostly benefited from the continuous development of carbon materials. As a result, in view of the dual remarkable highlights of ECs and carbon materials, a summary of recent research progress on carbon-based flexible EC electrode materials is presented in this review, including carbon fiber (CF, consisting of carbon microfiber-CMF and carbon nanofiber-CNF) networks, carbon nanotube (CNT) and graphene coatings, CNT and/or graphene papers (or films), and freestanding three-dimensional (3D) flexible carbon-based macroscopic architectures. Furthermore, some promising carbon materials for great potential applications in flexible ECs are introduced. Finally, the trends and challenges in the development of carbon-based electrode materials for flexible ECs and their smart applications are analyzed.

Crystalline Microporous Organosilicates with Reversed Functionalities of Organic and Inorganic Components for Room-Temperature Gas Sensing.

PubMed

Fabbri, Barbara; Bonoldi, Lucia; Guidi, Vincenzo; Cruciani, Giuseppe; Casotti, Davide; Malagù, Cesare; Bellussi, Giuseppe; Millini, Roberto; Montanari, Luciano; Carati, Angela; Rizzo, Caterina; Montanari, Erica; Zanardi, Stefano

2017-07-26

A deepened investigation on an innovative organic-inorganic hybrid material, referred to as ECS-14 (where ECS = Eni carbon silicates), revealed the possibility to use them as gas sensors. Indeed, among ECS phases, the crystalline state and the hexagonal microplateletlike morphology characteristic of ECS-14 seemed favorable properties to obtain continuous and uniform films. ECS-14 phase was used as functional material in screen-printable compositions and was thus deposited by drop coating for morphological, structural, thermal, and electrical characterizations. Possible operation at room temperature was investigated as technological progress, offering intrinsic safety in sensors working in harsh or industrial environments and avoiding high power consumption of most common sensors based on metal oxide semiconductors. Electrical characterization of the sensors based on ECS-14 versus concentrations of gaseous analytes gave significant results at room temperature in the presence of humidity, thereby demonstrating fundamental properties for a good quality sensor (speed, reversibility, and selectivity) that make them competitive with respect to systems currently in use. Remarkably, we observed functionality reversal of the organic and inorganic components; that is, in contrast to other hybrids, for ECS-14 the functional site has been ascribed to the inorganic phase while the organic component provided structural stability to the material. The sensing mechanism for humidity was also investigated.

Removal of fluoride, SDS, ammonia and turbidity from semiconductor wastewater by combined electrocoagulation-electroflotation.

PubMed

Aoudj, S; Khelifa, A; Drouiche, N

2017-08-01

Semiconductor industry effluents contain organic and inorganic pollutants, such as sodium dodecyl sulfate (SDS), fluoride and ammonia, at high levels which consists a major environmental issue. A combined EC-EF process is proposed as a post-treatment after precipitation for simultaneous clarification and removal of pollutants. In EC step, a hybrid Fe-Al was used as the soluble anode in order to avoid supplementary EC step. EC-Fe is more suitable for SDS removal; EC-Al is more suitable for fluoride removal, while EC with hybrid Al-Fe makes a good compromise. Clarification and ammonia oxidation were achieved in the EF step. Effects of anodic material, initial pH, current, anion nature, chloride concentration and initial pollutant concentration were studied. The final concentrations may reach 0.27, 6.23 and 0.22 mg L -1 for SDS, fluoride and ammonia respectively. These concentrations are far lower than the correspondent discharge limits. Similarly, the final turbidity was found 4.35 NTU which is lower than 5NTU and the treated water does not need further filtration before discharge. Furthermore, the EC-EF process proves to be sufficiently energy-efficient with less soluble electrode consumption. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prognostic Significance of POLE Proofreading Mutations in Endometrial Cancer

PubMed Central

Church, David N.; Stelloo, Ellen; Nout, Remi A.; Valtcheva, Nadejda; Depreeuw, Jeroen; ter Haar, Natalja; Noske, Aurelia; Amant, Frederic; Wild, Peter J.; Lambrechts, Diether; Jürgenliemk-Schulz, Ina M.; Jobsen, Jan J.; Smit, Vincent T. H. B. M.; Creutzberg, Carien L.; Bosse, Tjalling

2015-01-01

Background: Current risk stratification in endometrial cancer (EC) results in frequent over- and underuse of adjuvant therapy, and may be improved by novel biomarkers. We examined whether POLE proofreading mutations, recently reported in about 7% of ECs, predict prognosis. Methods: We performed targeted POLE sequencing in ECs from the PORTEC-1 and -2 trials (n = 788), and analyzed clinical outcome according to POLE status. We combined these results with those from three additional series (n = 628) by meta-analysis to generate multivariable-adjusted, pooled hazard ratios (HRs) for recurrence-free survival (RFS) and cancer-specific survival (CSS) of POLE-mutant ECs. All statistical tests were two-sided. Results: POLE mutations were detected in 48 of 788 (6.1%) ECs from PORTEC-1 and-2 and were associated with high tumor grade (P < .001). Women with POLE-mutant ECs had fewer recurrences (6.2% vs 14.1%) and EC deaths (2.3% vs 9.7%), though, in the total PORTEC cohort, differences in RFS and CSS were not statistically significant (multivariable-adjusted HR = 0.43, 95% CI = 0.13 to 1.37, P = .15; HR = 0.19, 95% CI = 0.03 to 1.44, P = .11 respectively). However, of 109 grade 3 tumors, 0 of 15 POLE-mutant ECs recurred, compared with 29 of 94 (30.9%) POLE wild-type cancers; reflected in statistically significantly greater RFS (multivariable-adjusted HR = 0.11, 95% CI = 0.001 to 0.84, P = .03). In the additional series, there were no EC-related events in any of 33 POLE-mutant ECs, resulting in a multivariable-adjusted, pooled HR of 0.33 for RFS (95% CI = 0.12 to 0.91, P = .03) and 0.26 for CSS (95% CI = 0.06 to 1.08, P = .06). Conclusion: POLE proofreading mutations predict favorable EC prognosis, independently of other clinicopathological variables, with the greatest effect seen in high-grade tumors. This novel biomarker may help to reduce overtreatment in EC. PMID:25505230

Effective Clinical Supervision in Substance Use Disorder Treatment Programs and Counselor Job Performance.

PubMed

Rothrauff-Laschober, Tanja C; Eby, Lillian Turner de Tormes; Sauer, Julia B

2013-01-01

When mental health counselors have limited and/or inadequate training in substance use disorders (SUDs), effective clinical supervision (ECS) may advance their professional development. The purpose of the current study was to investigate whether ECS is related to the job performance of SUD counselors. Data were obtained in person via paper-and-pencil surveys from 392 matched SUD counselor-clinical supervisor dyads working in 27 SUD treatment organizations across the United States. ECS was rated by counselors and measured with five multi-item scales (i.e., sponsoring counselors' careers, providing challenging assignments, role modeling, accepting/confirming counselors' competence, overall supervisor task proficiency). Clinical supervisors rated counselors' job performance, which was measured with two multi-item scales (i.e., task performance, performance within supervisory relationship). Using mixed-effects models, we found that most aspects of ECS are related to SUD counselor job performance. Thus, ECS may indeed enhance counselors' task performance and performance within the supervisory relationship, and, as a consequence, offset limited formal SUD training.

DOD Electronic Commerce (EC)/Electronic Data Interchange (EDI) in contracting report

NASA Astrophysics Data System (ADS)

1993-12-01

Use of Electronic Commerce (EC)/Electronic Data Interchange (EDI) to support Department of Defense (DoD) procurement processes has been under consideration for some time. A 1988 Deputy Secretary of Defense memo calls for maximum use of EDI, based on 10 years of DoD EDI investigation and experiments. In 1990, Defense Management Review Decision 941 stated, 'The strategic goal of DoD's current efforts is to provide the department with the capability to initiate, conduct, and maintain its external business related transactions and internal logistics, contracting, and financial activities without requiring the use of hard copy media.' The EC in Contracting PAT membership reflected a broad cross section of Military Services and Defense Agencies working on a full-time basis for 60 days. The diversity of the EC in Contracting PAT ensured that the needs and concerns of all DoD components were addressed during the creation of the report. The resultant plan, therefore, represents a comprehensive approach for implementing EC throughout the DoD.

Cerium oxide nanoparticles protect endothelial cells from apoptosis induced by oxidative stress.

PubMed

Chen, Shizhu; Hou, Yingjian; Cheng, Gong; Zhang, Cuimiao; Wang, Shuxiang; Zhang, Jinchao

2013-07-01

Oxidative stress is well documented to cause injury to endothelial cells (ECs), which in turn trigger cardiovascular diseases. Previous studies revealed that cerium oxide nanoparticles (nanoceria) had antioxidant property, but the protective effect of nanoceria on ROS injury to ECs and cardiovascular diseases has not been reported. In the current study, we investigated the protective effect and underlying mechanisms of nanoceria on oxidative injury to ECs. The cell viability, lactate dehydrogenase release, cellular uptake, intracellular localization and reactive oxygen species (ROS) levels, endocytosis mechanism, cell apoptosis, and mitochondrial membrane potential were performed. The results indicated that nanoceria had no cytotoxicity on ECs but had the ability to prevent injury by H2O2. Nanoceria could be uptaken into ECs through caveolae- and clathrin-mediated endocytosis and distributed throughout the cytoplasma. The internalized nanoceria effectively attenuated ROS overproduction induced by H2O2. Apoptosis was also alleviated greatly by nanoceria pretreatment. These results may be helpful for more rational application of nanoceria in biomedical fields in the future.

Effective Clinical Supervision in Substance Use Disorder Treatment Programs and Counselor Job Performance

PubMed Central

2013-01-01

When mental health counselors have limited and/or inadequate training in substance use disorders (SUDs), effective clinical supervision (ECS) may advance their professional development. The purpose of the current study was to investigate whether ECS is related to the job performance of SUD counselors. Data were obtained in person via paper-and-pencil surveys from 392 matched SUD counselor-clinical supervisor dyads working in 27 SUD treatment organizations across the United States. ECS was rated by counselors and measured with five multi-item scales (i.e., sponsoring counselors’ careers, providing challenging assignments, role modeling, accepting/confirming counselors’ competence, overall supervisor task proficiency). Clinical supervisors rated counselors’ job performance, which was measured with two multi-item scales (i.e., task performance, performance within supervisory relationship). Using mixed-effects models, we found that most aspects of ECS are related to SUD counselor job performance. Thus, ECS may indeed enhance counselors’ task performance and performance within the supervisory relationship, and, as a consequence, offset limited formal SUD training. PMID:25061265

Camouflaging endothelial cells: does it prolong graft survival?

PubMed

Stuhlmeier, K M; Lin, Y

1999-08-05

Camouflaging antigens on the surface of cells seems an appealing way to prevent activation of the immune system. We explored the possibility of preventing hyperacute rejection by chemically camouflaging endothelial cells (EC). In vitro as well as in vivo experiments were performed. First, the ability of mPEG coating to prevent antibody-antigen interactions was evaluated. Second, we tested the degree to which mPEG coating prevents activation of EC by stimuli such as TNF-alpha and LPS. Third, in vivo experiments were performed to test the ability of mPEG coating to prolong xenograft survival. We demonstrate that binding of several antibodies to EC or serum proteins can be inhibited by mPEG. Furthermore, binding of TNF-alpha as well as LPS to EC is blocked since mPEG treatment of EC inhibits the subsequent up-regulation of E-selectin by these stimuli. However, in vivo experiments revealed that currently this method alone is not sufficient to prevent hyperacute rejection.

Are metals emitted from electronic cigarettes a reason for health concern? A risk-assessment analysis of currently available literature.

PubMed

Farsalinos, Konstantinos E; Voudris, Vassilis; Poulas, Konstantinos

2015-05-15

Studies have found that metals are emitted to the electronic cigarette (EC) aerosol. However, the potential health impact of exposure to such metals has not been adequately defined. The purpose of this study was to perform a risk assessment analysis, evaluating the exposure of electronic cigarette (EC) users to metal emissions based on findings from the published literature. Two studies were found in the literature, measuring metals emitted to the aerosol from 13 EC products. We estimated that users take on average 600 EC puffs per day, but we evaluated the daily exposure from 1200 puffs. Estimates of exposure were compared with the chronic Permissible Daily Exposure (PDE) from inhalational medications defined by the U.S. Pharmacopeia (cadmium, chromium, copper, lead and nickel), the Minimal Risk Level (MRL) defined by the Agency for Toxic Substances and Disease Registry (manganese) and the Recommended Exposure Limit (REL) defined by the National Institute of Occupational Safety and Health (aluminum, barium, iron, tin, titanium, zinc and zirconium). The average daily exposure from 13 EC products was 2.6 to 387 times lower than the safety cut-off point of PDEs, 325 times lower than the safety limit of MRL and 665 to 77,514 times lower than the safety cut-off point of RELs. Only one of the 13 products was found to result in exposure 10% higher than PDE for one metal (cadmium) at the extreme daily use of 1200 puffs. Significant differences in emissions between products were observed. Based on currently available data, overall exposure to metals from EC use is not expected to be of significant health concern for smokers switching to EC use, but is an unnecessary source of exposure for never-smokers. Metal analysis should be expanded to more products and exposure can be further reduced through improvements in product quality and appropriate choice of materials.

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

PubMed Central

Rowe, Ian; Schams, Anthony; Mayhew, Christina

2017-01-01

Pseudomonas aeruginosa (PA) is an opportunistic pathogen with an exceptional ability to adapt to a range of environments. Part of its adaptive potential is the ability to survive drastic osmolarity changes. Upon a sudden dilution of external medium, such as during exposure to rain, bacteria evade mechanical rupture by engaging tension-activated channels that act as osmolyte release valves. In this study, we compare fast osmotic permeability responses in suspensions of wild-type PA and Escherichia coli (EC) strains in stopped-flow experiments and provide electrophysiological descriptions of osmotic-release channels in PA. Using osmotic dilution experiments, we first show that PA tolerates a broader range of shocks than EC. We record the kinetics of cell equilibration reported by light scattering responses to osmotic up- and down-shocks. PA exhibits a lower water permeability and faster osmolyte release rates during large osmotic dilutions than EC, which correlates with better survival. To directly characterize the PA tension-activated channels, we generate giant spheroplasts from this microorganism and record current responses in excised patches. Unlike EC, which relies primarily on two types of channels, EcMscS and EcMscL, to generate a distinctive two-wave pressure ramp response, PA exhibits a more gradual response that is dominated by MscL-type channels. Genome analysis, cloning, and expression reveal that PA possesses one MscL-type (PaMscL) and two MscS-type (PaMscS-1 and 2) proteins. In EC spheroplasts, both PaMscS channels exhibit a slightly earlier activation by pressure compared with EcMscS. Unitary currents reveal that PaMscS-2 has a smaller conductance, higher anionic preference, stronger inactivation, and slower recovery compared with PaMscS-1. We conclude that PA relies on MscL as the major valve defining a high rate of osmolyte release sufficient to curb osmotic swelling under extreme shocks, but it still requires MscS-type channels with a strong propensity to inactivation to properly terminate massive permeability response. PMID:28424229

Mass spectrometric methods for monitoring redox processes in electrochemical cells.

PubMed

Oberacher, Herbert; Pitterl, Florian; Erb, Robert; Plattner, Sabine

2015-01-01

Electrochemistry (EC) is a mature scientific discipline aimed to study the movement of electrons in an oxidation-reduction reaction. EC covers techniques that use a measurement of potential, charge, or current to determine the concentration or the chemical reactivity of analytes. The electrical signal is directly converted into chemical information. For in-depth characterization of complex electrochemical reactions involving the formation of diverse intermediates, products and byproducts, EC is usually combined with other analytical techniques, and particularly the hyphenation of EC with mass spectrometry (MS) has found broad applicability. The analysis of gases and volatile intermediates and products formed at electrode surfaces is enabled by differential electrochemical mass spectrometry (DEMS). In DEMS an electrochemical cell is sampled with a membrane interface for electron ionization (EI)-MS. The chemical space amenable to EC/MS (i.e., bioorganic molecules including proteins, peptides, nucleic acids, and drugs) was significantly increased by employing electrospray ionization (ESI)-MS. In the simplest setup, the EC of the ESI process is used to analytical advantage. A limitation of this approach is, however, its inability to precisely control the electrochemical potential at the emitter electrode. Thus, particularly for studying mechanistic aspects of electrochemical processes, the hyphenation of discrete electrochemical cells with ESI-MS was found to be more appropriate. The analytical power of EC/ESI-MS can further be increased by integrating liquid chromatography (LC) as an additional dimension of separation. Chromatographic separation was found to be particularly useful to reduce the complexity of the sample submitted either to the EC cell or to ESI-MS. Thus, both EC/LC/ESI-MS and LC/EC/ESI-MS are common. © 2013 The Authors. Mass Spectrometry Reviews published by Wiley Periodicals, Inc.

A Review of the Interactions between Alcohol and the Endocannabinoid System: Implications for Alcohol Dependence and Future Directions for Research

PubMed Central

Pava, Matthew J.; Woodward, John J.

2012-01-01

Over the past fifty years a significant body of evidence has been compiled suggesting an interaction between the endocannabinoid (EC) system and alcohol dependence. However, much of this work has been conducted only in the past two decades following the elucidation of the molecular constituents of the EC system that began with the serendipitous discovery of the cannabinoid 1 receptor (CB1). Since then, novel pharmacological and genetic tools have enabled researchers to manipulate select components of the EC system, to determine their contribution to the motivation to consume ethanol. From these preclinical studies, it is evident that CB1 contributes the motivational and reinforcing properties of ethanol, and chronic consumption of ethanol alters EC transmitter levels and CB1 expression in brain nuclei associated with addiction pathways. These results are augmented by in vitro and ex vivo studies showing that acute and chronic treatment with ethanol produces physiologically relevant alterations in the function of the EC system. This report provides a current and comprehensive review of the literature regarding the interactions between ethanol and the EC system. We begin be reviewing the studies published prior to the discovery of the EC system that compared the behavioral and physiological effects of cannabinoids with ethanol in addition to cross-tolerance between these drugs. Next, a brief overview of the molecular constituents of the EC system is provided as context for the subsequent review of more recent studies examining the interaction of ethanol with the EC system. These results are compiled into a summary providing a scheme for the known changes to the components of the EC system in different stages of alcohol dependence. Finally, future directions for research are discussed. PMID:22459871

Mass spectrometric methods for monitoring redox processes in electrochemical cells

PubMed Central

Oberacher, Herbert; Pitterl, Florian; Erb, Robert; Plattner, Sabine

2015-01-01

Electrochemistry (EC) is a mature scientific discipline aimed to study the movement of electrons in an oxidation–reduction reaction. EC covers techniques that use a measurement of potential, charge, or current to determine the concentration or the chemical reactivity of analytes. The electrical signal is directly converted into chemical information. For in-depth characterization of complex electrochemical reactions involving the formation of diverse intermediates, products and byproducts, EC is usually combined with other analytical techniques, and particularly the hyphenation of EC with mass spectrometry (MS) has found broad applicability. The analysis of gases and volatile intermediates and products formed at electrode surfaces is enabled by differential electrochemical mass spectrometry (DEMS). In DEMS an electrochemical cell is sampled with a membrane interface for electron ionization (EI)-MS. The chemical space amenable to EC/MS (i.e., bioorganic molecules including proteins, peptides, nucleic acids, and drugs) was significantly increased by employing electrospray ionization (ESI)-MS. In the simplest setup, the EC of the ESI process is used to analytical advantage. A limitation of this approach is, however, its inability to precisely control the electrochemical potential at the emitter electrode. Thus, particularly for studying mechanistic aspects of electrochemical processes, the hyphenation of discrete electrochemical cells with ESI-MS was found to be more appropriate. The analytical power of EC/ESI-MS can further be increased by integrating liquid chromatography (LC) as an additional dimension of separation. Chromatographic separation was found to be particularly useful to reduce the complexity of the sample submitted either to the EC cell or to ESI-MS. Thus, both EC/LC/ESI-MS and LC/EC/ESI-MS are common. PMID:24338642

Effect of streptavidin-biotin on endothelial vasoregulation and leukocyte adhesion.

PubMed

Chan, Bernard P; Reichert, William M; Truskey, George A

2004-08-01

The current study examines whether the adhesion promoting arginine-glycine-aspartate-streptavidin mutant (RGD-SA) also affects two important endothelial cell (EC) functions in vitro: vasoregulation and leukocyte adhesion. EC adherent to surfaces via fibronectin (Fn) or Fn plus RGD-SA were subjected to laminar shear flow and media samples were collected over a period of 4h to measure the concentration of nitric oxide (NO), prostacyclin (PGI(2)), and endothelin-1 (ET-1). Western blot analysis was used to quantify the levels of endothelial-derived nitric oxide synthase (eNOS) and cyclooxygenase II (COX II). In a separate set of experiments, fluorescent polymorphonuclear leukocyte (PMN) adhesion to EC was quantified for EC with and without exposure to flow preconditioning. When cell adhesion was supplemented with the SA-biotin system, flow-induced production of NO and PGI(2) increased significantly relative to cells adherent on Fn alone. Previous exposure of EC to shear flow also significantly decreased PMN attachment to SA-biotin supplemented EC, but only after 2h of exposure to shear flow. The observed decrease in PMN-EC adhesion was negated by NG-nitro-L-arginine methyl ester (L-NAME), an antagonist of NO synthesis, but not by indomethacin, an inhibitor to PGI(2) synthesis, indicating the induced effect of PMN-EC interaction is primarily NO-dependent. Results from this study suggest that the use of SA-biotin to supplement EC adhesion encourages vasodilation and PMN adhesion in vitro under physiological shear-stress conditions. We postulate that the presence of SA-biotin more efficiently transmits the shear-stress signal and amplifies the downstream events including the NO and PGI(2) release and leukocyte-EC inhibition. These results may have ramifications for reducing thrombus-induced vascular graft failure.

Demonstration of sawtooth period control with EC waves in KSTAR plasma

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

Jeong, J. H.; Bae, Y. S.; Joung, M.

2015-03-12

The sawtooth period control in tokamak is important issue in recent years because the sawtooth crash can trigger TM/NTM instabilities and drive plasmas unstable. The control of sawtooth period by the modification of local current profile near the q=1 surface using ECCD has been demonstrated in a number of tokamaks [1, 2] including KSTAR. As a result, developing techniques to control the sawtooth period as a way of controlling the onset of NTM has been an important area of research in recent years [3]. In 2012 KSTAR plasma campaign, the sawtooth period control is carried out by the different depositionmore » position of EC waves across the q=1 surface. The sawtooth period is shortened by on-axis co-ECCD (destabilization), and the stabilization of the sawtooth is also observed by off-axis co-ECCD at outside q=1 surface. In 2013 KSTAR plasma campaign, the sawtooth locking experiment with periodic forcing of 170 GHz EC wave is carried out to control the sawtooth period. The optimal target position which lengthens the sawtooth period is investigated by performing a scan of EC beam deposition position nearby q=1 surface at the toroidal magnetic field of 2.9 T and plasma current of 0.7 MA. The sawtooth locking by the modulated EC beam is successfully demonstrated as in [3-5] with the scan of modulation-frequency and duty-ratio at the low beta (β N~0.5) plasma. In this paper, the sawteeth behavior by the location of EC beam and the preliminary result of the sawtooth locking experiments in KSTAR will be presented.« less

Determining confounding sensitivities in eddy current thin film measurements

NASA Astrophysics Data System (ADS)

Gros, Ethan; Udpa, Lalita; Smith, James A.; Wachs, Katelyn

2017-02-01

Eddy current (EC) techniques are widely used in industry to measure the thickness of non-conductive films on a metal substrate. This is done by using a system whereby a coil carrying a high-frequency alternating current is used to create an alternating magnetic field at the surface of the instrument's probe. When the probe is brought near a conductive surface, the alternating magnetic field will induce ECs in the conductor. The substrate characteristics and the distance of the probe from the substrate (the coating thickness) affect the magnitude of the ECs. The induced currents load the probe coil affecting the terminal impedance of the coil. The measured probe impedance is related to the lift off between coil and conductor as well as conductivity of the test sample. For a known conductivity sample, the probe impedance can be converted into an equivalent film thickness value. The EC measurement can be confounded by a number of measurement parameters. It was the goal of this research to determine which physical properties of the measurement set-up and sample can adversely affect the thickness measurement. The eddy-current testing was performed using a commercially available, hand-held eddy-current probe (ETA3.3H spring-loaded eddy probe running at 8 MHz) that comes with a stand to hold the probe. The stand holds the probe and adjusts the probe on the z-axis to help position the probe in the correct area as well as make precise measurements. The signal from the probe was sent to a hand-held readout, where the results are recorded directly in terms of liftoff or film thickness. Understanding the effect of certain factors on the measurements of film thickness, will help to evaluate how accurate the ETA3.3H spring-loaded eddy probe was at measuring film thickness under varying experimental conditions. This research studied the effects of a number of factors such as i) conductivity, ii) edge effect, iii) surface finish of base material and iv) cable condition.

Convergent regulation of the lysosomal two-pore channel-2 by Mg2+, NAADP, PI(3,5)P2 and multiple protein kinases

PubMed Central

Jha, Archana; Ahuja, Malini; Patel, Sandip; Brailoiu, Eugen; Muallem, Shmuel

2014-01-01

Lysosomal Ca2+ homeostasis is implicated in disease and controls many lysosomal functions. A key in understanding lysosomal Ca2+ signaling was the discovery of the two-pore channels (TPCs) and their potential activation by NAADP. Recent work concluded that the TPCs function as a PI(3,5)P2 activated channels regulated by mTORC1, but not by NAADP. Here, we identified Mg2+ and the MAPKs, JNK and P38 as novel regulators of TPC2. Cytoplasmic Mg2+ specifically inhibited TPC2 outward current, whereas lysosomal Mg2+ partially inhibited both outward and inward currents in a lysosomal lumen pH-dependent manner. Under controlled Mg2+, TPC2 is readily activated by NAADP with channel properties identical to those in response to PI(3,5)P2. Moreover, TPC2 is robustly regulated by P38 and JNK. Notably, NAADP-mediated Ca2+ release in intact cells is regulated by Mg2+, PI(3,5)P2, and P38/JNK kinases, thus paralleling regulation of TPC2 currents. Our data affirm a key role for TPC2 in NAADP-mediated Ca2+ signaling and link this pathway to Mg2+ homeostasis and MAP kinases, pointing to roles for lysosomal Ca2+ in cell growth, inflammation and cancer. PMID:24502975

Convergent regulation of the lysosomal two-pore channel-2 by Mg²⁺, NAADP, PI(3,5)P₂ and multiple protein kinases.

PubMed

Jha, Archana; Ahuja, Malini; Patel, Sandip; Brailoiu, Eugen; Muallem, Shmuel

2014-03-03

Lysosomal Ca(2+) homeostasis is implicated in disease and controls many lysosomal functions. A key in understanding lysosomal Ca(2+) signaling was the discovery of the two-pore channels (TPCs) and their potential activation by NAADP. Recent work concluded that the TPCs function as a PI(3,5)P2 activated channels regulated by mTORC1, but not by NAADP. Here, we identified Mg(2+) and the MAPKs, JNK and P38 as novel regulators of TPC2. Cytoplasmic Mg(2+) specifically inhibited TPC2 outward current, whereas lysosomal Mg(2+) partially inhibited both outward and inward currents in a lysosomal lumen pH-dependent manner. Under controlled Mg(2+), TPC2 is readily activated by NAADP with channel properties identical to those in response to PI(3,5)P2. Moreover, TPC2 is robustly regulated by P38 and JNK. Notably, NAADP-mediated Ca(2+) release in intact cells is regulated by Mg(2+), PI(3,5)P2, and P38/JNK kinases, thus paralleling regulation of TPC2 currents. Our data affirm a key role for TPC2 in NAADP-mediated Ca(2+) signaling and link this pathway to Mg(2+) homeostasis and MAP kinases, pointing to roles for lysosomal Ca(2+) in cell growth, inflammation and cancer.

Note: Eddy current displacement sensors independent of target conductivity.

PubMed

Wang, Hongbo; Li, Wei; Feng, Zhihua

2015-01-01

Eddy current sensors (ECSs) are widely used for non-contact displacement measurement. In this note, the quantitative error of an ECS caused by target conductivity was analyzed using a complex image method. The response curves (L-x) of the ECS with different targets were similar and could be overlapped by shifting the curves on x direction with √2δ/2. Both finite element analysis and experiments match well with the theoretical analysis, which indicates that the measured error of high precision ECSs caused by target conductivity can be completely eliminated, and the ECSs can measure different materials precisely without calibration.

A review on emerging contaminants in wastewaters and the environment: current knowledge, understudied areas and recommendations for future monitoring.

PubMed

Petrie, Bruce; Barden, Ruth; Kasprzyk-Hordern, Barbara

2015-04-01

This review identifies understudied areas of emerging contaminant (EC) research in wastewaters and the environment, and recommends direction for future monitoring. Non-regulated trace organic ECs including pharmaceuticals, illicit drugs and personal care products are focused on due to ongoing policy initiatives and the expectant broadening of environmental legislation. These ECs are ubiquitous in the aquatic environment, mainly derived from the discharge of municipal wastewater effluents. Their presence is of concern due to the possible ecological impact (e.g., endocrine disruption) to biota within the environment. To better understand their fate in wastewaters and in the environment, a standardised approach to sampling is needed. This ensures representative data is attained and facilitates a better understanding of spatial and temporal trends of EC occurrence. During wastewater treatment, there is a lack of suspended particulate matter analysis due to further preparation requirements and a lack of good analytical approaches. This results in the under-reporting of several ECs entering wastewater treatment works (WwTWs) and the aquatic environment. Also, sludge can act as a concentrating medium for some chemicals during wastewater treatment. The majority of treated sludge is applied directly to agricultural land without analysis for ECs. As a result there is a paucity of information on the fate of ECs in soils and consequently, there has been no driver to investigate the toxicity to exposed terrestrial organisms. Therefore a more holistic approach to environmental monitoring is required, such that the fate and impact of ECs in all exposed environmental compartments are studied. The traditional analytical approach of applying targeted screening with low resolution mass spectrometry (e.g., triple quadrupoles) results in numerous chemicals such as transformation products going undetected. These can exhibit similar toxicity to the parent EC, demonstrating the necessity of using an integrated analytical approach which compliments targeted and non-targeted screening with biological assays to measure ecological impact. With respect to current toxicity testing protocols, failure to consider the enantiomeric distribution of chiral compounds found in the environment, and the possible toxicological differences between enantiomers is concerning. Such information is essential for the development of more accurate environmental risk assessment. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Ionic mechanisms of transient inward current in the absence of Na(+)-Ca2+ exchange in rabbit cardiac Purkinje fibres.

PubMed Central

Han, X; Ferrier, G R

1992-01-01

1. Membrane currents were measured with a two-microelectrode technique in voltage clamped rabbit cardiac Purkinje fibres under conditions known to cause intracellular calcium overload and to eliminate or minimize Na(+)-Ca2+ exchange. 2. Increasing [Ca2+]o from 2.5 to 5 mM or above and substituting external sodium with either sucrose, choline or Li+ induced an oscillatory transient inward current (TI) which peaked 200-300 ms after repolarization from a previous depolarizing pulse. The TI quickly disappeared upon return to normal Tyrode solution. Both the rate and configuration of action potentials of Purkinje fibres also returned to control upon return to Tyrode solution after 30 min of high Ca2+ exposure, if the Ca2+ concentration was 30 mM or less. 3. The TI in Na(+)-free solution was Ca2+ dependent. Either zero or low (2.5 mM) [Ca2+]o, or replacement of [Ca2+]o by BaCl prevented induction of the TI current upon repolarization from a previous depolarizing pulse. 4. In the presence of 30 mM-CaCl2 and with choline chloride as the substitute for NaCl, TI had a distinct reversal potential (Erev) of -25 mV. The time-to-peak TI, either inward or outward, did not shift significantly with change in voltage. Both inward and outward TI were simultaneously abolished by exposure to 1 microM-ryanodine, suggesting they were both activated by transient release of Ca2+ from the sarcoplasmic reticulum. The occurrence of TI in the absence of [Na+]o is not compatible with an electrogenic Na(+)-Ca2+ exchange mechanism. The existence of a clear-cut reversal potential suggests that an ionic channel may be responsible for the TI under these conditions. 5. Both the magnitude of peak TI and the Erev were affected by changes of CaCl2 concentration. (i) Under steady-state conditions, peak inward TI was significantly increased when the [Ca2+]o was elevated from 5 to 15 mM. The peak TI in the outward direction was significantly increased when [Ca2+]o was elevated from 15 to 30 mM; however, the difference in peak inward TI at 15 and 30 mM [Ca2+]o was small. (ii) Clear-cut reversals of TI were found at Ca2+ concentrations of 10 mM (Erev = -19.5 mV) or greater, and elevation of [Ca2+]o to 20, 30, 50 and 105 mM shifted the Erev to more negative potentials. (iii) In the presence of 5 mM [Ca2+]o the inward TI declined to zero at about -30 mV, and test voltages between -55 and +5 mV failed to reveal a distinct outward TI.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1284077

The Cooperstown Outward Bound Summer Program: An Informal Look at the Program's Impact on the Lives of Students.

ERIC Educational Resources Information Center

Sakofs, Mitchell S.; And Others

During the summer of 1987, 29 students from the Cooperstown High School in New York received scholarships and participated in an Outward Bound course. This report presents the results of a study assessing the impact of the Outward Bound experience on these students. Data gathering instruments included: the Self Report Survey (SRS), developed by…

Direct block of inward rectifier potassium channels by nicotine.

PubMed

Wang, H; Yang, B; Zhang, L; Xu, D; Wang, Z

2000-04-01

Nicotine has been shown to depolarize membrane potential and to lengthen action potential duration in isolated cardiac preparations. To investigate whether this is a consequence of direct interaction of nicotine with inward rectifier K(+) channels which are a key determinant of membrane potentials, we assessed the effects of nicotine on two cloned human inward rectifier K(+) channels, Kir2.1 and Kir2.2, expressed in Xenopus oocytes and the native inward rectifier K(+) current I(K1) in canine ventricular myocytes. Nicotine suppressed Kir2.1-expressed currents at varying potentials negative to -20 mV, with more pronounced effects on the outward current between -70 and -20 mV relative to the inward current at hyperpolarized potentials (below -70 mV). The inhibition was concentration dependent. For the outward currents recorded at -50 mV, the IC50 was 165 +/- 18 microM. Similar effects of nicotine were observed for Kir2.2. A more potent effect was seen with I(K1) in canine myocytes. Significant blockade ( approximately 60%) was found at a concentration as low as 0.5 microM and the IC50 was 4.0 +/- 0.4 microM. The effects in both oocytes and myocytes were partially reversible upon washout of nicotine. Antagonists of nicotinic receptors (mecamylamine, 100 microM), muscarinic receptors (atropine, 1 microM), and beta-adrenergic receptors (propranolol, 1 microM) all failed to restore the depressed currents, suggesting that nicotine acted directly on Kir channels, independent of catecholamine release. This property of nicotine may explain its membrane-depolarizing and action potential duration-prolonging effects in cardiac cells and may contribute in part to its ability to promote propensity for cardiac arrhythmias. Copyright 2000 Academic Press.

Action potentials and ion conductances in wild-type and CALHM1-knockout type II taste cells

PubMed Central

Saung, Wint Thu; Foskett, J. Kevin

2017-01-01

Taste bud type II cells fire action potentials in response to tastants, triggering nonvesicular ATP release to gustatory neurons via voltage-gated CALHM1-associated ion channels. Whereas CALHM1 regulates mouse cortical neuron excitability, its roles in regulating type II cell excitability are unknown. In this study, we compared membrane conductances and action potentials in single identified TRPM5-GFP-expressing circumvallate papillae type II cells acutely isolated from wild-type (WT) and Calhm1 knockout (KO) mice. The activation kinetics of large voltage-gated outward currents were accelerated in cells from Calhm1 KO mice, and their associated nonselective tail currents, previously shown to be highly correlated with ATP release, were completely absent in Calhm1 KO cells, suggesting that CALHM1 contributes to all of these currents. Calhm1 deletion did not significantly alter resting membrane potential or input resistance, the amplitudes and kinetics of Na+ currents either estimated from action potentials or recorded from steady-state voltage pulses, or action potential threshold, overshoot peak, afterhyperpolarization, and firing frequency. However, Calhm1 deletion reduced the half-widths of action potentials and accelerated the deactivation kinetics of transient outward currents, suggesting that the CALHM1-associated conductance becomes activated during the repolarization phase of action potentials. NEW & NOTEWORTHY CALHM1 is an essential ion channel component of the ATP neurotransmitter release mechanism in type II taste bud cells. Its contribution to type II cell resting membrane properties and excitability is unknown. Nonselective voltage-gated currents, previously associated with ATP release, were absent in cells lacking CALHM1. Calhm1 deletion was without effects on resting membrane properties or voltage-gated Na+ and K+ channels but contributed modestly to the kinetics of action potentials. PMID:28202574

Action potentials and ion conductances in wild-type and CALHM1-knockout type II taste cells.

PubMed

Ma, Zhongming; Saung, Wint Thu; Foskett, J Kevin

2017-05-01

Taste bud type II cells fire action potentials in response to tastants, triggering nonvesicular ATP release to gustatory neurons via voltage-gated CALHM1-associated ion channels. Whereas CALHM1 regulates mouse cortical neuron excitability, its roles in regulating type II cell excitability are unknown. In this study, we compared membrane conductances and action potentials in single identified TRPM5-GFP-expressing circumvallate papillae type II cells acutely isolated from wild-type (WT) and Calhm1 knockout (KO) mice. The activation kinetics of large voltage-gated outward currents were accelerated in cells from Calhm1 KO mice, and their associated nonselective tail currents, previously shown to be highly correlated with ATP release, were completely absent in Calhm1 KO cells, suggesting that CALHM1 contributes to all of these currents. Calhm1 deletion did not significantly alter resting membrane potential or input resistance, the amplitudes and kinetics of Na + currents either estimated from action potentials or recorded from steady-state voltage pulses, or action potential threshold, overshoot peak, afterhyperpolarization, and firing frequency. However, Calhm1 deletion reduced the half-widths of action potentials and accelerated the deactivation kinetics of transient outward currents, suggesting that the CALHM1-associated conductance becomes activated during the repolarization phase of action potentials. NEW & NOTEWORTHY CALHM1 is an essential ion channel component of the ATP neurotransmitter release mechanism in type II taste bud cells. Its contribution to type II cell resting membrane properties and excitability is unknown. Nonselective voltage-gated currents, previously associated with ATP release, were absent in cells lacking CALHM1. Calhm1 deletion was without effects on resting membrane properties or voltage-gated Na + and K + channels but contributed modestly to the kinetics of action potentials. Copyright © 2017 the American Physiological Society.

Permeation and block of TRPV1 channels by the cationic lidocaine derivative QX-314

PubMed Central

Puopolo, Michelino; Binshtok, Alexander M.; Yao, Gui-Lan; Oh, Seog Bae; Woolf, Clifford J.

2013-01-01

QX-314 (N-ethyl-lidocaine) is a cationic lidocaine derivative that blocks voltage-dependent sodium channels when applied internally to axons or neuronal cell bodies. Coapplication of external QX-314 with the transient receptor potential vanilloid 1 protein (TRPV1) agonist capsaicin produces long-lasting sodium channel inhibition in TRPV1-expressing neurons, suggestive of QX-314 entry into the neurons. We asked whether QX-314 entry occurs directly through TRPV1 channels or through a different pathway (e.g., pannexin channels) activated downstream of TRPV1 and whether QX-314 entry requires the phenomenon of “pore dilation” previously reported for TRPV1. With external solutions containing 10 or 20 mM QX-314 as the only cation, inward currents were activated by stimulation of both heterologously expressed and native TRPV1 channels in rat dorsal root ganglion neurons. QX-314-mediated inward current did not require pore dilation, as it activated within several seconds and in parallel with Cs-mediated outward current, with a reversal potential consistent with PQX-314/PCs = 0.12. QX-314-mediated current was no different when TRPV1 channels were expressed in C6 glioma cells, which lack expression of pannexin channels. Rapid addition of QX-314 to physiological external solutions produced instant partial inhibition of inward currents carried by sodium ions, suggesting that QX-314 is a permeant blocker. Maintained coapplication of QX-314 with capsaicin produced slowly developing reduction of outward currents carried by internal Cs, consistent with intracellular accumulation of QX-314 to concentrations of 50–100 μM. We conclude that QX-314 is directly permeant in the “standard” pore formed by TRPV1 channels and does not require either pore dilation or activation of additional downstream channels for entry. PMID:23303863

Chloride currents activated by caffeine in rat intestinal smooth muscle cells.

PubMed Central

Ohta, T; Ito, S; Nakazato, Y

1993-01-01

1. Current responses to caffeine in single smooth muscle cells isolated from rat intestine were studied with the whole-cell patch clamp technique. Intracellular calcium concentration, [Ca2+]i, was simultaneously monitored with fura-2 (0.1 mM) introduced into the cell through a patch pipette. 2. With a potassium-containing pipette solution, caffeine (10 mM) produced an outward current at a holding potential of 0 mV and an inward current at -60 mV, both of which were accompanied by parallel increases in [Ca2+]i. The outward current response disappeared after the removal of K+ from pipette solutions, indicating that caffeine activates a Ca(2+)-activated K+ conductance. 3. When NaCl was present in both pipette and external solutions as the major constituent, caffeine evoked an inward current at -60 mV simultaneously with a rise in [Ca2+]i. The reversal potential (Er) of this current was about 0 mV. 4. Substitution of Tris+ or choline+ for external Na+ did not alter the Er. When external Cl- was replaced by thiocyanate-, iodide- or glutamate-, the Er changed to respectively -55, -38 and +35 mV. 5. The current response to caffeine decreased with increasing concentration of EGTA in the pipette solution. The caffeine-induced current and the intracellular Ca2+ transient was still observed for a few minutes after exposure of the cells to Ca(2+)-free external solution containing 2 mM EGTA. Caffeine failed to produce an inward current and Ca2+ transient after treatment with extracellular ryanodine. 6. It is concluded that caffeine caused an increase in membrane Cl- conductance and in K+ conductance resulting from a rise in [Ca2+]i derived from ryanodine-sensitive intracellular Ca2+ stores in isolated smooth muscle cells of the rat intestine. PMID:8229831

Ferrous and ferric ion generation during iron electrocoagulation.

PubMed

Lakshmanan, Divagar; Clifford, Dennis A; Samanta, Gautam

2009-05-15

Our research on arsenate removal by iron electrocoagulation (EC) produced highly variable results, which appeared to be due to Fe2+ generation without subsequent oxidation to Fe3+. Because the environmental technology literature is contradictory with regard to the generation of ferric or ferrous ions during EC, the objective of this research was to establish the iron species generated during EC with iron anodes. Experimental results demonstrated that Fe2+, not Fe3+, was produced at the iron anode. Theoretical current efficiency was attained based on Fe2+ production with a clean iron rod, regardless of current, dissolved-oxygen (DO) level, or pH (6.5-8.5). The Fe2+ remaining after generation and mixing decreased with increasing pH and DO concentration due to rapid oxidation to Fe3+. At pH 8.5, Fe2+ was completely oxidized, which resulted in the desired Fe(OH)3(s)/ FeOOH(s), whereas, at pH 6.5 and 7.5, incomplete oxidation was observed, resulting in a mixture of soluble Fe2+ and insoluble Fe(OH)3(s)/FeOOH(s). When compared with Fe2+ chemical coagulation, a transient pH increase during EC led to faster Fe2+ oxidation. In summary, for EC in the pH 6.5-7.5 range and at low DO conditions, there is a likelihood of soluble Fe2+ species passing through a subsequentfiltration process resulting in secondary contamination and inefficient contaminant removals.

Cytokine-mediated dysregulation of zonula occludens-1 properties in human brain microvascular endothelium.

PubMed

Rochfort, Keith D; Cummins, Philip M

2015-07-01

Zonula occludens-1 (ZO-1) is essential to the proper assembly of interendothelial junction complexes that control blood-brain barrier (BBB) integrity. The goal of the current paper was to improve our understanding of how proinflammatory cytokines modulate ZO-1 properties within the human BBB microvascular endothelium. In this respect, we investigated the effects of TNF-α and IL-6 on ZO-1 using human brain microvascular endothelial cells (HBMvECs). Following treatment of HBMvECs with either cytokine (0-100 ng/ml, 18 h), we observed significantly decreased ZO-1 expression and ZO-1:occludin co-association, in parallel with increased ZO-1 phosphorylation (pTyr and pThr). All effects were dose-dependent. Either cytokine also caused extensive cell-cell border delocalization of ZO-1 in parallel with elevated HBMvEC permeability. Furthermore, pre-treatment of HBMvECs with antioxidants (superoxide dismutase, catalase, apocynin, N-acetylcysteine), or employing targeted inhibition of NADPH oxidase activation (NSC23766, gp91/p47 siRNA), were all found to comparably attenuate the cytokine-dependent decrease in ZO-1 protein expression. In summary, we present an in vitro model of how different proinflammatory cytokines can dysregulate ZO-1 properties in HBMvECs. A causal role for NADPH oxidase activation and oxidant signalling is also confirmed. Our findings add mechanistic depth to current in vivo models of BBB injury manifesting ZO-1 dysregulation. Copyright © 2015 Elsevier Inc. All rights reserved.

Electrochemical liquid-liquid-solid (ec-LLS) crystal growth: a low-temperature strategy for covalent semiconductor crystal growth.

PubMed

Fahrenkrug, Eli; Maldonado, Stephen

2015-07-21

This Account describes a new electrochemical synthetic strategy for direct growth of crystalline covalent group IV and III-V semiconductor materials at or near ambient temperature conditions. This strategy, which we call "electrochemical liquid-liquid-solid" (ec-LLS) crystal growth, marries the semiconductor solvation properties of liquid metal melts with the utility and simplicity of conventional electrodeposition. A low-temperature liquid metal (i.e., Hg, Ga, or alloy thereof) acts simultaneously as the source of electrons for the heterogeneous reduction of oxidized semiconductor precursors dissolved in an electrolyte as well as the solvent for dissolution of the zero-valent semiconductor. Supersaturation of the semiconductor in the liquid metal triggers eventual crystal nucleation and growth. In this way, the liquid electrolyte-liquid metal-solid crystal phase boundary strongly influences crystal growth. As a synthetic strategy, ec-LLS has several intrinsic features that are attractive for preparing covalent semiconductor crystals. First, ec-LLS does not require high temperatures, toxic precursors, or high-energy-density semiconductor reagents. This largely simplifies equipment complexity and expense. In practice, ec-LLS can be performed with only a beaker filled with electrolyte and an electrical circuit capable of supplying a defined current (e.g., a battery in series with a resistor). By this same token, ec-LLS is compatible with thermally and chemically sensitive substrates (e.g., plastics) that cannot be used as deposition substrates in conventional syntheses of covalent semiconductors. Second, ec-LLS affords control over a host of crystal shapes and sizes through simple changes in common experimental parameters. As described in detail herein, large and small semiconductor crystals can be grown both homogeneously within a liquid metal electrode and heterogeneously at the interface of a liquid metal electrode and a seed substrate, depending on the particular details chosen for ec-LLS. Third, the rate of introduction of zero-valent materials into the liquid metal is precisely gated with a high degree of resolution by the applied potential/current. The intent of this Account is to summarize the key elements of ec-LLS identified to date, first contextualizing this method with respect to other semiconductor crystal growth methods and then highlighting some unique capabilities of ec-LLS. Specifically, we detail ec-LLS as a platform to prepare Ge and Si crystals from bulk- (∼1 cm(3)), micro- (∼10(-10) cm(3)), and nano-sized (∼10(-16) cm(3)) liquid metal electrodes in common solvents at low temperature. In addition, we describe our successes in the preparation of more compositionally complex binary covalent III-V semiconductors.

Autophagy orchestrates adaptive responses to targeted therapy in endometrial cancer.

PubMed

Eritja, Núria; Chen, Bo-Juen; Rodríguez-Barrueco, Ruth; Santacana, Maria; Gatius, Sònia; Vidal, August; Martí, Maria Dolores; Ponce, Jordi; Bergadà, Laura; Yeramian, Andree; Encinas, Mario; Ribera, Joan; Reventós, Jaume; Boyd, Jeff; Villanueva, Alberto; Matias-Guiu, Xavier; Dolcet, Xavier; Llobet-Navàs, David

2017-03-04

Targeted therapies in endometrial cancer (EC) using kinase inhibitors rarely result in complete tumor remission and are frequently challenged by the appearance of refractory cell clones, eventually resulting in disease relapse. Dissecting adaptive mechanisms is of vital importance to circumvent clinical drug resistance and improve the efficacy of targeted agents in EC. Sorafenib is an FDA-approved multitarget tyrosine and serine/threonine kinase inhibitor currently used to treat hepatocellular carcinoma, advanced renal carcinoma and radioactive iodine-resistant thyroid carcinoma. Unfortunately, sorafenib showed very modest effects in a multi-institutional phase II trial in advanced uterine carcinoma patients. Here, by leveraging RNA-sequencing data from the Cancer Cell Line Encyclopedia and cell survival studies from compound-based high-throughput screenings we have identified the lysosomal pathway as a potential compartment involved in the resistance to sorafenib. By performing additional functional biology studies we have demonstrated that this resistance could be related to macroautophagy/autophagy. Specifically, our results indicate that sorafenib triggers a mechanistic MAPK/JNK-dependent early protective autophagic response in EC cells, providing an adaptive response to therapeutic stress. By generating in vivo subcutaneous EC cell line tumors, lung metastatic assays and primary EC orthoxenografts experiments, we demonstrate that targeting autophagy enhances sorafenib cytotoxicity and suppresses tumor growth and pulmonary metastasis progression. In conclusion, sorafenib induces the activation of a protective autophagic response in EC cells. These results provide insights into the unopposed resistance of advanced EC to sorafenib and highlight a new strategy for therapeutic intervention in recurrent EC.

EC power management in ITER for NTM control: the path from the commissioning phase to demonstration discharges

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

Poli, Francesca M.; Fredrickson, Eric; Henderson, Mark A.

Time dependent simulations that evolve consistently the magnetic equilibrium and plasma pressure profiles and the width and frequency rotation of magnetic islands under the effect of the Electron Cyclotron feedback system are used to assess whether the control of NTMs on ITER is compatible with other simulataneous functionalities of the EC system, like core heating and current profile tailoring, or sawtooth control. Furthermore, results indicate that the power needs for control can be reduced if the EC power is reserved and if pre-emptive control is used as opposed to an active search for an already developed island.

EC power management in ITER for NTM control: the path from the commissioning phase to demonstration discharges

DOE PAGES

Poli, Francesca M.; Fredrickson, Eric; Henderson, Mark A.; ...

2017-10-23

Time dependent simulations that evolve consistently the magnetic equilibrium and plasma pressure profiles and the width and frequency rotation of magnetic islands under the effect of the Electron Cyclotron feedback system are used to assess whether the control of NTMs on ITER is compatible with other simulataneous functionalities of the EC system, like core heating and current profile tailoring, or sawtooth control. Furthermore, results indicate that the power needs for control can be reduced if the EC power is reserved and if pre-emptive control is used as opposed to an active search for an already developed island.

Mouths of the Amazon River, Brazil, South America

NASA Image and Video Library

1992-08-08

STS046-80-009 (31 July-8 Aug. 1992) --- A view of the mouth of the Amazon River and the Amazon Delta shows a large sediment plume expanding outward into the Atlantic Ocean. The sediment plume can be seen hugging the coast north of the Delta. This is caused by the west-northwest flowing Guyana Current. The large island of Marajo is partially visible through the clouds.

Plasma convection in Saturn's magnetosphere: A diagnosis using Cassini observations of the magnetic field spiral

NASA Astrophysics Data System (ADS)

Smith, Edward; Dougherty, Michele K.

The global distribution of plasma and its flows inside Saturn's magnetosphere is complex. The large satellites in the inner magnetosphere are a persistent source of plasma that must make its way into the outer magnetosphere and exit through the magnetotail. The mass loaded into the magnetic field stretches the field lines outward resulting in the formation of the equatorial current sheet. The outward radial flow causes the closed stretched fields to spiral out of magnetic meridian planes. The angle associated with the spiralling is given by the ratio of the azimuthal field component, B , to the radial component Br : tan = B / Br . The magnetic spiral is directly related to the corresponding components of plasma velocity, v and v r, provided the conductivity of the ionosphere, , is high enough to enforce co-rotation of the field lines. If, as has been inferred, the conductivity is low, the field and plasma do not co-rotate and the conductivity also enters the expression for . Conditions are more uncertain further out in the magnetosphere where convective motions associated with magnetic reconnection between planetary and interplanetary fields and the motion of the shocked solar wind become dominant. The prevailing model is a superposition of two modes of plasma circulation inside the magnetosphere and magnetotail, the Dungey and Vasyliunas cycles, that depend on radial distance and local time with an x-line in the midnight sector that separates the two cycles. The measured spiral angle will be affected by this complexity and holds the promise of distinguishing the relative influences of v ,v r and . The two field components that define the spiral angle are also involved in the transfer of angular momentum from the ionosphere to the magnetospheric plasma and the outward mass flux. The spiral should also contain evidence, especially at high latitudes, of the return of the current to the ionosphere from the current sheet. Our major objective, therefore, is to characterize as a function of radius, latitude and local time using the global coverage provided by Cassini and apply the findings to the topics listed above.

Role of 5-HTTLPR polymorphism in the development of the inward/outward personality organization: a genetic association study.

PubMed

Nardi, Bernardo; Marini, Alessandra; Turchi, Chiara; Arimatea, Emidio; Tagliabracci, Adriano; Bellantuono, Cesario

2013-01-01

Reciprocity with primary caregivers affects subjects' adaptive abilities toward the construction of the most useful personal meaning organization (PMO) with respect to their developmental environment. Within cognitive theory the post-rationalist approach has outlined two basic categories of identity construction and of regulation of cognitive and emotional processes: the Outward and the Inward PMO. The presence of different, consistent clinical patterns in Inward and Outward subjects is paralleled by differences in cerebral activation during emotional tasks on fMRI and by different expression of some polymorphisms in serotonin pathways. Since several lines of evidence support a role for the 5-HTTLPR polymorphism in mediating individual susceptibility to environmental emotional stimuli, this study was conducted to investigate its influence in the development of the Inward/Outward PMO. PMO was assessed and the 5-HTTLPR polymorphism investigated in 124 healthy subjects who were subdivided into an Inward (n = 52) and an Outward (n = 72) group. Case-control comparisons of short allele (S) frequencies showed significant differences between Inwards and Outwards (p = 0.036, χ2 test; p = 0.026, exact test). Genotype frequencies were not significantly different although values slightly exceeded p ≤ 0.05 (p = 0.056, χ2 test; p = 0.059, exact test). Analysis of the 5-HTTLPR genotypes according to the recessive inheritance model showed that the S/S genotype increased the likelihood of developing an Outward PMO (p = 0.0178, χ2 test; p = 0.0143, exact test; OR = 3.43, CI (95%) = 1.188-9.925). A logistic regression analysis confirmed the association between short allele and S/S genotypes with the Outward PMO also when gender and age were considered. However none of the differences remained significant after correction for multiple testing, even though using the recessive model they approach significance. Overall our data seem to suggest a putative genetic basis for interindividual differences in PMO development.

Role of 5-HTTLPR Polymorphism in the Development of the Inward/Outward Personality Organization: A Genetic Association Study

PubMed Central

Nardi, Bernardo; Marini, Alessandra; Turchi, Chiara; Arimatea, Emidio; Tagliabracci, Adriano; Bellantuono, Cesario

2013-01-01

Reciprocity with primary caregivers affects subjects' adaptive abilities toward the construction of the most useful personal meaning organization (PMO) with respect to their developmental environment. Within cognitive theory the post-rationalist approach has outlined two basic categories of identity construction and of regulation of cognitive and emotional processes: the Outward and the Inward PMO. The presence of different, consistent clinical patterns in Inward and Outward subjects is paralleled by differences in cerebral activation during emotional tasks on fMRI and by different expression of some polymorphisms in serotonin pathways. Since several lines of evidence support a role for the 5-HTTLPR polymorphism in mediating individual susceptibility to environmental emotional stimuli, this study was conducted to investigate its influence in the development of the Inward/Outward PMO. PMO was assessed and the 5-HTTLPR polymorphism investigated in 124 healthy subjects who were subdivided into an Inward (n = 52) and an Outward (n = 72) group. Case-control comparisons of short allele (S) frequencies showed significant differences between Inwards and Outwards (p = 0.036, χ2 test; p = 0.026, exact test). Genotype frequencies were not significantly different although values slightly exceeded p≤0.05 (p = 0.056, χ2 test; p = 0.059, exact test). Analysis of the 5-HTTLPR genotypes according to the recessive inheritance model showed that the S/S genotype increased the likelihood of developing an Outward PMO (p = 0.0178, χ2 test; p = 0.0143, exact test; OR = 3.43, CI (95%) = 1.188–9.925). A logistic regression analysis confirmed the association between short allele and S/S genotypes with the Outward PMO also when gender and age were considered. However none of the differences remained significant after correction for multiple testing, even though using the recessive model they approach significance. Overall our data seem to suggest a putative genetic basis for interindividual differences in PMO development. PMID:24358153

Preference for and efficacy of oral levonorgestrel for emergency contraception with concomitant placement of a levonorgestrel IUD: a prospective cohort study.

PubMed

Turok, David K; Sanders, Jessica N; Thompson, Ivana S; Royer, Pamela A; Eggebroten, Jennifer; Gawron, Lori M

2016-06-01

We assessed intrauterine device (IUD) preference among women presenting for emergency contraception (EC) and the probability of pregnancy among concurrent oral levonorgestrel (LNG) plus LNG 52 mg IUD EC users. We offered women presenting for EC at a single family planning clinic the CuT380A IUD (copper IUD) or oral LNG 1.5 mg plus the LNG 52 mg IUD. Two weeks after IUD insertion, participants reported the results of a self-administered home urine pregnancy test. The primary outcome, EC failure, was defined as pregnancies resulting from intercourse occurring within five days prior to IUD insertion. One hundred eighty-eight women enrolled and provided information regarding their current menstrual cycle and recent unprotected intercourse. Sixty-seven (36%) chose the copper IUD and 121 (64%) chose oral LNG plus the LNG IUD. The probability of pregnancy two weeks after oral LNG plus LNG IUD EC use was 0.9% (95% CI 0.0-5.1%). The only positive pregnancy test after treatment occurred in a woman who received oral LNG plus the LNG IUD and who had reported multiple episodes of unprotected intercourse including an episode more than 5 days prior to treatment. Study participants seeking EC who desired an IUD preferentially chose oral LNG 1.5 mg with the LNG 52 mg IUD over the copper IUD. Neither group had EC treatment failures. Including the option of oral LNG 1.5 mg with concomitant insertion of the LNG 52 mg IUD in EC counseling may increase the number of EC users who opt to initiate highly effective reversible contraception. Consideration should be given to LNG IUD insertion with concomitant use of oral LNG 1.5 mg for EC. Use of this combination may increase the number of women initiating highly effective contraception at the time of their EC visit. Copyright © 2016 Elsevier Inc. All rights reserved.

Cholesterol-5,6-epoxides: chemistry, biochemistry, metabolic fate and cancer.

PubMed

Poirot, Marc; Silvente-Poirot, Sandrine

2013-03-01

In the nineteen sixties it was proposed that cholesterol might be involved in the etiology of cancers and cholesterol oxidation products were suspected of being causative agents. Researchers had focused their attention on cholesterol-5,6-epoxides (5,6-ECs) based on several lines of evidence: 1) 5,6-ECs contained an oxirane group that was supposed to confer alkylating properties such as those observed for aliphatic and aromatic epoxides. 2) cholesterol-5,6-epoxide hydrolase (ChEH) was induced in pre-neoplastic lesions of skin from rats exposed to ultraviolet irradiations and ChEH was proposed to be involved in detoxification processes like other epoxide hydrolases. However, 5,6-ECs failed to induce carcinogenicity in rodents which ruled out a potent carcinogenic potential for 5,6-ECs. Meanwhile, clinical studies revealed an anomalous increase in the concentrations of 5,6β-EC in the nipple fluids of patients with pre-neoplastic breast lesions and in the blood of patients with endometrious cancers, suggesting that 5,6-ECs metabolism could be linked with cancer. Paradoxically, ChEH has been recently shown to be totally inhibited by therapeutic concentrations of tamoxifen (Tam), which is one of the main drugs used in the hormonotherapy and the chemoprevention of breast cancers. These data would suggest that the accumulation of 5,6-ECs could represent a risk factor, but we found that 5,6-ECs were involved in the induction of breast cancer cell differentiation and death induced by Tam suggesting a positive role of 5,6-ECs. These observations meant that the biochemistry and the metabolism of 5,6-ECs needed to be extensively studied. We will review the current knowledge and the future direction of 5,6-ECs chemistry, biochemistry, metabolism, and relationship with cancer. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Effect of electron cyclotron beam width to neoclassical tearing mode stabilization by minimum seeking control in ITER

NASA Astrophysics Data System (ADS)

Park, Minho; Na, Yong-Su; Seo, Jaemin; Kim, M.; Kim, Kyungjin

2018-01-01

We report the effect of the electron cyclotron (EC) beam width on the full suppression time of neoclassical tearing mode (NTM) using the finite difference method (FDM) based minimum seeking controller in ITER. An integrated numerical system is setup for time-dependent simulations of the NTM evolution in ITER by solving the modified Rutherford equation together with the plasma equilibrium, transport, and EC heating and current drive. The calculated magnetic island width and growth rate is converted to the Mirnov diagnostic signal as an input to the controller to mimic the real experiment. In addition, 10% of the noise is enforced to this diagnostic signal to evaluate the robustness of the controller. To test the dependency of the NTM stabilization time on the EC beam width, the EC beam width scan is performed for a perfectly aligned case first, then for cases with the feedback control using the minimum seeking controller. When the EC beam is perfectly aligned, the narrower the EC beam width, the smaller the NTM stabilization time is observed. As the beam width increases, the required EC power increases exponentially. On the other hand, when the minimum seeking controller is applied, NTM stabilization sometimes fails as the EC beam width decreases. This is consistently observed in the simulation with various representations of the noise as well as without the noise in the Mirnov signal. The higher relative misalignment, misalignment divided by the beam width, is found to be the reason for the failure with the narrower beam widths. The EC stabilization effect can be lower for the narrower beam widths than the broader ones even at the same misalignment due to the smaller ECCD at the island O-point. On the other hand, if the EC beam is too wide, the NTM stabilization time takes too long. Accordingly, the optimal EC beam width range is revealed to exist in the feedback stabilization of NTM.

Large prospective birth cohort studies on environmental contaminants and child health - goals, challenges, limitations and needs.

PubMed

Luo, Zhong-Cheng; Liu, Jian-Meng; Fraser, William D

2010-02-01

The adverse health effects of environmental contaminants (ECs) are a rising public health concern, and a major threat to sustainable socioeconomic development. The developing fetuses and growing children are particularly vulnerable to the adverse effects of ECs. However, assessing the health impact of ECs presents a major challenge, given that multiple outcomes may arise from one exposure, multiple exposures may result in one outcome, and the complex interactions between ECs, and between ECs, nutrients and genetic factors, and the dynamic temporal changes in EC exposures during the life course. Large-scale prospective birth cohort studies collecting extensive data and specimen starting from the prenatal or pre-conception period, although costly, hold promise as a means to more clearly quantify the health effects of ECs, and to unravel the complex interactions between ECs, nutrients and genotypes. A number of such large-scale studies have been launched in some developed counties. We present an overview of "why", "what" and "how" behind these efforts with an objective to uncover major unidentified limitations and needs. Three major limitations were identified: (1) limited data and bio-specimens regarding early life EC exposure assessments in some birth cohort studies; (2) heavy participant burdens in some birth cohort studies may bias participant recruitment, and risk substantial loss to follow-up, protocol deviations limiting the quality of data and specimens collection, with an overall potential bias towards the null effect; (3) lack of concerted efforts in building comparable birth cohorts across countries to take advantage of natural "experiments" (large EC exposure level differences between countries) for more in-depth assessments of dose-response relationships, threshold exposure levels, and positive and negative effect modifiers. Addressing these concerns in current or future large-scale birth cohort studies may help to produce better evidence on the health effects of ECs.

Deletion of the Slo3 gene abolishes alkalization-activated K+ current in mouse spermatozoa

PubMed Central

Zeng, Xu-Hui; Yang, Chengtao; Kim, Sung Tae; Lingle, Christopher J.; Xia, Xiao-Ming

2011-01-01

Mouse spermatozoa express a pH-dependent K+ current (KSper) thought to be composed of subunits encoded by the Slo3 gene. However, the equivalence of KSper and Slo3-dependent current remains uncertain, because heterologous expression of Slo3 results in currents that are less effectively activated by alkalization than are native KSper currents. Here, we show that genetic deletion of Slo3 abolishes all pH-dependent K+ current at physiological membrane potentials in corpus epididymal sperm. A residual pH-dependent outward current (IKres) is observed in Slo3−/− sperm at potentials of >0 mV. Differential inhibition of KSper/Slo3 and IKres by clofilium reveals that the amplitude of IKres is similar in both wild-type (wt) and Slo3−/− sperm. The properties of IKres suggest that it likely represents outward monovalent cation flux through CatSper channels. Thus, KSper/Slo3 may account for essentially all mouse sperm K+ current and is the sole pH-dependent K+ conductance in these sperm. With physiological ionic gradients, alkalization depolarizes Slo3−/− spermatozoa, presumably from CatSper activation, in contrast to Slo3/KSper-mediated hyperpolarization in wt sperm. Slo3−/− male mice are infertile, but Slo3−/− sperm exhibit some fertility within in vitro fertilization assays. Slo3−/− sperm exhibit a higher incidence of morphological abnormalities accentuated by hypotonic challenge and also exhibit deficits in motility in the absence of bicarbonate, revealing a role of KSper under unstimulated conditions. Together, these results show that KSper/Slo3 is the primary spermatozoan K+ current, that KSper may play a critical role in acquisition of normal morphology and sperm motility when faced with hyperosmotic challenges, and that Slo3 is critical for fertility. PMID:21427226

Effects of premature stimulation on HERG K+ channels

PubMed Central

Lu, Yu; Mahaut-Smith, Martyn P; Varghese, Anthony; Huang, Christopher L-H; Kemp, Paul R; Vandenberg, Jamie I

2001-01-01

The unusual kinetics of human ether-à-go-go-related gene (HERG) K+ channels are consistent with a role in the suppression of arrhythmias initiated by premature beats. Action potential clamp protocols were used to investigate the effect of premature stimulation on HERG K+ channels, transfected in Chinese hamster ovary cells, at 37 °C. HERG K+ channel currents peaked during the terminal repolarization phase of normally paced action potential waveforms. However, the magnitude of the current and the time point at which conductance was maximal depended on the type of action potential waveform used (epicardial, endocardial, Purkinje fibre or atrial). HERG K+ channel currents recorded during premature action potentials consisted of an early transient outward current followed by a sustained outward current. The magnitude of the transient current component showed a biphasic dependence on the coupling interval between the normally paced and premature action potentials and was maximal at a coupling interval equivalent to 90% repolarization (APD90) for ventricular action potentials. The largest transient current response occurred at shorter coupling intervals for Purkinje fibre (APD90– 20 ms) and atrial (APD90– 30 ms) action potentials. The magnitude of the sustained current response following premature stimulation was similar to that recorded during the first action potential for ventricular action potential waveforms. However, for Purkinje and atrial action potentials the sustained current response was significantly larger during the premature action potential than during the normally paced action potential. A Markov model that included three closed states, one open and one inactivated state with transitions permitted between the pre-open closed state and the inactivated state, successfully reproduced our results for the effects of premature stimuli, both during square pulse and action potential clamp waveforms. These properties of HERG K+ channels may help to suppress arrhythmias initiated by early afterdepolarizations and premature beats in the ventricles, Purkinje fibres or atria. PMID:11744759

Oceanic response to Typhoon Nari (2007) in the East China Sea

NASA Astrophysics Data System (ADS)

Oh, Kyung-Hee; Lee, Seok; Kang, Sok-Kuh; Song, Kyu-Min

2017-06-01

The oceanic response to a typhoon in the East China Sea (ECS) was examined using thermal and current structures obtained from ocean surface drifters and a bottom-moored current profiler installed on the right side of the typhoon's track. Typhoon Nari (2007) had strong winds as it passed the central region of the ECS. The thermal structure in the ECS responded to Typhoon Nari (2007) very quickly: the seasonal thermocline abruptly collapsed and the sea surface temperature dropped immediately by about 4°C after the typhoon passed. The strong vertical mixing and surface cooling caused by the typhoon resulted in a change in the thermal structure. Strong near-inertial oscillation occurred immediately after the typhoon passed and lasted for at least 4-5 days, during which a strong vertical current existed in the lower layer. Characteristics of the near-inertial internal oscillation were observed in the middle layer. The clockwise component of the inertial frequency was enhanced in the surface layer and at 63 m depth after the typhoon passed, with these layers almost perfectly out of phase. The vertical shear current was intensified by the interaction of the wind-driven current in the upper layer and the background semi-diurnal tidal current during the arrival of the typhoon, and also by the near-inertial internal oscillation after the typhoon passage. The strong near-inertial internal oscillation persisted without significant interfacial structure after the mixing of the thermocline, which could enhance the vertical mixing over several days.

Distributed practice can boost evaluative conditioning by increasing memory for the stimulus pairs.

PubMed

Richter, Jasmin; Gast, Anne

2017-09-01

When presenting a neutral stimulus (CS) in close temporal and spatial proximity to a positive or negative stimulus (US) the former is often observed to adopt the valence of the latter, a phenomenon named evaluative conditioning (EC). It is already well established that under most conditions, contingency awareness is important for an EC effect to occur. In addition to that, some findings suggest that awareness of the stimulus pairs is not only relevant during the learning phase, but that it is also relevant whether memory for the pairings is still available during the measurement phase. As previous research has shown that memory is better after temporally distributed than after contiguous (massed) repetitions, it seems plausible that also EC effects are moderated by distributed practice manipulations. This was tested in the current studies. In two experiments with successful distributed practice manipulations on memory, we show that also the magnitude of the EC effect was larger for pairs learned under spaced compared to massed conditions. Both effects, on memory and on EC, are found after a within-participant and after a between-participant manipulation. However, we did not find significant differences in the EC effect for different conditions of spaced practice. These findings are in line with the assumption that EC is based on similar processes as memory for the pairings. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Kim, Kyung-Jin; Department of Biomedical Science, College of Medicine, Seoul National University, Seoul 110-799; Yun, Jang-Hyuk

Highlights: • PEDF was expressed and induced during the involuting phase of IH. • PEDF inhibited the cell growth of the involuting HemECs in an autocrine manner. • PEDF suppression restored the impaired cell growth of the involuting HemECs. - Abstract: Hemangioma is a benign tumor derived from abnormal blood vessel growth. Unlike other vascular tumor counterparts, a hemangioma is known to proliferate during its early stage but it is followed by a stage of involution where regression of the tumor occurs. The critical onset leading to the involution of hemangioma is currently not well understood. This study focused onmore » the molecular identities of the involution of hemangioma. We demonstrated that a soluble factor released from the involuting phase of hemangioma-derived endothelial cells (HemECs) and identified pigment epithelium-derived factor (PEDF) as an anti-angiogenic factor that was associated with the growth inhibition of the involuting HemECs. The growth inhibition of the involuting HemECs was reversed by suppression of PEDF in the involuting HemECs. Furthermore, we found that PEDF was more up-regulated in the involuting phase of hemangioma tissues than in the proliferating or the involuted. Taken together, we propose that PEDF accelerates the involution of hemangioma by growth inhibition of HemECs in an autocrine manner. The regulatory mechanism of PEDF expression could be a potential therapeutic target to treat hemangiomas.« less

Modulation of neuronal sodium channels by the sea anemone peptide BDS-I

PubMed Central

Liu, Pin; Jo, Sooyeon

2012-01-01

Blood-depressing substance I (BDS-I), a 43 amino-acid peptide from sea anemone venom, is used as a specific inhibitor of Kv3-family potassium channels. We found that BDS-I acts with even higher potency to modulate specific types of voltage-dependent sodium channels. In rat dorsal root ganglion (DRG) neurons, 3 μM BDS-I strongly enhanced tetrodotoxin (TTX)-sensitive sodium current but weakly inhibited TTX-resistant sodium current. In rat superior cervical ganglion (SCG) neurons, which express only TTX-sensitive sodium current, BDS-I enhanced current elicited by small depolarizations and slowed decay of currents at all voltages (EC50 ∼ 300 nM). BDS-I acted with exceptionally high potency and efficacy on cloned human Nav1.7 channels, slowing inactivation by 6-fold, with an EC50 of approximately 3 nM. BDS-I also slowed inactivation of sodium currents in N1E-115 neuroblastoma cells (mainly from Nav1.3 channels), with an EC50 ∼ 600 nM. In hippocampal CA3 pyramidal neurons (mouse) and cerebellar Purkinje neurons (mouse and rat), BDS-I had only small effects on current decay (slowing inactivation by 20–50%), suggesting relatively weak sensitivity of Nav1.1 and Nav1.6 channels. The biggest effect of BDS-I in central neurons was to enhance resurgent current in Purkinje neurons, an effect reflected in enhancement of sodium current during the repolarization phase of Purkinje neuron action potentials. Overall, these results show that BDS-I acts to modulate sodium channel gating in a manner similar to previously known neurotoxin receptor site 3 anemone toxins but with different isoform sensitivity. Most notably, BDS-I acts with very high potency on human Nav1.7 channels. PMID:22442564

Functional expression of P2X4 receptor in capillary endothelial cells of the cochlear spiral ligament and its role in regulating the capillary diameter.

PubMed

Wu, T; Dai, M; Shi, X R; Jiang, Z G; Nuttall, A L

2011-07-01

The cochlear lateral wall generates the endocochlear potential (EP), which creates a driving force for the hair cell transduction current and is essential for normal hearing. Blood flow at the cochlear lateral wall is critically important for maintaining the EP. The vulnerability of the EP to hypoxia suggests that the blood flow in the cochlear lateral wall is dynamically and precisely regulated to meet the changing metabolic needs of the cochlear lateral wall. It has been reported that ATP, an important extracellular signaling molecule, plays an essential role in regulating cochlear blood flow. However, the cellular mechanism underlying ATP-induced regional blood flow changes has not been investigated. In the current study, we demonstrate that 1) the P2X4 receptor is expressed in endothelial cells (ECs) of spiral ligament (SL) capillaries. 2) ATP elicits a characteristic current through P2X4 on ECs in a dose-dependent manner (EC(50) = 0.16 mM). The ATP current has a reversal potential at ∼0 mV; is inhibited by 5-(3-bromophenyl)-1,3-dihydro-2H-benzofuro[3,2-e]-1,4-diazepin-2-one (5-BDBD), LaCl(3), pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid) tetrasodium salt hydrate (PPADS), and extracellular acidosis; and is less sensitive to α,β-methyleneadenosine 5'-triphosphate (α,β-MeATP) and 2'- and 3'-O-(4-benzoyl-benzoyl) adenosine 5'-triphosphate (BzATP). 3) ATP elicits a transient increase of intracellular Ca(2+) in ECs. 4) In accordance with the above in vitro findings, perilymphatic ATP (1 mM) caused dilation in SL capillaries in vivo by 11.5%. N(ω)-nitro-l-arginine methyl ester hydrochloride (l-NAME), a nonselective inhibitor of nitric oxide synthase, or 5-BDBD, the specific P2X4 inhibitor, significantly blocked the dilation. These findings support our hypothesis that extracellular ATP regulates cochlear lateral blood flow through P2X4 activation in ECs.

Serum antibodies and DNA indicate a high prevalence of equine papillomavirus 2 (EcPV2) among horses in Switzerland.

PubMed

Fischer, Nina M; Favrot, Claude; Birkmann, Katharina; Jackson, Michele; Schwarzwald, Colin C; Müller, Martin; Tobler, Kurt; Geisseler, Marco; Lange, Christian E

2014-06-01

The DNA of equine papillomavirus type 2 (EcPV2) is consistently found in equine papillomas and squamous cell carcinomas, indicating a causal association of EcPV2 in the pathogenesis of these tumours; however, little is known about the prevalence of this virus. The aim of this study was to determine the geno- and seroprevalence of EcPV2 in clinically healthy horses in Switzerland. Fifty horses presented to the equine department of the university clinic, displaying no skin or mucous membrane lesions or severe signs of other diseases, were sampled. Cytobrush samples from the penis or vulva and serum samples were collected. To determine the genoprevalence of EcPV2, DNA was extracted from cytobrush samples and tested for viral DNA with a PCR assay amplifying a 338 bp fragment of the E7/E1 region of the viral genome. Seroprevalence was tested using an enzyme-linked immunosorbent assay aimed to detect antibodies against the major capsid protein (L1) of EcPV2. In five of 50 horses (10%), EcPV2-specific DNA was amplified but no antibodies could be detected, whereas in 14 of 50 horses (28%), antibodies against EcPV2 but no DNA were demonstrated. Both antibodies and viral DNA were detected in four of 50 horses (8%). Neither antibodies nor viral DNA were found in 27 of 50 horses (54%). The seroprevalence suggests that EcPV2 is prevalent in the Swiss equine population, while the genoprevalence indicates that currently ongoing infections are less common. The discrepancy between geno- and seroprevalence probably indicates different stages of infection in the tested cohort. © 2014 ESVD and ACVD.

Electrical conduction along endothelial cell tubes from mouse feed arteries: confounding actions of glycyrrhetinic acid derivatives

PubMed Central

Behringer, Erik J; Socha, Matthew J; Polo-Parada, Luis; Segal, Steven S

2012-01-01

BACKGROUND AND PURPOSE Electrical conduction along endothelium of resistance vessels has not been determined independently of the influence of smooth muscle, surrounding tissue or blood. Two interrelated hypotheses were tested: (i) Intercellular conduction of electrical signals is manifest in endothelial cell (EC) tubes; and (ii) Inhibitors of gap junction channels (GJCs) have confounding actions on EC electrical and Ca2+ signalling. EXPERIMENTAL APPROACH Intact EC tubes were isolated from abdominal muscle feed (superior epigastric) arteries of C57BL/6 mice. Hyperpolarization was initiated with indirect (ACh) and direct (NS309) stimulation of intermediate- and small-conductance Ca2+-activated K+ channels (IKCa/SKCa). Remote membrane potential (Vm) responses to intracellular current injection defined the length constant (λ) for electrical conduction. Dye coupling was evaluated following intracellular microinjection of propidium iodide. Intracellular Ca2+ dynamics were determined using Fura-2 photometry. Carbenoxolone (CBX) or β-glycyrrhetinic acid (βGA) was used to investigate the role of GJCs. KEY RESULTS Steady-state Vm of ECs was −25 mV. ACh and NS309 hyperpolarized ECs by −40 and −60 mV respectively. Electrical conduction decayed monoexponentially with distance (λ∼1.4 mm). Propidium iodide injected into one EC spread into surrounding ECs. CBX or βGA inhibited dye transfer, electrical conduction and EC hyperpolarization reversibly. Both agents elevated resting Ca2+ while βGA inhibited responses to ACh. CONCLUSIONS AND IMPLICATIONS Individual cells were effectively coupled to each other within EC tubes. Inhibiting GJCs with glycyrrhetinic acid derivatives blocked hyperpolarization mediated by IKCa/SKCa channels, regardless of Ca2+ signalling, obviating use of these agents in distinguishing key determinants of electrical conduction along the endothelium. PMID:22168386

Simulation of tropospheric chemistry and aerosols with the climate model EC-Earth

NASA Astrophysics Data System (ADS)

van Noije, T. P. C.; Le Sager, P.; Segers, A. J.; van Velthoven, P. F. J.; Krol, M. C.; Hazeleger, W.

2014-03-01

We have integrated the atmospheric chemistry and transport model TM5 into the global climate model EC-Earth version 2.4. We present an overview of the TM5 model and the two-way data exchange between TM5 and the integrated forecasting system (IFS) model from the European Centre for Medium-Range Weather Forecasts (ECMWF), the atmospheric general circulation model of EC-Earth. In this paper we evaluate the simulation of tropospheric chemistry and aerosols in a one-way coupled configuration. We have carried out a decadal simulation for present-day conditions and calculated chemical budgets and climatologies of tracer concentrations and aerosol optical depth. For comparison we have also performed offline simulations driven by meteorological fields from ECMWF's ERA-Interim reanalysis and output from the EC-Earth model itself. Compared to the offline simulations, the online-coupled system produces more efficient vertical mixing in the troposphere, which likely reflects an improvement of the treatment of cumulus convection. The chemistry in the EC-Earth simulations is affected by the fact that the current version of EC-Earth produces a cold bias with too dry air in large parts of the troposphere. Compared to the ERA-Interim driven simulation, the oxidizing capacity in EC-Earth is lower in the tropics and higher in the extratropics. The methane lifetime is 7% higher in EC-Earth, but remains well within the range reported in the literature. We evaluate the model by comparing the simulated climatologies of surface carbon monoxide, tropospheric and surface ozone, and aerosol optical depth against observational data. The work presented in this study is the first step in the development of EC-Earth into an Earth system model with fully interactive atmospheric chemistry and aerosols.

Contraceptive use among women presenting to pharmacies for emergency contraception: an opportunity for intervention.

PubMed

Michie, Lucy; Cameron, Sharon T; Glasier, Anna; Greed, Elizabeth

2014-07-01

Most women who use emergency contraception (EC) do so because of unprotected sexual intercourse or condom failure and so remain at risk of pregnancy unless they commence an effective method of contraception. In Great Britain, increasingly women now choose to obtain EC from a pharmacy; however, pharmacists do not currently provide effective ongoing contraception. We sought to determine the views of women obtaining EC from pharmacies and clinicians working in sexual and reproductive health care (SRH) about the possibility of pharmacists providing a temporary supply of a progestogen-only pill (POP) together with EC. Self-administered, anonymous questionnaires of (1) women requesting EC from pharmacies in Edinburgh, Scotland and (2) SRH clinicians attending a major UK scientific meeting. A total of 211/232 women completed questionnaires in pharmacies (a 91% response rate). Of those women not using a hormonal method of contraception at the time of EC (n=166; 79%), almost half (44%) wished to use an effective method. Most women (64%) agreed that the option of a pharmacist being able to supply a POP would have been helpful. Among the SRH clinicians, 110 completed questionnaires out of 150 distributed (a 73% response rate). The majority of respondents (92%) were positive about a pharmacist supplying a POP at the time of EC. A reasonable proportion of women requesting EC would like to start using an effective contraceptive method. Both the women and the SRH clinicians we surveyed are positive about the option of a short supply of a POP being provided by the pharmacy in the UK together with EC. Published by the BMJ Publishing Group Limited.

Inward rectifier potassium (Kir2.1) channels as end‐stage boosters of endothelium‐dependent vasodilators

PubMed Central

Dalsgaard, Thomas; Bonev, Adrian D.; Nelson, Mark T.

2016-01-01

Key points Increase in endothelial cell (EC) calcium activates calcium‐sensitive intermediate and small conductance potassium (IK and SK) channels, thereby causing hyperpolarization and endothelium‐dependent vasodilatation.Endothelial cells express inward rectifier potassium (Kir) channels, but their role in endothelium‐dependent vasodilatation is not clear.In the mesenteric arteries, only ECs, but not smooth muscle cells, displayed Kir currents that were predominantly mediated by the Kir2.1 isoform.Endothelium‐dependent vasodilatations in response to muscarinic receptor, TRPV4 (transient receptor potential vanilloid 4) channel and IK/SK channel agonists were highly attenuated by Kir channel inhibitors and by Kir2.1 channel knockdown.These results point to EC Kir channels as amplifiers of vasodilatation in response to increases in EC calcium and IK/SK channel activation and suggest that EC Kir channels could be targeted to treat endothelial dysfunction, which is a hallmark of vascular disorders. Abstract Endothelium‐dependent vasodilators, such as acetylcholine, increase intracellular Ca2+ through activation of transient receptor potential vanilloid 4 (TRPV4) channels in the plasma membrane and inositol trisphosphate receptors in the endoplasmic reticulum, leading to stimulation of Ca2+‐sensitive intermediate and small conductance K+ (IK and SK, respectively) channels. Although strong inward rectifier K+ (Kir) channels have been reported in the native endothelial cells (ECs) their role in EC‐dependent vasodilatation is not clear. Here, we test the idea that Kir channels boost the EC‐dependent vasodilatation of resistance‐sized arteries. We show that ECs, but not smooth muscle cells, of small mesenteric arteries have Kir currents, which are substantially reduced in EC‐specific Kir2.1 knockdown (EC‐Kir2.1 −/−) mice. Elevation of extracellular K+ to 14 mm caused vasodilatation of pressurized arteries, which was prevented by endothelial denudation and Kir channel inhibitors (Ba2+, ML‐133) or in the arteries from EC‐Kir2.1 −/− mice. Potassium‐induced dilatations were unaffected by inhibitors of TRPV4, IK and SK channels. The Kir channel blocker, Ba2+, did not affect currents through TRPV4, IK or SK channels. Endothelial cell‐dependent vasodilatations in response to activation of muscarinic receptors, TRPV4 channels or IK/SK channels were reduced, but not eliminated, by Kir channel inhibitors or EC‐Kir2.1 −/−. In angiotensin II‐induced hypertension, the Kir channel function was not altered, although the endothelium‐dependent vasodilatation was severely impaired. Our results support the concept that EC Kir2 channels boost vasodilatory signals that are generated by Ca2+‐dependent activation of IK and SK channels. PMID:26840527

Retrograde Amnesia in Rats, Produced by Electron Beam Exposure.

DTIC Science & Technology

1983-02-01

radiation. Am J Physiol 215:803-806, 1968. 6. Cronholm, B., and L. Molander. Memory disturbances after electroconvulsive therapy : conditions one month after...stimuli have been demonstrated to be effective in producing RA: e.g., electroconvulsive shock (ECS) (14,19); hypoxia (9); and drugs (3,7). Preliminary...effect argues against ionization as a mechanism of CNS activation. Current induction via electroconvulsive shock (ECS) is known to produce RA (14,19

Enhanced degradation of Orange G by permanganate with the employment of iron anode.

PubMed

Bu, Lingjun; Shi, Zhou; Zhou, Shiqing

2017-01-01

Iron anode was employed to enhance the degradation of Orange G (OG) by permanganate (EC/KMnO 4 ). Continuously generated Fe 2+ from iron anode facilitated the formation of fresh MnO 2 , which plays a role in catalyzing permanganate oxidation. The EC/KMnO 4 system also showed a better performance to remove OG than Fe 2+ /KMnO 4 , indicating the importance of in situ formed fresh MnO 2 . Besides, the effects of applied current, KMnO 4 dosage, solution pH, and natural organics were evaluated and results demonstrated that high current and oxidant dosage are favorable for OG removal. And the application of iron anode has a promoting effect on the KMnO 4 oxidation over a wide pH range (5.0-9.0), while the Fe 2+ /KMnO 4 process does not. For natural organics, its presence could inhibit OG removal due to its competitive role. And the promoting effect of OG removal by the EC/KMnO 4 process in natural water was confirmed. At last, the EC/KMnO 4 process showed a satisfying performance on the decolorization and mineralization of OG. This study provides a potential technology to enhance permanganate oxidation and broadens the knowledge of azo dye removal.

Combination of novel coalescing oil water separator and electrocoagulation technique for treatment of petroleum compound contaminated groundwater.

PubMed

Oladzad, Sepideh; Fallah, Narges; Nasernejad, Bahram

2017-07-01

In the present study a combination of a novel coalescing oil water separator (COWS) and electrocoagulation (EC) technique was used for treatment of petroleum product contaminated groundwater. In the first phase, COWS was used as the primary treatment. Two different types of coalescing media and two levels of flow rates were examined in order to find the optimum conditions. The effluent of COWS was collected in optimum conditions and was treated using an EC process in the second phase of the research. In this phase, preliminary experiments were conducted in order to investigate the effect of EC reaction time and sedimentation time on chemical oxygen demand (COD) removal efficiency. Best conditions for EC reaction time and sedimentation time were obtained to be 5 min and 30 min, respectively. Response surface methodology was applied to evaluate the effect of initial pH, current density and aeration rate on settling velocity (V s ) and effluent COD. The optimum conditions, for achieving maximum values of V s as well as the values of effluent COD, in the range of results were obtained at conditions of 7, 34 mA·cm -2 and 1.5 L·min -1 for initial pH, current density and aeration rate, respectively.

Self-consistent modeling of CFETR baseline scenarios for steady-state operation

NASA Astrophysics Data System (ADS)

Chen, Jiale; Jian, Xiang; Chan, Vincent S.; Li, Zeyu; Deng, Zhao; Li, Guoqiang; Guo, Wenfeng; Shi, Nan; Chen, Xi; CFETR Physics Team

2017-07-01

Integrated modeling for core plasma is performed to increase confidence in the proposed baseline scenario in the 0D analysis for the China Fusion Engineering Test Reactor (CFETR). The steady-state scenarios are obtained through the consistent iterative calculation of equilibrium, transport, auxiliary heating and current drives (H&CD). Three combinations of H&CD schemes (NB + EC, NB + EC + LH, and EC + LH) are used to sustain the scenarios with q min > 2 and fusion power of ˜70-150 MW. The predicted power is within the target range for CFETR Phase I, although the confinement based on physics models is lower than that assumed in 0D analysis. Ideal MHD stability analysis shows that the scenarios are stable against n = 1-10 ideal modes, where n is the toroidal mode number. Optimization of RF current drive for the RF-only scenario is also presented. The simulation workflow for core plasma in this work provides a solid basis for a more extensive research and development effort for the physics design of CFETR.

Biodegradability and toxicity assessment of a real textile wastewater effluent treated by an optimized electrocoagulation process.

PubMed

Manenti, Diego R; Módenes, Aparecido N; Soares, Petrick A; Boaventura, Rui A R; Palácio, Soraya M; Borba, Fernando H; Espinoza-Quiñones, Fernando R; Bergamasco, Rosângela; Vilar, Vítor J P

2015-01-01

In this work, the application of an iron electrode-based electrocoagulation (EC) process on the treatment of a real textile wastewater (RTW) was investigated. In order to perform an efficient integration of the EC process with a biological oxidation one, an enhancement in the biodegradability and low toxicity of final compounds was sought. Optimal values of EC reactor operation parameters (pH, current density and electrolysis time) were achieved by applying a full factorial 3(3) experimental design. Biodegradability and toxicity assays were performed on treated RTW samples obtained at the optimal values of: pH of the solution (7.0), current density (142.9 A m(-2)) and different electrolysis times. As response variables for the biodegradability and toxicity assessment, the Zahn-Wellens test (Dt), the ratio values of dissolved organic carbon (DOC) relative to low-molecular-weight carboxylates anions (LMCA) and lethal concentration 50 (LC50) were used. According to the Dt, the DOC/LMCA ratio and LC50, an electrolysis time of 15 min along with the optimal values of pH and current density were suggested as suitable for a next stage of treatment based on a biological oxidation process.

Emergency contraceptive pills as a backup for lactational amenorrhea method (LAM) of contraception: a randomized controlled trial.

PubMed

Shaaban, Omar M; Hassen, Shaimaa G; Nour, Sanna A; Kames, Mervat A; Yones, Entsar M

2013-03-01

The use of breastfeeding as a method of birth spacing occasionally ends in "unplanned pregnancy." This is due to unexpected expiration of one or more of the lactation amenorrhea method (LAM) prerequisites. The current study tests a new concept that the in-advance provision of single packet of progestogen emergency contraception (EC) pills during the postpartum LAM counseling may decrease the incidence of unplanned pregnancy during breastfeeding. This was a registered two-armed randomized controlled trial (NCT 01111929). Women intending to breastfeed and to postpone pregnancy for 1 year or more were approached. They received adequate postpartum contraceptive counseling. Women intending to use LAM were randomly assigned to one of two groups. The LAM-only group received the proper LAM counseling and did not receive counseling about EC. The LAM-EC group received counseling for both LAM and EC with in-advance provision of one packet of EC pills. They were advised to use these pills if one of the prerequisites of LAM expires and sexual relation has occurred before the initiation of another regular contraceptive protection. All the participants were advised that they need to use another regular method upon expiration of any of the LAM prerequisites. Eligible women were 1158 parturients randomized into two equal groups. Forty-four percent of the women provided with EC used them. Significantly more women in the LAM-EC group initiated regular contraception within or shortly after the first 6 months postpartum when compared with those in the LAM-only group (30.5% vs. 7.3%, respectively; p=.0004). Pregnancy occurred in 5% of the LAM-only group as compared with 0.8% in the LAM-EC group (p=.005). Minimal side effects were reported after EC use. In-advance provision of EC pills can increase the rate of initiation of regular contraception once one or more of the prerequisites of LAM expire. Consequently, the use of EC pills as a temporary backup of LAM can decrease the incidence of unplanned pregnancy during breastfeeding. The use of progestogen EC pill during lactation is safe and tolerable. Copyright © 2013 Elsevier Inc. All rights reserved.

Transplantation of Endothelial Cells to Mitigate Acute and Chronic Radiation Injury to Vital Organs.

PubMed

Rafii, Shahin; Ginsberg, Michael; Scandura, Joseph; Butler, Jason M; Ding, Bi-Sen

2016-08-01

Current therapeutic approaches for treatment of exposure to radiation involve the use of antioxidants, chelating agents, recombinant growth factors and transplantation of stem cells (e.g., hematopoietic stem cell transplantation). However, exposure to high-dose radiation is associated with severe damage to the vasculature of vital organs, often leading to impaired healing, tissue necrosis, thrombosis and defective regeneration caused by aberrant fibrosis. It is very unlikely that infusion of protective chemicals will reverse severe damage to the vascular endothelial cells (ECs). The role of irradiated vasculature in mediating acute and chronic radiation syndromes has not been fully appreciated or well studied. New approaches are necessary to replace and reconstitute ECs in organs that are irreversibly damaged by radiation. We have set forth the novel concept that ECs provide paracrine signals, also known as angiocrine signals, which not only promote healing of irradiated tissue but also direct organ regeneration without provoking fibrosis. We have developed innovative technologies that enable manufacturing and banking of human GMP-grade ECs. These ECs can be transplanted intravenously to home to and engraft to injured tissues where they augment organ repair, while preventing maladaptive fibrosis. In the past, therapeutic transplantation of ECs was not possible due to a shortage of availability of suitable donor cell sources and preclinical models, a lack of understanding of the immune privilege of ECs, and inadequate methodologies for expansion and banking of engraftable ECs. Recent advances made by our group as well as other laboratories have breached the most significant of these obstacles with the development of technologies to manufacture clinical-scale quantities of GMP-grade and human ECs in culture, including genetically diverse reprogrammed human amniotic cells into vascular ECs (rAC-VECs) or human pluripotent stem cells into vascular ECs (iVECs). This approach provides a path to therapeutic EC transplantation that can be infused concomitantly or sequentially with hematopoietic stem cell transplantation more than 24 h after irradiation to support multi-organ regeneration, thereby improving immediate and long-term survival, while limiting long-term morbidity resulting from nonregenerative damage repair pathways.

Factors associated with dual use of tobacco and electronic cigarettes: A case control study.

PubMed

Farsalinos, Konstantinos E; Romagna, Giorgio; Voudris, Vassilis

2015-06-01

Many electronic cigarette (EC) users reduce cigarette consumption without completely quitting. It is important to assess the characteristics and experiences of these users, commonly called "dual users", in comparison with EC users who have completely substituted smoking (non-smoking vapers). A questionnaire was uploaded in an online survey tool. EC users were invited to participate irrespective of their current smoking status. Dual users were matched for age and gender with non-smoking vapers. From 19,441 participants, 3682 were dual users. After random 1:1 matching with non-smoking vapers (all of whom were former smokers), 3530 participants in each group were compared. Dual users had longer smoking history, lower daily cigarette consumption and similar cigarette dependence compared to non-smoking vapers. Their daily consumption was reduced after initiation of EC use from 20 to 4 cigarettes per day. Most of them were using ECs daily, however, more were occasional EC users compared to non-smoking vapers. Use of advanced (third generation) devices and daily liquid consumption was lower in dual users compared to non-smoking vapers. The most important reason for initiating EC use was to reduce smoking and exposure of family members to smoke for both groups, but higher scores were given to "avoid smoking ban in public places" by dual users compared to non-smoking vapers. The strongest predictors of being dual user from multivariate analysis were: higher risk perception for ECs (OR=2.27, 95% CI=1.40-3.68), use of first-generation EC devices (OR=1.98, 95% CI=1.47-2.66), use of prefilled cartomizers (OR=1.94, 95% CI=1.23-3.06) and occasional use of ECs (OR=1.62, 95% CI=1.21-2.17). The results of this case-control study indicate that higher risk perceptions about, and less frequent use of, ECs was associated with dual use of ECs and tobacco cigarettes. Since this is a cross-sectional survey, which explores association but not causation, longitudinal studies are warranted to further explore the reasons for dual use. Copyright © 2015 Elsevier B.V. All rights reserved.

Voltage-clamp analysis of membrane currents and excitation-contraction coupling in a crustacean muscle.

PubMed

Weiss, T; Erxleben, C; Rathmayer, W

2001-01-01

A single fibre preparation from the extensor muscle of a marine isopod crustacean is described which allows the analysis of membrane currents and simultaneously recorded contractions under two-electrode voltage-clamp conditions. We show that there are three main depolarisation-gated currents, two are outward and carried by K+, the third is an inward Ca2+ current, I(Ca). Normally, the K+ currents which can be isolated by using K+ channel blockers, mask I(Ca). I(Ca) activates at potentials more positive than -40 mV, is maximal around 0 mV, and shows strong inactivation at higher depolarisation. Inactivation depends on current rather than voltage. Ba2+, Sr2+ and Mg2+ can substitute for Ca2+. Ba2+ currents are about 80% larger than Ca2+ currents and inactivate little. The properties of I(Ca) characterise it as a high threshold L-type current. The outward current consists primarily of a fast, transient A current, I(K(A)) and a maintained, delayed rectifier current, I(K(V)). In some fibres, a small Ca2+-dependent K+ current is also present. I(K(A)) activates fast at depolarisation above -45 mV, shows pronounced inactivation and is almost completely inactivated at holding potentials more positive than -40 mV. I(K(A)) is half-maximally blocked by 70 microM 4-aminopyridine (4-AP), and 70 mM tetraethylammonium (TEA). I(K(V)) activates more slowly, at about -30 mV, and shows no inactivation. It is half-maximally blocked by 2 mM TEA but rather insensitive to 4-AP. Physiologically, the two K+ currents prevent all-or-nothing action potentials and determine the graded amplitude of active electrical responses and associated contractions. Tension development depends on and is correlated with depolarisation-induced Ca2+ influx mediated by I(Ca). The voltage dependence of peak tension corresponds directly to the voltage dependence of the integrated I(Ca). The threshold potential for contraction is at about -38 mV. Peak tension increases with increasing voltage steps, reaches maximum at around 0 mV, and declines with further depolarisation.

The NO donor DETA-NONOate reversibly activates an inward current in neurones and is not mediated by the released nitric oxide

PubMed Central

Thompson, AJ; Mander, PK; Brown, GC

2009-01-01

Background and purpose: It has been previously shown that high levels of nitric oxide (NO), from NO donors, kill neurones, but the mechanisms are unclear. Experimental approach: The effects of NO donors on the electrical properties of rat cultured cerebellar granule cells (CGC neurones) were investigated using the whole-cell patch-clamp technique. Key results: The NO donor (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NONOate or NOC-18) caused a rapid, persistent, but fully reversible inward current that was associated with an increase in baseline noise and was concentration dependent (100 µM–10 mM). The response to 3 mM DETA-NONOate was completely inhibited by 1 mM gadolinium, but not by NO scavengers (1 mM haemoglobin or 1 mM PTIO) or glutamate receptor antagonists (10 µM MK-801 or 60 µM CNQX). Application of decomposed 3 mM DETA-NONOate or 3 mM nitrite had no effect. In contrast, the NO donor S-nitrosoglutathione (GSNO) caused a rapid, persistent, but fully reversible outward current that was also concentration dependent (1–10 mM). The 3 mM GSNO response was unaltered by NO scavengers, glutamate antagonists or gadolinium, but was mimicked by decomposed 3 mM GSNO and 3 mM oxidized glutathione. Conclusions and implications: These results suggest that DETA-NONOate directly activates cation-selective channels, causing an inward current in CGCs. In contrast, GSNO causes an outward current in these cells. Some of the effects of these NO donors are independent of NO, and thus caution is required in interpreting results when using high concentrations of these compounds. PMID:19785659

The NO donor DETA-NONOate reversibly activates an inward current in neurones and is not mediated by the released nitric oxide.

PubMed

Thompson, A J; Mander, P K; Brown, G C

2009-11-01

It has been previously shown that high levels of nitric oxide (NO), from NO donors, kill neurones, but the mechanisms are unclear. The effects of NO donors on the electrical properties of rat cultured cerebellar granule cells (CGC neurones) were investigated using the whole-cell patch-clamp technique. The NO donor (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NONOate or NOC-18) caused a rapid, persistent, but fully reversible inward current that was associated with an increase in baseline noise and was concentration dependent (100 microM-10 mM). The response to 3 mM DETA-NONOate was completely inhibited by 1 mM gadolinium, but not by NO scavengers (1 mM haemoglobin or 1 mM PTIO) or glutamate receptor antagonists (10 microM MK-801 or 60 microM CNQX). Application of decomposed 3 mM DETA-NONOate or 3 mM nitrite had no effect. In contrast, the NO donor S-nitrosoglutathione (GSNO) caused a rapid, persistent, but fully reversible outward current that was also concentration dependent (1-10 mM). The 3 mM GSNO response was unaltered by NO scavengers, glutamate antagonists or gadolinium, but was mimicked by decomposed 3 mM GSNO and 3 mM oxidized glutathione. These results suggest that DETA-NONOate directly activates cation-selective channels, causing an inward current in CGCs. In contrast, GSNO causes an outward current in these cells. Some of the effects of these NO donors are independent of NO, and thus caution is required in interpreting results when using high concentrations of these compounds.

Developing rods transplanted into the degenerating retina of Crx-knockout mice exhibit neural activity similar to native photoreceptors

PubMed Central

Homma, Kohei; Okamoto, Satoshi; Mandai, Michiko; Gotoh, Norimoto; Rajasimha, Harsha K.; Chang, Yi-Sheng; Chen, Shan; Li, Wei; Cogliati, Tiziana; Swaroop, Anand; Takahashi, Masayo

2013-01-01

Replacement of dysfunctional or dying photoreceptors offers a promising approach for retinal neurodegenerative diseases, including age-related macular degeneration and retinitis pigmentosa. Several studies have demonstrated the integration and differentiation of developing rod photoreceptors when transplanted in wild type or degenerating retina; however, the physiology and function of the donor cells are not adequately defined. Here, we describe the physiological properties of developing rod photoreceptors that are tagged with GFP driven by the promoter of rod differentiation factor, Nrl. GFP-tagged developing rods show Ca2+ responses and rectifier outward currents that are smaller than those observed in fully developed photoreceptors, suggesting their immature developmental state. These immature rods also exhibit hyperpolarization-activated current (Ih) induced by the activation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. When transplanted into the subretinal space of wild type or retinal degeneration mice, GFP-tagged developing rods can integrate into the photoreceptor outer nuclear layer in wild-type mouse retina, and exhibit Ca2+ responses and membrane current comparable to native rod photoreceptors. A proportion of grafted rods develop rhodopsin-positive outer segment-like structures within two weeks after transplantation into the retina of Crx-knockout mice, and produce rectifier outward current and Ih upon membrane depolarization and hyperpolarization. GFP-positive rods derived from induced pluripotent stem (iPS) cells also display similar membrane current Ih as native developing rod photoreceptors, express rod-specific phototransduction genes, and HCN-1 channels. We conclude that Nrl-promoter driven GFP-tagged donor photoreceptors exhibit physiological characteristics of rods and that iPS cell-derived rods in vitro may provide a renewable source for cell replacement therapy. PMID:23495178

Atrial cellular electrophysiological changes in patients with ventricular dysfunction may predispose to AF

PubMed Central

Workman, Antony J; Pau, Davide; Redpath, Calum J; Marshall, Gillian E; Russell, Julie A; Norrie, John; Kane, Kathleen A; Rankin, Andrew C

2009-01-01

Background Left ventricular systolic dysfunction (LVSD) is a risk factor for atrial fibrillation (AF), but the atrial cellular electrophysiological mechanisms in humans are unclear. Objective To investigate whether LVSD in patients who are in sinus rhythm (SR) is associated with atrial cellular electrophysiological changes which could predispose to AF. Methods Right atrial myocytes were obtained from 214 consenting patients in SR who were undergoing cardiac surgery. Action potentials or ion currents were measured using the whole-cell-patch clamp technique. Results The presence of moderate or severe LVSD was associated with a shortened atrial cellular effective refractory period, ERP (209±8 ms; 52 cells, 18 patients vs 233±7 ms; 134 cells, 49 patients; P<0.05); confirmed by multiple linear regression analysis. The LV ejection fraction (LVEF) was markedly lower in patients with moderate or severe LVSD (36±4%, n=15) than in those without LVSD (62±2%, n=31; P<0.05). In cells from patients with LVEF≤45%, the ERP and action potential duration at 90% repolarisation were shorter than in those from patients with LVEF>45%, by 24 and 18%, respectively. The LVEF and ERP were positively correlated (r=0.65, P<0.05). The L-type calcium ion current, inward rectifier potassium ion current, and sustained outward ion current was unaffected by LVSD. The transient outward potassium ion current was decreased by 34%, with a positive shift in its activation voltage, and no change in its decay kinetics. Conclusion LVSD in patients in SR is independently associated with a shortening of the atrial cellular ERP, which may be expected to contribute to a predisposition to AF. PMID:19324301

Modulation of ventricular transient outward K+ current by acidosis and its effects on excitation-contraction coupling

PubMed Central

Saegusa, Noriko; Garg, Vivek

2013-01-01

The contribution of transient outward current (Ito) to changes in ventricular action potential (AP) repolarization induced by acidosis is unresolved, as is the indirect effect of these changes on calcium handling. To address this issue we measured intracellular pH (pHi), Ito, L-type calcium current (ICa,L), and calcium transients (CaTs) in rabbit ventricular myocytes. Intracellular acidosis [pHi 6.75 with extracellular pH (pHo) 7.4] reduced Ito by ∼50% in myocytes with both high (epicardial) and low (papillary muscle) Ito densities, with little effect on steady-state inactivation and activation. Of the two candidate α-subunits underlying Ito, human (h)Kv4.3 and hKv1.4, only hKv4.3 current was reduced by intracellular acidosis. Extracellular acidosis (pHo 6.5) shifted Ito inactivation toward less negative potentials but had negligible effect on peak current at +60 mV when initiated from −80 mV. The effects of low pHi-induced inhibition of Ito on AP repolarization were much greater in epicardial than papillary muscle myocytes and included slowing of phase 1, attenuation of the notch, and elevation of the plateau. Low pHi increased AP duration in both cell types, with the greatest lengthening occurring in epicardial myocytes. The changes in epicardial AP repolarization induced by intracellular acidosis reduced peak ICa,L, increased net calcium influx via ICa,L, and increased CaT amplitude. In summary, in contrast to low pHo, intracellular acidosis has a marked inhibitory effect on ventricular Ito, perhaps mediated by Kv4.3. By altering the trajectory of the AP repolarization, low pHi has a significant indirect effect on calcium handling, especially evident in epicardial cells. PMID:23585132

Enhanced functional expression of transient outward current in hypertrophied feline myocytes.

PubMed

Ten Eick, R E; Zhang, K; Harvey, R D; Bassett, A L

1993-08-01

Cardiac hypertrophy can decrease myocardial contractility and alter the electrophysiological activity of the heart. It is well documented that action potentials recorded from hypertrophied feline ventricular cells can exhibit depressed plateau voltages and prolonged durations. Similar findings have been made by others in rabbit, rat, guinea pig, and human heart. Whole-cell patch voltage-clamp studies designed to explain these changes in the action potential suggest that the only component of the membrane current recorded from feline right ventricular (RV) myocytes found to be substantially different from normal is the 4-amino-pyridine-sensitive transient outward current (I(to)). However, it was not clear if the change in I(to) could explain the changes in the action potential of hypertrophied cardiocytes, nor was it clear if these changes reflect an alteration in the electrophysiological character of the channels underlying I(to). A kinetic comparison of I(to) elicited by hypertrophied RV myocytes with that elicited by comparable normal RV myocytes previously revealed no differences, suggesting that the increased magnitude of the peak I(to) recorded from hypertrophied myocytes arises because the current density increases and not because of any alteration in the kinetic parameters governing the current. This finding suggests that in hypertrophy additional normal channels are expressed rather than a kinetically different channel subtype emerging. Investigations designed to determine if enhancement of I(to) could explain the hypertrophy-induced changes in plateau voltage and action potential duration suggest that a change in I(to) density can indeed explain the entire effect of hypertrophy on RV action potentials. If this notion is correct, the likelihood of "sudden death" in patients with myocardial hypertrophy might be decreased by a blocker selective for cardiac I(to).

The Effects of Nicotinic and Muscarinic Receptor Activation on Patch-Clamped Cells in the Optic Tectum of Rana Pipiens

PubMed Central

Yu, C.-J.; Debski, E. A.

2008-01-01

Both nicotinic and muscarinic cholinergic receptors are present in the optic tectum. To begin to understand how the activation of these receptors affects visual activity patterns, we have determined the types of physiological responses induced by their activation. Using tectal brain slices from the leopard frog, we found that application of nicotine (100 μM) evoked long-lasting responses in 60% of patch-clamped tectal cells. Thirty percent of these responses consisted of an increase in spontaneous postsynaptic currents (sPSCs) and had both a glutamatergic and GABAergic component as determined by the use of 6-cyano-7-nitroquinoxaline-2,3-dione (50 μM) and bicuculline (25 μM), respectively. Remaining response types consisted of an inward membrane current (16%) and an increase in sPSCs combined with an inward membrane current (14%). All responses could be elicited in the presence of tetrodotoxin (0.5 μM). Muscarinic receptor-mediated responses, induced by carbachol (100 μM) application after nicotinic receptor desensitization, produced responses in 70% of tectal cells. In contrast to responses elicited by nicotine, carbachol-induced responses could be evoked multiple times without significant decrement. Responses consisted of either an outward current (57%), a decrease in sPSCs (5%) or an increase in sPSCs, with (almost 6%) or without (almost 3%) an outward current. The response elicited by carbachol was not predicted by the response of the cell to nicotine. Our results suggest that nicotinic receptors are found predominantly at presynaptic locations in the optic tectum while muscarinic receptors are most often present at postsynaptic sites. We conclude that both of these receptor types could substantially modulate visual activity by changing either the input to tectal neurons or the level of their response to that input. PMID:12676145

The effects of nicotinic and muscarinic receptor activation on patch-clamped cells in the optic tectum of Rana pipiens.

PubMed

Yu, C-J; Debski, E A

2003-01-01

Both nicotinic and muscarinic cholinergic receptors are present in the optic tectum. To begin to understand how the activation of these receptors affects visual activity patterns, we have determined the types of physiological responses induced by their activation. Using tectal brain slices from the leopard frog, we found that application of nicotine (100 microM) evoked long-lasting responses in 60% of patch-clamped tectal cells. Thirty percent of these responses consisted of an increase in spontaneous postsynaptic currents (sPSCs) and had both a glutamatergic and GABAergic component as determined by the use of 6-cyano-7-nitroquinoxaline-2,3-dione (50 microM) and bicuculline (25 microM), respectively. Remaining response types consisted of an inward membrane current (16%) and an increase in sPSCs combined with an inward membrane current (14%). All responses could be elicited in the presence of tetrodotoxin (0.5 microM). Muscarinic receptor-mediated responses, induced by carbachol (100 microM) application after nicotinic receptor desensitization, produced responses in 70% of tectal cells. In contrast to responses elicited by nicotine, carbachol-induced responses could be evoked multiple times without significant decrement. Responses consisted of either an outward current (57%), a decrease in sPSCs (5%) or an increase in sPSCs, with (almost 6%) or without (almost 3%) an outward current. The response elicited by carbachol was not predicted by the response of the cell to nicotine. Our results suggest that nicotinic receptors are found predominantly at presynaptic locations in the optic tectum while muscarinic receptors are most often present at postsynaptic sites. We conclude that both of these receptor types could substantially modulate visual activity by changing either the input to tectal neurons or the level of their response to that input.

Combination induction plasma tube and current concentrator for introducing a sample into a plasma

DOEpatents

Hull, Donald E.; Bieniewski, Thomas M.

1988-01-01

An induction plasma tube in combination with a current concentrator. The rent concentrator has a substantially cylindrical body having an open end and a partially closed end which defines an aperture. A first slot extends the longitudinal length of the cylindrical body and a second slot extends radially outward from the aperture. Together the first and second slots form a single L-shaped slot. The current concentrator is disposed within a volume bounded by an induction coil substantially along the axis thereof, and when power is applied to the induction coil a concentrated current is induced within the current concentrator aperture. The concentrator is moveable relative to the coil along the longitudinal axis of the coil to control the amount of current which is concentrated at the aperture.

Post-Inhibitory Rebound Spikes in Rat Medial Entorhinal Layer II/III Principal Cells: In Vivo, In Vitro, and Computational Modeling Characterization

PubMed Central

Ferrante, Michele; Shay, Christopher F.; Tsuno, Yusuke; William Chapman, G.; Hasselmo, Michael E.

2017-01-01

Abstract Medial entorhinal cortex Layer-II stellate cells (mEC-LII-SCs) primarily interact via inhibitory interneurons. This suggests the presence of alternative mechanisms other than excitatory synaptic inputs for triggering action potentials (APs) in stellate cells during spatial navigation. Our intracellular recordings show that the hyperpolarization-activated cation current (Ih) allows post-inhibitory-rebound spikes (PIRS) in mEC-LII-SCs. In vivo, strong inhibitory-post-synaptic potentials immediately preceded most APs shortening their delay and enhancing excitability. In vitro experiments showed that inhibition initiated spikes more effectively than excitation and that more dorsal mEC-LII-SCs produced faster and more synchronous spikes. In contrast, PIRS in Layer-II/III pyramidal cells were harder to evoke, voltage-independent, and slower in dorsal mEC. In computational simulations, mEC-LII-SCs morphology and Ih homeostatically regulated the dorso-ventral differences in PIRS timing and most dendrites generated PIRS with a narrow range of stimulus amplitudes. These results suggest inhibitory inputs could mediate the emergence of grid cell firing in a neuronal network. PMID:26965902

Direct Isolation, Culture and Transplant of Mouse Skeletal Muscle Derived Endothelial Cells with Angiogenic Potential

PubMed Central

Ieronimakis, Nicholas; Balasundaram, Gayathri; Reyes, Morayma

2008-01-01

Background Although diseases associated with microvascular endothelial dysfunction are among the most prevalent illnesses to date, currently no method exists to isolate pure endothelial cells (EC) from skeletal muscle for in vivo or in vitro study. Methodology By utilizing multicolor fluorescent-activated cell sorting (FACS), we have isolated a distinct population of Sca-1+, CD31+, CD34dim and CD45− cells from skeletal muscles of C57BL6 mice. Characterization of this population revealed these cells are functional EC that can be expanded several times in culture without losing their phenotype or capabilities to uptake acetylated low-density lipoprotein (ac-LDL), produce nitric oxide (NO) and form vascular tubes. When transplanted subcutaneously or intramuscularly into the tibialis anterior muscle, EC formed microvessels and integrated with existing vasculature. Conclusion This method, which is highly reproducible, can be used to study the biology and role of EC in diseases such as peripheral vascular disease. In addition this method allows us to isolate large quantities of skeletal muscle derived EC with potential for therapeutic angiogenic applications. PMID:18335025

Blockade by N-3 polyunsaturated fatty acid of the Kv4.3 current stably expressed in Chinese hamster ovary cells

PubMed Central

Singleton, C B; Valenzuela, S M; Walker, B D; Tie, H; Wyse, K R; Bursill, J A; Qiu, M R; Breit, S N; Campbell, T J

1999-01-01

The Kv4.3 gene is believed to encode a large proportion of the transient outward current (Ito), responsible for the early phase of repolarization of the human cardiac action potential. There is evidence that this current is involved in the dispersion of refractoriness which develops during myocardial ischaemia and which predisposes to the development of potentially fatal ventricular tachyarrhythmias. Epidemiological, clinical, animal, and cellular studies indicate that these arrhythmias may be ameliorated in myocardial ischaemia by n-3 polyunsaturated fatty acids (n-3 PUFA) present in fish oils. We describe stable transfection of the Kv4.3 gene into a mammalian cell line (Chinese hamster ovary cells), and using patch clamp techniques have shown that the resulting current closely resembles human Ito. The current is rapidly activating and inactivating, with both processes being well fit by double exponential functions (time constants of 3.8±0.2 and 5.3±0.4 ms for activation and 20.0±1.2 and 96.6±6.7 ms for inactivation at +45 mV at 23°C). Activation and steady state inactivation both show voltage dependence (V1/2 of activation=−6.7±2.5 mV, V1/2 of steady state inactivation=−51.3±0.2 mV at 23°C). Current inactivation and recovery from inactivation are faster at physiologic temperature (37°C) compared to room temperature (23°C). The n-3 PUFA docosahexaenoic acid blocks the Kv4.3 current with an IC50 of 3.6 μmol L−1. Blockade of the transient outward current may be an important mechanism by which n-3 PUFA provide protection against the development of ventricular fibrillation during myocardial ischaemia. PMID:10433502

Nonlinear reconnecting edge localized modes in current-carrying plasmas

DOE PAGES

Ebrahimi, F.

2017-05-22

Nonlinear edge localized modes in a tokamak are examined using global three-dimensional resistive magnetohydrodynamics simulations. Coherent current-carrying filament (ribbon-like) structures wrapped around the torus are nonlinearly formed due to nonaxisymmetric reconnecting current sheet instabilities, the so-called peeling-like edge localized modes. These fast growing modes saturate by breaking axisymmetric current layers isolated near the plasma edge and go through repetitive relaxation cycles by expelling current radially outward and relaxing it back. The local bidirectional fluctuation-induced electromotive force (emf) from the edge localized modes, the dynamo action, relaxes the axisymmetric current density and forms current holes near the edge. Furthermore, the three-dimensionalmore » coherent current-carrying filament structures (sometimes referred to as 3-D plasmoids) observed here should also have strong implications for solar and astrophysical reconnection.« less

Ringing After a High-Energy Collision: Ambipolar Oscillations During Impact Plasma Expansion

NASA Technical Reports Server (NTRS)

Zimmerman, M. I.; Farrell, W. M.; Stubbs, T. J.

2012-01-01

High-velocity impacts on the Moon and other airless bodies deliver energy and material to the lunar surface and exosphere. The target and i mpactor material may become vaporized and ionized to form a collision al plasma that expands outward and eventually becomes collisionless. In the present work, kinetic simulations of the later collision less stage of impact plasma expansion are performed. Attention is paid to characterizing "ambipolar oscillations" in which thermodynamic distur bances propagate outward to generate "ringing" within the expanding e lectron cloud, which could radiate an electromagnetic signature of lo cal plasma conditions. The process is not unlike a beam-plasma intera ction, with the perturbing electron population in the present case ac ting as a highly thermal "beam" that resonates along the expanding de nsity gradient. Understanding the electromagnetic aspects of impact p lasma expansion could provide insight into the lasting effects of nat ural, impact-generated currents on airless surfaces and charging haza rds to human exploration infrastructure and instrumentation.

Membrane potential bistability in nonexcitable cells as described by inward and outward voltage-gated ion channels.

PubMed

Cervera, Javier; Alcaraz, Antonio; Mafe, Salvador

2014-10-30

The membrane potential of nonexcitable cells, defined as the electrical potential difference between the cell cytoplasm and the extracellular environment when the current is zero, is controlled by the individual electrical conductance of different ion channels. In particular, inward- and outward-rectifying voltage-gated channels are crucial for cell hyperpolarization/depolarization processes, being amenable to direct physical study. High (in absolute value) negative membrane potentials are characteristic of terminally differentiated cells, while low membrane potentials are found in relatively depolarized, more plastic cells (e.g., stem, embryonic, and cancer cells). We study theoretically the hyperpolarized and depolarized values of the membrane potential, as well as the possibility to obtain a bistability behavior, using simplified models for the ion channels that regulate this potential. The bistability regions, which are defined in the multidimensional state space determining the cell state, can be relevant for the understanding of the different model cell states and the transitions between them, which are triggered by changes in the external environment.

Some aspects of the cosmogonic outward migration of Neptune. Co-planar migration

NASA Astrophysics Data System (ADS)

Neslušan, L.; Jakubík, M.

2013-10-01

Considering a simple model of the cosmogonic outward migration of Neptune, we investigate if the assumption of an extremely low orbital inclination of small bodies in a once-existing proto-planetary disk could influence the structure of reservoirs of the objects in the trans-Neptunian region. We found no significant influence. Our models predict only the existence of the mean-motion resonances (MMRs) with Neptune 2:3, 3:5, 1:2, and an anemic scattered disk (MMRs 3:4, 5:7, and 9:11 are also indicated). To explain the classical Edgeworth-Kuiper belt, relatively abundant 4:7 and 2:5 MMRs, and the more numerous scattered disk, we need to assume that, e.g., the outer boundary of the original proto-planetary disk considerably exceeded the distance of the current Neptune's orbit (Neptune probably ended its migration at the distance, where the disk's density started to be sub-critical), or that some Pluto-sized objects resided inside the MMRs and in the distant parts of the original proto-planetary disk.

Effect of Er,Cr:YSGG laser on human dentin fluid flow.

PubMed

Al-Omari, Wael M; Palamara, Joseph E

2013-11-01

The aim of the current investigation was to assess the rate and magnitude of dentin fluid flow of dentinal surfaces irradiated with Er,Cr:YSGG laser. Twenty extracted third molars were sectioned, mounted, and irradiated with Er,Cr:YSGG laser at 3.5 and 4.5 W power settings. Specimens were connected to an automated fluid flow measurement apparatus (Flodec). The rate, magnitude, and direction of dentin fluid flow were recorded at baseline and after irradiation. Nonparametric Wilcoxon signed ranks repeated measure t test revealed a statistically significant reduction in fluid flow for all the power settings. The 4.5-W power output reduced the flow significantly more than the 3.5 W. The samples showed a baseline outward flow followed by inward flow due to irradiation then followed by decreased outward flow. It was concluded that Er,Cr:YSGG laser irradiation at 3.5 and 4.5 W significantly reduced dentinal fluid flow rate. The reduction was directly proportional to power output.

Outward Migration of Giant Planets in Orbital Resonance

NASA Astrophysics Data System (ADS)

D'Angelo, G.; Marzari, F.

2013-05-01

A pair of giant planets interacting with a gaseous disk may be subject to convergent orbital migration and become locked into a mean motion resonance. If the orbits are close enough, the tidal gaps produced by the planets in the disk may overlap. This represents a necessary condition to activate the outward migration of the pair. However, a number of other conditions must also be realized in order for this mechanism to operate. We have studied how disk properties, such as turbulence viscosity, temperature, surface density gradient, mass, and age, may affect the outcome of the outward migration process. We have also investigated the implications on this mechanism of the planets' gas accretion. If the pair resembles Jupiter and Saturn, the 3:2 orbital resonance may drive them outward until they reach stalling radii for migration, which are within ~10 AU of the star for disks representative of the early proto-solar nebula. However, planet post-formation conditions in the disk indicate that such planets become typically locked in the 1:2 orbital resonance, which does not lead to outward migration. Planet growth via gas accretion tends to alter the planets' mass-ratio and/or the disk accretion rate toward the star, reducing or inhibiting outward migration. Support from NASA Outer Planets Research Program and NASA Origins of Solar Systems Program is gratefully acknowledged.

Portable Lock-in Amplifier-Based Electrochemical Method to Measure an Array of 64 Sensors for Point-of-Care Applications.

PubMed

Hrdý, Radim; Kynclová, Hana; Klepáčová, Ivana; Bartošík, Martin; Neužil, Pavel

2017-09-05

We present a portable lock-in amplifier-based electrochemical sensing system. The basic unit (cluster) consists of four electrochemical cells (EC), each containing one pseudoreference electrode (PRE) and one working electrode (WE). All four ECs are simultaneously interrogated, each at different frequencies, with square wave pulses superposed on a sawtooth signal for cyclic voltammetry (CV). Lock-in amplification provides independent read-out of four signals, with excellent noise suppression. We expanded a single cluster system into an array of 16 clusters by using electronic switches. The chip with an array of ECs was fabricated using planar technology with a gap between a WE and a PRE of ≈2 μm, which results in partial microelectrode-type behavior. The basic electrode characterization was performed with the model case using a ferricyanide-ferrocyanide redox couple (Fe 2+ /Fe 3+ ) reaction, performing CV and differential pulse voltammetry (DPV). We then used this system to perform cyclic lock-in voltammetry (CLV) to measure concurrently responses of the four ECs. We repeated this method with all 64 ECs on the chip. The standard deviation of a peak oxidation and reduction current in a single channel consisting of 13 ECs was ≈7.46% and ≈5.6%, respectively. The four-EC configuration in each measured spot allows determination of nonperforming ECs and, thus, to eliminate potential false results. This system is built in a portable palm-size format suitable for point-of-care applications. It can perform either individual or multiple measurements of active compounds, such as biomarkers.

Biomaterials trigger endothelial cell activation when co-incubated with human whole blood.

PubMed

Herklotz, Manuela; Hanke, Jasmin; Hänsel, Stefanie; Drichel, Juliane; Marx, Monique; Maitz, Manfred F; Werner, Carsten

2016-10-01

Endothelial cell activation resulting from biomaterial contact or biomaterial-induced blood activation may in turn also affect hemostasis and inflammatory processes in the blood. Current in vitro hemocompatibility assays typically ignore these modulating effects of the endothelium. This study describes a co-incubation system of human whole blood, biomaterial and endothelial cells (ECs) that was developed to overcome this limitation. First, human endothelial cells were characterized in terms of their expression of coagulation- and inflammation-relevant markers in response to various activators. Subsequently, their capacity to regulate hemostasis as well as complement and granulocyte activation was monitored in a hemocompatibility assay. After blood contact, quiescent ECs exhibited anticoagulant and anti-inflammatory properties. When they were co-incubated with surfaces exhibiting pro-coagulant or pro-inflammatory characteristics, the ECs down-regulated coagulation but not complement or leukocyte activation. Analysis of intracellular levels of the endothelial activation markers E-selectin and tissue factor showed that co-incubation with model surfaces and blood significantly increased the activation state of ECs. Finally, the coagulation- and inflammation-modulating properties of the ECs were tested after blood/biomaterial exposure. Pre-activation of ECs by biomaterials in the blood induced a pro-coagulant and pro-inflammatory state of the ECs, wherein the pro-coagulant response was higher for biomaterial/blood pre-activated ECs than for TNF-α-pre-activated cells. This work provides evidence that biomaterials, even without directly contacting the endothelium, affect the endothelial activation state with and have consequences for plasmatic and cellular reactions in the blood. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of tobacco smoke and electronic cigarette vapor exposure on the oral and gut microbiota in humans: a pilot study.

PubMed

Stewart, Christopher J; Auchtung, Thomas A; Ajami, Nadim J; Velasquez, Kenia; Smith, Daniel P; De La Garza, Richard; Salas, Ramiro; Petrosino, Joseph F

2018-01-01

The use of electronic cigarettes (ECs) has increased drastically over the past five years, primarily as an alternative to smoking tobacco cigarettes. However, the adverse effects of acute and long-term use of ECs on the microbiota have not been explored. In this pilot study, we sought to determine if ECs or tobacco smoking alter the oral and gut microbiota in comparison to non-smoking controls. We examined a human cohort consisting of 30 individuals: 10 EC users, 10 tobacco smokers, and 10 controls. We collected cross-sectional fecal, buccal swabs, and saliva samples from each participant. All samples underwent V4 16S rRNA gene sequencing. Tobacco smoking had a significant effect on the bacterial profiles in all sample types when compared to controls, and in feces and buccal swabs when compared to EC users. The most significant associations were found in the gut, with an increased relative abundance of Prevotella ( P = 0.006) and decreased Bacteroides ( P = 0.036) in tobacco smokers. The Shannon diversity was also significantly reduced ( P = 0.009) in fecal samples collected from tobacco smokers compared to controls. No significant difference was found in the alpha diversity, beta-diversity or taxonomic relative abundances between EC users and controls. From a microbial ecology perspective, the current pilot data demonstrate that the use of ECs may represent a safer alternative compared to tobacco smoking. However, validation in larger cohorts and greater understanding of the short and long-term impact of EC use on microbiota composition and function is warranted.

'Oxytocin' for the outwardly oriented: Evidence for interactive effects in placebo responding.

PubMed

Darragh, Margot; Booth, Roger J; Consedine, Nathan S

2016-04-01

In order to harness the placebo effect for clinical benefit, more research is needed to determine who might be responsive to a placebo treatment. Recently, a two-faceted Transactional Model of Placebo Responding (TMPR) was offered, which suggests different personality types might respond to different contextual cues. The current study directly tested this model by manipulating treatment descriptors to match the two purported facets of responsiveness. Physically healthy volunteers (N=77) experiencing life stress were randomised to either the: (1) wait-list control, (2) 'serotonin treatment' group; or (3) 'oxytocin treatment' group. Both treatment groups received an 'antistress' intranasal spray (placebo). The 'serotonin' and 'oxytocin' treatments were described to appeal to the two purported facets responsiveness set out in the TMPR, inward and outward orientation. The BIS/BAS scale was used as proxies for inward (BIS) and outward (BAS) orientation. It was hypothesised that high BAS types would be more responsive to the 'oxytocin' and high BIS types would be more responsive to the 'serotonin'. Findings provide partial support for hypotheses, with high but not low BAS types having a greater response to the 'oxytocin' placebo; but the pattern of responses from high BIS types were contrary to predictions. Findings indicate interactions between personality type and environmental cues may contribute to placebo responding, but more research is needed to investigate possible operationalisations of responsiveness and the contextual cues to which different types may respond. Copyright © 2016 Elsevier Inc. All rights reserved.

Synergistic Effect of Light and Fusicoccin on Stomatal Opening 1

PubMed Central

Assmann, Sarah M.; Schwartz, Amnon

1992-01-01

Upon incubation of epidermal peels of Commelina communis in 1 millimolar KCl, a synergistic effect of light and low fusicoccin (FC) concentrations on stomatal opening is observed. In 1 millimolar KCl, stomata remain closed even in the light. However, addition of 0.1 micromolar FC results in opening up to 12 micrometers. The same FC concentration stimulates less than 5 micrometers of opening in darkness. The synergistic effect (a) decreases with increasing FC or KCl concentrations; (b) is dark-reversible; (c) like stomatal opening in high KCl concentrations (120 millimolar) is partially inhibited by the K+ channel blocker, tetraethyl-ammonium+ (20 millimolar). In whole-cell patch-clamp experiments with guard cell protoplasts of Vicia faba, FC (1 or 10 micromolar) stimulates an increase in outward current that is essentially voltage independent between - 100 and +60 millivolts, and occurs even when the membrane potential is held at a voltage (−60 millivolts) at which K+ channels are inactivated. These results are indicative of FC activation of a H+ pump. FC effects on the magnitude of inward and outward K+ currents are not observed. Epidermal peel and patch clamp data are both consistent with the hypothesis that the plasma membrane H+ ATPase of guard cells is a primary locus for the FC effect on stomatal apertures. PMID:16668799

Biogeochemistry of Dimethylsulfide, Dimethylsulfoniopropionate, and Acrylic Acid in the Changjiang Estuary and the East China Sea

NASA Astrophysics Data System (ADS)

Wu, Xi; Li, Pei-Feng; Liu, Chun-Ying; Zhang, Hong-Hai; Yang, Gui-Peng; Zhang, Sheng-Hui; Zhu, Mao-Xu

2017-12-01

The distributions of dimethylsulfide (DMS), dimethylsulfoniopropionate (DMSP), and acrylic acid (AA) were investigated in the Changjiang Estuary during winter (dry season) and summer (wet season) 2014 and in the East China Sea (ECS) during summer 2015. The rates of dissolved DMSP (DMSPd) degradation with DMS and AA production, DMS degradation, and AA degradation in the ECS were also studied. Significant seasonal variations in DMS(P) and AA concentrations were observed in the Changjiang Estuary with higher values during the wet season than during the dry season. The maximum ratio of AA/chlorophyll a (Chl a) occurred at the mouth of the Changjiang Estuary due to the combined effects of production from DMSP and terrestrial inputs from the Changjiang Estuary. The distributions of DMS(P) and AA in the ECS were dramatically influenced by the Kuroshio Current and the upwelling caused by the Taiwan Warm Current. The ratios of DMS(P)/Chl a and AA/Chl a exhibited similar patterns in the surface seawater of the ECS, which indicated that phytoplankton species and biomass might play important roles in controlling the distributions of DMS(P) and AA. In vertical profiles, high values of AA emerged in the upper water column and bottom seawater of the Changjiang Estuary. Meanwhile, the maxima of DMS(P) and AA generally appeared in the surface or euphotic layer, whereas their minima arose in the bottom seawater of the ECS. The degradation rates of DMSPd, DMS, and AA in the inshore waters were higher than those in the open sea.

Conceptual design of the EU DEMO EC-system: main developments and R&D achievements

NASA Astrophysics Data System (ADS)

Granucci, G.; Aiello, G.; Alberti, S.; Avramidis, K. A.; Braunmüller, F.; Bruschi, A.; Chelis, J.; Franck, J.; Figini, L.; Gantenbein, G.; Garavaglia, S.; Grossetti, G.; Illy, S.; Ioannidis, Z.; Jelonnek, J.; Kalaria, P.; Latsas, G.; Moro, A.; Pagonakis, I. Gr.; Peponis, D.; Poli, E.; Rispoli, N.; Rzesnicki, T.; Scherer, T.; Strauss, D.; Thumm, M.; Tigelis, I.; Tsironis, C.; Wu, C.; Franke, T.; Tran, M. Q.

2017-11-01

For the development of a DEMOnstration Fusion Power Plant the design of auxiliary heating systems is a key activity in order to achieve controlled burning plasma. The present heating mix considers electron cyclotron resonance heating (ECRH), neutral beam injection (NBI) and ion cyclotron resonance heating (ICRH) with a target power to the plasma of about 50 MW for each system. The main tasks assigned to the EC system are plasma breakdown and assisted start-up, heating to L-H transition and plasma current ramp up to burn, MHD stability control and assistance in plasma current ramp down. The consequent requirements are used for the conceptual design of the EC system, from the RF source to the launcher, with an extensive R&D program focused on relevant technologies to be developed. Gyrotron: the R&D and Advanced Developments on EC RF sources are targeting for gyrotrons operating at 240 GHz, considered as optimum EC Current Drive frequency in case of higher magnetic field than for the 2015 EU DEMO1 baseline. Multi-purpose (multi-frequency) and frequency step-tunable gyrotrons are under investigation to increase the flexibility of the system. As main targets an output power of significantly above 1 MW (target: 2 MW) and a total efficiency higher than 60% are set. The principle feasibility at limits of a 236 GHz, conventional-cavity and, alternatively, of a 238 GHz coaxial-cavity gyrotron are under investigation together with the development of a synthetic diamond Brewster-angle window technology. Advanced developments are on-going in the field of multi-stage depressed collector technologies. Transmission line (TL): different TL options are under investigation and a preliminary study of an evacuated quasi-optical multiple-beam TL, considered for a hybrid solution, is presented and discussed in terms of layout, dimensions and theoretical losses. Launcher: remote steering antennas have been considered as a possible launcher solution especially under the constraints to avoid movable mirrors close to the plasma. With dedicated beam tracing calculations, the deposition locations coverage and the wave absorption efficiency have been investigated, considering a selection of frequencies, injection angles and launching points. An option for the EC system structure is proposed in clusters, in order to allow the necessary redundancy and flexibility to guarantee the required EC power in the different phases of the plasma pulse. Number and composition of the clusters are analysed to have high availability and therefore maximum reliability with a minimum number of components.

Nitric oxide releasing hydrogel promotes endothelial differentiation of mouse embryonic stem cells.

PubMed

Nie, Yan; Zhang, Kaiyue; Zhang, Shuaiqiang; Wang, Dan; Han, Zhibo; Che, Yongzhe; Kong, Deling; Zhao, Qiang; Han, Zhongchao; He, Zuo-Xiang; Liu, Na; Ma, Fengxia; Li, Zongjin

2017-11-01

Transplantation of endothelial cells (ECs) holds great promise for treating various kinds of ischemic diseases. However, the major challenge in ECs-based therapy in clinical applications is to provide high quality and enough amounts of cells. In this study, we developed a simple and efficient system to direct endothelial differentiation of mouse embryonic stem cells (ESCs) using a controllable chitosan nitric oxide (NO)-releasing hydrogel (CS-NO). ESCs were plated onto the hydrogel culture system, and the expressions of differentiation markers were measured. We found that the expression of Flk-1 (early ECs marker) and VE-cadherin (mature ECs marker) increased obviously under the controlled NO releasing environment. Moreover, the Flk-1 upregulation was accompanied by the activation of the phospho-inositide-3 kinase (PI3K)/Akt signaling. We also found that in the presence of the PI3K inhibitor (LY294002), the endothelial commitment of ESCs was abolished, indicating the importance of Akt phosphorylation in the endothelial differentiation of ESCs. Interestingly, in the absence of NO, the activation of Akt phosphorylation alone by using AKT activator (SC-79) did not profoundly promote the endothelial differentiation of ESCs, suggesting an interdependent relationship between NO and the Akt phosphorylation in driving endothelial fate specification of ESCs. Taken together, we demonstrated that NO releasing in a continuous and controlled manner is a simple and efficient method for directing the endothelial differentiation of ESCs without adding growth factors. Fascinating data continues to show that artificial stem cell niche not only serve as a physical supporting scaffold for stem cells proliferation, but also as a novel platform for directing stem cell differentiation. Because of the lack of proper microenvironment for generating therapeutic endothelial cells (ECs) in vitro, the source of ECs for transplantation is the major limitation in ECs-based therapy to clinical applications. The current study established a feeder cell-free, 2-dimensional culture system for promoting the differentiation processes of embryonic stem cells (ESCs) committed to the endothelial lineage via using a nitric oxide (NO) controlled releasing hydrogel (CS-NO). Notably, the NO releasing from the hydrogel could selectively up-regulate Flk-1 (early ECs marker) and VE-cadherin (mature ECs marker) in the absence of growth factors, which was of crucial importance in the endothelial differentiation of ESCs. In summary, the current study proposes a simple and efficient method for directing the endothelial differentiation of ESCs without extra growth factors. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Challenges and benefits on long-term eddy covariance measurements over lakes

NASA Astrophysics Data System (ADS)

Vesala, Timo; Golub, Malgorzata; Desai, Ankur; Heiskanen, Jouni; Provenzale, Maria; Rantakari, Miitta; Ojala, Anne; Mammarella, Ivan

2017-04-01

Eddy Covariance (EC) data on carbon dioxide fluxes is presently available on about 30 lakes but the time series are mostly short, order of one year. Longer EC series together with chamber measurements and appropriate auxiliary data on water column allow for more accurate estimates of the aquatic component in terrestrial carbon balance and analysis of the environmental controls. We discuss on challenges for long-term EC measurements over freshwater ecosystems and demonstrate the benefits of EC data for carbon cycle studies via examples from long-term sites EC sites in Finland. We discuss on the auxiliary measurements needed and the general design of the whole measurement set-up to get representative information. We discuss on challenges related to the CO2 flux partitioning for freshwater ecosystems and introduce a new method to estimate the net primary productivity (NPP) on EC data, which is superior to more traditional methods (bottle incubations, 14C technique) with a poor temporal resolution. Finally, we collected and analyzed CO2 fluxes from 19 globally distributed lakes and reservoirs representing six climate zones. The mean flux was c. 0.3 micro mole / m2 s. We applied a simple upscaling to the direct observations and ended up to the estimate which is about half of the current emission estimate for lentic systems.

ChinaSpec: a network of SIF observations to bridge flux measurements and remote sensing data

NASA Astrophysics Data System (ADS)

Zhang, Y.; Wang, S.; Liu, L.; Ju, W.; Zhu, X.

2017-12-01

Accurately quantifying atmosphere-biosphere interactions across multiple scale still remains a challenge. Remote sensing, especially satellite data, has been widely used as a solution to resolve the broad scale estimation of carbon flux by upscaling the point measurements of eddy covariance (EC) technique. However, critical gaps remain between the EC observations and coarse satellite data due to the scale mismatch. In this regard, it is necessary to build a network of in situ optical observations to bridge the scale-mismatch between EC measurements and satellite remote sensing data. Internationally, a few networks have already been established (e.g., SpecNet and EuroSpec), but still at its early stage. ChinaSpec is a network of linking in situ spectral measurements, especially sun-induce chlorophyll fluorescence (SIF), with point EC observations for better understanding the interactions of atmosphere-biosphere. One main focus of ChinsSpec is to conduct continuous field SIF measurements at multiple EC sites across the mainland of China. This will help us better understand the mechanics of SIF and photosynthesis, and resolve the missing gaps between recent SIF retrievals from coarse satellite data and EC observations. In this presentation, we introduce the background, current stage, and the development of ChinaSpec network.

METHOD OF PRODUCING AND ACCELERATING AN ION BEAM

NASA Technical Reports Server (NTRS)

Foster, John E. (Inventor)

2005-01-01

A method of producing and accelerating an ion beam comprising the steps of providing a magnetic field with a cusp that opens in an outward direction along a centerline that passes through a vertex of the cusp: providing an ionizing gas that sprays outward through at least one capillary-like orifice in a plenum that is positioned such that the orifice is on the centerline in the cusp, outward of the vortex of the cusp; providing a cathode electron source, and positioning it outward of the orifice and off of the centerline; and positively charging the plenum relative to the cathode electron source such that the plenum functions as m anode. A hot filament may be used as the cathode electron source, and permanent magnets may be used to provide the magnetic field.

Smart-device environmental control systems: experiences of people with cervical spinal cord injuries.

PubMed

Hooper, Bethany; Verdonck, Michele; Amsters, Delena; Myburg, Michelle; Allan, Emily

2017-09-06

Environmental control systems (ECS) are devices that enable people with severe physical limitations to independently control household appliances. Recent advancements in the area of environmental control technology have led to the development of ECS that can be controlled through mainstream smart-devices. There is limited research on ECS within Australia and no known research addressing smart-device ECS. The current study sought to explore users' experiences with smart-device ECS within Australia. The study followed a single embedded case study method. Participants (n = 5) were existing ECS users with a cervical spinal cord injury. Data were collected through semi-structured interviews with participants, reflexive journals and field notes. An inductive approach was used to analyze the data thematically. The experience of using a smart-device ECS presented both opportunities and costs to users. The opportunities included: independent control, choice, peace of mind, connection, effective resource use, and control over smart-phone functions and applications. The associated costs included: financial, time, frustration, and technical limitations. While findings are similar to previous research into traditional ECS this study indicates that smart-device ECS also offered a new opportunity for users to access mainstream smart-device functions and applications. Future research should investigate methods and resources that practitioners could utilize to better support new users of smart-device ECS. Implications for Rehabilitation As with traditional environmental control systems, users of smart environmental control systems report increased independence, choice and control. Smart-device environmental control systems provide users with access to mainstream smart-device functions and applications, which facilitate connection to family and the outside world. The costs to the user of smart-device environmental control systems include monetary and time investment, dealing with technical limitations and resulting frustration. Prescribers and installers must consider ways to mitigate these costs experienced by users.

Understanding performance limitation and suppression of leakage current or self-discharge in electrochemical capacitors: a review.

PubMed

Ike, Innocent S; Sigalas, Iakovos; Iyuke, Sunny

2016-01-14

Self-discharge is known to have considerable adverse effects on the performance and application of electrochemical capacitors (ECs). Thus, obtaining an understanding of EC self-discharge mechanism(s) and subsequent derivation and solution of EC models, subject to a particular mechanism or combination of mechanisms during charging, discharging and storage of the device, is the only way to solve problems associated with EC self-discharge. In this review, we summarize recent progress with respect to EC self-discharge by considering the two basic types, electric double-layer capacitors (EDLC) and pseudocapacitors, and their hybrids with their respective charge storage mechanisms, distinguishable self-discharge mechanisms, charge redistribution and charge/energy loss during self-discharge. It was clearly observed that most of the voltage reduction is not purely due to the self-discharge effect but is basically due to redistribution of charge carriers deep inside pores and can therefore be retrieved from a capacitor during long-time discharging. Tuning the self-discharge rate is therefore feasible for single-walled carbon nanotube (SWNT) ECs and can be achieved by simply adjusting the surface chemistry of the nanotubes. The effects of surface chemistry modification on EC self-discharge are very important in studying and suppressing the self-discharge process and will benefit potential applications of ECs with respect to energy retention. Self-discharge can be averted by the use of redox couples that are transformed to insoluble species via electrolysis and adsorbed onto the activated carbon electrode in redox-couple EDLCs, thus transforming the EDLC electrolyte into a material that can store charge. Self-discharge in ECs can also be successfully suppressed by utilizing an ion-interchange layer (ion-exchange membrane), separator or CuSO4 mobile electrolyte that can be converted into an insoluble species by electrolysis during the charge/discharge process. This will help in producing a modern-day blueprint for ECs with high capacitance and improved energy sustainability.

European Conference: "Training for Start-Ups: Existing Programmes and Policies in the Twelve Member States of the EC" (Madrid, Spain, October 24-25, 1991).

ERIC Educational Resources Information Center

Melis, Africa

This document provides a summary of the proceedings of a conference on business start-ups and creation in the 12 member states of the European Community (EC). Section I discusses the current relevance of the issue. Major topics are the explosion of interest in business creation as a means of creating more stable employment and political concern…

Current limiting mechanisms in electron and ion beam experiments

NASA Technical Reports Server (NTRS)

Olsen, R. C.

1990-01-01

The emission and collection of current from satellites or rockets in the ionosphere is a process which, at equilibrium, requires a balance between inward and outward currents. In most active experiments in the ionosphere and magnetosphere, the emitted current exceeds the integrated thermal current by one or more orders of magnitude. The system response is typically for the emitted current to be limited by processes such as differential charging of insulating surfaces, interactions between an emitted beam and the local plasma, and interactions between the beam and local neutral gas. These current limiting mechanisms have been illustrated for 20 years in sounding rocket and satellite experiments, which are reviewed here. Detailed presentations of the Spacecraft Charging at High Altitude (SCATHA) electron and ion gun experiments are used to demonstrate the general range of observed phenomena.

A Computational Model of the Ionic Currents, Ca2+ Dynamics and Action Potentials Underlying Contraction of Isolated Uterine Smooth Muscle

PubMed Central

Tong, Wing-Chiu; Choi, Cecilia Y.; Karche, Sanjay; Holden, Arun V.; Zhang, Henggui; Taggart, Michael J.

2011-01-01

Uterine contractions during labor are discretely regulated by rhythmic action potentials (AP) of varying duration and form that serve to determine calcium-dependent force production. We have employed a computational biology approach to develop a fuller understanding of the complexity of excitation-contraction (E-C) coupling of uterine smooth muscle cells (USMC). Our overall aim is to establish a mathematical platform of sufficient biophysical detail to quantitatively describe known uterine E-C coupling parameters and thereby inform future empirical investigations of physiological and pathophysiological mechanisms governing normal and dysfunctional labors. From published and unpublished data we construct mathematical models for fourteen ionic currents of USMCs: currents (L- and T-type), current, an hyperpolarization-activated current, three voltage-gated currents, two -activated current, -activated current, non-specific cation current, - exchanger, - pump and background current. The magnitudes and kinetics of each current system in a spindle shaped single cell with a specified surface area∶volume ratio is described by differential equations, in terms of maximal conductances, electrochemical gradient, voltage-dependent activation/inactivation gating variables and temporal changes in intracellular computed from known fluxes. These quantifications are validated by the reconstruction of the individual experimental ionic currents obtained under voltage-clamp. Phasic contraction is modeled in relation to the time constant of changing . This integrated model is validated by its reconstruction of the different USMC AP configurations (spikes, plateau and bursts of spikes), the change from bursting to plateau type AP produced by estradiol and of simultaneous experimental recordings of spontaneous AP, and phasic force. In summary, our advanced mathematical model provides a powerful tool to investigate the physiological ionic mechanisms underlying the genesis of uterine electrical E-C coupling of labor and parturition. This will furnish the evolution of descriptive and predictive quantitative models of myometrial electrogenesis at the whole cell and tissue levels. PMID:21559514

Reconstruction of ionic currents in a molluscan photoreceptor.

PubMed Central

Sakakibara, M.; Ikeno, H.; Usui, S.; Collin, C.; Alkon, D. L.

1993-01-01

Two-microelectrode voltage-clamp measurements were made to determine the kinetics and voltage dependence of ionic currents across the soma membrane of the Hermissenda type B photoreceptor. The voltage-dependent outward potassium currents, IA and ICa(2+)-K+, the inward voltage-dependent calcium current, ICa2+ and the light-induced current, IIgt, were then described with Hodgkin-Huxley-type equations. The fast-activating and inactivating potassium current, IA, was described by the equation; IA(t) = gA(max)(ma infinity[1-exp(-t/tau ma)])3 x (ha infinity [1-exp(-t/tau ha)] + exp(-t/tau ha)) (Vm-EK), where the parameters ma infinity, ha infinity, tau ma, and tau ha are functions of membrane potential, Vm, and ma infinity and ha infinity are steady-state activation and inactivation parameters. Similarly, the calcium-dependent outward potassium current, ICa(2+)-K+, was described by the equation, ICa(2+)-K+ (t) = gc(max)(mc infinity(VC)(1-exp[-t/tau mc (VC)]))pc (hc infinity(VC) [1-exp(-t/tau hc)] + exp(-t/tau hc(VC)])pc(VC-EK). In high external potassium, ICa(2+)-K+ could be measured in approximate isolation from other currents as a voltage-dependent inward tail current following a depolarizing command pulse from a holding potential of -60 mV. A voltage-dependent inward calcium current across the type B soma membrane, ICa2+, activated rapidly, showed little inactivation, and was described by the equation: ICa2+ = gCa(max) [1 + exp](-Vm-5)/7]-1 (Vm-ECa), where gCa(max) was 0.5 microS. The light-induced current with both fast and slow phases was described by: IIgt(t) = IIgt1 + IIgt2 + IIgt3, IIgti = gIgti [1-exp(- ton/tau mi)] exp(-ton/tau hi)(Vm-EIgti) (i = 1, 2). For i = 3, /Igt(t) = gigt3m33h3(Vm - Eigt3)exp(-ton/Ton) x exp(-tfoff/t Off). Based on these reconstructions of ionic currents, learning-induced enhancement of the long lasting depolarization (LLD) of the photoreceptor'slight response was shown to arise from progressive inactivation of /A, lca2+ -K+, and lCa2+. PMID:8369456

Calcium-activated K(+) channel (K(Ca)3.1) activity during Ca(2+) store depletion and store-operated Ca(2+) entry in human macrophages.

PubMed

Gao, Ya-dong; Hanley, Peter J; Rinné, Susanne; Zuzarte, Marylou; Daut, Jurgen

2010-07-01

STIM1 'senses' decreases in endoplasmic reticular (ER) luminal Ca(2+) and induces store-operated Ca(2+) (SOC) entry through plasma membrane Orai channels. The Ca(2+)/calmodulin-activated K(+) channel K(Ca)3.1 (previously known as SK4) has been implicated as an 'amplifier' of the Ca(2+)-release activated Ca(2+) (CRAC) current, especially in T lymphocytes. We have previously shown that human macrophages express K(Ca)3.1, and here we used the whole-cell patch-clamp technique to investigate the activity of these channels during Ca(2+) store depletion and store-operated Ca(2+) influx. Using RT-PCR, we found that macrophages express the elementary CRAC channel components Orai1 and STIM1, as well as Orai2, Orai3 and STIM2, but not the putatively STIM1-activated channels TRPC1, TRPC3-7 or TRPV6. In whole-cell configuration, a robust Ca(2+)-induced outwardly rectifying K(+) current inhibited by clotrimazole and augmented by DC-EBIO could be detected, consistent with K(Ca)3.1 channel current (also known as intermediate-conductance IK1). Introduction of extracellular Ca(2+) following Ca(2+) store depletion via P2Y(2) receptors induced a robust charybdotoxin (CTX)- and 2-APB-sensitive outward K(+) current and hyperpolarization. We also found that SOC entry induced by thapsigargin treatment induced CTX-sensitive K(+) current in HEK293 cells transiently expressing K(Ca)3.1. Our data suggest that SOC and K(Ca)3.1 channels are tightly coupled, such that a small Ca(2+) influx current induces a much large K(Ca)3.1 channel current and hyperpolarization, providing the necessary electrochemical driving force for prolonged Ca(2+) signaling and store repletion. Copyright 2010 Elsevier Ltd. All rights reserved.

7 CFR 1940.552 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... basic State Factor (SF). The data sources used for each criteria is believed to be the most current and... given the criteria. The transition formula first checks whether the current year's basic formula... year's BFA). EC14NO91.000 If the current year's State BFA is not within this transition range, the...

Sex Differences Influencing Micro- and Macrovascular Endothelial Phenotype In Vitro.

PubMed

Huxley, Virginia H; Kemp, Scott S; Schramm, Christine; Sieveking, Steve; Bingaman, Susan; Yu, Yang; Zaniletti, Isabella; Stockard, Kevin; Wang, Jianjie

2018-06-09

Endothelial dysfunction is an early hallmark of multiple disease states that also display sex differences with respect to age of onset, frequency, and severity. Results of in vivo studies of basal and stimulated microvascular barrier function revealed sex differences difficult to ascribe to specific cells or environmental factors. The present study evaluated endothelial cells (EC) isolated from macro- and/or microvessels of reproductively mature rats under the controlled conditions of low-passage culture to test the assumption that EC phenotype would be sex-independent. The primary finding was that EC, regardless of where they are derived, retain a sex-bias in low-passage culture, independent of varying levels of reproductive hormones. Implications of the work include the fallacy of expecting a universal set of mechanisms derived from study of EC from one sex and/or one vascular origin to apply uniformly to all EC under unstimulated conditions no less in the disease state. Vascular endothelial cells (EC) are heterogeneous with respect to phenotype reflecting at least organ of origin, location within the vascular network, and physical forces. Sex, as an independent influence on EC functions in health or etiology, susceptibility, and progression of dysfunction in numerous disease states, has been largely ignored. The current study focussed on EC isolated from aorta (macrovascular) and skeletal muscle vessels (microvascular) of age-matched male and female rats under identical conditions of short term (passage 4) culture. We tested the hypothesis that genomic sex would not influence endothelial growth, wound healing, morphology, lactate production, or messenger RNA and protein expression of key proteins (sex hormone receptors for androgen (AR) and oestrogen (ERα and ERβ); PECAM-1 and VE-CAD mediating barrier function; α v β 3 and N-Cadherin influencing matrix interactions; ICAM-1 and VCAM-1 mediating EC/white cell adhesion). The hypothesis was rejected as EC origin (macro- versus microvessel) and sex influenced multiple phenotypic characteristics. Statistical model analysis of EC growth demonstrated an hierarchy of variable importance, recapitulated for other phenotypic characteristics, wherein predictions assuming EC homogeneity < Sex < Vessel Origin < Sex and Vessel Origin. Further, patterns of EC mRNA expression by vessel origin and by sex did not predict protein expression. Overall the study demonstrated that accurate assessment of sex-linked EC dysfunction first requires understanding of EC function by position in the vascular tree and by sex. Results from a single EC tissue source/species/sex cannot provide universal insight into the mechanisms regulating in vivo endothelial function in health, no less disease. (250) This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Substrate transport pathway inside outward open conformation of EmrD: a molecular dynamics simulation study.

PubMed

Xianwei, Tan; Diannan, Lu; Boxiong, Wang

2016-07-19

The EmrD transporter, which is a classical major facilitator superfamily (MFS) protein, can extrude a range of drug molecules out of E. coil. The drug molecules transport through the channel of MFS in an outward open state, an important issue in research about bacterial drug resistance, which however, is still unknown. In this paper, we construct a starting outward-open model of the EmrD transporter using a state transition method. The starting model is refined by a conventional molecular dynamics simulation. Locally enhanced sampling simulation (LES) is used to validate the outward-open model of EmrD. In the locally enhanced sampling simulation, ten substrates are placed along the channel of the outward-open EmrD, and these substrates are sampled in the outward-open center cavity. It is found that the translocation pathway of these substrates from the inside to the outside of the cell through the EmrD transporter is composed of two sub-pathways, one sub-pathway, including H2, H4, and H5, and another sub-pathway, including H8, H10, and H11. The results give us have a further insight to the ways of substrate translocation of an MFS protein. The model method is based on common features of an MFS protein, so this modeling method can be used to construct various MFS protein models which have a desired state with other conformations not known in the alternating-access mechanism.

Octopamine increases the excitability of neurons in the snail feeding system by modulation of inward sodium current but not outward potassium currents.

PubMed

Vehovszky, Agnes; Szabó, Henriette; Elliott, Christopher J H

2005-12-06

Although octopamine has long been known to have major roles as both transmitter and modulator in arthropods, it has only recently been shown to be functionally important in molluscs, playing a role as a neurotransmitter in the feeding network of the snail Lymnaea stagnalis. The synaptic potentials cannot explain all the effects of octopamine-containing neurons on the feeding network, and here we test the hypothesis that octopamine is also a neuromodulator. The excitability of the B1 and B4 motoneurons in the buccal ganglia to depolarising current clamp pulses is significantly (P < < 0.05) increased by (10 microM) octopamine, whereas the B2 motoneuron becomes significantly less excitable. The ionic currents evoked by voltage steps were recorded using 2-electrode voltage clamp. The outward current of B1, B2 and B4 motoneurons had two components, a transient IA current and a sustained IK delayed-rectifier current, but neither was modulated by octopamine in any of these three buccal neurons. The fast inward current was eliminated in sodium-free saline and so is likely to be carried by sodium ions. 10 microM octopamine enhanced this current by 33 and 45% in the B1 and B4 motoneurons respectively (P < < 0.05), but a small reduction was seen in the B2 neuron. A Hodgkin-Huxley style simulation of the B1 motoneuron confirms that a 33% increase in the fast inward current by octopamine increases the excitability markedly. We conclude that octopamine is also a neuromodulator in snails, changing the excitability of the buccal neurons. This is supported by the close relationship from the voltage clamp data, through the quantitative simulation, to the action potential threshold, changing the properties of neurons in a rhythmic network. The increase in inward sodium current provides an explanation for the polycyclic modulation of the feeding system by the octopamine-containing interneurons, making feeding easier to initiate and making the feeding bursts more intense.

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

Stoltzfus-Dueck, T.; Scott, B.

An often-neglected portion of the radialmore » $$\\boldsymbol{E}\\times \\boldsymbol{B}$$ drift is shown to drive an outward flux of co-current momentum when free energy is transferred from the electrostatic potential to ion parallel flows. This symmetry breaking is fully nonlinear, not quasilinear, necessitated simply by free-energy balance in parameter regimes for which significant energy is dissipated via ion parallel flows. The resulting rotation peaking is counter-current and has a scaling and order of magnitude that are comparable with experimental observations. Finally, the residual stress becomes inactive when frequencies are much higher than the ion transit frequency, which may explain the observed relation of density peaking and counter-current rotation peaking in the core.« less

Is slack an intrinsic seizure terminator?

PubMed

Igelström, Kajsa M

2013-06-01

Understanding how epileptic seizures are initiated and propagated across large brain networks is difficult, but an even greater mystery is what makes them stop. Failure of spontaneous seizure termination leads to status epilepticus-a state of uninterrupted seizure activity that can cause death or permanent brain damage. Global factors, like changes in neuromodulators and ion concentrations, are likely to play major roles in spontaneous seizure cessation, but individual neurons also have intrinsic active ion currents that may contribute. The recently discovered gene Slack encodes a sodium-activated potassium channel that mediates a major proportion of the outward current in many neurons. Although given little attention, the current flowing through this channel may have properties consistent with a role in seizure termination.

The Safety Course Design and Operations of Composite Overwrapped Pressure Vessels (COPV)

NASA Technical Reports Server (NTRS)

Saulsberry, Regor; Prosser, William

2015-01-01

Following a Commercial Launch Vehicle On-Pad COPV (Composite Overwrapped Pressure Vessels) failure, a request was received by the NESC (NASA Engineering and Safety Center) June 14, 2014. An assessment was approved July 10, 2014, to develop and assess the capability of scanning eddy current (EC) nondestructive evaluation (NDE) methods for mapping thickness and inspection for flaws. Current methods could not identify thickness reduction from necking and critical flaw detection was not possible with conventional dye penetrant (PT) methods, so sensitive EC scanning techniques were needed. Developmental methods existed, but had not been fully developed, nor had the requisite capability assessment (i.e., a POD (Probability of Detection) study) been performed.

Nonlinear, non-stationary image processing technique for eddy current NDE

NASA Astrophysics Data System (ADS)

Yang, Guang; Dib, Gerges; Kim, Jaejoon; Zhang, Lu; Xin, Junjun; Udpa, Lalita

2012-05-01

Automatic analysis of eddy current (EC) data has facilitated the analysis of large volumes of data generated in the inspection of steam generator tubes in nuclear power plants. The traditional procedure for analysis of EC data includes data calibration, pre-processing, region of interest (ROI) detection, feature extraction and classification. Accurate ROI detection has been enhanced by pre-processing, which involves reducing noise and other undesirable components as well as enhancing defect indications in the raw measurement. This paper presents the Hilbert-Huang Transform (HHT) for feature extraction and support vector machine (SVM) for classification. The performance is shown to significantly better than the existing rule based classification approach used in industry.

Effects of green tea catechins on gramicidin channel function and inferred changes in bilayer properties

PubMed Central

Ingólfsson, Helgi I.; Koeppe, Roger E.; Andersen, Olaf S.

2011-01-01

Green tea's health benefits have been attributed to its major polyphenols, the catechins: (−)-epigallocatechin gallate (EGCG), (−)-epicatechin gallate (ECG), (−)-epigallocatechin (EGC), and epicatechin (EC). Catechins (especially EGCG) modulate a wide range of biologically important molecules, including many membrane proteins. Yet, little is known about their mechanism(s) of action. We tested the catechins' bilayer-modifying potency using gramicidin A (gA) channels as molecular force probes. All the catechins alter gA channel function and modify bilayer properties, with a 500-fold range in potency (EGCG > ECG >> EGC > EC). Additionally, the gallate group causes current block, as evident by brief downward current transitions (flickers). PMID:21896274

Improving treatment for obese women with early stage cancer of the uterus: rationale and design of the levonorgestrel intrauterine device ± metformin ± weight loss in endometrial cancer (feMME) trial.

PubMed

Hawkes, A L; Quinn, M; Gebski, V; Armes, J; Brennan, D; Janda, M; Obermair, A

2014-09-01

Endometrial adenocarcinoma (EC) is the most common gynaecologic cancer. Up to 90% of EC patients are obese which poses a health threat to patients post-treatment. Standard treatment for EC includes hysterectomy, although this has significant side effects for obese women at high risk of surgical complications and for women of childbearing age. This trial investigates the effectiveness of non-surgical or conservative treatment options for obese women with early stage EC. The primary aim is to determine the efficacy of: levonorgestrel intrauterine device (LNG-IUD); with or without metformin (an antidiabetic drug); and with or without a weight loss intervention to achieve a pathological complete response (pCR) in EC at six months from study treatment initiation. The secondary aim is to enhance understanding of the molecular processes and to predict a treatment response by investigating EC biomarkers. An open label, three-armed, randomised, phase-II, multi-centre trial of LNG-IUD ± metformin ± weight loss intervention. 165 participants from 28 centres are randomly assigned in a 3:3:5 ratio to the treatment arms. Clinical, quality of life and health behavioural data will be collected at baseline, six weeks, three and six months. EC biomarkers will be assessed at baseline, three and six months. There is limited prospective evidence for conservative treatment for EC. Trial results could benefit patients and reduce health system costs through a reduction in hospitalisations and through lower incidence of adverse events currently observed with standard treatment. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Elements including metals in the atomizer and aerosol of disposable electronic cigarettes and electronic hookahs.

PubMed

Williams, Monique; Bozhilov, Krassimir; Ghai, Sanjay; Talbot, Prue

2017-01-01

Our purpose was to quantify 36 inorganic chemical elements in aerosols from disposable electronic cigarettes (ECs) and electronic hookahs (EHs), examine the effect of puffing topography on elements in aerosols, and identify the source of the elements. Thirty-six inorganic chemical elements and their concentrations in EC/EH aerosols were determined using inductively coupled plasma optical emission spectroscopy, and their source was identified by analyzing disassembled atomizers using scanning electron microscopy and energy dispersive X-ray spectroscopy. Of 36 elements screened, 35 were detected in EC/EH aerosols, while only 15 were detected in conventional tobacco smoke. Some elements/metals were present in significantly higher concentrations in EC/EH aerosol than in cigarette smoke. Concentrations of particular elements/metals within EC/EH brands were sometimes variable. Aerosols generated at low and high air-flow rates produced the same pattern of elements, although the total element concentration decreased at the higher air flow rate. The relative amount of elements in the first and last 60 puffs was generally different. Silicon was the dominant element in aerosols from all EC/EH brands and in cigarette smoke. The elements appeared to come from the filament (nickel, chromium), thick wire (copper coated with silver), brass clamp (copper, zinc), solder joints (tin, lead), and wick and sheath (silicon, oxygen, calcium, magnesium, aluminum). Lead was identified in the solder and aerosol of two brands of EHs (up to 0.165 μg/10 puffs). These data show that EC/EH aerosols contain a mixture of elements, including heavy metals, with concentrations often significantly higher than in conventional cigarette smoke. While the health effects of inhaling mixtures of heated metals is currently not known, these data will be valuable in future risk assessments involving EC/EH elements/metals.

Effects of tobacco smoke and electronic cigarette vapor exposure on the oral and gut microbiota in humans: a pilot study

PubMed Central

Auchtung, Thomas A.; Ajami, Nadim J.; Velasquez, Kenia; De La Garza, Richard; Petrosino, Joseph F.

2018-01-01

Background The use of electronic cigarettes (ECs) has increased drastically over the past five years, primarily as an alternative to smoking tobacco cigarettes. However, the adverse effects of acute and long-term use of ECs on the microbiota have not been explored. In this pilot study, we sought to determine if ECs or tobacco smoking alter the oral and gut microbiota in comparison to non-smoking controls. Methods We examined a human cohort consisting of 30 individuals: 10 EC users, 10 tobacco smokers, and 10 controls. We collected cross-sectional fecal, buccal swabs, and saliva samples from each participant. All samples underwent V4 16S rRNA gene sequencing. Results Tobacco smoking had a significant effect on the bacterial profiles in all sample types when compared to controls, and in feces and buccal swabs when compared to EC users. The most significant associations were found in the gut, with an increased relative abundance of Prevotella (P = 0.006) and decreased Bacteroides (P = 0.036) in tobacco smokers. The Shannon diversity was also significantly reduced (P = 0.009) in fecal samples collected from tobacco smokers compared to controls. No significant difference was found in the alpha diversity, beta-diversity or taxonomic relative abundances between EC users and controls. Discussion From a microbial ecology perspective, the current pilot data demonstrate that the use of ECs may represent a safer alternative compared to tobacco smoking. However, validation in larger cohorts and greater understanding of the short and long-term impact of EC use on microbiota composition and function is warranted. PMID:29736335

Oilfield water treatment by electrocoagulation-reverse osmosis for agricultural use: effects on germination and early growth characteristics of sunflower.

PubMed

de Souza, Paulo S A; Cerqueira, Alexandre A; Rigo, Michelle M; de Paiva, Julieta L; Couto, Rafael S P; Merçon, Fábio; Perez, Daniel V; Marques, Monica R C

2017-05-01

This study aims to evaluate the effects of oilfield water (OW), treated by a hybrid process of electrocoagulation and reverse osmosis (EC-RO), on seed germination and early growth characteristics of sunflower (Heliantus annus L.). In the EC step, tests were conducted with 28.6 A m -2 current density and 4 min. reaction time. In the RO step, the system was operated with 1 L min -1 constant flow and 2 MPa, 2.5 MPa and 3 MPa feed pressures. In all feed pressures, RO polymeric membranes achieved very high removals of chemical oxygen demand (up to 89%) and oils and greases (100%) from EC-treated effluent. In best feed pressure (2.5 MPa), turbidity, total dissolved salts, electrical conductivity, salinity, toxic ions and sodium adsorption ratio values attained internationally recognized standards for irrigation water. Using EC-RO (feed pressure:2.5 MPa) treated OW, germinated sunflower seeds percentage (86 ± 6%), speed of germination (30 ± 2) and biomass production (49 ± 5 mg) were statistically similar to control (distilled water) results. Vigor index average values obtained using OW treated by EC-RO (3871)were higher than that obtained by OW water treated by EC (3300). The results of this study indicate that EC-RO seems to be a promising alternative for treatment of OW aiming sunflower crops irrigation, since the use of this treated effluent did not affect adversely seed germination and seedling development, and improved seedling vigor. Furthermore, OW treatment by EC-RO reduces sodium levels into acceptable standards values avoiding soil degradation.

Risk factors and spatial distribution of extended spectrum β-lactamase-producing- Escherichia coli at retail poultry meat markets in Malaysia: a cross-sectional study.

PubMed

Aliyu, A B; Saleha, A A; Jalila, A; Zunita, Z

2016-08-02

The significant role of retail poultry meat as an important exposure pathway for the acquisition and transmission of extended spectrum β-lactamase-producing Escherichia coli (ESBL-EC) into the human population warrants understanding concerning those operational practices associated with dissemination of ESBL-EC in poultry meat retailing. Hence, the objective of this study was to determine the prevalence, spatial distribution and potential risk factors associated with the dissemination of ESBL-EC in poultry meat retail at wet-markets in Selangor, Malaysia. Poultry meat (breast, wing, thigh, and keel) as well as the contact surfaces of weighing scales and cutting boards were sampled to detect ESBL-EC by using culture and disk combination methods and polymerase chain reaction assays. Besides, questionnaire was used to obtain data and information pertaining to those operational practices that may possibly explain the occurrence of ESBL-EC. The data were analysed using logistic regression analysis at 95 % CI. The overall prevalence of ESBL-EC was 48.8 % (95 % CI, 42 - 55 %). Among the risk factors that were explored, type of countertop, sanitation of the stall environment, source of cleaning water, and type of cutting board were found to be significantly associated with the presence of ESBL-EC. Thus, in order to prevent or reduce the presence of ESBL-EC and other contaminants at the retail-outlet, there is a need to design a process control system based on the current prevailing practices in order to reduce cross contamination, as well as to improve food safety and consumer health.

Awareness and practice of emergency contraception at a private university in Nigeria.

PubMed

Awoleke, Jacob Olumuyiwa; Adanikin, Abiodun Idowu; Awoleke, Adeola; Odanye, Moyinoluwa

2015-06-04

The pursuit of formal education now causes many people in developing countries to marry later in life, thereby leading to increased premarital sex and unintended pregnancies. Efforts have been made to characterize awareness and use of emergency contraception (EC) among undergraduate students in public universities in Nigeria; however, it is not known if students in private tertiary institutions adopt different practices or if having an affluent family background plays a role. This pilot study therefore aimed to assess the awareness and use of EC among students at a private Nigerian university toward assisting education planners in developing strategies in improving students' reproductive well-being. Out of 94 female students, 42 (44.7%) had sexual experience, but only 32 (34.0%) were currently sexually active. Six students (6.4%) had had unwanted pregnancies, of which all but one were terminated. Fifty-seven respondents (60.6%) were aware of EC, though only 10 (10.6%) ever practiced it. The greatest source of EC information was from health workers and peers; the lowest source was family or relatives. Most respondents desired orientation and availability of EC on campus. EC awareness among the students was predicted by upper social class background (adjusted odds ratio [OR], 2.73; 95% confidence interval [CI], 1.06-7.45) and upbringing in the Federal Capital Territory (adjusted OR, 4.45; 95% CI, 1.56-14.22). Though awareness of EC was higher among the private university students in this study than at most public universities, there was no difference in EC usage. A high pregnancy termination rate was observed; dilatation and curettage were mainly adopted. In Nigeria, youth-friendly reproductive health information and access should not be limited to government-owned tertiary institutions but also extended to private ones.

Relation of Field-Aligned Currents Measured by the Network of Iridium® Spacecraft to Solar Wind and Substorms

NASA Astrophysics Data System (ADS)

McPherron, R. L.; Anderson, B. J.; Chu, Xiangning

2018-03-01

The strength of field-aligned currents coupling the magnetosphere to the ionosphere was obtained by the Active Magnetosphere and Planetary Electrodynamics Response Experiment (AMPERE) using the network of Iridium® spacecraft. The distribution of current was integrated giving total current in and out of the ionosphere on the dayside and nightside of the Earth in both hemispheres. The onset of auroral zone negative bays and midlatitude positive bays corresponds to an increase in nightside upward current. The total outward current tends toward saturation with increasing solar wind driver strength. The optimum solar wind coupling function for AL index predicts 73% of the variance in nightside upward current. The dayside and nightside predictors of upward current rise to a peak at 30-45 min and decay slowly over 2.5 hr. Nightside response is delayed relative to dayside.

Electrocoagulation pretreatment of wet-spun acrylic fibers manufacturing wastewater to improve its biodegradability.

PubMed

Gong, Chenhao; Zhang, Zhongguo; Li, Haitao; Li, Duo; Wu, Baichun; Sun, Yuwei; Cheng, Yanjun

2014-06-15

The electrocoagulation (EC) process was used to pretreat wastewater from the manufacture of wet-spun acrylic fibers, and the effects of varying the operating parameters, including the electrode area/wastewater volume (A/V) ratio, current density, interelectrode distance and pH, on the EC treatment process were investigated. About 44% of the total organic carbon was removed using the optimal conditions in a 100 min procedure. The optimal conditions were a current density of 35.7 mA cm(-2), an A/V ratio of 0.28 cm(-1), a pH of 5, and an interelectrode distance of 0.8 cm. The biodegradability of the contaminants in the treated water was improved by the EC treatment (using the optimal conditions), increasing the five-day biological oxygen demand/chemical oxygen demand ratio to 0.35, which could improve the effectiveness of subsequent biological treatments. The improvement in the biodegradability of the contaminants in the wastewater was attributed to the removal and degradation of aromatic organic compounds, straight-chain paraffins, and other organic compounds, which we identified using gas chromatography-mass spectrometry and Fourier transform infrared spectroscopy. The EC process was proven to be an effective alternative pretreatment for wastewater from the manufacture of wet-spun acrylic fibers, prior to biological treatments. Copyright © 2014 Elsevier B.V. All rights reserved.

[Investigation into the relationship between outpatient haemodialysis centres and referring hospitals in Spain].

PubMed

Arenas, M D; Bernat, A; Ramos, R; Berdud, I; Blanco, A

2009-01-01

To guarantee continuity and equity in the clinical assistance of patients on hemodialysis in extrahospitalary centers (EC) a close relationship and a good level of communication between them and their reference hospitals (RH) is essential. The aim of this study was to assess the present situation of this relationship in our country (Spain) so as to be able to detect improvement opportunities. Descriptive and transversal study using two self-report anonymous surveys: one for EC (81 questions) and one for RH (56 questions) sent by e-mail to all Spanish EC and RH registered in the Spanish Society of Nephrology. We received answers from 80 EC and 30 RH. 70% of the EC were managed by multinational companies; only 16 % EC were placed in a hospital. 64% of the EC need to employ non-nephrological medical staff. Nearly 40% of the EC nephrologists also go on duty at their RH. More than three quarters of the EC nephrologists are alone during their workday. Bidirectional telephone communication is very frequent between EC and RH. Around a third of the patients sent from RH to EC arrive without current viral serology and/or without a functioning vascular access. Most of the patients sent from EC to RH bring an up-to-date complete medical report. 41,3 % of the EC answered that they were usually consulted by their RH doctor colleagues about decisions to be taken regarding their patients. Routine blood and other medical protocol tests of CE are well defined in the formal agreement with their RH in 65 % of the cases, although they can be modified by the EC through consensus with the RH in more than 50 % of the cases. 60 % of the EC can directly consult other specialists in the RH but more than 50 % need to do so through the RH nephrologist. Parenteral medication used in the ECs is mostly supplied by their RH, but a third of ECs have some limitations with uncommon or not concert-specified parenteral drugs. RHs refer that most of the vascular accesses are done in the hospital, whereas ECs say that this is true only in half of the cases. More than a third of the fistulae of predialysis patients are done in the ECs as part of their collaboration with RHs. The majority of ECs can share the decision about patients' inclusion in renal transplant waiting list. In only a fifth of the cases is there a common database between CE and RH, and less than half share common protocols or objectives. 62,5% of CEs participate with RHs in clinical trials. More than half of the dialysis private companies provide continuous training and education to their ECs personnel, either directly through the company or facilitating assistance to courses or congresses. Some of the relationship aspects that appear to be clearly improvable are: CEs nephrologist solitude and their limited access to continuous training and education, an adequate referral of the patients from the RHs, CEs nephrologist's autonomy at making consultations to specialists or their limitations when asking for hospital medications. A closer relationship between CEs and RHs is of the utmost importance in guaranteeing continuity and equity in the clinical assistance of our hemodialysis patients. The creation of a debate forum would favour discussion and common resolution of such aspects.

Investigation of low leakage current radiation detectors on n-type 4H-SiC epitaxial layers

NASA Astrophysics Data System (ADS)

Nguyen, Khai V.; Chaudhuri, Sandeep K.; Mandal, Krishna C.

2014-09-01

The surface leakage current of high-resolution 4H-SiC epitaxial layer Schottky barrier detectors has been improved significantly after surface passivations of 4H-SiC epitaxial layers. Thin (nanometer range) layers of silicon dioxide (SiO2) and silicon nitride (Si3N4) were deposited on 4H-SiC epitaxial layers using plasma enhanced chemical vapor deposition (PECVD) on 20 μm thick n-type 4H-SiC epitaxial layers followed by the fabrication of large area (~12 mm2) Schottky barrier radiation detectors. The fabricated detectors have been characterized through current-voltage (I-V), capacitance-voltage (C-V), and alpha pulse height spectroscopy measurements; the results were compared with that of detectors fabricated without surface passivations. Improved energy resolution of ~ 0.4% for 5486 keV alpha particles was observed after passivation, and it was found that the performance of these detectors were limited by the presence of macroscopic and microscopic crystal defects affecting the charge transport properties adversely. Capacitance mode deep level transient studies (DLTS) revealed the presence of a titanium impurity related shallow level defects (Ec-0.19 eV), and two deep level defects identified as Z1/2 and Ci1 located at Ec-0.62 and ~ Ec-1.40 eV respectively.

Removal of emerging contaminants from the environment by adsorption.

PubMed

Sophia A, Carmalin; Lima, Eder C

2018-04-15

Emerging contaminants (EC's) are pollutants of growing concern. They are mainly organic compounds such as: pesticides, pharmaceuticals and personal care products, hormones, plasticizers, food additives, wood preservatives, laundry detergents, surfactants, disinfectants, flame retardants, and other organic compounds that were found recently in natural wastewater stream generated by human and industrial activities. A majority of ECs does not have standard regulations and could lead to lethal effects on human and aquatic life even at small concentrations. The conventional primary and secondary water treatment plants do not remove or degrade these toxic pollutants efficiently and hence need cost effective tertiary treatment method. Adsorption is a promising method worldwide for EC removal since it is low initial cost for implementation, highly-efficient and has simple operating design. Research has shown that the application of different adsorbents such as, activated carbons(ACs), modified biochars (BCs), nanoadsorbents (carbon nanotubes and graphene), composite adsorbents, and other are being used for EC's removal from water and wastewater. The current review intends to investigate adsorption process as an efficient method for the treatment of ECs. The mechanism of adsorption has also been discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

Tunable high-power blue external cavity semiconductor laser

NASA Astrophysics Data System (ADS)

Ding, Ding; Lv, Xueqin; Chen, Xinyi; Wang, Fei; Zhang, Jiangyong; Che, Kaijun

2017-09-01

A commercially available high-power GaN-based blue laser diode has been operated in a simple Littrow-type external cavity (EC). Two kinds of EC configurations with the grating lines perpendicular (A configuration) and parallel (B configuration) to the p-n junction are evaluated. Good performance has been demonstrated for the EC laser with B configuration due to the better mode selection effect induced by the narrow feedback wavelength range from the grating. Under an injection current of 1100 mA, the spectral linewidth is narrowed significantly down to ∼0.1 nm from ∼1 nm (the free-running width), with a good wavelength-locking behavior and a higher than 35 dB-amplified spontaneous emission suppression ratio. Moreover, a tuning bandwidth of 3.6 nm from 443.9 nm to 447.5 nm is realized with output power of 1.24 W and EC coupling efficiency of 80% at the central wavelength. The grating-coupled blue EC laser with narrow spectral linewidth, flexible wavelength tunability, and high output power shows potential applications in atom cooling and trapping, high-resolution spectroscopy, second harmonic generation, and high-capacity holographic data storage.

Studies on absorption of EC waves in assisted startup experiment on FTU

NASA Astrophysics Data System (ADS)

Granucci, G.; Ricci, D.; Farina, D.; Figini, L.; Iraji, D.; Tudisco, O.; Ramponi, G.; Bin, W.

2012-09-01

Assistance of EC wave for plasma breakdown and current ramp up is the proposed scenario for the ITER case, characterized by low toroidal electric field. The experimental results on many tokamaks clearly indicate the capabilities of the proposed scheme to have a robust breakdown in ITER. The key aspect of this technique is the EC power required, strongly related to the absorption of the wave in the initial stage of plasma formation. This aspect is generally neglected due to the diagnostics difficulties in the plasma formation phase. As a consequence a multi-pass absorption scheme is usually considered reasonable, leading to a strong absorption after many reflections on the walls. The present study exploits the high temporal and spatial resolution of the fast scanning interferometer of FTU together with the measure of residual power obtained by a sniffer probe. The absorbed EC power is calculated considering also the polarization rotation and the subsequent mode conversion after incidence on the internal wall and compared with that derived from experimental data. The resulting EC power distribution can explain differences observed between perpendicular and oblique injection results, indicating future investigations to define ITER power requirements.

Endothelial dysfunction in the regulation of portal hypertension

PubMed Central

Iwakiri, Yasuko

2013-01-01

Portal hypertension is caused by an increased intrahepatic resistance, a major consequence of cirrhosis. Endothelial dysfunction in liver sinusoidal endothelial cells (LSECs) decreases the production of vasodilators, such as nitric oxide (NO) and favors vasoconstriction. This contributes to an increased vascular resistance in the intrahepatic/sinusoidal microcirculation. Portal hypertension, once developed, causes endothelial cell (EC) dysfunction in the extrahepatic, i.e. splanchnic and systemic, circulation. Unlike LSEC dysfunction, EC dysfunction in the splanchnic and systemic circulation overproduces vasodilator molecules, leading to arterial vasodilatation. In addition, portal hypertension leads to the formation of portosystemic collateral vessels. Both arterial vasodilatation and portosystemic collateral vessel formation exacerbate portal hypertension by increasing the blood flow through the portal vein. Pathologic consequences, such as esophageal varices and ascites, result. While the sequence of pathological vascular events in cirrhosis and portal hypertension have been elucidated, the underlying cellular and molecular mechanisms causing EC dysfunctions are not yet fully understood. This review article summarizes the current cellular and molecular studies on EC dysfunctions found during the development of cirrhosis and portal hypertension with a focus on intra- and extrahepatic circulation. The article ends by discussing future directions of study for EC dysfunctions. PMID:21745318

Mitigating the effects of landscape development on streams in urbanizing watersheds

USGS Publications Warehouse

Hogan, Dianna M.; Jarnagin, S. Taylor; Loperfido, John V.; Van Ness, Keith

2013-01-01

This collaborative study examined urbanization and impacts on area streams while using the best available sediment and erosion control (S&EC) practices in developing watersheds in Maryland, United States. During conversion of the agricultural and forested watersheds to urban land use, land surface topography was graded and vegetation was removed creating a high potential for sediment generation and release during storm events. The currently best available S&EC facilities were used during the development process to mitigate storm runoff water quality, quantity, and timing before entering area streams. Detailed Geographic Information System (GIS) maps were created to visualize changing land use and S&EC practices, five temporal collections of LiDAR (light detection and ranging) imagery were used to map the changing landscape topography, and streamflow, physical geomorphology, and habitat data were used to assess the ability of the S&EC facilities to protect receiving streams during development. Despite the use of the best available S&EC facilities, receiving streams experienced altered flow, geomorphology, and decreased biotic community health. These impacts on small streams during watershed development affect sediment and nutrient loads to larger downstream aquatic ecosystems such as the Chesapeake Bay.

Esophageal cancer stem cells and implications for future therapeutics.

PubMed

Qian, Xia; Tan, Cheng; Wang, Feng; Yang, Baixia; Ge, Yangyang; Guan, Zhifeng; Cai, Jing

2016-01-01

Esophageal carcinoma (EC) is a lethal disease with high morbidity and mortality worldwide, and the incidence has been increasing in recent years. Although the diagnosis and treatment of EC have improved considerably, EC has rapidly progressed in the clinical setting and has a poor prognosis for its metastasis and recurrence. The general idea of cancer stem cells (CSCs) is primarily based on clinical and experimental observations, indicating the existence of a subpopulation of cells that can self-renew and differentiate. The EC stem cells, which can be isolated from normal pluripotent stem cells by applying similar biomarkers, may participate in promoting esophageal tumorigenesis through renewal and repair. In this review, major emphasis is given to CSC markers, altered CSC-specific pathways, and molecular targeting agents currently available to target CSCs of esophageal cancer. The roles of numerous markers (CD44, aldehyde dehydrogenase, CD133, and ATP-binding cassette subfamily G member 2) and developmental signaling pathways (Wnt/β-catenin, Notch, hedgehog, and Hippo) in isolating esophageal CSCs are discussed in detail. Targeting CSCs can be a logical strategy to treat EC, as these cells are responsible for carcinoma recurrence and chemoradiation resistance.

The EBIT Calorimeter Spectrometer: a new, permanent user facility at the LLNL EBIT

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

Porter, F S; Beiersdorfer, P; Brown, G V

The EBIT Calorimeter Spectrometer (ECS) is currently being completed and will be installed at the EBIT facility at the Lawrence Livermore National Laboratory in October 2007. The ECS will replace the smaller XRS/EBIT microcalorimeter spectrometer that has been in almost continuous operation since 2000. The XRS/EBIT was based on a spare laboratory cryostat and an engineering model detector system from the Suzaku/XRS observatory program. The new ECS spectrometer was built to be a low maintenance, high performance implanted silicon microcalorimeter spectrometer with 4 eV resolution at 6 keV, 32 detector channels, 10 {micro}s event timing, and capable of uninterrupted acquisitionmore » sessions of over 60 hours at 50 mK. The XRS/EBIT program has been very successful, producing many results on topics such as laboratory astrophysics, atomic physics, nuclear physics, and calibration of the spectrometers for the National Ignition Facility. The ECS spectrometer will continue this work into the future with improved spectral resolution, integration times, and ease-of-use. We designed the ECS instrument with TES detectors in mind by using the same highly successful magnetic shielding as our laboratory TES cryostats. This design will lead to a future TES instrument at the LLNL EBIT. Here we discuss the legacy of the XRS/EBIT program, the performance of the new ECS spectrometer, and plans for a future TES instrument.« less

High-throughput identification of small molecules that affect human embryonic vascular development

PubMed Central

Vazão, Helena; Rosa, Susana; Barata, Tânia; Costa, Ricardo; Pitrez, Patrícia R.; Honório, Inês; de Vries, Margreet R.; Papatsenko, Dimitri; Benedito, Rui; Saris, Daniel; Khademhosseini, Ali; Quax, Paul H. A.; Pereira, Carlos F.; Mercader, Nadia; Ferreira, Lino

2017-01-01

Birth defects, which are in part caused by exposure to environmental chemicals and pharmaceutical drugs, affect 1 in every 33 babies born in the United States each year. The current standard to screen drugs that affect embryonic development is based on prenatal animal testing; however, this approach yields low-throughput and limited mechanistic information regarding the biological pathways and potential adverse consequences in humans. To develop a screening platform for molecules that affect human embryonic development based on endothelial cells (ECs) derived from human pluripotent stem cells, we differentiated human pluripotent stem cells into embryonic ECs and induced their maturation under arterial flow conditions. These cells were then used to screen compounds that specifically affect embryonic vasculature. Using this platform, we have identified two compounds that have higher inhibitory effect in embryonic than postnatal ECs. One of them was fluphenazine (an antipsychotic), which inhibits calmodulin kinase II. The other compound was pyrrolopyrimidine (an antiinflammatory agent), which inhibits vascular endothelial growth factor receptor 2 (VEGFR2), decreases EC viability, induces an inflammatory response, and disrupts preformed vascular networks. The vascular effect of the pyrrolopyrimidine was further validated in prenatal vs. adult mouse ECs and in embryonic and adult zebrafish. We developed a platform based on human pluripotent stem cell-derived ECs for drug screening, which may open new avenues of research for the study and modulation of embryonic vasculature. PMID:28348206

Comprehensive Insights into the Reactivity of Electrolytes Based on Sodium Ions.

PubMed

Eshetu, Gebrekidan Gebresilassie; Grugeon, Sylvie; Kim, Huikyong; Jeong, Sangsik; Wu, Liming; Gachot, Gregory; Laruelle, Stephane; Armand, Michel; Passerini, Stefano

2016-03-08

We report a systematic investigation of Na-based electrolytes that comprise various NaX [X=hexafluorophosphate (PF6 ), perchlorate (ClO4 ), bis(trifluoromethanesulfonyl)imide (TFSI), fluorosulfonyl-(trifluoromethanesulfonyl)imide (FTFSI), and bis(fluorosulfonyl)imide (FSI)] salts and solvent mixtures [ethylene carbonate (EC)/dimethyl carbonate (DMC), EC/diethyl carbonate (DEC), and EC/propylene carbonate (PC)] with respect to the Al current collector stability, formation of soluble degradation compounds, reactivity towards sodiated hard carbon (Nax -HC), and solid-electrolyte interphase (SEI) layer formation. Cyclic voltammetry demonstrates that the stability of Al is highly influenced by the nature of the anions, solvents, and additives. GC-MS analysis reveals that the formation of SEI telltales depends on the nature of the linear alkyl carbonates and the battery chemistry (Li(+) vs. Na(+) ). FTIR spectroscopy shows that double alkyl carbonates are the main components of the SEI layer on Nax -HC. In the presence of Na salts, EC/DMC and EC/DEC presented a higher reactivity towards Nax -HC than EC/PC. For a fixed solvent mixture, the onset temperature follows the sequence NaClO4

High-throughput identification of small molecules that affect human embryonic vascular development.

PubMed

Vazão, Helena; Rosa, Susana; Barata, Tânia; Costa, Ricardo; Pitrez, Patrícia R; Honório, Inês; de Vries, Margreet R; Papatsenko, Dimitri; Benedito, Rui; Saris, Daniel; Khademhosseini, Ali; Quax, Paul H A; Pereira, Carlos F; Mercader, Nadia; Fernandes, Hugo; Ferreira, Lino

2017-04-11

Birth defects, which are in part caused by exposure to environmental chemicals and pharmaceutical drugs, affect 1 in every 33 babies born in the United States each year. The current standard to screen drugs that affect embryonic development is based on prenatal animal testing; however, this approach yields low-throughput and limited mechanistic information regarding the biological pathways and potential adverse consequences in humans. To develop a screening platform for molecules that affect human embryonic development based on endothelial cells (ECs) derived from human pluripotent stem cells, we differentiated human pluripotent stem cells into embryonic ECs and induced their maturation under arterial flow conditions. These cells were then used to screen compounds that specifically affect embryonic vasculature. Using this platform, we have identified two compounds that have higher inhibitory effect in embryonic than postnatal ECs. One of them was fluphenazine (an antipsychotic), which inhibits calmodulin kinase II. The other compound was pyrrolopyrimidine (an antiinflammatory agent), which inhibits vascular endothelial growth factor receptor 2 (VEGFR2), decreases EC viability, induces an inflammatory response, and disrupts preformed vascular networks. The vascular effect of the pyrrolopyrimidine was further validated in prenatal vs. adult mouse ECs and in embryonic and adult zebrafish. We developed a platform based on human pluripotent stem cell-derived ECs for drug screening, which may open new avenues of research for the study and modulation of embryonic vasculature.

Thermally stimulated capacitance in gamma irradiated epitaxial 4H-SiC Schottky barrier diodes

NASA Astrophysics Data System (ADS)

Vigneshwara Raja, P.; Narasimha Murty, N. V. L.

2018-04-01

Deep level defects in 4H-SiC Schottky barrier diodes (SBDs) fabricated on n-type epitaxial 4H-SiC have been identified by thermally stimulated capacitance (TSCAP) spectroscopy prior to and after 60Co-gamma irradiation. The TSCAP measurements on the non-irradiated SBDs reveal two electron traps at Ec-0.63 eV (˜250 K) and Ec-1.13 eV (˜525 K), whereas only one trap at Ec-0.63 eV is identified by conventional thermally stimulated current (TSC) measurements. Hence, TSCAP spectroscopy is more effective in identifying deep level defects in epitaxial 4 H-SiC SBDs as compared to the TSC spectroscopy. Upon exposure to 60Co-gamma rays up to a dose of 100 Mrad, significant changes in the concentration of the traps at Ec-0.63 eV, Ec-1.13 eV, and one new trap at Ec-0.89 eV (˜420 K) are observed. The electrical characteristics of the SBDs are considerably changed after gamma irradiation. The dominant mechanisms responsible for the irradiation induced changes in the SBD electrical characteristics are analyzed by incorporating the trap signatures in the commercial Silvaco® TCAD device simulator. The extracted trap parameters of the irradiated SBDs may be helpful in predicting the survival of 4H-SiC SBD detectors at higher irradiation levels.

Simulation of tropospheric chemistry and aerosols with the climate model EC-Earth

NASA Astrophysics Data System (ADS)

van Noije, T. P. C.; Le Sager, P.; Segers, A. J.; van Velthoven, P. F. J.; Krol, M. C.; Hazeleger, W.; Williams, A. G.; Chambers, S. D.

2014-10-01

We have integrated the atmospheric chemistry and transport model TM5 into the global climate model EC-Earth version 2.4. We present an overview of the TM5 model and the two-way data exchange between TM5 and the IFS model from the European Centre for Medium-Range Weather Forecasts (ECMWF), the atmospheric general circulation model of EC-Earth. In this paper we evaluate the simulation of tropospheric chemistry and aerosols in a one-way coupled configuration. We have carried out a decadal simulation for present-day conditions and calculated chemical budgets and climatologies of tracer concentrations and aerosol optical depth. For comparison we have also performed offline simulations driven by meteorological fields from ECMWF's ERA-Interim reanalysis and output from the EC-Earth model itself. Compared to the offline simulations, the online-coupled system produces more efficient vertical mixing in the troposphere, which reflects an improvement of the treatment of cumulus convection. The chemistry in the EC-Earth simulations is affected by the fact that the current version of EC-Earth produces a cold bias with too dry air in large parts of the troposphere. Compared to the ERA-Interim driven simulation, the oxidizing capacity in EC-Earth is lower in the tropics and higher in the extratropics. The atmospheric lifetime of methane in EC-Earth is 9.4 years, which is 7% longer than the lifetime obtained with ERA-Interim but remains well within the range reported in the literature. We further evaluate the model by comparing the simulated climatologies of surface radon-222 and carbon monoxide, tropospheric and surface ozone, and aerosol optical depth against observational data. The work presented in this study is the first step in the development of EC-Earth into an Earth system model with fully interactive atmospheric chemistry and aerosols.

Polymerase ε (POLE) ultra-mutation in uterine tumors correlates with T lymphocyte infiltration and increased resistance to platinum-based chemotherapy in vitro

PubMed Central

Bellone, Stefania; Eliana, Bignotti; Lonardi, Silvia; Ferrari, Francesca; Centritto, Floriana; Masserdotti, Alice; Pettinella, Francesca; Black, Jonathan; Menderes, Gulden; Altwerger, Gary; Hui, Pei; Lopez, Salvatore; de Haydu, Christopher; Bonazzoli, Elena; Predolini, Federica; Zammataro, Luca; Cocco, Emiliano; Ferrari, Federico; Ravaggi, Antonella; Romani, Chiara; Facchettie, Fabio; Sartori, Enrico; Odicino, Franco E.; Silasi, Dan-Arin; Litkouhi, Babak; Ratner, Elena; Azodi, Masoud; Schwartz, Peter E.; Santin, Alessandro D.

2016-01-01

Objective Up to 12 % of all endometrial-carcinomas (EC) harbor DNA-polymerase-ε-(POLE) mutations. It is currently unknown whether the favorable prognosis of POLE-mutated EC is derived from their low metastatic capability, extraordinary number of somatic mutations thus imparting immunogenicity, or a high sensitivity to chemotherapy. Methods Polymerase-chain-reaction-amplification and Sanger-sequencing were used to test for POLE exonuclease-domain-mutations (exons 9–14) 131 EC. Infiltration of CD4+ and CD8+ T-lymphocytes (TIL) and PD-1-expression in POLE-mutated vs POLE wild-type EC was studied by immunohistochemistry (IHC) and the correlations between survival and molecular features were investigated. Finally, primary POLE-mutated and POLE-wild-type EC cell lines were established and compared in-vitro for their sensitivity to chemotherapy. Results Eleven POLE-mutated EC (8.5%) were identified. POLE-mutated tumors were associated with improved progression-free-survival (P<0.05) and displayed increased numbers of CD4+ (44.5 vs 21.8; P = .001) and CD8+ (32.8 vs 13.5; P < .001) TILs when compared to wild-type POLE EC. PD-1 receptor was overexpressed in TILs from POLE-mutated vs wild-type-tumors (81% vs 28%; P < .001). Primary POLE tumor cell lines were significantly more resistant to platinum-chemotherapy in-vitro when compared to POLE-wild-type tumors (P < 0.004). Conclusions POLE ultra-mutated EC are heavily infiltrated with CD4+/CD8+ TIL, overexpress PD-1 immune-check-point (i.e., features consistent with chronic antigen-exposure), and have a better prognosis when compared to other molecular subtypes of EC patients. POLE-mutated tumor-cell lines are resistant to platinum-chemotherapy in-vitro suggesting that the better prognosis of POLE-patients is not secondary to a higher sensitivity to chemotherapy but likely linked to enhanced immunogenicity. PMID:27894751

Absorption properties of chromophoric dissolved organic matter (CDOM) in the East China Sea and the waters off eastern Taiwan

NASA Astrophysics Data System (ADS)

Zhou, Fengxia; Gao, Xuelu; Song, Jinming; Chen, Chen-Tung Arthur; Yuan, Huamao; Xing, Qianguo

2018-05-01

The absorption properties of chromophoric dissolved organic matter (CDOM) in the East China Sea (ECS) and the waters off eastern Taiwan (WET) were studied during May 2014. CDOM absorption coefficient (a280) and spectral slope (S275-295) revealed considerable spatial variations. In the ECS, the values of a280 and S275-295 presented a reverse distribution pattern. In the WET, a280 values were generally low while S275-295 values were generally high. Vertical distributions of a280 and S275-295 also varied in different regions. Terrestrial input, phytoplankton production, sediment release or photobleaching may be responsible for the dynamics of CDOM. Relationships among CDOM related parameters could partly support this conclusion. a280 were also used to trace different water masses and the result showed that the influence of Changjiang Diluted Water could reach the outer shelf of the northern ECS, and that the Kuroshio Current had a strong influence on the middle shelf of the southern ECS.

Testing Women With Endometrial Cancer for Lynch Syndrome: Should We Test All?

PubMed Central

Ma, Jun; Ledbetter, Nancy; Glenn, Lyn

2013-01-01

Women with Lynch syndrome (LS) are at equal or higher risk for gynecologic cancers compared with their risk for colorectal cancer (CRC). Endometrial cancer (EC) often precedes CRC as patients’ sentinel malignancy. Identifying these patients is believed to reduce their substantial risk for synchronous and metachronous tumors and has profound implications for reducing cancer-related morbidity and mortality in other family members. Routine screening of patients with CRC for LS has become increasingly common, but routine screening for LS in women with EC is rarely performed. Current screening guidelines for identifying LS in women with EC vary but rely heavily on patient age and personal/family history, with or without incorporation of tumor pathology. Because each of these strategies misses a significant proportion of women with LS, more inclusive screening strategies that make good economic and clinical sense are needed. In recent years, emerging medicoeconomic evidence supports the fact that screening EC patients for LS may be cost-effective. Implementation of such a strategy requires multidisciplinary collaboration and partnership. PMID:25032011

Aerosol-jet-printed, 1 volt H-bridge drive circuit on plastic with integrated electrochromic pixel.

PubMed

Ha, Mingjing; Zhang, Wei; Braga, Daniele; Renn, Michael J; Kim, Chris H; Frisbie, C Daniel

2013-12-26

In this report, we demonstrate a printed, flexible, and low-voltage circuit that successfully drives a polymer electrochromic (EC) pixel as large as 4 mm(2) that is printed on the same substrate. All of the key components of the drive circuitry, namely, resistors, capacitors, and transistors, were aerosol-jet-printed onto a plastic foil; metallic electrodes and interconnects were the only components prepatterned on the plastic by conventional photolithography. The large milliampere drive currents necessary to switch a 4 mm(2) EC pixel were controlled by printed electrolyte-gated transistors (EGTs) that incorporate printable ion gels for the gate insulator layers and poly(3-hexylthiophene) for the semiconductor channels. Upon application of a 1 V input pulse, the circuit switches the printed EC pixel ON (red) and OFF (blue) two times in approximately 4 s. The performance of the circuit and the behavior of the individual resistors, capacitors, EGTs, and the EC pixel are analyzed as functions of the printing parameters and operating conditions.

Associations Between Parenting Styles and Perceived Child Effortful Control Within Chinese Families in the United States, the United Kingdom, and Taiwan

PubMed Central

Huang, Ching-Yu; Cheah, Charissa S. L.; Lamb, Michael E.; Zhou, Nan

2017-01-01

The current study examined the associations between parentally perceived child effortful control (EC) and the parenting styles of 122 Chinese mothers (36 first-generation Chinese immigrants in the United Kingdom, 40 first-generation Chinese immigrants in the United States, and 46 Taiwanese mothers) of 5- to 7-year-old (M age = 5.82 years, SD = .805; 68 boys and 54 girls) children. The findings showed significant cultural group differences in mothers’ reported authoritarian parenting style. Significant associations also emerged between mothers’ reports of their children’s EC and some parenting dimensions, although there were no cultural group differences in perceived child EC. Different patterns of associations between perceived child EC and parenting styles in these three groups also demonstrated heterogeneity within the Chinese population, and highlighted the need to consider differences between original and receiving societies when seeking to understand parenting and child development in different immigrant groups. PMID:29276309

Identification, quantification, and sensory characterization of steviol glycosides from differently processed Stevia rebaudiana commercial extracts.

PubMed

Espinoza, María Inés; Vincken, Jean-Paul; Sanders, Mark; Castro, Cristian; Stieger, Markus; Agosin, Eduardo

2014-12-10

Stevia rebaudiana is known for its sweet-tasting ent-kaurene diterpenoid glycosides. Several manufacturing strategies are currently employed to obtain Stevia sweeteners with the lowest possible off-flavors. The chemical composition of four commercial S. rebaudiana extracts, obtained by different technologies, was characterized using UHPLC-ESI-MS(n). The composition of one of the ethanol-crystallized extracts (EC2) was entirely rebaudioside A, whereas the enzymatically modified (EM) extract contained the lowest concentration of this compound (2.7 mg/100 mg). The membrane-purified (MP) extract had the highest content of minor natural steviol glycosides (23.7 mg/100 mg total extract) versus an average of 2.4 mg/100 mg total extract for the EC samples. Thirteen trained panelists evaluated sweetness, bitterness, licorice, and metallic attributes of all four extracts. The highest licorice intensity (p ≤ 0.05) was found for MP. Both samples EC1 and EC2, despite their different chemical compositions, showed no significant differences in sensory perception.

Associations Between Parenting Styles and Perceived Child Effortful Control Within Chinese Families in the United States, the United Kingdom, and Taiwan.

PubMed

Huang, Ching-Yu; Cheah, Charissa S L; Lamb, Michael E; Zhou, Nan

2017-07-01

The current study examined the associations between parentally perceived child effortful control (EC) and the parenting styles of 122 Chinese mothers (36 first-generation Chinese immigrants in the United Kingdom, 40 first-generation Chinese immigrants in the United States, and 46 Taiwanese mothers) of 5- to 7-year-old ( M age = 5.82 years, SD = .805; 68 boys and 54 girls) children. The findings showed significant cultural group differences in mothers' reported authoritarian parenting style. Significant associations also emerged between mothers' reports of their children's EC and some parenting dimensions, although there were no cultural group differences in perceived child EC. Different patterns of associations between perceived child EC and parenting styles in these three groups also demonstrated heterogeneity within the Chinese population, and highlighted the need to consider differences between original and receiving societies when seeking to understand parenting and child development in different immigrant groups.

Modeling drain current of indium zinc oxide thin film transistors prepared by solution deposition technique

NASA Astrophysics Data System (ADS)

Qiang, Lei; Liang, Xiaoci; Cai, Guangshuo; Pei, Yanli; Yao, Ruohe; Wang, Gang

2018-06-01

Indium zinc oxide (IZO) thin film transistor (TFT) deposited by solution method is of considerable technological interest as it is a key component for the fabrication of flexible and cheap transparent electronic devices. To obtain a principal understanding of physical properties of solution-processed IZO TFT, a new drain current model that account for the charge transport is proposed. The formulation is developed by incorporating the effect of gate voltage on mobility and threshold voltage with the carrier charges. It is demonstrated that in IZO TFTs the below threshold regime should be divided into two sections: EC - EF > 3kT and EC - EF ≤ 3kT, where kT is the thermal energy, EF and EC represent the Fermi level and the conduction band edge, respectively. Additionally, in order to describe conduction mechanisms more accurately, the extended mobility edge model is conjoined, which can also get rid of the complicated and lengthy computations. The good agreement between measured and calculated results confirms the efficiency of this model for the design of integrated large-area thin film circuits.

Nicotine is a potent blocker of the cardiac A-type K(+) channels. Effects on cloned Kv4.3 channels and native transient outward current.

PubMed

Wang, H; Shi, H; Zhang, L; Pourrier, M; Yang, B; Nattel, S; Wang, Z

2000-09-05

Nicotine is a main constituent of cigarette smoke and smokeless tobacco, known to increase the risk of sudden cardiac death. This study aimed at establishing ionic mechanisms underlying potential electrophysiological effects of nicotine. Effects of nicotine on Kv4.3 and Kv4.2 channels expressed in Xenopus oocytes were studied at the whole-cell and single-channel levels. The effects of nicotine on the transient outward K(+) current (I:(to)) were studied by use of whole-cell patch-clamp techniques in canine ventricular myocytes. Nicotine potently inhibited Kv4 current. The concentration for half-maximal inhibition (IC(50)) was 40+/-4 nmol/L, and the current was abolished by 100 micromol/L nicotine. The IC(50) for block of native I:(to) was 270+/-43 nmol/L. The steady-state activation properties of Kv4.3 and I:(to) were unaltered by nicotine, whereas positive shifts of the inactivation curves were observed. Of the total inhibition of Kv4.3 and I:(to) by nicotine, 40% was due to tonic block and 60% was attributable to use-dependent block. Activation, inactivation, and reactivation kinetics were not significantly changed by nicotine. Nicotine reduced single-channel conductance, open probability, and open time but increased the closed time of Kv4.3. The effects of nicotine were not altered by antagonists to various neurotransmitter receptors, indicating direct effects on I:(to) channels. Nicotine is a potent inhibitor of cardiac A-type K(+) channels, with blockade probably due to block of closed and open channels. This action may contribute to the ability of nicotine to affect cardiac electrophysiology and induce arrhythmias.

A mathematical model of the electrophysiological alterations in rat ventricular myocytes in type-I diabetes.

PubMed

Pandit, Sandeep V; Giles, Wayne R; Demir, Semahat S

2003-02-01

Our mathematical model of the rat ventricular myocyte (Pandit et al., 2001) was utilized to explore the ionic mechanism(s) that underlie the altered electrophysiological characteristics associated with the short-term model of streptozotocin-induced, type-I diabetes. The simulations show that the observed reductions in the Ca(2+)-independent transient outward K(+) current (I(t)) and the steady-state outward K(+) current (I(ss)), along with slowed inactivation of the L-type Ca(2+) current (I(CaL)), can result in the prolongation of the action potential duration, a well-known experimental finding. In addition, the model demonstrates that the slowed reactivation kinetics of I(t) in diabetic myocytes can account for the more pronounced rate-dependent action potential duration prolongation in diabetes, and that a decrease in the electrogenic Na(+)-K(+) pump current (I(NaK)) results in a small depolarization in the resting membrane potential (V(rest)). This depolarization reduces the availability of the Na(+) channels (I(Na)), thereby resulting in a slower upstroke (dV/dt(max)) of the diabetic action potential. Additional simulations suggest that a reduction in the magnitude of I(CaL), in combination with impaired sarcoplasmic reticulum uptake can lead to a decreased sarcoplasmic reticulum Ca(2+) load. These factors contribute to characteristic abnormal [Ca(2+)](i) homeostasis (reduced peak systolic value and rate of decay) in myocytes from diabetic animals. In combination, these simulation results provide novel information and integrative insights concerning plausible ionic mechanisms for the observed changes in cardiac repolarization and excitation-contraction coupling in rat ventricular myocytes in the setting of streptozotocin-induced, type-I diabetes.

Treatment and toxicity reduction of textile dyeing wastewater using the electrocoagulation-electroflotation process.

PubMed

Kim, Han-Lae; Cho, Jong-Bok; Park, Yong-Jin; Cho, Il-Hyoung

2016-07-02

A pilot-scale study was conducted using the electrocoagulation-electroflotation (EC-EF) process to treat textile dyeing raw wastewater to evaluate treatment performance. The effects of some key factors, such as current density, hydraulic retention time (HRT), and removal of conductivity, total suspended solids (TSS), chemical oxygen demand (COD), and color were investigated. The operating variables were current density of 0-300 A m(-2), HRT of 0-30 min, and a coagulant (anionic polyacrylamide (A-PAM)) dosage of 0-30 mg L(-1). Daphnia magna was used to test acute toxicity in raw and treated wastewater. Under the operating conditions without added coagulant, maxima of 51%, 88%, 84%, and 99% of conductivity, TSS, COD, and color were removed, respectively, with a HRT of 30 min. The coagulant enhanced removal of all wastewater parameters. Removal maxima of 59%, 92%, 94%, and 98% for conductivity, TSS, COD, and color were observed, respectively, with an optimal dosage of 30 mg L(-1) and a shortened HRT of 20 min. The 48 h-LC50 D. magna test showed that the raw wastewater was highly toxic. However, the EC-EF process decreased toxicity of the treated samples significantly, and >70% toxicity reduction was achieved by the EC-EF process with the addition of 15-30 mg L(-1) coagulant, HRT of 20 min, and current density of 150-300 A m(-2). The pilot scale test (0.3 m(3 )h(-1)) shows that the EC-EF process with added coagulant effectively treated textile dyeing wastewater.

Outward Bound Goes to the Inner City.

ERIC Educational Resources Information Center

Buchanan, David

1993-01-01

A program at the Thompson Island Outward Bound Education Center in Boston (Massachusetts) supplements the traditional program of ropes and rocks with community service, giving urban students opportunities to try out new leadership skills in local neighborhoods. (MLF)

Fading Away

NASA Image and Video Library

2009-06-09

This NAC image from MESSENGER’s second Mercury flyby shows a crater with a set of light-colored rays radiating outward from it. Such rays are formed when an impact excavates material from below the surface and throws it outward from the crater.

Effect of thiopental sodium on N-methyl-D-aspartate-gated currents.

PubMed

Liu, Hongliang; Dai, Tijun; Yao, Shanglong

2006-05-01

N-methyl-D-aspartate (NMDA) receptors in the prefrontal cortex (PFC) are closely related with the excitability of pyramidal neurons and PFC function. As the effect of thiopental sodium on the central nervous system may partly result from the inhibition of PFC NMDA receptors, we investigated the effect of thiopental sodium with different concentrations on NMDA-gated currents in acutely dissociated rat PFC pyramidal neurons. We sought to determine whether thiopental sodium inhibits NMDA receptor function. Three to four week old male Sprague-Dawley rats were sacrificed and the PFC was dissected. Pyramidal neurons from the PFC were prepared and standard whole-cell patch clamp recordings were performed. Escalating concentrations from 3-1000 microM NMDA were applied 100 microm from the pyramidal cells, and the concentration in the effect compartment related to 50% effect (EC50) of NMDA was determined for the ensuing experiments. One hundred microM NMDA alone (control) or NMDA with different concentrations (10-1000 microM) of thiopental sodium were applied. After the inhibitory concentration, in 50% of NMDA effect (IC50) of thiopental sodium was established this IC50 and NMDA 3-1000 microM were applied 100 microm from the pyramidal cells. The EC50 value of NMDA under the effect of IC50 thiopental sodium was determined. N-methyl-D-aspartate induced inward currents in a concentration-dependent manner, which were completely antagonized by 50 microM AP5. The maximal amplitude of NMDA-induced current was 1.15 +/- 0.27 nA. The EC50 of NMDA was 53.6 +/- 12.4 microM. The NMDA (100 microM)-gated current was inhibited by thiopental sodium in a concentration-dependent manner, and the IC50 of thiopental sodium was 33.6 +/- 6.1 microM. Under the effect of 33.6 microM thiopental sodium, the maximal amplitude of NMDA-induced current was 0.87 +/- 0.17 nA. The concentration-response curve of NMDA was shifted rightwards. The EC50 of NMDA was 128 +/- 15 microM, which was greater than that of NMDA without thiopental sodium (P < 0.01). Thiopental sodium decreases NMDA-gated currents in acutely dissociated rat prefrontal cortical pyramidal neurons in a concentration-dependent manner.

Original non-stationary eddy current imaging process for the evaluation of defects in metallic structures

NASA Astrophysics Data System (ADS)

Placko, Dominique; Bore, Thierry; Rivollet, Alain; Joubert, Pierre-Yves

2015-10-01

This paper deals with the problem of imaging defects in metallic structures through eddy current (EC) inspections, and proposes an original process for a possible tomographical crack evaluation. This process is based on a semi analytical modeling, called "distributed point source method" (DPSM) which is used to describe and equate the interactions between the implemented EC probes and the structure under test. Several steps will be successively described, illustrating the feasibility of this new imaging process dedicated to the quantitative evaluation of defects. The basic principles of this imaging process firstly consist in creating a 3D grid by meshing the volume potentially inspected by the sensor. As a result, a given number of elemental volumes (called voxels) are obtained. Secondly, the DPSM modeling is used to compute an image for all occurrences in which only one of the voxels has a different conductivity among all the other ones. The assumption consists to consider that a real defect may be truly represented by a superimposition of elemental voxels: the resulting accuracy will naturally depend on the density of space sampling. On other hand, the excitation device of the EC imager has the capability to be oriented in several directions, and driven by an excitation current at variable frequency. So, the simulation will be performed for several frequencies and directions of the eddy currents induced in the structure, which increases the signal entropy. All these results are merged in a so-called "observation matrix" containing all the probe/structure interaction configurations. This matrix is then used in an inversion scheme in order to perform the evaluation of the defect location and geometry. The modeled EC data provided by the DPSM are compared to the experimental images provided by an eddy current imager (ECI), implemented on aluminum plates containing some buried defects. In order to validate the proposed inversion process, we feed it with computed images of various acquisition configurations. Additive noise was added to the images so that they are more representative of actual EC data. In the case of simple notch type defects, for which the relative conductivity may only take two extreme values (1 or 0), a threshold was introduced on the inverted images, in a post processing step, taking advantage of a priori knowledge of the statistical properties of the restored images. This threshold allowed to enhance the image contrast and has contributed to eliminate both the residual noise and the pixels showing non-realistic values.

Demonstration of current drive by a rotating magnetic dipole field

NASA Astrophysics Data System (ADS)

Giersch, L.; Slough, J. T.; Winglee, R.

2007-04-01

Abstract.A dipole-like rotating magnetic field was produced by a pair of circular, orthogonal coils inside a metal vacuum chamber. When these coils were immersed in plasma, large currents were driven outside the coils: the currents in the plasma were generated and sustained by the rotating magnetic dipole (RMD) field. The peak RMD-driven current was at roughly two RMD coil radii, and this current (60 kA m-) was sufficient to reverse the ambient magnetic field (33 G). Plasma density, electron temperature, magnetic field and current probes indicated that plasma formed inside the coils, then expanded outward until the plasma reached equilibrium. This equilibrium configuration was adequately described by single-fluid magnetohydrodynamic equilibrium, wherein the cross product of the driven current and magnetic filed was approximately equal to the pressure gradient. The ratio of plasma pressure to magnetic field pressure, β, was locally greater than unity.

Separation of the pace-maker and plateau components of delayed rectification in cardiac Purkinje fibres

PubMed Central

Hauswirth, O.; Noble, D.; Tsien, R. W.

1972-01-01

1. Experiments on sheep Purkinje fibres were designed to determine whether the current mechanisms responsible for delayed rectification at the pace-maker (negative to -50 mV) and plateau (positive to -50 mV) ranges of potential are kinetically separable and independent. 2. Hyperpolarizations from the plateau range were shown to produce decay of a single component of outward current within the plateau range, but two components were evident when the hyperpolarizations entered the pace-maker range. 3. The time courses of recovery of the two components were too similar at -25 mV to allow temporal resolution at this potential. Clear temporal resolution was, however, possible at potentials between -55 and -95 mV. An indirect method of resolving the two components at -25 mV was used. 4. The kinetic properties of the two components correspond to those previously described for the pace-maker potassium current, iK2, and the outward plateau current, ix1 (Noble & Tsien, 1968, 1969a). 5. The instantaneous (fully activated) current—voltage relation for iK2 was reconstructed from the analysed current records. It was found that this relation shows a negative slope conductance at all potentials positive to -75 mV and that the current tends towards zero at zero membrane potential. 6. The results are compared with those predicted by two reaction models of the iK2 and ix1 mechanisms. It is concluded that iK2 and ix1 are kinetically separable but that it is not possible with present techniques to decide whether they are controlled by the same or completely independent membrane structures. It is also shown that the instantaneous current—voltage relation calculated for iK2 does not depend on whether the controlling mechanisms are assumed to be independent or linked. PMID:4679715

Addressing Water Consumption of Evaporative Coolers with Greywater

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

Sahai, Rashmi; Shah, Nihar; Phadke, Amol

Evaporative coolers (ECs) provide significant gains in energy efficiency compared to vapor compression air conditioners, but simultaneously have significant onsite water demand. This can be a major barrier to deployment in areas of the world with hot and arid climates. To address this concern, this study determined where in the world evaporative cooling is suitable, the water consumption of ECs in these cities, and the potential that greywater can be used reduce the consumption of potable water in ECs. ECs covered 69percent of the cities where room air conditioners are may be deployed, based on comfort conditions alone. The averagemore » water consumption due to ECs was found to be 400 L/household/day in the United States and Australia, with the potential for greywater to provide 50percent this amount. In the rest of the world, the average water consumption was 250 L/household/day, with the potential for greywater to supply 80percent of this amount. Home size was the main factor that contributed to this difference. In the Mediterranean, the Middle East, Northern India, and the Midwestern and Southwestern United States alkalinity levels are high and water used for bleeding will likely contribute significantly to EC water consumption. Although technically feasible, upfront costs for household GW systems are currently high. In both developed and developing parts of the world, however, a direct EC and GW system is cost competitive with conventional vapor compression air conditioners. Moreover, in regions of the world that face problems of water scarcity the benefits can substantially outweigh the costs.« less

Evaluating Emergent Constraints for Equilibrium Climate Sensitivity

DOE PAGES

Caldwell, Peter M.; Zelinka, Mark D.; Klein, Stephen A.

2018-04-23

Emergent constraints are quantities that are observable from current measurements and have skill predicting future climate. Here, this study explores 19 previously proposed emergent constraints related to equilibrium climate sensitivity (ECS; the global-average equilibrium surface temperature response to CO 2 doubling). Several constraints are shown to be closely related, emphasizing the importance for careful understanding of proposed constraints. A new method is presented for decomposing correlation between an emergent constraint and ECS into terms related to physical processes and geographical regions. Using this decomposition, one can determine whether the processes and regions explaining correlation with ECS correspond to the physicalmore » explanation offered for the constraint. Shortwave cloud feedback is generally found to be the dominant contributor to correlations with ECS because it is the largest source of intermodel spread in ECS. In all cases, correlation results from interaction between a variety of terms, reflecting the complex nature of ECS and the fact that feedback terms and forcing are themselves correlated with each other. For 4 of the 19 constraints, the originally proposed explanation for correlation is borne out by our analysis. These four constraints all predict relatively high climate sensitivity. The credibility of six other constraints is called into question owing to correlation with ECS coming mainly from unexpected sources and/or lack of robustness to changes in ensembles. Another six constraints lack a testable explanation and hence cannot be confirmed. Lastly, the fact that this study casts doubt upon more constraints than it confirms highlights the need for caution when identifying emergent constraints from small ensembles.« less

An active learning approach for rapid characterization of endothelial cells in human tumors.

PubMed

Padmanabhan, Raghav K; Somasundar, Vinay H; Griffith, Sandra D; Zhu, Jianliang; Samoyedny, Drew; Tan, Kay See; Hu, Jiahao; Liao, Xuejun; Carin, Lawrence; Yoon, Sam S; Flaherty, Keith T; Dipaola, Robert S; Heitjan, Daniel F; Lal, Priti; Feldman, Michael D; Roysam, Badrinath; Lee, William M F

2014-01-01

Currently, no available pathological or molecular measures of tumor angiogenesis predict response to antiangiogenic therapies used in clinical practice. Recognizing that tumor endothelial cells (EC) and EC activation and survival signaling are the direct targets of these therapies, we sought to develop an automated platform for quantifying activity of critical signaling pathways and other biological events in EC of patient tumors by histopathology. Computer image analysis of EC in highly heterogeneous human tumors by a statistical classifier trained using examples selected by human experts performed poorly due to subjectivity and selection bias. We hypothesized that the analysis can be optimized by a more active process to aid experts in identifying informative training examples. To test this hypothesis, we incorporated a novel active learning (AL) algorithm into FARSIGHT image analysis software that aids the expert by seeking out informative examples for the operator to label. The resulting FARSIGHT-AL system identified EC with specificity and sensitivity consistently greater than 0.9 and outperformed traditional supervised classification algorithms. The system modeled individual operator preferences and generated reproducible results. Using the results of EC classification, we also quantified proliferation (Ki67) and activity in important signal transduction pathways (MAP kinase, STAT3) in immunostained human clear cell renal cell carcinoma and other tumors. FARSIGHT-AL enables characterization of EC in conventionally preserved human tumors in a more automated process suitable for testing and validating in clinical trials. The results of our study support a unique opportunity for quantifying angiogenesis in a manner that can now be tested for its ability to identify novel predictive and response biomarkers.

Evaluating Emergent Constraints for Equilibrium Climate Sensitivity

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

Caldwell, Peter M.; Zelinka, Mark D.; Klein, Stephen A.

Emergent constraints are quantities that are observable from current measurements and have skill predicting future climate. Here, this study explores 19 previously proposed emergent constraints related to equilibrium climate sensitivity (ECS; the global-average equilibrium surface temperature response to CO 2 doubling). Several constraints are shown to be closely related, emphasizing the importance for careful understanding of proposed constraints. A new method is presented for decomposing correlation between an emergent constraint and ECS into terms related to physical processes and geographical regions. Using this decomposition, one can determine whether the processes and regions explaining correlation with ECS correspond to the physicalmore » explanation offered for the constraint. Shortwave cloud feedback is generally found to be the dominant contributor to correlations with ECS because it is the largest source of intermodel spread in ECS. In all cases, correlation results from interaction between a variety of terms, reflecting the complex nature of ECS and the fact that feedback terms and forcing are themselves correlated with each other. For 4 of the 19 constraints, the originally proposed explanation for correlation is borne out by our analysis. These four constraints all predict relatively high climate sensitivity. The credibility of six other constraints is called into question owing to correlation with ECS coming mainly from unexpected sources and/or lack of robustness to changes in ensembles. Another six constraints lack a testable explanation and hence cannot be confirmed. Lastly, the fact that this study casts doubt upon more constraints than it confirms highlights the need for caution when identifying emergent constraints from small ensembles.« less

Solar absorption by elemental and brown carbon determined from spectral observations.

PubMed

Bahadur, Ranjit; Praveen, Puppala S; Xu, Yangyang; Ramanathan, V

2012-10-23

Black carbon (BC) is functionally defined as the absorbing component of atmospheric total carbonaceous aerosols (TC) and is typically dominated by soot-like elemental carbon (EC). However, organic carbon (OC) has also been shown to absorb strongly at visible to UV wavelengths and the absorbing organics are referred to as brown carbon (BrC), which is typically not represented in climate models. We propose an observationally based analytical method for rigorously partitioning measured absorption aerosol optical depths (AAOD) and single scattering albedo (SSA) among EC and BrC, using multiwavelength measurements of total (EC, OC, and dust) absorption. EC is found to be strongly absorbing (SSA of 0.38) whereas the BrC SSA varies globally between 0.77 and 0.85. The method is applied to the California region. We find TC (EC + BrC) contributes 81% of the total absorption at 675 nm and 84% at 440 nm. The BrC absorption at 440 nm is about 40% of the EC, whereas at 675 nm it is less than 10% of EC. We find an enhanced absorption due to OC in the summer months and in southern California (related to forest fires and secondary OC). The fractions and trends are broadly consistent with aerosol chemical-transport models as well as with regional emission inventories, implying that we have obtained a representative estimate for BrC absorption. The results demonstrate that current climate models that treat OC as nonabsorbing are underestimating the total warming effect of carbonaceous aerosols by neglecting part of the atmospheric heating, particularly over biomass-burning regions that emit BrC.

[The modification of electrophysiology affected by ectopic synapse in ON-retinal bipolar cells of RCS rats].

PubMed

Zhang, Chen-xing; Yin, Zheng-qin; Weng, Chuan-huang; Zeng, Yu-xiao

2011-03-01

To study the influence of the ectopic synapse for electrophysiological characteristics modification in ON retinal bipolar cells (ON-RBCs) of RCS rat. Immunofluorescence of the retinal frozen section was taken in P60 d, P90 d of RCS rat (RCS) and control rat (CTR) with the anti-mGluR6 and anti-Synaptophysin, Lucifer Yellow staining solo ON-RBCs was taken in all the group. The whole cell recording was performed in the retinal slice of P60 d, P90 d in RCS and CTR. The modification of the passive membrane properties and the outward currents properties in RCS-ON-RBCs, CTR-ON-RBCs and CTR-OFF-RBCs were observed. RCS-ON-RBCs stretched out the ectopic neurite in different direction and the activity of synapse could be detected around the ectopic neurite. From Pn60d, passive membrane properties of RCS-ON-RBCs kept immature, The RMP in RCS-ON-RBCs and CTR-ON-RBCs were (-61.8 ± 3.07), (-50.44 ± 1.36) mV and (-63.1 ± 2.59), (-48.37 ± 3.69) mV when P60 d and P90 d, there ware significantly higher than CTR group (t = 2.191, 2.435, 5.817, 6.912;P < 0.05). The IR in RCS-ON-RBCs and CTR-ON-RBCs were (323.3 ± 42.6), (337.6 ± 71.3) MΩ and (321.2 ± 58.6), (340.3 ± 62.8) MΩ when P60 d and P90 d, there ware significantly higher than CTR group (t = 3.561, 1.987, 5.211, 4.034; P < 0.05). Outward currents were recorded when giving hyper- and depolarized voltage steps. In retinal degeneration, the amplitude of outward currents in RCS-ON-RBCs is significantly different with CTR-ON-RBCs (t = 5.561, 6.341; P < 0.05) or CTR-OFF-RBCs (t = 5.357, 6.997; P < 0.05). The ectopic neurite from RCS-ON-RBCs has the possibility for translating the signal. In retinitis pigmentosa, the modification of electrophysiology characteristics in RCS-ON-RBCs was significantly different with CTR-ON-RBCs and CTR-OFF-RBCs. Influence with the ectopic neurite is the possible cause.

Can extracapsular lymph node involvement be a tool to fine-tune pN1 for adenocarcinoma of the oesophagus and gastro-oesophageal junction in the Union Internationale contre le Cancer (UICC) TNM 7th edition?†.

PubMed

Nafteux, Philippe; Lerut, Toni; De Hertogh, Gert; Moons, Johnny; Coosemans, Willy; Decker, Georges; Van Veer, Hans; De Leyn, Paul

2014-06-01

The current (7th) International Union Against Cancer (UICC) pN staging system is based on the number of positive lymph nodes but does not take into consideration the characteristics of the metastatic lymph nodes itself. In particular, it has been suggested that tumour penetration beyond the lymph node capsule in metastatic lymph nodes, which is also called extracapsular lymph node involvement, has a prognostic impact. The aim of the current study was to assess the prognostic value of extracapsular (EC) and intracapsular (IC) lymph node involvement (LNI) in adenocarcinoma of the oesophagus and gastro-oesophageal junction (GOJ) and to assess its potential impact on the 7th edition of the UICC TNM manual. From 2000 to 2010, all consecutive adenocarcinoma patients with primary R0-resection (n = 499) were prospectively included for analysis. The number of resected lymph nodes, number of positive lymph nodes and number of EC-LNI/IC-LNI were determined. Extracapsular spread was defined as infiltration of cancer cells beyond the capsule of the positive lymph node. Two hundred and eighteen (43%) patients had positive lymph nodes. Cancer-specific 5-year survival in lymph node-positive patients was significantly (P < 0.0001) worse compared with lymph node-negative patients, being 88.3 vs 28.7%, respectively. In 128 (58.7%) cases EC-LNI was detected. EC-LNI showed significantly worse cancer-specific 5-year survival compared with IC-LNI, 19.6 vs 44.0% (P < 0.0001). In the pN1 category (1 or 2 positive LN's-UICC stages IIB and IIIA), this was 30.4% vs 58%; (P = 0.029). In higher pN categories, this effect was no longer noticed. Integrating these findings into an adapted TNM classification resulted in improved homogeneity, monotonicity of gradients and discriminatory ability indicating an improved performance of the staging system. EC-LNI is associated with worse survival compared with IC-LNI. EC-LNI patients show survival rates that are more closely associated with the current TNM stage IIIB, while IC-LNI patients have a survival more similar to TNM stage IIB. Incorporating the EC-IC factor in the TNM classification results in an increased performance of the TNM model. Further confirmation from other centres is required within the context of future adaptations of the UICC/AJCC (American Joint Committee on Cancer) staging system for oesophageal cancer. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Comparing the sensitivity of chlorophytes, cyanobacteria, and diatoms to major-use antibiotics.

PubMed

Guo, Jiahua; Selby, Katherine; Boxall, Alistair B A

2016-10-01

The occurrence of antibiotic residues in the aquatic environment is an emerging concern. In contrast to daphnia and fish, algae are known to be particularly sensitive to antibiotic exposure. However, to date, a systematic evaluation of the sensitivity of different algal species to antibiotics has not been performed. The aim of the present study was therefore to explore the sensitivity of a battery of algal species toward antibiotic exposures. The present study investigated the growth inhibition effects of 3 major-use antibiotics, tylosin, lincomycin, and trimethoprim, on 7 algal species from the chlorophyte, cyanobacteria, and diatom groups. Based on median effective concentration (EC50) values, cyanobacteria (EC50 = 0.095-0.13 μmol/L) were found to be the most sensitive group to lincomycin followed by chlorophytes (EC50 = 7.36-225.73 μmol/L) and diatoms (EC50 > 225.73 μmol/L). Cyanobacteria were also the most sensitive group to tylosin (EC50 = 0.09-0.092 μmol/L), but, for this compound, diatoms (EC50 = 1.33-5.7 μmol/L) were more sensitive than chlorophytes (EC50 = 4.14-81.2 μmol/L). Diatoms were most sensitive to trimethoprim (EC50 = 7.36-74.61 μmol/L), followed by cyanobacteria (EC50 = 315.78-344.45 μmol/L), and chlorophytes (EC50 > 344.45 μmol/L) for trimethoprim. Although these results partly support the current approach to regulatory environmental risk assessment (whereby cyanobacterial species are recommended for use with antibiotic compounds), they indicate that for some antibiotics this group might not be the most appropriate test organism. It is therefore suggested that environmental risk assessments consider data on 3 algal groups (chlorophytes, cyanobacteria, and diatoms) and use test species from these groups, which are consistently found to be the most sensitive (Pseudokirchneriella subcapitata, Anabaena flos-aquae, and Navicula pelliculosa). Environ Toxicol Chem 2016;35:2587-2596. © 2016 SETAC. © 2016 SETAC.

Increasing Type 1 Poliovirus Capsid Stability by Thermal Selection

PubMed Central

Adeyemi, Oluwapelumi O.; Nicol, Clare

2016-01-01

ABSTRACT Poliomyelitis is a highly infectious disease caused by poliovirus (PV). It can result in paralysis and may be fatal. Integrated global immunization programs using live-attenuated oral (OPV) and/or inactivated (IPV) PV vaccines have systematically reduced its spread and paved the way for eradication. Immunization will continue posteradication to ensure against reintroduction of the disease, but there are biosafety concerns for both OPV and IPV. They could be addressed by the production and use of virus-free virus-like particle (VLP) vaccines that mimic the “empty” capsids (ECs) normally produced in viral infection. Although ECs are antigenically indistinguishable from mature virus particles, they are less stable and readily convert into an alternative conformation unsuitable for vaccine purposes. Stabilized ECs, expressed recombinantly as VLPs, could be ideal candidate vaccines for a polio-free world. However, although genome-free PV ECs have been expressed as VLPs in a variety of systems, their inherent antigenic instability has proved a barrier to further development. In this study, we selected thermally stable ECs of type 1 PV (PV-1). The ECs are antigenically stable at temperatures above the conversion temperature of wild-type (wt) virions. We have identified mutations on the capsid surface and in internal networks that are responsible for EC stability. With reference to the capsid structure, we speculate on the roles of these residues in capsid stability and postulate that such stabilized VLPs could be used as novel vaccines. IMPORTANCE Poliomyelitis is a highly infectious disease caused by PV and is on the verge of eradication. There are biosafety concerns about reintroduction of the disease from current vaccines that require live virus for production. Recombinantly expressed virus-like particles (VLPs) could address these inherent problems. However, the genome-free capsids (ECs) of wt PV are unstable and readily change antigenicity to a form not suitable as a vaccine. Here, we demonstrate that the ECs of type 1 PV can be stabilized by selecting heat-resistant viruses. Our data show that some capsid mutations stabilize the ECs and could be applied as candidates to synthesize stable VLPs as future genome-free poliovirus vaccines. PMID:27928008

A slow calcium-dependent component of charge movement in Rana temporaria cut twitch fibres.

PubMed

Hui, C S

1998-06-15

1. Charge movement was studied in highly stretched frog cut twitch fibres in a double Vaseline-gap voltage-clamp chamber, with the internal solution containing either 0.1 mM EGTA or 20 mM EGTA plus 1. 8 mM total Ca2+. 2. Fibres were stimulated with TEST pulses lasting 100-400 ms. Replacement of the external Cl- with an 'impermeant' anion, such as SO42-, CH3SO3-, gluconate or glutamate, greatly reduced the calcium-dependent Cl- current in the ON segment and generated a slowly decaying inward OFF current in charge movement traces. 3. Application of 20 mM EGTA to the internal solution abolished the slow inward OFF current, implying that the activation of the current depended on the presence of Ca2+ in the myoplasm. The possibility that the slow inward OFF current was carried by cations flowing inwards or anions flowing outwards was studied and determined to be unlikely. 4. During a long (2000 ms) TEST pulse, a slowly decaying ON current was also observed. When the slow ON and OFF currents were included as parts of the total charge movement, ON-OFF charge equality was preserved. This slow capacitive current is named Idelta. 5. When Cl- was the major anion in the external solution, the OFF Idelta was mostly cancelled by a slow outward current carried by the inflow of Cl-. 6. The OFF Idelta component showed a rising phase. The average values of the rising time constants in CH3SO3- and SO42- were similar and about half of that in gluconate. 7. The OFF Idelta component in CH3SO3- had a larger magnitude and longer time course than that in SO42-. The maximum amount of Qdelta in CH3SO3- was about three times as much as that in SO42-, whereas the voltage dependence of Qdelta was similar in the two solutions. 8. Since the existence of Qdelta depends on the presence of Ca2+ in the myoplasm, it is speculated that Qdelta could be a function of intracellular calcium release.

Distribution, expression and functional effects of small conductance Ca-activated potassium (SK) channels in rat myometrium.

PubMed

Noble, Karen; Floyd, Rachel; Shmygol, Andre; Shmygol, Anatoly; Mobasheri, A; Wray, Susan

2010-01-01

Calcium-activated potassium channels are important in a variety of smooth muscles, contributing to excitability and contractility. In the myometrium previous work has focussed on the large conductance channels (BK), and the role of small conductance channels (SK) has received scant attention, despite the finding that over-expression of an SK channel isoform (SK3) results in uterine dysfunction and delayed parturition. This study therefore characterises the expression of the three SK channel isoforms (SK1-3) in rat myometrium throughout pregnancy and investigates their effect on cytosolic [Ca] and force and compares this with that of BK channels. Consistent expression of all SK isoform transcripts and clear immunostaining of SK1-3 was found. Inhibition of SK1-3 channels (apamin, scyllatoxin) significantly inhibited outward current, caused membrane depolarisation and elicited action potentials in previously quiescent cells. Apamin or scyllatoxin increased the amplitude of [Ca] and force in spontaneously contracting myometrial strips throughout gestation. The functional effect of SK inhibition was larger than that of BK channel inhibition. Thus we show for the first time that SK1-3 channels are expressed and translated throughout pregnancy and contribute to outward current, regulate membrane potential and hence Ca signals in pregnant rat myometrium. They contribute more to quiescence that BK channels. 2009 Elsevier Ltd. All rights reserved.

Development of a current sheet in the wake of a fast coronal mass ejection

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

Ling, A. G.; Webb, D. F.; Burkepile, J. T.

2014-04-01

A bright ray that developed in the wake of a fast coronal mass ejection (CME) on 2005 September 7 presents a unique opportunity to study the early development and physical characteristics of a reconnecting current sheet (CS). Polarization brightness images from the Mk4 K-Coronameter at the Mauna Loa Solar Observatory are used to determine the structure of the ray along its axis low in the corona as it progressed outward. Coverage of the early development of the ray out to ∼1.3 R {sub ☉} for a period of ∼27 hr after the start of the event enables for the firstmore » time in white light a measurement of a CME CS from the top of the arcade to the base of the flux rope. Measured widths of the ray are combined to obtain the kinematics of the upper and lower {sup Y-}points described in reconnection flux-rope models such as that of Lin and Forbes. The time dependence of these points are used to derive values for the speed and acceleration of the growth of the CS. We note the appearance of a large structure which increases in size as it expands outward in the early development of the ray and an apparent oscillation with a period of ∼0.5 hr in the position angle of the ray.« less

Mefenamic acid bi-directionally modulates the transient outward K{sup +} current in rat cerebellar granule cells

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

Zhang Man; Shi Wenjie; Fei Xiaowei

2008-02-01

The effect of non-steroidal anti-inflammatory drugs (NSAIDs) on ion channels has been widely studied in several cell models, but less is known about their modulatory mechanisms. In this report, the effect of mefenamic acid on voltage-activated transient outward K{sup +} current (I{sub A}) in cultured rat cerebellar granule cells was investigated. At a concentration of 5 {mu}M to 100 {mu}M, mefenamic acid reversibly inhibited I{sub A} in a dose-dependent manner. However, mefenamic acid at a concentration of 1 {mu}M significantly increased the amplitude of I{sub A} to 113 {+-} 1.5% of the control. At more than 10 {mu}M, mefenamic acidmore » inhibited the amplitude of I{sub A} without any effect on activation or inactivation. In addition, a higher concentration of mefenamic acid induced a significant acceleration of recovery from inactivation with an increase of the peak amplitude elicited by the second test pulse. Intracellular application of mefenamic acid could significantly increase the amplitude of I{sub A}, but had no effect on the inhibition induced by extracellular mefenamic acid, implying that mefenamic acid may exert its effect from both inside and outside the ion channel. Furthermore, the activation of current induced by intracellular application of mefenamic acid was mimicked by other cyclooxygenase inhibitors and arachidonic acid. Our data demonstrate that mefenamic acid is able to bi-directionally modulate I{sub A} channels in neurons at different concentrations and by different methods of application, and two different mechanisms may be involved.« less

Neurovascular coupling protects neurons against hypoxic injury via inhibition of potassium currents by generation of nitric oxide in direct neuron and endothelium cocultures.

PubMed

Wu, Kun-Wei; Kou, Zeng-Wei; Mo, Jia-Lin; Deng, Xu-Xu; Sun, Feng-Yan

2016-10-15

This study examined the effect of neuron-endothelial coupling on the survival of neurons after ischemia and the possible mechanism underlying that effect. Whole-cell patch-clamp experiments were performed on cortical neurons cultured alone or directly cocultured with brain microvascular endothelial cells (BMEC). Propidium iodide (PI) and NeuN staining were performed to examine neuronal death following oxygen and glucose deprivation (OGD). We found that the neuronal transient outward potassium currents (I A ) decreased in the coculture system, whereas the outward delayed-rectifier potassium currents (I K ) did not. Sodium nitroprusside, a NO donor, enhanced BMEC-induced I A inhibition and nitro-l-arginine methylester, a NOS inhibitor, partially prevented this inhibition. Moreover, the neurons directly cocultured with BMEC showed more resistance to OGD-induced injury compared with the neurons cultured alone, and that neuroprotective effect was abolished by treatment with NS5806, an activator of the I A . These results indicate that vascular endothelial cells assist neurons to prevent hypoxic injury via inhibiting neuronal I A by production of NO in the direct neuron-BMEC coculture system. These results further provide direct evidence of functional coupling between neurons and vascular endothelial cells. This study clearly demonstrates that vascular endothelial cells play beneficial roles in the pathophysiological processes of neurons after hypoxic injury, suggesting that the improvement of neurovascular coupling or functional remodeling may become an important therapeutic target for preventing brain injury. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Endothelial cells: From innocent bystanders to active participants in immune responses.

PubMed

Al-Soudi, A; Kaaij, M H; Tas, S W

2017-09-01

The endothelium is crucially important for the delivery of oxygen and nutrients throughout the body under homeostatic conditions. However, it also contributes to pathology, including the initiation and perpetuation of inflammation. Understanding the function of endothelial cells (ECs) in inflammatory diseases and molecular mechanisms involved may lead to novel approaches to dampen inflammation and restore homeostasis. In this article, we discuss the various functions of ECs in inflammation with a focus on pathological angiogenesis, attraction of immune cells, antigen presentation, immunoregulatory properties and endothelial-to-mesenchymal transition (EndMT). We also review the current literature on approaches to target these processes in ECs to modulate immune responses and advance anti-inflammatory therapies. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Evolutionary Technologies: Fundamentals and Applications to Information/Communication Systems and Manufacturing/Logistics Systems

NASA Astrophysics Data System (ADS)

Gen, Mitsuo; Kawakami, Hiroshi; Tsujimura, Yasuhiro; Handa, Hisashi; Lin, Lin; Okamoto, Azuma

As efficient utilization of computational resources is increasing, evolutionary technology based on the Genetic Algorithm (GA), Genetic Programming (GP), Evolution Strategy (ES) and other Evolutionary Computations (ECs) is making rapid progress, and its social recognition and the need as applied technology are increasing. This is explained by the facts that EC offers higher robustness for knowledge information processing systems, intelligent production and logistics systems, most advanced production scheduling and other various real-world problems compared to the approaches based on conventional theories, and EC ensures flexible applicability and usefulness for any unknown system environment even in a case where accurate mathematical modeling fails in the formulation. In this paper, we provide a comprehensive survey of the current state-of-the-art in the fundamentals and applications of evolutionary technologies.

The Cosmic Battery in Astrophysical Accretion Disks

NASA Astrophysics Data System (ADS)

Contopoulos, Ioannis; Nathanail, Antonios; Katsanikas, Matthaios

2015-06-01

The aberrated radiation pressure at the inner edge of the accretion disk around an astrophysical black hole imparts a relative azimuthal velocity on the electrons with respect to the ions which gives rise to a ring electric current that generates large-scale poloidal magnetic field loops. This is the Cosmic Battery established by Contopoulos and Kazanas in 1998. In the present work we perform realistic numerical simulations of this important astrophysical mechanism in advection-dominated accretion flows, ADAFs. We confirm the original prediction that the inner parts of the loops are continuously advected toward the central black hole and contribute to the growth of the large-scale magnetic field, whereas the outer parts of the loops are continuously diffusing outward through the turbulent accretion flow. This process of inward advection of the axial field and outward diffusion of the return field proceeds all the way to equipartition, thus generating astrophysically significant magnetic fields on astrophysically relevant timescales. We confirm that there exists a critical value of the magnetic Prandtl number between unity and 10 in the outer disk above which the Cosmic Battery mechanism is suppressed.

Implementation of a transcutaneous charger for fully implantable middle ear hearing device.

PubMed

Lim, H; Yoon, Y; Lee, C; Park, I; Song, B; Cho, J

2005-01-01

A transcutaneous charger for the fully implantable middle ear hearing device (F-IMEHD), which can monitor the charging level of battery, has been designed and implemented. In order to recharge the battery of F-IMEHD, the electromagnetic coupling between primary coil at outer body and secondary coil at inner body has been used. Considering the implant condition of the F-IMEHD, the primary coil and the secondary coil have been designed. Using the resonance of LC tank circuit at each coil, transmission efficiency was increased. Since the primary and the secondary coil are magnetically coupled, the current variation of the primary coil is related with the impedance of internal resonant circuit. Using the principle mentioned above, the implanted module could transmit outward the information about charging state of battery or coupling between two coils by the changing internal impedance. As in the demonstrated results of experiment, the implemented charger has supplied the sufficient operating voltage for the implanted battery within about 10 mm distance. And also, it has been confirmed that the implanted module can transmit information outward by control of internal impedance.

Momentum flux parasitic to free-energy transfer

DOE PAGES

Stoltzfus-Dueck, T.; Scott, B.

2017-05-11

An often-neglected portion of the radialmore » $$\\boldsymbol{E}\\times \\boldsymbol{B}$$ drift is shown to drive an outward flux of co-current momentum when free energy is transferred from the electrostatic potential to ion parallel flows. This symmetry breaking is fully nonlinear, not quasilinear, necessitated simply by free-energy balance in parameter regimes for which significant energy is dissipated via ion parallel flows. The resulting rotation peaking is counter-current and has a scaling and order of magnitude that are comparable with experimental observations. Finally, the residual stress becomes inactive when frequencies are much higher than the ion transit frequency, which may explain the observed relation of density peaking and counter-current rotation peaking in the core.« less

16 CFR Figures 1 and 2 to Part 1204 - Suggested Instrumentation for Current Monitoring Device and High Voltage Facility

Code of Federal Regulations, 2012 CFR

2012-01-01

... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Suggested Instrumentation for Current Monitoring Device and High Voltage Facility 1 Figures 1 and 2 to Part 1204 Commercial Practices CONSUMER... Instrumentation for Current Monitoring Device and High Voltage Facility EC03OC91.008 ...

16 CFR Figures 1 and 2 to Part 1204 - Suggested Instrumentation for Current Monitoring Device and High Voltage Facility

Code of Federal Regulations, 2014 CFR

2014-01-01

... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Suggested Instrumentation for Current Monitoring Device and High Voltage Facility 1 Figures 1 and 2 to Part 1204 Commercial Practices CONSUMER... Instrumentation for Current Monitoring Device and High Voltage Facility EC03OC91.008 ...

16 CFR Figures 1 and 2 to Part 1204 - Suggested Instrumentation for Current Monitoring Device and High Voltage Facility

Code of Federal Regulations, 2013 CFR

2013-01-01

... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Suggested Instrumentation for Current Monitoring Device and High Voltage Facility 1 Figures 1 and 2 to Part 1204 Commercial Practices CONSUMER... Instrumentation for Current Monitoring Device and High Voltage Facility EC03OC91.008 ...

Simulations towards the achievement of non-inductive current ramp-up and sustainment in the National Spherical Torus Experiment Upgrade

DOE PAGES

Poli, F. M.; Andre, R. G.; Bertelli, N.; ...

2015-10-30

One of the goals of the National Spherical Torus Experiment Upgrade (NSTX-U) (Menard et al 2012 Nucl. Fusion 52 083015) is the demonstration of fully non-inductive start-up, current ramp-up and sustainment. This work discusses predictive simulations where the available heating and current drive systems are combined to maximize the non-inductive current and minimize the solenoidal contribution. Radio-frequency waves at harmonics higher than the ion cyclotron resonance (high-harmonic fast waves (HHFW)) and neutral beam injection are used to ramp the plasma current non-inductively starting from an initial Ohmic plasma. An interesting synergy is observed in the simulations between the HHFW andmore » electron cyclotron (EC) wave heating. Furthermore, time-dependent simulations indicate that, depending on the phasing of the HHFW antenna, EC wave heating can significantly increase the effectiveness of the radio-frequency power, by heating the electrons and increasing the current drive efficiency, thus relaxing the requirements on the level of HHFW power that needs to be absorbed in the core plasma to drive the same amount of fast-wave current.« less

Protein architecture and core residues in unwound α-helices provide insights to the transport function of plant AtCHX17

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

Czerny, Daniel D.; Padmanaban, Senthilkumar; Anishkin, Andriy

Using Arabidopsis thaliana AtCHX17 as an example, we combine structural modeling and mutagenesis to provide insights on its protein architecture and transport function which is poorly characterized. This approach is based on the observation that protein structures are significantly more conserved in evolution than linear sequences, and mechanistic similarities among diverse transporters are emerging. Two homology models of AtCHX17 were obtained that show a protein fold similar to known structures of bacterial Na +/H + antiporters, EcNhaA and TtNapA. The distinct secondary and tertiary structure models highlighted residues at positions potentially important for CHX17 activity. Mutagenesis showed that asparagine-N200 andmore » aspartate-D201 inside transmembrane5 (TM5), and lysine-K355 inside TM10 are critical for AtCHX17 activity. We reveal previously unrecognized threonine-T170 and lysine-K383 as key residues at unwound regions in the middle of TM4 and TM11 α-helices, respectively. Mutation of glutamate-E111 located near the membrane surface inhibited AtCHX17 activity, suggesting a role in pH sensing. The long carboxylic tail of unknown purpose has an alternating β-sheet and α-helix secondary structure that is conserved in prokaryote universal stress proteins. Here, these results support the overall architecture of AtCHX17 and identify D201, N200 and novel residues T170 and K383 at the functional core which likely participates in ion recognition, coordination and/or translocation, similar to characterized cation/H + exchangers. The core of AtCHX17 models according to EcNhaA and TtNapA templates faces inward and outward, respectively, which may reflect two conformational states of the alternating access transport mode for proteins belonging to the plant CHX family.« less

Protein architecture and core residues in unwound α-helices provide insights to the transport function of plant AtCHX17

DOE PAGES

Czerny, Daniel D.; Padmanaban, Senthilkumar; Anishkin, Andriy; ...

2016-05-11

Using Arabidopsis thaliana AtCHX17 as an example, we combine structural modeling and mutagenesis to provide insights on its protein architecture and transport function which is poorly characterized. This approach is based on the observation that protein structures are significantly more conserved in evolution than linear sequences, and mechanistic similarities among diverse transporters are emerging. Two homology models of AtCHX17 were obtained that show a protein fold similar to known structures of bacterial Na +/H + antiporters, EcNhaA and TtNapA. The distinct secondary and tertiary structure models highlighted residues at positions potentially important for CHX17 activity. Mutagenesis showed that asparagine-N200 andmore » aspartate-D201 inside transmembrane5 (TM5), and lysine-K355 inside TM10 are critical for AtCHX17 activity. We reveal previously unrecognized threonine-T170 and lysine-K383 as key residues at unwound regions in the middle of TM4 and TM11 α-helices, respectively. Mutation of glutamate-E111 located near the membrane surface inhibited AtCHX17 activity, suggesting a role in pH sensing. The long carboxylic tail of unknown purpose has an alternating β-sheet and α-helix secondary structure that is conserved in prokaryote universal stress proteins. Here, these results support the overall architecture of AtCHX17 and identify D201, N200 and novel residues T170 and K383 at the functional core which likely participates in ion recognition, coordination and/or translocation, similar to characterized cation/H + exchangers. The core of AtCHX17 models according to EcNhaA and TtNapA templates faces inward and outward, respectively, which may reflect two conformational states of the alternating access transport mode for proteins belonging to the plant CHX family.« less

Electrocoagulation of bio-filtrated landfill leachate: Fractionation of organic matter and influence of anode materials.

PubMed

Dia, Oumar; Drogui, Patrick; Buelna, Gerardo; Dubé, Rino; Ihsen, Ben Salah

2017-02-01

Electrocoagulation (EC) was employed to treat residual organic matter from a landfill leachate pretreated by an aerated bio-filter system. Organic matter (humic acids (HA), fulvic acids (FA) and hydrophilic compounds (Hyl)) was fractionated using DAX-8 resin in order to estimate the efficiency of EC on each fraction. Initial characterization of the bio-filtrated landfill leachate showed that humic substances (HA + FA) represented nearly 90% of TOC. The effects of current densities, type of anode (Aluminum versus iron), and treatment time on the performance of COD removal were investigated. The best COD removal performances were recorded at a current density ranging between 8.0 and 10 mA cm -2 during 20 min of treatment time. Under these conditions, 70% and 65% of COD were removed using aluminum and iron electrodes, respectively. The fractionating of organic matter after EC treatment revealed that HA was completely removed using either aluminum or iron anode. However, FA and Hyl fractions were partially removed, with the percentages varying from 57 to 60% and 37-46%, respectively. FA and Hyl removal were quite similar using either aluminum or iron anode. Likewise, a significant decrease in 254-nm absorbance was recorded (UV 254 removal of 79-80%) using either type of anode. These results proved that EC is a suitable and efficient approach for treating the residual refractory organic matter from a landfill leachate previously treated by a biological system. Copyright © 2016 Elsevier Ltd. All rights reserved.

Voltage clamp methods for the study of membrane currents and SR Ca2+ release in adult skeletal muscle fibres

PubMed Central

Hernández-Ochoa, Erick O.; Schneider, Martin F.

2012-01-01

Skeletal muscle excitation-contraction (E-C)1 coupling is a process composed of multiple sequential stages, by which an action potential triggers sarcoplasmic reticulum (SR)2 Ca2+ release and subsequent contractile activation. The various steps in the E-C coupling process in skeletal muscle can be studied using different techniques. The simultaneous recordings of sarcolemmal electrical signals and the accompanying elevation in myoplasmic Ca2+, due to depolarization-initiated SR Ca2+ release in skeletal muscle fibres, have been useful to obtain a better understanding of muscle function. In studying the origin and mechanism of voltage dependency of E-C coupling a variety of different techniques have been used to control the voltage in adult skeletal fibres. Pioneering work in muscles isolated from amphibians or crustaceans used microelectrodes or ‘high resistance gap’ techniques to manipulate the voltage in the muscle fibres. The development of the patch clamp technique and its variant, the whole-cell clamp configuration that facilitates the manipulation of the intracellular environment, allowed the use of the voltage clamp techniques in different cell types, including skeletal muscle fibres. The aim of this article is to present an historical perspective of the voltage clamp methods used to study skeletal muscle E-C coupling as well as to describe the current status of using the whole-cell patch clamp technique in studies in which the electrical and Ca2+ signalling properties of mouse skeletal muscle membranes are being investigated. PMID:22306655

In vitro Method to Observe E-selectin-mediated Interactions Between Prostate Circulating Tumor Cells Derived From Patients and Human Endothelial Cells

PubMed Central

Gakhar, Gunjan; Bander, Neil H.; Nanus, David M.

2014-01-01

Metastasis is a process in which tumor cells shed from the primary tumor intravasate blood vascular and lymphatic system, thereby, gaining access to extravasate and form a secondary niche. The extravasation of tumor cells from the blood vascular system can be studied using endothelial cells (ECs) and tumor cells obtained from different cell lines. Initial studies were conducted using static conditions but it has been well documented that ECs behave differently under physiological flow conditions. Therefore, different flow chamber assemblies are currently being used to studying cancer cell interactions with ECs. Current flow chamber assemblies offer reproducible results using either different cell lines or fluid at different shear stress conditions. However, to observe and study interactions with rare cells such as circulating tumor cells (CTCs), certain changes are required to be made to the conventional flow chamber assembly. CTCs are a rare cell population among millions of blood cells. Consequently, it is difficult to obtain a pure population of CTCs. Contamination of CTCs with different types of cells normally found in the circulation is inevitable using present enrichment or depletion techniques. In the present report, we describe a unique method to fluorescently label circulating prostate cancer cells and study their interactions with ECs in a self-assembled flow chamber system. This technique can be further applied to observe interactions between prostate CTCs and any protein of interest. PMID:24894373

A computational model of the ionic currents, Ca2+ dynamics and action potentials underlying contraction of isolated uterine smooth muscle.

PubMed

Tong, Wing-Chiu; Choi, Cecilia Y; Kharche, Sanjay; Karche, Sanjay; Holden, Arun V; Zhang, Henggui; Taggart, Michael J

2011-04-29

Uterine contractions during labor are discretely regulated by rhythmic action potentials (AP) of varying duration and form that serve to determine calcium-dependent force production. We have employed a computational biology approach to develop a fuller understanding of the complexity of excitation-contraction (E-C) coupling of uterine smooth muscle cells (USMC). Our overall aim is to establish a mathematical platform of sufficient biophysical detail to quantitatively describe known uterine E-C coupling parameters and thereby inform future empirical investigations of physiological and pathophysiological mechanisms governing normal and dysfunctional labors. From published and unpublished data we construct mathematical models for fourteen ionic currents of USMCs: Ca2+ currents (L- and T-type), Na+ current, an hyperpolarization-activated current, three voltage-gated K+ currents, two Ca2+-activated K+ current, Ca2+-activated Cl current, non-specific cation current, Na+-Ca2+ exchanger, Na+-K+ pump and background current. The magnitudes and kinetics of each current system in a spindle shaped single cell with a specified surface area:volume ratio is described by differential equations, in terms of maximal conductances, electrochemical gradient, voltage-dependent activation/inactivation gating variables and temporal changes in intracellular Ca2+ computed from known Ca2+ fluxes. These quantifications are validated by the reconstruction of the individual experimental ionic currents obtained under voltage-clamp. Phasic contraction is modeled in relation to the time constant of changing [Ca2+]i. This integrated model is validated by its reconstruction of the different USMC AP configurations (spikes, plateau and bursts of spikes), the change from bursting to plateau type AP produced by estradiol and of simultaneous experimental recordings of spontaneous AP, [Ca2+]i and phasic force. In summary, our advanced mathematical model provides a powerful tool to investigate the physiological ionic mechanisms underlying the genesis of uterine electrical E-C coupling of labor and parturition. This will furnish the evolution of descriptive and predictive quantitative models of myometrial electrogenesis at the whole cell and tissue levels.

Parent Education: What We Mean and What that Means.

ERIC Educational Resources Information Center

McCollum, Jeanette A.

1999-01-01

This response to Mahoney et al. (EC 623 392) agrees that there is currently less emphasis on parent education in the early-intervention literature but suggests that the current emphasis on family-centered services can be integrated with parent education while supporting family empowerment. (DB)

Calcium-sensitive and insensitive transient outward current in rabbit ventricular myocytes.

PubMed Central

Hiraoka, M; Kawano, S

1989-01-01

1. A suction pipette whole-cell voltage-clamp technique was used to record membrane currents and potentials of isolated ventricular myocytes from rabbit hearts. 2. Transient outward current (Ito) was activated by voltage steps positive to -20 mV, increasing in amplitude with further depolarization to reach a maximum around +70 mV. The current attained its peak within 10 ms and then it inactivated for 100-200 ms. 3. A large portion of Ito still remained after the calcium current (ICa) was blocked when depolarizing pulses were applied at a frequency of 0.1 Hz or less. Therefore, this current component is referred to as calcium-insensitive Ito or It. 4. It showed voltage- and time-dependent inactivation similar to that observed in Purkinje fibres and other cardiac preparations. 5. The reversal potential of It depended on external K+ concentration, [K+]o, with a slope of 32 mV per 10-fold change in the presence of a normal [Na+]o (143 mM), while the slope was 48 mV per 10-fold change in low [Na+]o (1.0 mM). 6. It was completely inhibited by 2-4 mM-4-aminopyridine. Ito in the presence of ICa was also partially blocked by 4-aminopyridine and the remainder was abolished by 5 mM-caffeine. 7. The calcium-insensitive and caffeine-sensitive Ito differed in their decay rates as well as in their recovery time courses. The former was predominantly available at a slow pulsing rate, while the latter increased its amplitude with high-frequency depolarization. 8. The caffeine-sensitive Ito was inhibited by a blockade of ICa, by replacing Ca2+ with Sr2+, by external application of ryanodine and by internal application of EGTA. This indicates that the current is calcium-sensitive and is dependent on increased myoplasmic Ca2+ through Ca2+ influx via the sarcolemma and Ca2+ release from the sarcoplasmic reticulum. The current is therefore designated as IK, Ca. 9. The physiological functions of IK, Ca and It are indicated by their contribution to ventricular repolarization at fast and slow heart rates, respectively. PMID:2552080

The influence of executive capacity on selective attention and subsequent processing

PubMed Central

Daffner, Kirk R.; Tarbi, Elise C.; Haring, Anna E.; Zhuravleva, Tatyana Y.; Sun, Xue; Rentz, Dorene M.; Holcomb, Phillip J.

2012-01-01

Recent investigations that suggest selective attention (SA) is dependent on top-down control mechanisms lead to the expectation that individuals with high executive capacity (EC) would exhibit more robust neural indices of SA. This prediction was tested by using event-related potentials (ERPs) to examine differences in markers of information processing across 25 subjects divided into two groups based on high vs. average EC, as defined by neuropsychological test scores. Subjects performed an experimental task requiring SA to a specified color. In contrast to expectation, individuals with high and average EC did not differ in the size of ERP indices of SA: the anterior Selection Positivity (SP) and posterior Selection Negativity (SN). However, there were substantial differences between groups in markers of subsequent processing, including the anterior N2 (a measure of attentional control) and the P3a (an index of the orienting of attention). EC predicted speed of processing at both early and late attentional stages. Individuals with lower EC exhibited prolonged SN, P3a, and P3b latencies. However, the delays in carrying out SA operations did not account for subsequent delays in decision making, or explain excessive orienting and reduced attentional control mechanisms in response to stimuli that should have been ignored. SN latency, P3 latency, and the size of the anterior N2 made independent contributions to the variance of EC. In summary, our findings suggest that current views regarding the relationship between top-down control mechanisms and SA may need refinement. PMID:22701415

A transparent electrochromic metal-insulator switching device with three-terminal transistor geometry

NASA Astrophysics Data System (ADS)

Katase, Takayoshi; Onozato, Takaki; Hirono, Misako; Mizuno, Taku; Ohta, Hiromichi

2016-05-01

Proton and hydroxyl ion play an essential role for tuning functionality of oxides because their electronic state can be controlled by modifying oxygen off-stoichiometry and/or protonation. Tungsten trioxide (WO3), a well-known electrochromic (EC) material for smart window, is a wide bandgap insulator, whereas it becomes a metallic conductor HxWO3 by protonation. Although one can utilize electrochromism together with metal-insulator (MI) switching for one device, such EC-MI switching cannot be utilized in current EC devices because of their two-terminal structure with parallel-plate configuration. Here we demonstrate a transparent EC-MI switchable device with three-terminal TFT-type structure using amorphous (a-) WO3 channel layer, which was fabricated on glass substrate at room temperature. We used water-infiltrated nano-porous glass, CAN (calcium aluminate with nano-pores), as a liquid-leakage-free solid gate insulator. At virgin state, the device was fully transparent in the visible-light region. For positive gate voltage, the active channel became dark blue, and electrical resistivity of the a-WO3 layer drastically decreased with protonation. For negative gate voltage, deprotonation occurred and the active channel returned to transparent insulator. Good cycleability of the present transparent EC-MI switching device would have potential for the development of advanced smart windows.

Perception of autonomy and connectedness prior to the onset of anorexia nervosa and bulimia nervosa.

PubMed

Huemer, Julia; Haidvogl, Maria; Mattejat, Fritz; Wagner, Gudrun; Nobis, Gerald; Fernandez-Aranda, Fernando; Collier, David A; Treasure, Janet L; Karwautz, Andreas F K

2012-01-01

This study examines retrospective correlates of nonshared family environment prior to onset of disease, by means of multiple familial informants, among anorexia and bulimia nervosa patients. A total of 332 participants was included (anorexia nervosa, restrictive type (AN-R): n = 41 plus families); bulimic patients (anorexia nervosa, binge-purging type; bulimia nervosa: n = 59 plus families). The EATAET Lifetime Diagnostic Interview was used to establish the diagnosis; the Subjective Family Image Test was used to derive emotional connectedness (EC) and individual autonomy (IA). Bulimic and AN-R patients perceived significantly lower EC prior to onset of disease compared to their healthy sisters. Bulimic patients perceived significantly lower EC prior to onset of disease compared to AN-R patients and compared to their mothers and fathers. A low family sum - sister pairs sum comparison - of EC had a significant influence on the risk of developing bulimia nervosa. Contrary to expectations, AN-R patients did not perceive significantly lower levels of IA compared to their sisters, prior to onset of disease. Findings of low IA in currently ill AN-R patients may represent a disease consequence, not a risk factor. Developmental child psychiatrists should direct their attention to disturbances of EC, which may be present prior to the onset of the disease.

Endocannabinoid system dysfunction in mood and related disorders.

PubMed

Ashton, C H; Moore, P B

2011-10-01

The endocannabinoid (EC) system is widely distributed throughout the brain and modulates many functions. It is involved in mood and related disorders, and its activity may be modified by exogenous cannabinoids. This article examines the therapeutic potential of cannabinoids in psychiatric disorders. An overview is presented of the literature focussed on the functions of the EC system, its dysfunction in mood disorders and the therapeutic potential of exogenous cannabinoids. We propose (hypothesize) that the EC system, which is homoeostatic in cortical excitation and inhibition, is dysfunctional in mood and related disorders. Anandamide, tetrahydrocannabinol (THC) and cannabidiol (CBD) variously combine antidepressant, antipsychotic, anxiolytic, analgesic, anticonvulsant actions, suggesting a therapeutic potential in mood and related disorders. Currently, cannabinoids find a role in pain control. Post mortem and other studies report EC system abnormalities in depression, schizophrenia and suicide. Abnormalities in the cannabinoid-1 receptor (CNR1) gene that codes for cannabinoid-1 (CB1) receptors are reported in psychiatric disorders. However, efficacy trials of cannabinoids in psychiatric disorders are limited but offer some encouragement. Research is needed to elucidate the role of the EC system in psychiatric disorders and for clinical trials with THC, CBD and synthetic cannabinoids to assess their therapeutic potential. © 2011 John Wiley & Sons A/S.

Quality of life research in endometrial cancer: what is needed to advance progress in this disease site? Methodological considerations from the Gynecologic Cancer InterGroup Symptom Benefit Working Group brainstorming session, Leiden 2012.

PubMed

McAlpine, Jessica N; Greimel, Elfriede; Brotto, Lori A; Nout, Remy A; Shash, Emad; Avall-Lundqvist, Elisabeth; Friedlander, Michael L; Joly, Florence

2014-11-01

Quality of life (QoL) in endometrial cancer (EC) is understudied. Incorporation of QoL questionnaires and patient-reported outcomes in clinical trials has been inconsistent, and the tools and interpretation of these measures are unfamiliar to most practitioners. In 2012, the Gynecologic Cancer InterGroup Symptom Benefit Working Group convened for a brainstorming collaborative session to address deficiencies and work toward improving the quality and quantity of QoL research in women with EC. Through literature review and international expert contributions, we compiled a comprehensive appraisal of current generic and disease site-specific QoL assessment tools, strengths and weaknesses of these measures, assessment of sexual health, statistical considerations, and an exploration of the unique array of histopathologic and clinical factors that may influence QoL outcomes in women with EC. This collaborative composition is the first publication specific to EC that addresses methodology in QoL research and the components necessary to achieve high quality QoL data in clinical trials. Future recommendations regarding (1) the incorporation of patient-reported outcomes in all clinical trials in EC, (2) definition of an a priori hypothesis, (3) utilization of validated tools and consideration of new tools corresponding to new therapies or specific symptoms, (4) publication within the same time frame as clinical outcome data, and (5) attempt to correct for disease site-specific potential confounders are presented. Improved understanding of methodology in QoL research and an increased undertaking of EC-specific QoL research in clinical trials are imperative if we are to improve outcomes in women with EC.

Normal T-cell activation in elite controllers with preserved CD4+ T-cell counts.

PubMed

Bansal, Anju; Sterrett, Sarah; Erdmann, Nathan; Westfall, Andrew O; Dionne-Odom, Jodie; Overton, Edgar T; Goepfert, Paul A

2015-11-01

HIV elite controllers suppress HIV viremia without antiretroviral therapy (ART), yet previous studies demonstrated that elite controllers maintain an activated T-cell phenotype. Chronic immune activation has detrimental consequences and thus ART has been advocated for all elite controllers. However, elite controllers are not a clinically homogenous group. Since CD4% is among the best predictors of AIDS-related events, in the current study, we assessed whether this marker can be used to stratify elite controllers needing ART. Sixteen elite controllers were divided into two groups based on CD4% (EC > 40% and EC ≤40%), and T-cell subsets were analyzed for markers of memory/differentiation (CD45RA, CCR7, CD28), activation (CD38/HLA-DR), immunosenescence (CD57), costimulation (CD73, CD28) and exhaustion (PD-1, CD160, Tim-3). Monocyte subsets (CD14, CD16) were also analyzed and sCD14 levels were quantified using ELISA. In the EC group, expression of activation, exhaustion, and immunosensescence markers on T cells were significantly reduced compared with the EC group and similar to the seronegative controls. The EC group expressed higher levels of costimulatory molecules CD28 and CD73 and had lower levels of monocyte activation (HLA-DR expression) with a reduced frequency of inflammatory monocyte (CD14 CD16) subset. Furthermore, the EC group maintained a stable CD4% during a median follow-up of 6 years. Elite controllers with preserved CD4T cells (EC) have normal T-cell and monocyte phenotypes and therefore may have limited benefit from ART. CD4% can be an important marker for evaluating future studies aimed at determining the need for ART in this group of individuals.

Defining the extent of cables loss in endometrial cancer subtypes and its effectiveness as an inhibitor of cell proliferation in malignant endometrial cells in vitro and in vivo.

PubMed

DeBernardo, Robert L; Littell, Ramey D; Luo, Hongwei; Duska, Linda R; Oliva, Esther; Kirley, Sandra D; Lynch, Maureen P; Zukerberg, Lawrence R; Rueda, Bo R

2005-01-01

Loss of Cables expression is associated with a high incidence of endometrial hyperplasia and endometrial adenocarcinoma in humans. The Cables mutant mouse develops endometrial hyperplasia and following exposure to chronic estrogen develops early endometrial adenocarcinoma. The objectives of the current study were to determine if: (1) loss of Cables expression occurred in high grade endometrioid adenocarcinoma, uterine serous and clear cell carcinoma as observed in endometrial hyperplasia and low grade endometrial adenocarcinoma; (2) overexpression of Cables inhibited cell proliferation in endometrial cancer (EC) cells in vitro and in vivo; and (3) progesterone could regulate the expression of Cables mRNA. Hyperplastic endometrium and low and high grade endometrioid adenocarcinoma showed loss of Cables expression when compared to benign control secretory endometrium. Loss of Cables expression in serous and clear cell tumors was similar to that observed in endometrioid adenocarcinomas with greater than 80% showing loss of protein expression. Treatment of EC lines with progesterone increased cables expression in low-grade EC whereas it had no effect on cables expression in cells derived from high-grade EC. The progesterone-induced increase in cables was abrogated in the presence of a progesterone receptor (PR) antagonist, suggesting the PR mediates the increase. Cables overexpression inhibited cell proliferation of well differentiated EC cells and had no effect on the poorly differentiated EC cells. The capacity to form tumors was dramatically reduced in the Cables overexpressing cell lines compared to those cells containing the control vector. Collectively these results suggest that Cables is an important regulator of cell proliferation and loss of Cables expression contributes to the development of all types of EC.

A High-Throughput Regeneration and Transformation Platform for Production of Genetically Modified Banana.

PubMed

Tripathi, Jaindra N; Oduor, Richard O; Tripathi, Leena

2015-01-01

Banana (Musa spp.) is an important staple food as well as cash crop in tropical and subtropical countries. Various bacterial, fungal, and viral diseases and pests such as nematodes are major constraints in its production and are currently destabilizing the banana production in sub-Saharan Africa. Genetic engineering is a complementary option used for incorporating useful traits in banana to bypass the long generation time, polyploidy, and sterility of most of the cultivated varieties. A robust transformation protocol for farmer preferred varieties is crucial for banana genomics and improvement. A robust and reproducible system for genetic transformation of banana using embryogenic cell suspensions (ECS) has been developed in this study. Two different types of explants (immature male flowers and multiple buds) were tested for their ability to develop ECS in several varieties of banana locally grown in Africa. ECS of banana varieties "Cavendish Williams" and "Gros Michel" were developed using multiple buds, whereas ECS of "Sukali Ndiizi" was developed using immature male flowers. Regeneration efficiency of ECS was about 20,000-50,000 plantlets per ml of settled cell volume (SCV) depending on variety. ECS of three different varieties were transformed through Agrobacterium-mediated transformation using gusA reporter gene and 20-70 independent transgenic events per ml SCV of ECS were regenerated on selective medium. The presence and integration of gusA gene in transgenic plants was confirmed by PCR, dot blot, and Southern blot analysis and expression by histochemical GUS assays. The robust transformation platform was successfully used to generate hundreds of transgenic lines with disease resistance. Such a platform will facilitate the transfer of technologies to national agricultural research systems (NARS) in Africa.

A High-Throughput Regeneration and Transformation Platform for Production of Genetically Modified Banana

PubMed Central

Tripathi, Jaindra N.; Oduor, Richard O.; Tripathi, Leena

2015-01-01

Banana (Musa spp.) is an important staple food as well as cash crop in tropical and subtropical countries. Various bacterial, fungal, and viral diseases and pests such as nematodes are major constraints in its production and are currently destabilizing the banana production in sub-Saharan Africa. Genetic engineering is a complementary option used for incorporating useful traits in banana to bypass the long generation time, polyploidy, and sterility of most of the cultivated varieties. A robust transformation protocol for farmer preferred varieties is crucial for banana genomics and improvement. A robust and reproducible system for genetic transformation of banana using embryogenic cell suspensions (ECS) has been developed in this study. Two different types of explants (immature male flowers and multiple buds) were tested for their ability to develop ECS in several varieties of banana locally grown in Africa. ECS of banana varieties “Cavendish Williams” and “Gros Michel” were developed using multiple buds, whereas ECS of “Sukali Ndiizi” was developed using immature male flowers. Regeneration efficiency of ECS was about 20,000–50,000 plantlets per ml of settled cell volume (SCV) depending on variety. ECS of three different varieties were transformed through Agrobacterium-mediated transformation using gusA reporter gene and 20–70 independent transgenic events per ml SCV of ECS were regenerated on selective medium. The presence and integration of gusA gene in transgenic plants was confirmed by PCR, dot blot, and Southern blot analysis and expression by histochemical GUS assays. The robust transformation platform was successfully used to generate hundreds of transgenic lines with disease resistance. Such a platform will facilitate the transfer of technologies to national agricultural research systems (NARS) in Africa. PMID:26635849

The dynamic programming high-order Dynamic Bayesian Networks learning for identifying effective connectivity in human brain from fMRI.

PubMed

Dang, Shilpa; Chaudhury, Santanu; Lall, Brejesh; Roy, Prasun Kumar

2017-06-15

Determination of effective connectivity (EC) among brain regions using fMRI is helpful in understanding the underlying neural mechanisms. Dynamic Bayesian Networks (DBNs) are an appropriate class of probabilistic graphical temporal-models that have been used in past to model EC from fMRI, specifically order-one. High-order DBNs (HO-DBNs) have still not been explored for fMRI data. A fundamental problem faced in the structure-learning of HO-DBN is high computational-burden and low accuracy by the existing heuristic search techniques used for EC detection from fMRI. In this paper, we propose using dynamic programming (DP) principle along with integration of properties of scoring-function in a way to reduce search space for structure-learning of HO-DBNs and finally, for identifying EC from fMRI which has not been done yet to the best of our knowledge. The proposed exact search-&-score learning approach HO-DBN-DP is an extension of the technique which was originally devised for learning a BN's structure from static data (Singh and Moore, 2005). The effectiveness in structure-learning is shown on synthetic fMRI dataset. The algorithm reaches globally-optimal solution in appreciably reduced time-complexity than the static counterpart due to integration of properties. The proof of optimality is provided. The results demonstrate that HO-DBN-DP is comparably more accurate and faster than currently used structure-learning algorithms used for identifying EC from fMRI. The real data EC from HO-DBN-DP shows consistency with previous literature than the classical Granger Causality method. Hence, the DP algorithm can be employed for reliable EC estimates from experimental fMRI data. Copyright © 2017 Elsevier B.V. All rights reserved.

Prolonged colonisation with Escherichia coli O25:ST131 versus other extended-spectrum beta-lactamase-producing E. coli in a long-term care facility with high endemic level of rectal colonisation, the Netherlands, 2013 to 2014.

PubMed

Overdevest, Ilse; Haverkate, Manon; Veenemans, Jacobien; Hendriks, Yvonne; Verhulst, Carlo; Mulders, Ans; Couprie, Willemijn; Bootsma, Martin; Johnson, James; Kluytmans, Jan

2016-10-20

The extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli clone ST131 (ESBL-ST131) has spread in healthcare settings worldwide. The reasons for its successful spread are unknown, but might include more effective transmission and/or longer persistence. We evaluated the colonisation dynamics of ESBL-producing E. coli (ESBL-EC), including ESBL-ST131, in a long-term care facility (LTCF) with an unusually high prevalence of rectal ESBL-EC colonisation. During a 14-month period, rectal or faecal samples were obtained from 296 residents during six repetitive prevalence surveys, using ESBL-selective culture. Transmission rates, reproduction numbers, and durations of colonisation were compared for ESBL-ST131 vs other ESBL-EC. Furthermore, the likely time required for ESBL-ST131 to disappear from the LTCF was estimated. Over time, the endemic level of ESBL-ST131 remained elevated whereas other ESBL-EC returned to low-level prevalence, despite comparable transmission rates. Survival analysis showed a half-life of 13 months for ESBL-ST131 carriage, vs two to three months for other ESBL-EC (p < 0.001). Per-admission reproduction numbers were 0.66 for ESBL-ST131 vs 0.56 for other ESBL-EC, predicting a mean time of three to four years for ESBL-ST131 to disappear from the LTCF under current conditions. Transmission rates were comparable for ESBL-ST131 vs other ESBL-EC. Prolonged rectal carriage explained the persistence of ESBL-ST131 in the LTCF. This article is copyright of The Authors, 2016.

Effects of Disturbed Flow on Vascular Endothelium: Pathophysiological Basis and Clinical Perspectives

PubMed Central

Chiu, Jeng-Jiann; Chien, Shu

2013-01-01

Vascular endothelial cells (ECs) are exposed to hemodynamic forces, which modulate EC functions and vascular biology/pathobiology in health and disease. The flow patterns and hemodynamic forces are not uniform in the vascular system. In straight parts of the arterial tree, blood flow is generally laminar and wall shear stress is high and directed; in branches and curvatures, blood flow is disturbed with nonuniform and irregular distribution of low wall shear stress. Sustained laminar flow with high shear stress upregulates expressions of EC genes and proteins that are protective against atherosclerosis, whereas disturbed flow with associated reciprocating, low shear stress generally upregulates the EC genes and proteins that promote atherogenesis. These findings have led to the concept that the disturbed flow pattern in branch points and curvatures causes the preferential localization of atherosclerotic lesions. Disturbed flow also results in postsurgical neointimal hyperplasia and contributes to pathophysiology of clinical conditions such as in-stent restenosis, vein bypass graft failure, and transplant vasculopathy, as well as aortic valve calcification. In the venous system, disturbed flow resulting from reflux, outflow obstruction, and/or stasis leads to venous inflammation and thrombosis, and hence the development of chronic venous diseases. Understanding of the effects of disturbed flow on ECs can provide mechanistic insights into the role of complex flow patterns in pathogenesis of vascular diseases and can help to elucidate the phenotypic and functional differences between quiescent (nonatherogenic/nonthrombogenic) and activated (atherogenic/thrombogenic) ECs. This review summarizes the current knowledge on the role of disturbed flow in EC physiology and pathophysiology, as well as its clinical implications. Such information can contribute to our understanding of the etiology of lesion development in vascular niches with disturbed flow and help to generate new approaches for therapeutic interventions. PMID:21248169

The turbulent generation of outward traveling Alfvenic fluctuations in the solar wind

NASA Technical Reports Server (NTRS)

Matthaeus, W. H.; Goldstein, M. L.; Montgomery, D. C.

1983-01-01

From an analysis of the incompressible MHD equations, it is concluded that the frequent observation of outward propagating Alfvenic fluctuations in the solar wind can arise from early stages of in situ turbulent evolution, and need not reflect coronal processes.

The correlation between Prorocentrum donghaiense blooms and the Taiwan warm current in the East China Sea - evidence for the "Pelagic Seed Bank" hypothesis.

PubMed

Dai, Xinfeng; Lu, Douding; Guan, Weibing; Xia, Ping; Wang, Hongxia; He, Piaoxia; Zhang, Dongsheng

2013-01-01

During the last two decades, large-scale high biomass algal blooms of the dinoflagellate Prorocentrum donghaiense Lu have occurred frequently in the East China Sea (ECS). The role of increasing nutrient concentrations in driving those blooms is well-established, but the source population that initiates them is poorly understood. We hypothesized that the front of Taiwan Warm Current (TWC) may serve as a 'seed bank' that initiates P. donghaiense blooms in the ECS, as the physiochemical conditions in the TWC are suitable for the growth of P. donghaiense. In order to test this hypothesis, two surveys at different spatio-temporal scales were conducted in 2010 and 2011. We found a strong correlation in space and time between the abundance of P. donghaiense and the TWC. The spatial extent of the P. donghaiense bloom coincided with the TWC front in both 2010 and 2011. During the early development of the blooms, P. donghaiense concentration was highest at the TWC front, and then the bloom mass shifted inshore over the course of our 2011 survey. The TWC also moved inshore, albeit after the appearance of P. donghaiense. Overall, these results support our hypothesis that P. donghaiense blooms develop from the population at the TWC front in the ECS, suggesting the role of the ocean current front as a seed bank to dinoflagellate blooms.

Transformation and removal of arsenic in groundwater by sequential anodic oxidation and electrocoagulation

NASA Astrophysics Data System (ADS)

Zhang, Peng; Tong, Man; Yuan, Songhu; Liao, Peng

2014-08-01

Oxidation of As(III) to As(V) is generally essential for the efficient remediation of As(III)-contaminated groundwater. The performance and mechanisms of As(III) oxidation by an as-synthesized active anode, SnO2 loaded onto Ti-based TiO2 nanotubes (Ti/TiO2NTs/Sb-SnO2), were investigated. The subsequent removal of total arsenic by electrocoagulation (EC) was further tested. The Ti/TiO2NTs/Sb-SnO2 anode showed a high and lasting electrochemical activity for As(III) oxidation. 6.67 μM As(III) in synthetic groundwater was completely oxidized to As(V) within 60 min at 50 mA. Direct electron transfer was mainly responsible at the current below 30 mA, while hydroxyl radicals contributed increasingly with the increase in the current above 30 mA. As(III) oxidation was moderately inhibited by the presence of bicarbonate (20 mM), while was dramatically increased with increasing the concentration of chloride (0-10 mM). After the complete oxidation of As(III) to As(V), total arsenic was efficiently removed by EC in the same reactor by reversing electrode polarity. The removal efficiency increased with increasing the current but decreased by the presence of phosphate and silica. Anodic oxidation represents an effective pretreatment approach to increasing EC removal of As(III) in groundwater under O2-limited conditions.

Revealing an outward-facing open conformational state in a CLC Cl –/H + exchange transporter

DOE PAGES

Khantwal, Chandra M.; Abraham, Sherwin J.; Han, Wei; ...

2016-01-22

CLC secondary active transporters exchange Cl - for H + . Crystal structures have suggested that the conformational change from occluded to outward-facing states is unusually simple, involving only the rotation of a conserved glutamate (Glu ex ) upon its protonation. Using 19 F NMR, we show that as [H + ] is increased to protonate Glu ex and enrich the outward-facing state, a residue ~20 Å away from Glu ex , near the subunit interface, moves from buried to solvent-exposed. Consistent with functional relevance of this motion, constriction via inter-subunit cross-linking reduces transport. Molecular dynamics simulations indicate that themore » cross-link dampens extracellular gate-opening motions. In support of this model, mutations that decrease steric contact between Helix N (part of the extracellular gate) and Helix P (at the subunit interface) remove the inhibitory effect of the cross-link. Together, these results demonstrate the formation of a previously uncharacterized 'outward-facing open' state, and highlight the relevance of global structural changes in CLC function.« less

Inhibitory action of ICI-182,780, an estrogen receptor antagonist, on BK(Ca) channel activity in cultured endothelial cells of human coronary artery.

PubMed

Liu, Yen-Chin; Lo, Yi-Ching; Huang, Chin-Wei; Wu, Sheng-Nan

2003-11-15

ICI-182,780 is known to be a selective inhibitor of the intracellular estrogen receptors. The effect of ICI-182,780 on ion currents was studied in cultured endothelial cells of human coronary artery. In whole-cell current recordings, ICI-182,780 reversibly decreased the amplitude of K(+) outward currents. The decrease in outward current caused by ICI-182,780 could be counteracted by further application of magnolol or nordihydroguaiaretic acid, yet not by 17beta-estradiol. Under current-clamp condition, ICI-182,780 (3microM) depolarized the membrane potentials of the cells, and magnolol (10 microM) or nordihydroguaiaretic acid (10 microM) reversed ICI-182,780-induced depolarization. In inside-out patches, ICI-182,780 added to the bath did not alter single-channel conductance of large-conductance Ca(2+)-activated K(+) channels (BK(Ca) channels), but decreased their open probability. ICI-182,780 reduced channel activity in a concentration-dependent manner with an IC(50) value of 3 microM. After BK(Ca) channel activity was suppressed by 2-methoxyestradiol (3 microM), subsequent application of ICI-182,780 (3 microM) did not further reduce the channel activity. The application of ICI-182,780 shifted the activation curve of BK(Ca) channels to positive potentials. Its decrease in the open probability primarily involved a reduction in channel open duration. ICI-182,780 also suppressed the proliferation of these endothelial cells with an IC(50) value of 2 microM. However, in coronary smooth muscle cells, a bell-shaped concentration-response curve for the ICI-182,780 effect on BK(Ca) channel activity was observed. This study provides evidence that ICI-182,780 can inhibit BK(Ca) channels in vascular endothelial cells in a mechanism unlikely to be linked to its anti-estrogen activity. The inhibitory effects on these channels may partly contribute to the underlying mechanisms by which ICI-182,780 affects endothelial function.

Route, mechanism, and implications of proton import during Na+/K+ exchange by native Na+/K+-ATPase pumps

PubMed Central

Vedovato, Natascia

2014-01-01

A single Na+/K+-ATPase pumps three Na+ outwards and two K+ inwards by alternately exposing ion-binding sites to opposite sides of the membrane in a conformational sequence coupled to pump autophosphorylation from ATP and auto-dephosphorylation. The larger flow of Na+ than K+ generates outward current across the cell membrane. Less well understood is the ability of Na+/K+ pumps to generate an inward current of protons. Originally noted in pumps deprived of external K+ and Na+ ions, as inward current at negative membrane potentials that becomes amplified when external pH is lowered, this proton current is generally viewed as an artifact of those unnatural conditions. We demonstrate here that this inward current also flows at physiological K+ and Na+ concentrations. We show that protons exploit ready reversibility of conformational changes associated with extracellular Na+ release from phosphorylated Na+/K+ pumps. Reversal of a subset of these transitions allows an extracellular proton to bind an acidic side chain and to be subsequently released to the cytoplasm. This back-step of phosphorylated Na+/K+ pumps that enables proton import is not required for completion of the 3 Na+/2 K+ transport cycle. However, the back-step occurs readily during Na+/K+ transport when external K+ ion binding and occlusion are delayed, and it occurs more frequently when lowered extracellular pH raises the probability of protonation of the externally accessible carboxylate side chain. The proton route passes through the Na+-selective binding site III and is distinct from the principal pathway traversed by the majority of transported Na+ and K+ ions that passes through binding site II. The inferred occurrence of Na+/K+ exchange and H+ import during the same conformational cycle of a single molecule identifies the Na+/K+ pump as a hybrid transporter. Whether Na+/K+ pump–mediated proton inflow may have any physiological or pathophysiological significance remains to be clarified. PMID:24688018

Modulation of contraction by intracellular Na+ via Na(+)-Ca2+ exchange in single shark (Squalus acanthias) ventricular myocytes.

PubMed Central

Näbauer, M; Morad, M

1992-01-01

1. The effect of direct alteration of intracellular Na+ concentration on contractile properties of whole-cell clamped shark ventricular myocytes was studied using an array of 256 photodiodes to monitor the length of the isolated myocytes. 2. In myocytes dialysed with Na(+)-free solution, the voltage dependence of Ca2+ current (ICa) and contraction were similar and bell shaped. Contractions activated at all voltages were completely suppressed by nifedipine (5 microM), and failed to show significant tonic components, suggesting dependence of the contraction on Ca2+ influx through the L-type Ca2+ channel. 3. In myocytes dialysed with 60 mM Na+, a ICa-dependent and a ICa-independent component of contraction could be identified. The Ca2+ current-dependent component was prominent in voltages between -30 to +10 mV. The ICa-independent contractions were maintained for the duration of depolarization, increased with increasing depolarization between +10 to +100 mV, and were insensitive to nifedipine. 4. In such myocytes, repolarization produced slowly decaying inward tail currents closely related to the time course of relaxation and the degree of shortening prior to repolarization. 5. With 60 mM Na+ in the pipette solution, positive clamp potentials activated decaying outward currents which correlated to the size of contraction. These outward currents appeared to be generated by the Na(+)-Ca(2+)-exchanger since they depended on the presence of intracellular Na+, and were neither suppressed by nifedipine nor by K+ channel blockers. 6. The results suggest that in shark (Squalus acanthias) ventricular myocytes, which lack functionally relevant Ca2+ release pools, both Ca2+ channel and the Na(+)-Ca2+ exchanger deliver sufficient Ca2+ to activate contraction, though the effectiveness of the latter mechanism was highly dependent on the [Na+]i. PMID:1338467

"I don't know what I would have done." Women's experiences acquiring ulipristal acetate emergency contraception online from 2011 to 2015.

PubMed

Smith, Nicole K; Cleland, Kelly; Wagner, Brandon; Trussell, James

2017-04-01

This study describes women's reasons for seeking ulipristal acetate (UPA) for emergency contraception (EC) through the only authorized online retailer for UPA EC in the US. Women aged 14 to 59 years, living in states that allow prescription medications to be shipped from out-of-state, accessed the KwikMed online pharmacy between January 2011 and December 2015. After completing a medical eligibility screener, women answered optional multiple-choice questions. To obtain UPA through KwikMed, individuals must be female, 50 years of age or younger, not currently pregnant or breastfeeding and not attempting to order UPA more than once within 30 days or more than four times per year. Over the 5-year period, KwikMed provided 8019 prescriptions for UPA, and the number of women using this service more than tripled over time. Among women who responded to the survey questions (n=7133; response rate = 89%), most sought EC because of a condom failure (45.3%) or because they did not use regular contraception (41.2%). More than half (53.5%) of women reported that they chose UPA because of its effectiveness compared to levonorgestrel EC pills, and 58.9% preferred ordering UPA online because they found it easier than getting it from a doctor, clinic or pharmacy. This study documents the importance of providing confidential services for acquiring EC online. Benefits of online access include convenience, less embarrassment, avoiding situations in which a provider might refuse to provide EC because of their own ideological belief and more reliable availability for this time-sensitive contraceptive. Though physical, logistical and societal barriers can restrict women's access to EC, this study demonstrates that providing access to UPA online empowers women to obtain EC when they need it. Copyright © 2016 Elsevier Inc. All rights reserved.

An in vitro model to study interactions between Escherichia coli and lactic acid bacterial inoculants for silage in rumen fluid.

PubMed

Weinberg, Z G; Chen, Y; Volchinski, V; Sela, S; Ogunade, I M; Adesogan, A

2016-07-01

Previous studies have shown that silages treated with lactic acid bacteria (LAB) inoculants enhance ruminants' performance. The objective of the current experiments was to develop an in vitro model to study interactions between LAB silage inoculants and inoculated silages and Escherichia coli (EC) in rumen fluid (RF). Our hypothesis was that some inoculants inhibit EC in RF. For that purpose buffered RF was incubated under anaerobic conditions at 39°C with commercial strains of LAB silage inoculants or with laboratory corn and wheat silages treated with these LAB, an EC strain and with various ruminant feed ingredients. The EC strain was originally isolated from cattle manure and tagged with a plasmid expressing the green fluorescence protein and kanamycin and streptomycin resistance. Results indicate that the LAB or the treated silages did not suppress EC numbers in the RF. When the pH of the RF decreased below 5·0 the EC disappeared. We conclude that both LAB inoculants for silage and EC survived in RF for several days; however, the inoculants and silages treated with such inoculants did not inhibit EC in RF in vitro. Forage crops, silage and hay are initial stages of the food chain for humans. Cattle harbours and sheds enterobacteria regularly, some strains of which are pathogens. These can contaminate forage crops through field fertilization with cattle manure. The objective of this study was to develop an in vitro model to test whether lactic acid bacteria, which are used in silage inoculants, alone or in treated silages can inhibit Escherichia coli in rumen fluid. This study presents safety aspects and it is also part of a broad research effort aimed at finding out how LAB silage inoculants and inoculated silages enhance ruminant performance or exert probiotic effects in ruminants. © 2016 The Society for Applied Microbiology.

ORENZA: a web resource for studying ORphan ENZyme activities

PubMed Central

Lespinet, Olivier; Labedan, Bernard

2006-01-01

Background Despite the current availability of several hundreds of thousands of amino acid sequences, more than 36% of the enzyme activities (EC numbers) defined by the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) are not associated with any amino acid sequence in major public databases. This wide gap separating knowledge of biochemical function and sequence information is found for nearly all classes of enzymes. Thus, there is an urgent need to explore these sequence-less EC numbers, in order to progressively close this gap. Description We designed ORENZA, a PostgreSQL database of ORphan ENZyme Activities, to collate information about the EC numbers defined by the NC-IUBMB with specific emphasis on orphan enzyme activities. Complete lists of all EC numbers and of orphan EC numbers are available and will be periodically updated. ORENZA allows one to browse the complete list of EC numbers or the subset associated with orphan enzymes or to query a specific EC number, an enzyme name or a species name for those interested in particular organisms. It is possible to search ORENZA for the different biochemical properties of the defined enzymes, the metabolic pathways in which they participate, the taxonomic data of the organisms whose genomes encode them, and many other features. The association of an enzyme activity with an amino acid sequence is clearly underlined, making it easy to identify at once the orphan enzyme activities. Interactive publishing of suggestions by the community would provide expert evidence for re-annotation of orphan EC numbers in public databases. Conclusion ORENZA is a Web resource designed to progressively bridge the unwanted gap between function (enzyme activities) and sequence (dataset present in public databases). ORENZA should increase interactions between communities of biochemists and of genomicists. This is expected to reduce the number of orphan enzyme activities by allocating gene sequences to the relevant enzymes. PMID:17026747

Elements including metals in the atomizer and aerosol of disposable electronic cigarettes and electronic hookahs

PubMed Central

Williams, Monique; Bozhilov, Krassimir; Ghai, Sanjay; Talbot, Prue

2017-01-01

Objective Our purpose was to quantify 36 inorganic chemical elements in aerosols from disposable electronic cigarettes (ECs) and electronic hookahs (EHs), examine the effect of puffing topography on elements in aerosols, and identify the source of the elements. Methods Thirty-six inorganic chemical elements and their concentrations in EC/EH aerosols were determined using inductively coupled plasma optical emission spectroscopy, and their source was identified by analyzing disassembled atomizers using scanning electron microscopy and energy dispersive X-ray spectroscopy. Results Of 36 elements screened, 35 were detected in EC/EH aerosols, while only 15 were detected in conventional tobacco smoke. Some elements/metals were present in significantly higher concentrations in EC/EH aerosol than in cigarette smoke. Concentrations of particular elements/metals within EC/EH brands were sometimes variable. Aerosols generated at low and high air-flow rates produced the same pattern of elements, although the total element concentration decreased at the higher air flow rate. The relative amount of elements in the first and last 60 puffs was generally different. Silicon was the dominant element in aerosols from all EC/EH brands and in cigarette smoke. The elements appeared to come from the filament (nickel, chromium), thick wire (copper coated with silver), brass clamp (copper, zinc), solder joints (tin, lead), and wick and sheath (silicon, oxygen, calcium, magnesium, aluminum). Lead was identified in the solder and aerosol of two brands of EHs (up to 0.165 μg/10 puffs). Conclusion These data show that EC/EH aerosols contain a mixture of elements, including heavy metals, with concentrations often significantly higher than in conventional cigarette smoke. While the health effects of inhaling mixtures of heated metals is currently not known, these data will be valuable in future risk assessments involving EC/EH elements/metals. PMID:28414730

Mouths of the Amazon River, Brazil, South America

NASA Technical Reports Server (NTRS)

1992-01-01

In this view of the Amazon River Mouth (0.0, 51.0W), a large sediment plume can be seen expanding outward into the Atlantic Ocean. The sediment plume can be seen hugging the coast north of the delta as a result of the northwest flowing coastal Guyana Current. In recent years, the flow of the Amazon has become heavily laden with sediment as soil runoff from the denuded landscape of the interior enters the Amazon River (and other rivers) drainage system.

Comparative genomics of enterohemorrhagic Escherichia coli O145:H28 demonstrates a common evolutionary lineage with Escherichia coli O157:H7

PubMed Central

2014-01-01

Background Although serotype O157:H7 is the predominant enterohemorrhagic Escherichia coli (EHEC), outbreaks of non-O157 EHEC that cause severe foodborne illness, including hemolytic uremic syndrome have increased worldwide. In fact, non-O157 serotypes are now estimated to cause over half of all the Shiga toxin-producing Escherichia coli (STEC) cases, and outbreaks of non-O157 EHEC infections are frequently associated with serotypes O26, O45, O103, O111, O121, and O145. Currently, there are no complete genomes for O145 in public databases. Results We determined the complete genome sequences of two O145 strains (EcO145), one linked to a US lettuce-associated outbreak (RM13514) and one to a Belgium ice-cream-associated outbreak (RM13516). Both strains contain one chromosome and two large plasmids, with genome sizes of 5,737,294 bp for RM13514 and 5,559,008 bp for RM13516. Comparative analysis of the two EcO145 genomes revealed a large core (5,173 genes) and a considerable amount of strain-specific genes. Additionally, the two EcO145 genomes display distinct chromosomal architecture, virulence gene profile, phylogenetic origin of Stx2a prophage, and methylation profile (methylome). Comparative analysis of EcO145 genomes to other completely sequenced STEC and other E. coli and Shigella genomes revealed that, unlike any other known non-O157 EHEC strain, EcO145 ascended from a common lineage with EcO157/EcO55. This evolutionary relationship was further supported by the pangenome analysis of the 10 EHEC str ains. Of the 4,192 EHEC core genes, EcO145 shares more genes with EcO157 than with the any other non-O157 EHEC strains. Conclusions Our data provide evidence that EcO145 and EcO157 evolved from a common lineage, but ultimately each serotype evolves via a lineage-independent nature to EHEC by acquisition of the core set of EHEC virulence factors, including the genes encoding Shiga toxin and the large virulence plasmid. The large variation between the two EcO145 genomes suggests a distinctive evolutionary path between the two outbreak strains. The distinct methylome between the two EcO145 strains is likely due to the presence of a BsuBI/PstI methyltransferase gene cassette in the Stx2a prophage of the strain RM13514, suggesting a role of horizontal gene transfer-mediated epigenetic alteration in the evolution of individual EHEC strains. PMID:24410921

Outward transport of high-temperature materials around the midplane of the solar nebula.

PubMed

Ciesla, Fred J

2007-10-26

The Stardust samples collected from Comet 81P/Wild 2 indicate that large-scale mixing occurred in the solar nebula, carrying materials from the hot inner regions to cooler environments far from the Sun. Similar transport has been inferred from telescopic observations of protoplanetary disks around young stars. Models for protoplanetary disks, however, have difficulty explaining the observed levels of transport. Here I report the results of a new two-dimensional model that shows that outward transport of high-temperature materials in protoplanetary disks is a natural outcome of disk formation and evolution. This outward transport occurs around the midplane of the disk.

Turbine assembly containing an inner shroud

DOEpatents

Bagepalli, Bharat Sampathkumaran; Corman, Gregory Scot; Dean, Anthony John; DiMascio, Paul Stephen; Mirdamadi, Massoud

2000-01-01

A turbine assembly having a turbine stator, a ceramic inner shroud, and a first spring. The stator has a longitudinal axis and an outer shroud block with opposing and longitudinally outward facing first and second sides. The first side has a longitudinally outward projecting first ledge and has a first side portion located radially outward of the first ledge. The ceramic inner shroud has a first hook portion longitudinally and radially surrounding the first ledge. The first spring is attached to one of the first side portion and the first hook portion and unattachedly and resiliently contacts the other of the first side portion and the first hook portion.

Does anesthetic additivity imply a similar molecular mechanism of anesthetic action at N-methyl-D-aspartate receptors?

PubMed

Brosnan, Robert J; Pham, Trung L

2011-03-01

Isoflurane and carbon dioxide (CO(2)) negatively modulate N-methyl-d-aspartate (NMDA) receptors, but via different mechanisms. Isoflurane is a competitive antagonist at the NMDA receptor glycine binding site, whereas CO(2) inhibits NMDA receptor current through extracellular acidification. Isoflurane and CO(2) exhibit additive minimum alveolar concentration effects in rats, but we hypothesized that they would not additively inhibit NMDA receptor currents in vitro because they act at different molecular sites. NMDA receptors were expressed in frog oocytes and studied using 2-electrode voltage clamp techniques. A glycine concentration response for NMDA was measured in the presence and absence of CO(2). Concentration-response curves for isoflurane, H(+), CO(2), and ketamine as a function of NMDA inhibition were measured, and a Hill equation was used to calculate the EC(50) for each compound. Binary drug combinations containing ½ EC(50) were additive if NMDA current inhibition was not statistically different from 50%. The ½ EC(50) binary drug combinations decreased the percentage baseline NMDA receptor current as follows (mean ± SD, n = 5 to 6 oocytes each): CO(2)+ H(+) (51% ± 5%), CO(2 )+ isoflurane (54% ± 5%), H(+) + isoflurane (51% ± 3%), CO(2)+ ketamine (67% ± 8%), and H(+) + ketamine (64% ± 2%). In contrast to our hypothesis, NMDA receptor inhibition by CO(2) and isoflurane is additive. Possibly, CO(2) acidification modulates a pH-sensitive loop on the NMDA receptor that in turn alters glycine binding affinity on the GluN1 subunit. However, ketamine plus either CO(2) or H(+) synergistically inhibits NMDA receptor currents. Drugs acting via different mechanisms can thus exhibit additive or synergistic receptor effects. Additivity may not robustly indicate commonality between molecular anesthetic mechanisms.

Repeated electroconvulsive shock (ECS) alters the phosphorylation of glutamate receptor subunits in the rat hippocampus.

PubMed

Fumagalli, Fabio; Pasini, Matteo; Sartorius, Alexander; Scherer, Rosine; Racagni, Giorgio; Riva, Marco A; Gass, Peter

2010-10-01

Glutamate and its receptors are involved in the pathophysiology of mood disorders and have recently emerged as potential targets for the pharmacotherapy of depression. In rats, we investigated plasticity changes of the glutamatergic system evoked by electroconvulsive shock (ECS), which represents the most effective therapy for patients who are refractory to antidepressants. Chronic ECS produced a marked increase in the phosphorylation of the regulatory NMDA receptor subunit NR2B (Ser1303) and the AMPA receptor subunit GluR-A (Ser831) in the hippocampus, with no effects on the obligatory subunit NR1. No effects were found on total receptor subunit expression levels. We suggest that, at least in part, ECS exerts its clinical activity through the modulation of the glutamatergic synapses, via potentiation of AMPA currents mediated by GluR-A (Ser831) phosphorylation, and a reduction of NMDA receptor activity through the phosphorylation of NR2B (Ser1303), presumably uncoupling NR2B from its signalling partner CaMKII. These effects functionally resemble the recently described antidepressant effects of ketamine.

Strategy for the elucidation of elemental compositions of trace analytes based on a mass resolution of 100,000 full width at half maximum.

PubMed

Kaufmann, Anton

2010-07-30

Elemental compositions (ECs) can be elucidated by evaluating the high-resolution mass spectra of unknown or suspected unfragmented analyte ions. Classical approaches utilize the exact mass of the monoisotopic peak (M + 0) and the relative abundance of isotope peaks (M + 1 and M + 2). The availability of high-resolution instruments like the Orbitrap currently permits mass resolutions up to 100,000 full width at half maximum. This not only allows the determination of relative isotopic abundances (RIAs), but also the extraction of other diagnostic information from the spectra, such as fully resolved signals originating from (34)S isotopes and fully or partially resolved signals related to (15)N isotopes (isotopic fine structure). Fully and partially resolved peaks can be evaluated by visual inspection of the measured peak profiles. This approach is shown to be capable of correctly discarding many of the EC candidates which were proposed by commercial EC calculating algorithms. Using this intuitive strategy significantly extends the upper mass range for the successful elucidation of ECs. Copyright 2010 John Wiley & Sons, Ltd.

THE ENDOTHELIUM IN SEPSIS

PubMed Central

Ince, Can; Mayeux, Philip R.; Nguyen, Trung; Gomez, Hernando; Kellum, John A.; Ospina-Tascón, Gustavo A.; Hernandez, Glenn; Murray, Patrick; De Backer, Daniel

2017-01-01

Sepsis affects practically all aspects of endothelial cell (EC) function and is thought to be the key factor in the progression from sepsis to organ failure. Endothelial functions affected by sepsis include vasoregulation, barrier function, inflammation, and hemostasis. These are among other mechanisms often mediated by glycocalyx shedding, such as abnormal nitric oxide metabolism, up-regulation of reactive oxygen species generation due to down-regulation of endothelial-associated antioxidant defenses, transcellular communication, proteases, exposure of adhesion molecules, and activation of tissue factor. This review covers current insight in EC-associated hemostatic responses to sepsis and the EC response to inflammation. The endothelial cell lining is highly heterogeneous between different organ systems and consequently also in its response to sepsis. In this context, we discuss the response of the endothelial cell lining to sepsis in the kidney, liver, and lung. Finally, we discuss evidence as to whether the EC response to sepsis is adaptive or maladaptive. This study is a result of an Acute Dialysis Quality Initiative XIV Sepsis Workgroup meeting held in Bogota, Columbia, between October 12 and 15, 2014. PMID:26871664

Flow Perturbation Mediates Neutrophil Recruitment and Potentiates Endothelial Injury via TLR2 in Mice – Implications for Superficial Erosion

PubMed Central

Franck, Grégory; Mawson, Thomas; Sausen, Grasiele; Salinas, Manuel; Masson, Gustavo Santos; Cole, Andrew; Beltrami-Moreira, Marina; Chatzizisis, Yiannis; Quillard, Thibault; Tesmenitsky, Yevgenia; Shvartz, Eugenia; Sukhova, Galina K.; Swirski, Filip K.; Nahrendorf, Matthias; Aikawa, Elena; Croce, Kevin J.; Libby, Peter

2017-01-01

Rationale Superficial erosion currently causes up to a third of acute coronary syndromes (ACS), yet we lack understanding of its mechanisms. Thrombi due to superficial intimal erosion characteristically complicate matrix-rich atheromata in regions of flow perturbation. Objective This study tested in vivo the involvement of disturbed flow, and of neutrophils, hyaluronan, and TLR2 ligation in superficial intimal injury, a process implicated in superficial erosion. Methods and Results : In mouse carotid arteries with established intimal lesions tailored to resemble the substrate of human eroded plaques, acute flow perturbation promoted downstream endothelial cell (EC) activation, neutrophil accumulation, EC death and desquamation, and mural thrombosis. Neutrophil loss-of-function limited these findings. TLR2 agonism activated luminal ECs, and deficiency of this innate immune receptor decreased intimal neutrophil adherence in regions of local flow disturbance, reducing EC injury and local thrombosis (p<0.05). Conclusions These results implicate flow disturbance, neutrophils, and TLR2 signaling as mechanisms that contribute to superficial erosion, a cause of ACS of likely growing importance in the statin era. PMID:28428204

Electrochemical control of iodine disinfectant for space transportation system and space station potable water

NASA Technical Reports Server (NTRS)

Geer, Richard D.

1989-01-01

An electrochemical microbial check valve method (EC-MCV) for controlling the iodine disinfectant in potable water (PW) for NASA's space operations was proposed. The factors affecting the design and performance of the unit were analyzed. This showed that it would be feasible to construct a recyclable unit in a small volume that will operate in either an iodine removal or addition mode. The EC-MCV should remove active iodine species rapidly from PW, but the rapid delivery rates at end-use may make complete removal of excess I(-) difficult under some conditions. Its performace change with AgI buildup needs to be investigated, as this controls the time for recycling the unit. The EC-MCV has advantages over the passive microbial check valve (MCV) method currently in use, as it would allow precise control of the I2 level and would not introduce excess I(-) to the water. The presence of oxygen in the EC-MCV needs to be investigated as it could affect the efficiency of I2 addition and excess I(-) removal.

Azo dyes wastewater treatment and simultaneous electricity generation in a novel process of electrolysis cell combined with microbial fuel cell.

PubMed

Zou, Haiming; Wang, Yan

2017-07-01

A new process of electrolysis cell (EC) coupled with microbial fuel cell (MFC) was developed here and its feasibility in methyl red (MR) wastewater treatment and simultaneous electricity generation was assessed. Results indicate that an excellent MR removal and electricity production performance was achieved, where the decolorization and COD removal efficiencies were 100% and 89.3%, respectively and a 0.56V of cell voltage output was generated. Electrolysis voltage showed a positive influence on decolorization rate (DR) but also cause a rapid decrease in current efficiency (CE). Although a low COD removal rate of 38.5% was found in EC system, biodegradability of MR solution was significantly enhanced, where the averaged DR was 85.6%. Importantly, COD removal rate in EC-MFC integrated process had a 50.8% improvement compared with the single EC system. The results obtained here would be beneficial to provide a prospective alternative for azo dyes wastewater treatment and power production. Copyright © 2017 Elsevier Ltd. All rights reserved.

Can electrocoagulation process be an appropriate technology for phosphorus removal from municipal wastewater?

PubMed

Nguyen, D Duc; Ngo, H Hao; Guo, W; Nguyen, T Thanh; Chang, Soon W; Jang, A; Yoon, Yong S

2016-09-01

This paper evaluated a novel pilot scale electrocoagulation (EC) system for improving total phosphorus (TP) removal from municipal wastewater. This EC system was operated in continuous and batch operating mode under differing conditions (e.g. flow rate, initial concentration, electrolysis time, conductivity, voltage) to evaluate correlative phosphorus and electrical energy consumption. The results demonstrated that the EC system could effectively remove phosphorus to meet current stringent discharge standards of less than 0.2mg/L within 2 to 5min. This target was achieved in all ranges of initial TP concentrations studied. It was also found that an increase in conductivity of solution, voltages, or electrolysis time, correlated with improved TP removal efficiency and reduced specific energy consumption. Based on these results, some key economic considerations, such as operating costs, cost-effectiveness, product manufacturing feasibility, facility design and retrofitting, and program implementation are also discussed. This EC process can conclusively be highly efficient in a relatively simple, easily managed, and cost-effective for wastewater treatment system. Copyright © 2016 Elsevier B.V. All rights reserved.

The Articulatory In-Out Effect Resists Oral Motor Interference

ERIC Educational Resources Information Center

Lindau, Berit; Topolinski, Sascha

2018-01-01

People prefer words with inward directed consonantal patterns (e.g., MENIKA) compared to outward patterns (KENIMA), because inward (outward) articulation movements resemble positive (negative) mouth actions such as swallowing (spitting). This effect might rely on covert articulation simulations, or subvocalizations, since it occurs also under…

Summer in the City

ERIC Educational Resources Information Center

Gewertz, Catherine

2005-01-01

This article describes the different experiences of the participants in an Outward Bound-sponsored "urban expedition" to New York City that was designed to make them better teachers by examining their beliefs and biases. The participants in this "urban expedition" came from schools that work with Outward Bound USA, the…

Colorado Outward Bound School Rafting Manual.

ERIC Educational Resources Information Center

Brown, Al

River rafting trips at the Colorado Outward Bound School (COBS) present participants with an opportunity for developing self-confidence, self-awareness, and concern for others through challenging and adventuresome group effort, combined with a program of instruction in rafting skills, safety consciousness, and awareness of the natural environment.…

Logistics Handbook, 1976. Colorado Outward Bound School.

ERIC Educational Resources Information Center

Colorado Outward Bound School, Denver.

Logistics, a support mission, is vital to the successful operation of the Colorado Outward Bound School (COBS) courses. Logistics is responsible for purchasing, maintaining, transporting, and replenishing a wide variety of items, i.e., food, mountaineering and camping equipment, medical and other supplies, and vehicles. The Logistics coordinator…

The Equivalent Electrokinetic Circuit Model of Ion Concentration Polarization Layer: Electrical Double Layer, Extended Space Charge and Electro-convection

NASA Astrophysics Data System (ADS)

Cho, Inhee; Huh, Keon; Kwak, Rhokyun; Lee, Hyomin; Kim, Sung Jae

2016-11-01

The first direct chronopotentiometric measurement was provided to distinguish the potential difference through the extended space charge (ESC) layer which is formed with the electrical double layer (EDL) near a perm-selective membrane. From this experimental result, the linear relationship was obtained between the resistance of ESC and the applied current density. Furthermore, we observed the step-wise distributions of relaxation time at the limiting current regime, confirming the existence of ESC capacitance other than EDL's. In addition, we proposed the equivalent electrokinetic circuit model inside ion concentration polarization (ICP) layer under rigorous consideration of EDL, ESC and electro-convection (EC). In order to elucidate the voltage configuration in chronopotentiometric measurement, the EC component was considered as the "dependent voltage source" which is serially connected to the ESC layer. This model successfully described the charging behavior of the ESC layer with or without EC, where both cases determined each relaxation time, respectively. Finally, we quantitatively verified their values utilizing the Poisson-Nernst-Planck equations. Therefore, this unified circuit model would provide a key insight of ICP system and potential energy-efficient applications.

Conductivity tomography based on pulsed eddy current with SQUID magnetometer

NASA Astrophysics Data System (ADS)

Panaitov, G. I.; Krause, H.-J.; Zhang, Y.

2002-05-01

Pulsed eddy current (EC) techniques have the advantage of potentially covering a broader depth range than standard single frequency EC testing. We developed a novel pulsed EC technique using a liquid-nitrogen cooled SQUID magnetometer. For two reasons, SQUID magnetometers are particularly well suited as sensors: first they constitute an extremely sensitive magnetic field sensor, second they measure the field directly which decays more slowly than its time derivative picked up by induction coils. A square waveform transmitter signal was used, with alternating slopes in order to eliminate drift effect, and stacking synchronous to the power line frequency in order to improve signal-to-noise. The early time (high frequency) data of the recorded transient correspond to the upper layers of the conducting medium, while late time data or low frequencies deliver information on deep layers. Measurements of cracks at different depths in a stacked aluminum sample are presented. From the measured data, the apparent conductivity of the sample was calculated for each position and depth by applying a technique known from geophysical data interpretation. Thus, the position and depth of the crack was determined from the tomographic conductivity image of the sample.

Purification and detoxification of petroleum refinery wastewater by electrocoagulation process.

PubMed

Gousmi, N; Sahmi, A; Li, H Z; Poncin, S; Djebbar, R; Bensadok, K

2016-09-01

The treatment of synthetic oily wastewater having the characteristics of a typical petroleum refinery wastewater (PRW) by electrocoagulation (EC) using iron and aluminum electrodes was conducted in an electrolytic reactor equipped with fluid recirculation. During the treatment, the emulsion stability was followed by the measurement of Zeta potential and particle sizes. Effects of some operating conditions such as electrodes material, current density and electrolysis time on removal efficiencies of turbidity, and chemical oxygen demand (COD) were investigated in detail. The PRW purification by the EC process was found to be the most effective using aluminum as the anode and cathode, current density of 60 A/m(2) and 30 min of electrolysis time. Under these conditions, the process efficiencies were 83.52% and 99.94%, respectively, for COD and turbidity removals which correspond to final values of 96 mg O2/L and 0.5 NTU. A moderate energy consumption (0.341 kWh) was needed to treat 1 m(3) of PRW. Besides, the ecotoxicity test proved that toxic substances presented in the PRW, and those inhibiting the germination growth of whet, were eliminated by the EC technique.

Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression

PubMed Central

Sigrist, Hannes; Seifritz, Erich; Fikse, Lianne; Bosker, Fokko J.; Schoevers, Robert A.; Klein, Hans C.

2017-01-01

Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the mechanism of ECT antidepressant function but does provide evidence for pathophysiological mechanisms that might contribute to important ECT side-effects. PMID:28910337

Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression.

PubMed

van Buel, Erin M; Sigrist, Hannes; Seifritz, Erich; Fikse, Lianne; Bosker, Fokko J; Schoevers, Robert A; Klein, Hans C; Pryce, Christopher R; Eisel, Ulrich Lm

2017-01-01

Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the mechanism of ECT antidepressant function but does provide evidence for pathophysiological mechanisms that might contribute to important ECT side-effects.

Database search of spontaneous reports and pharmacological investigations on the sulfonylureas and glinides-induced atrophy in skeletal muscle

PubMed Central

Mele, Antonietta; Calzolaro, Sara; Cannone, Gianluigi; Cetrone, Michela; Conte, Diana; Tricarico, Domenico

2014-01-01

The ATP-sensitive K+ (KATP) channel is an emerging pathway in the skeletal muscle atrophy which is a comorbidity condition in diabetes. The “in vitro” effects of the sulfonylureas and glinides were evaluated on the protein content/muscle weight, fibers viability, mitochondrial succinic dehydrogenases (SDH) activity, and channel currents in oxidative soleus (SOL), glycolitic/oxidative flexor digitorum brevis (FDB), and glycolitic extensor digitorum longus (EDL) muscle fibers of mice using biochemical and cell-counting Kit-8 assay, image analysis, and patch-clamp techniques. The sulfonylureas were: tolbutamide, glibenclamide, and glimepiride; the glinides were: repaglinide and nateglinide. Food and Drug Administration-Adverse Effects Reporting System (FDA-AERS) database searching of atrophy-related signals associated with the use of these drugs in humans has been performed. The drugs after 24 h of incubation time reduced the protein content/muscle weight and fibers viability more effectively in FDB and SOL than in the EDL. The order of efficacy of the drugs in reducing the protein content in FDB was: repaglinide (EC50 = 5.21 × 10−6) ≥ glibenclamide(EC50 = 8.84 × 10−6) > glimepiride(EC50 = 2.93 × 10−5) > tolbutamide(EC50 = 1.07 × 10−4) > nateglinide(EC50 = 1.61 × 10−4) and it was: repaglinide(7.15 × 10−5) ≥ glibenclamide(EC50 = 9.10 × 10−5) > nateglinide(EC50 = 1.80 × 10−4) ≥ tolbutamide(EC50 = 2.19 × 10−4) > glimepiride(EC50=–) in SOL. The drug-induced atrophy can be explained by the KATP channel block and by the enhancement of the mitochondrial SDH activity. In an 8-month period, muscle atrophy was found in 0.27% of the glibenclamide reports in humans and in 0.022% of the other not sulfonylureas and glinides drugs. No reports of atrophy were found for the other sulfonylureas and glinides in the FDA-AERS. Glibenclamide induces atrophy in animal experiments and in human patients. Glimepiride shows less potential for inducing atrophy. PMID:25505577

Universal screening of both endometrial and colon cancers increases the detection of Lynch syndrome.

PubMed

Adar, Tomer; Rodgers, Linda H; Shannon, Kristen M; Yoshida, Makoto; Ma, Tianle; Mattia, Anthony; Lauwers, Gregory Y; Iafrate, Anthony J; Hartford, Nicole M; Oliva, Esther; Chung, Daniel C

2018-05-11

Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC) and endometrial cancer (EC). Screening of all CRCs for LS is currently recommended, but screening of ECs is inconsistent. The objective of this study was to determine the added value of screening both CRC and EC tumors in the same population. A prospective, immunohistochemistry (IHC)-based screening program for all patients with newly diagnosed CRCs and ECs was initiated in 2011 and 2013, respectively, at 2 centers (primary and tertiary). Genetic testing was recommended for those who had tumors with absent mutS homolog 2 (MSH2), MSH6, or postmeiotoic segregation increased 2 (PMS2) expression and for those who had tumors with absent mutL homolog 1 (MLH1) expression and no v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutation or MLH1 promoter methylation. Amsterdam II criteria, revised Bethesda criteria, and scores from prediction models for gene mutations (the PREMM 1,2,6 and PREMM 5 prediction models) were ascertained in patients with LS. In total, 1290 patients with CRC and 484 with EC were screened for LS, and genetic testing was recommended for 137 patients (10.6%) and 32 patients (6.6%), respectively (P = .01). LS was identified in 16 patients (1.2%) with CRC and in 8 patients (1.7%) with EC. Among patients for whom genetic testing was recommended, the LS diagnosis rate was higher among those with EC (25.0% vs 11.7%, P = .052). The Amsterdam II criteria, revised Bethesda criteria, and both PREMM calculators would have missed 62.5%, 50.0%, and 12.5% of the identified patients with LS, respectively. Expanding a universal screening program for LS to include patients who had EC identified 50% more patients with LS, and many of these patients would have been missed by risk assessment tools (including PREMM 5 ). Universal screening programs for LS should include both CRC and EC. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

The impact of simulated microgravity on purinergic signaling in an endothelial and smooth muscle cell co-culture model

NASA Astrophysics Data System (ADS)

Zhang, Yu; Hemmersbach, Ruth; Lau, Patrick; Pansky, Andreas; Kassack, Matthias; Tobiasch, Edda

Astronauts suffer from cardiovascular deconditioning when they are exposed to microgravity conditions during space missions. Thus, current research focuses on the identification of the underlying mechanism also with respect to therapy and countermeasures. Endothelial cells (ECs) and smooth muscle cells (SMCs) play a key role in a variety of vascular functions. Gene expression, cytoskeleton morphology and apoptosis in both, ECs and SMCs, have shown alterations under simulated and real microgravity condition. However, all these data were observed during single culturing of either ECs or SMCs under microgravity conditions, which is different from the in vivo situation. Purinergic 2 (P2) receptors bind extracellular nucleotides and can regulate the vascular tone and vascular cell proliferation, migration and apoptosis. In this study primary ECs and SMCs were obtained from bovine aorta and characterized using specific markers. Here we show for the first time that the P2-receptor expressions pattern in ECs and in SMCs is altered after 24h in simulated microgravity. Specific receptors are down- or up-regulated on the gene and protein level. In addition the supernatant of ECs during culture was used as conditioned medium for SMCs and vice visa to investigate the influence of either cell type on the other. ECs and SMCs secret cytokines which induce pathogenic proliferation and an altered migration behavior under simulated microgravity conditions. Interestingly, co-culturing with condition medium could compensate this change. In detail, P2X7 was down-regulated in ECs after 24h clinorotation but recovered to the 1 g level when cultured with conditioned medium from SMCs collected under normal gravity. In conclusion, our data indicate that the paracrine effect between ECs and SMCs is an important regulator of cell behavior, also under altered gravity conditions. P2-receptor gene and protein expression were altered during microgravity. Since several P2-receptor artificial ligands are already established as drugs, P2-receptors might be a reasonable candidate for drug development for astronaut treatment of vascular deconditioning in the future. Keywords: simulated microgravity, purinergic signaling, endothelial cells, smooth muscle cells, co-culture, clinostat

DoD Electronic Commerce (EC)/Electronic Data Interchange (EDI) in Contracting Report

DTIC Science & Technology

1993-12-20

Electronic Commerce (EC)/Electronic Data Interchange (EDI) to support Department of Defense (DoD) procurement processes has been under consideration for some time. A 1988 Deputy Secretary of Defense memo calls for maximum use of EDI, based on 10 years of DoD EDI investigation and experiments. In 1990, Defense Management Review Decision 941 stated, ’The strategic goal of DoD’s current efforts is to provide the department with the capability to initiate, conduct, and maintain its external business related transactions and internal logistics, contracting, and

Does Anger Regulation Mediate the Discrimination-Mental Health Link among Mexican-Origin Adolescents? A Longitudinal Mediation Analysis Using Multilevel Modeling

PubMed Central

Park, Irene J. K.; Wang, Lijuan; Williams, David R.; Alegría, Margarita

2016-01-01

Although prior research has consistently documented the association between racial/ethnic discrimination and poor mental health outcomes, the mechanisms that underlie this link are still unclear. The present three-wave longitudinal study tested the mediating role of anger regulation in the discrimination—mental health link among 269 Mexican-origin adolescents (Mage = 14.1 years, SD = 1.6; 57% girls), 12 – 17 years old. Three competing anger regulation variables were tested as potential mediators: outward anger expression, anger suppression, and anger control. Longitudinal mediation analyses were conducted using multilevel modeling that disaggregated within-person effects from between-person effects. Results indicated that outward anger expression was a significant mediator; anger suppression and anger control were not significant mediators. Within a given individual, greater racial/ethnic discrimination was associated with more frequent outward anger expression. In turn, more frequent outward anger expression was associated with higher levels of anxiety and depression at a given time point. Gender, age, and nativity status were not significant moderators of the hypothesized mediation models. By identifying outward anger expression as an explanatory mechanism in the discrimination-distress link among Latino youths, this study points to a malleable target for prevention and intervention efforts aimed at mitigating the detrimental impact of racism on Latino youths’ mental health during the developmentally critical period of adolescence. PMID:27893238

Active ion transport in dog tongue: a possible role in taste.

PubMed

DeSimone, J A; Heck, G L; DeSimone, S K

1981-11-27

An in vitro preparation of the dorsal epithelium of the dog tongue actively transports ions, producing a transepithelial potential difference characteristic of the ions and their concentration. Hypertonic sodium chloride solutions generally cause increased potentials and short-circuit currents and reduced resistances when placed on the mucosal surface. This hypertonic flux is eliminated by ouabain and is not found in ventral lingual epithelia. When either sodium acetate or tetramethylammonium chloride is substituted for sodium chloride in the mucosal medium, the currents are diminished but their sum at a given concentration approximates that for sodium chloride at the same concentration. This result suggests a current composed of inward sodium ion movement and outward chloride ion movement. Actively regulated potentials and currents, whether generated in the taste buds or in supporting cells, may be important in both normal chemotransduction and in taste responses evoked by currents passing through the tongue.

Transverse field focused system

DOEpatents

Anderson, O.A.

1983-06-01

It is an object of the invention to provide a transport apparatus for a high current negative-ion beam which will bend the beam around corners through a baffled path in a differential pump or a neutron trap. It is another object of the invention to provide a transport apparatus for a high current negative-ion beam which will allow gas molecules in the beam to exit outwardly from the transport apparatus. A further object of the invention is to provide a multi-stage accelerator for a high current negative-ion beam which will enable acceleration of the beam to very high energy levels with a minimum loss of current carrying capacity. A still further object of the invention is to provide an apparatus for transport or accelertion of a sheet beam of negative ions which is shaped to confine the beam against divergence or expansion.

The role of Na-Ca exchange current in the cardiac action potential.

PubMed

Janvier, N C; Boyett, M R

1996-07-01

Since 1981, when Mullins published his provocative book proposing that the Na-Ca exchanger is electrogenic, it has been shown, first by computer simulation by Noble and later by experiment by various investigators, that inward iNaCa triggered by the Ca2+ transient is responsible for the low plateau of the atrial action potential and contributes to the high plateau of the ventricular action potential. Reduction or complete block of inward iNaCa by buffering intracellular Ca2+ with EGTA or BAPTA, by blocking SR Ca2+ release or by substituting extracellular Na+ with Li+ can result in a shortening of the action potential. The effect of block of outward iNaCa or complete block of both inward and outward iNaCa on the action potential has not been investigated experimentally, because of the lack of a suitable blocker, and remains a goal for the future. An increase in the intracellular Na+ concentration (after the application of cardiac glycoside or an increase in heart rate) or an increase in extracellular Ca2+ are believed to lead to an outward shift in iNaCa at plateau potentials and a shortening of the action potential. Changes in the Ca2+ transient are expected to result in changes in inward iNaCa and thus the action potential. This may explain the shortening of the premature action potential as well as the prolongation of the action potential when a muscle is allowed to shorten during the action potential. Inward iNaCa may play an important role in both normal and abnormal pacemaker activity in the heart.

Outward foreign direct investments and home country's economic growth

NASA Astrophysics Data System (ADS)

Ciesielska, Dorota; Kołtuniak, Marcin

2017-09-01

The study examines the time stability of the causality direction and cross-correlations between the home country's economic growth and pace of growth of its outward foreign direct investment (OFDI) stocks within the complex system of the Polish national economy. The research has been performed in order to verify, using both the time and frequency domains time series analyses, if economic agents' long term decisions on outward foreign direct investments, leading to cross-border value chains and production fragmentation processes, are of adaptive or predictive character. Consequently, the aim was to check if the home country's economic growth leads the internationalization processes of domestic enterprises, which stays in line with Dunning's Investment Development Path (IDP) paradigm, or if these complex processes, thanks to entrepreneurs' ability to formulate relevant rational expectations, precede the home country's economic growth, which would be supported with the introduction of the policy on reinforcing the internationalization processes of domestic enterprises. The presence of the unidirectional economic growth-led internationalization, consistent with the IDP concept's base assumptions, has been ascertained by the results of the short term Granger causality tests. Nevertheless, the results of the wavelet analyses, supported with the results of the econometric block exogeneity long term causality Wald tests, have revealed that in the long term the OFDI stocks' growth permanently precedes the home country's economic growth, which stays in the unequivocal contrast with the IDP paradigm's premises, as well as with the indicated above short term Granger causality tests' outcomes and indicates that economic agents' choices are not strictly of adaptive but also of predictive character, which influences the current state of knowledge on economic complex systems' characteristics. Such a result is of a great importance in the light of the existence of the significant and still unexploited internationalization potential of Polish enterprises.

Outdoor Education Academic Programs in the United States

ERIC Educational Resources Information Center

Bell, Brent J.; Seaman, Jayson; Trauntvein, Nate

2017-01-01

The growth of outdoor adventure programs developed, in part, from the Outward Bound movement in the 1970s (MacArthur, 1979; Outward Bound, 1968), which created a demand for specialized collegiate training. Since the inaugural conference on outdoor pursuits in higher education at Appalachian State University in 1974 (Smathers, 1974), approximately…

Outward Bound...Into the Mainstream of Education.

ERIC Educational Resources Information Center

Outward Bound, Inc., Andover, MA.

Outward Bound schools have instituted advanced courses designed specifically for adults engaged in education and youth work. Benefits for teachers include greater development of capacitites and potentialities, greater confidence in their abilities, and the ability to relate more effectively to others. Some of the specific training elements in an…

Instructor's Field Manual: North Carolina Outward Bound School.

ERIC Educational Resources Information Center

Outward Bound, Morganton, NC.

A supplement to the North Carolina Outward Bound School's Instructor's Handbook, this field manual presents useful, but not required, information gleaned from old timers and resource books which may enable the instructor to conduct a better course. Section one considers advantages and disadvantages and provides directions and topographical maps…

An Investigation of the Outward Bound Final Expedition

ERIC Educational Resources Information Center

Bobilya, Andrew J.; Kalisch, Ken; Daniel, Brad

2011-01-01

Research of wilderness programs indicates a clear need for additional investigation of specific program components and their influence on participant outcomes. This study examines one component of the Outward Bound wilderness program--the Final Expedition. The Final Expedition is a student-led wilderness expedition and is also referred to as an…

Adapted Outward Bound Programmes: An Alternative for Corrections.

ERIC Educational Resources Information Center

Cardwell, G. R.

A number of programmes for delinquent youth have been established throughout North America based on the Outward Bound concept: to involve volunteer participants in an outdoor programme which offers challenging and adventuresome tasks in a high-impact environment. Project D.A.R.E. (Development through Adventure, Responsibility and Education) in…

Alternate Semester 1972. An Evaluation.

ERIC Educational Resources Information Center

Copp, Barry D.; And Others

Five students from a Boston high school and 35 from Lincoln-Sudbury took part in an alternate semester consisting of 5 units: Outward Bound, environmental issues, urban, rural, and river/building. Students had to be juniors or seniors, have parental permission, and meet graduation requirements. The alternate semester began with Outward Bound, a…

Girls Leading Outward

ERIC Educational Resources Information Center

Hamed, Heather; Reyes, Jazmin; Moceri, Dominic C.; Morana, Laura; Elias, Maurice J.

2011-01-01

The authors describe a program implemented in Red Bank Middle School in New Jersey to help at-risk, minority middle school girls realize their leadership potential. The GLO (Girls Leading Outward) program was developed by the Developing Safe and Civil Schools Project at Rutgers University and is facilitated by university students. Selected middle…

Determining Confounding Sensitivities In Eddy Current Thin Film Measurements

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

Gros, Ethan; Udpa, Lalita; Smith, James A.

Determining Confounding Sensitivities In Eddy Current Thin Film Measurements Ethan Gros, Lalita Udpa, Electrical Engineering, Michigan State University, East Lansing MI 48824 James A. Smith, Experiment Analysis, Idaho National Laboratory, Idaho Falls ID 83415 Eddy current (EC) techniques are widely used in industry to measure the thickness of non-conductive films on a metal substrate. This is done using a system whereby a coil carrying a high-frequency alternating current is used to create an alternating magnetic field at the surface of the instrument's probe. When the probe is brought near a conductive surface, the alternating magnetic field will induce ECs inmore » the conductor. The substrate characteristics and the distance of the probe from the substrate (the coating thickness) affect the magnitude of the ECs. The induced currents load the probe coil affecting the terminal impedance of the coil. The measured probe impedance is related to the lift off between coil and conductor as well as conductivity of the test sample. For a known conductivity sample, the probe impedance can be converted into an equivalent film thickness value. The EC measurement can be confounded by a number of measurement parameters. It is the goal of this research to determine which physical properties of the measurement set-up and sample can adversely affect the thickness measurement. The eddy current testing is performed using a commercially available, hand held eddy current probe (ETA3.3H spring loaded eddy probe running at 8 MHz) that comes with a stand to hold the probe. The stand holds the probe and adjusts the probe on the z-axis to help position the probe in the correct area as well as make precise measurements. The signal from the probe is sent to a hand held readout, where the results are recorded directly in terms of liftoff or film thickness. Understanding the effect of certain factors on the measurements of film thickness, will help to evaluate how accurate the ETA3.3H spring loaded eddy probe is at measuring film thickness under varying experimental conditions. This research will study the effects of a number of factors such as i) calibration, ii) conductivity, iii) edge effect, iv) surface finish of base material and v) cable condition and compare with the long term reproducibility of a standard measurement. This work was performed with support from the Department of Energy under the United States National Nuclear Security Administration (NNSA) at the Idaho National Laboratory.« less

Tobacco Consumption and Toxicant Exposure of Cigarette Smokers Using Electronic Cigarettes.

PubMed

Pulvers, Kim; Emami, Ashley S; Nollen, Nicole L; Romero, Devan R; Strong, David R; Benowitz, Neal L; Ahluwalia, Jasjit S

2018-01-05

There is considerable debate about the benefits and risks of electronic cigarettes (ECs). To better understand the risk-benefit ratio of ECs, more information is needed about net nicotine consumption and toxicant exposure of cigarette smokers switching to ECs. Forty cigarette smokers (≥1 year of smoking) interested in switching to ECs but not necessarily quitting smoking were enrolled in a 4-week observational study and provided an e-Go C non-variable battery and refillable atomizers and choice of eight flavors in 12 or 24 mg nicotine dosage. Measurement of urinary cotinine (metabolite of nicotine), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL; a pulmonary carcinogen), and eight volatile organic compounds (VOCs) that are toxic tobacco smoke constituents was conducted at baseline and week 4. All participants with follow-up data (92.5%) reported using the study EC. Of the 40 smokers, 16 reported no cigarettes at week 2 (40%) and six continued to report no cigarettes at week 4 (15%). Change in nicotine intake over the 4 weeks was non-significant (p = .90). Carbon monoxide (p < .001), NNAL (p < .01) and metabolites of benzene (p < .01) and acrylonitrile (p = .001) were significantly decreased in the study sample. Smokers switching exclusively to ECs for at least half of the study period demonstrated significant reductions in metabolites of ethylene oxide (p = .03) and acrylamide (p < .01). Smokers using ECs over 4 weeks maintained cotinine levels and experienced significant reductions in carbon monoxide, NNAL, and two out of eight measured VOC metabolites. Those who switched exclusively to ECs for at least half of the study period significantly reduced two additional VOCs. This study extends current literature by measuring change in smoking dependence and disease-associated biomarkers, NNAL and a panel of eight common VOCs that are toxic tobacco smoke constituents in smokers who switch to ECs. The findings support the idea of harm reduction, however some levels of toxicant exposure are still of clinical concern, particularly for dual users. Extrapolation of these results must be careful to separate the different toxic exposure results for exclusive switchers versus dual cigarette + EC users, and not to equate harm reduction with the idea that using ECs is harmless. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

14 CFR 1260.6 - Publication.

Code of Federal Regulations, 2010 CFR

2010-01-01

... § 1260.6 Publication. The official site for accessing the NASA Grant and Cooperative Agreement Handbook, including current Grant Notices, is on the internet at: http://ec.msfc.nasa.gov/hq/grcover.htm ...

14 CFR 1260.6 - Publication.

Code of Federal Regulations, 2012 CFR

2012-01-01

... § 1260.6 Publication. The official site for accessing the NASA Grant and Cooperative Agreement Handbook, including current Grant Notices, is on the internet at: http://ec.msfc.nasa.gov/hq/grcover.htm ...

14 CFR 1260.6 - Publication.

Code of Federal Regulations, 2013 CFR

2013-01-01

... § 1260.6 Publication. The official site for accessing the NASA Grant and Cooperative Agreement Handbook, including current Grant Notices, is on the internet at: http://ec.msfc.nasa.gov/hq/grcover.htm ...

14 CFR 1260.6 - Publication.

Code of Federal Regulations, 2011 CFR

2011-01-01

... § 1260.6 Publication. The official site for accessing the NASA Grant and Cooperative Agreement Handbook, including current Grant Notices, is on the internet at: http://ec.msfc.nasa.gov/hq/grcover.htm ...

Malignant transformation of a residual cerebellopontine angle epidermoid cyst.

PubMed

Pikis, Stylianos; Margolin, Emil

2016-11-01

Malignant transformation is a rare but devastating complication following partial resection of an intracranial epidermoid cyst (EC). Time to malignant transformation is highly variable and optimal management is unclear. A literature search from 1965 to January 2016 identified manuscripts discussing clinical presentation, management, and outcome of malignant transformation of a remnant intracranial EC. One male patient diagnosed with malignant transformation of a remnant intracranial EC in our institution was also included in the study. There were 21 patients with malignant transformation of a remnant intracranial EC, including the current patient. Mean age was 51.4years (range 36 to 77) and there was a female predominance (12 women, 9 men, ratio 1.33:1). The mean time interval from partial resection of a benign intracranial EC to malignant transformation was 7.74years (range from 3months to 33years). Surgical resection of the tumor alone was the treatment of choice in 10 patients with one of them requiring a second operation and radiotherapy 2months following the first operation. Adjuvant treatment modalities were employed in 11 patients and included radiotherapy (n=4), stereotactic radiosurgery (SRS) (n=3), chemotherapy (n=1), chemotherapy combined with SRS (n=1) and with radiotherapy (n=1) and radiotherapy combined with SRS and followed by a second tumor resection (n=1). Follow-up period ranged from 1 day to 5years and 11/19 patients (57.8%) were reported dead on follow-up. Prospective studies are required to define the optimal management of malignant transformation of remnant intracranial EC. Copyright © 2016 Elsevier Ltd. All rights reserved.

Flow Cytometric Quantification of Peripheral Blood Cell β-Adrenergic Receptor Density and Urinary Endothelial Cell-Derived Microparticles in Pulmonary Arterial Hypertension.

PubMed

Rose, Jonathan A; Wanner, Nicholas; Cheong, Hoi I; Queisser, Kimberly; Barrett, Patrick; Park, Margaret; Hite, Corrine; Naga Prasad, Sathyamangla V; Erzurum, Serpil; Asosingh, Kewal

2016-01-01

Pulmonary arterial hypertension (PAH) is a heterogeneous disease characterized by severe angiogenic remodeling of the pulmonary artery wall and right ventricular hypertrophy. Thus, there is an increasing need for novel biomarkers to dissect disease heterogeneity, and predict treatment response. Although β-adrenergic receptor (βAR) dysfunction is well documented in left heart disease while endothelial cell-derived microparticles (Ec-MPs) are established biomarkers of angiogenic remodeling, methods for easy large clinical cohort analysis of these biomarkers are currently absent. Here we describe flow cytometric methods for quantification of βAR density on circulating white blood cells (WBC) and Ec-MPs in urine samples that can be used as potential biomarkers of right heart failure in PAH. Biotinylated β-blocker alprenolol was synthesized and validated as a βAR specific probe that was combined with immunophenotyping to quantify βAR density in circulating WBC subsets. Ec-MPs obtained from urine samples were stained for annexin-V and CD144, and analyzed by a micro flow cytometer. Flow cytometric detection of alprenolol showed that βAR density was decreased in most WBC subsets in PAH samples compared to healthy controls. Ec-MPs in urine was increased in PAH compared to controls. Furthermore, there was a direct correlation between Ec-MPs and Tricuspid annular plane systolic excursion (TAPSE) in PAH patients. Therefore, flow cytometric quantification of peripheral blood cell βAR density and urinary Ec-MPs may be useful as potential biomarkers of right ventricular function in PAH.

Flow Cytometric Quantification of Peripheral Blood Cell β-Adrenergic Receptor Density and Urinary Endothelial Cell-Derived Microparticles in Pulmonary Arterial Hypertension

PubMed Central

Rose, Jonathan A.; Wanner, Nicholas; Cheong, Hoi I.; Queisser, Kimberly; Barrett, Patrick; Park, Margaret; Hite, Corrine; Naga Prasad, Sathyamangla V.; Erzurum, Serpil; Asosingh, Kewal

2016-01-01

Pulmonary arterial hypertension (PAH) is a heterogeneous disease characterized by severe angiogenic remodeling of the pulmonary artery wall and right ventricular hypertrophy. Thus, there is an increasing need for novel biomarkers to dissect disease heterogeneity, and predict treatment response. Although β-adrenergic receptor (βAR) dysfunction is well documented in left heart disease while endothelial cell-derived microparticles (Ec-MPs) are established biomarkers of angiogenic remodeling, methods for easy large clinical cohort analysis of these biomarkers are currently absent. Here we describe flow cytometric methods for quantification of βAR density on circulating white blood cells (WBC) and Ec-MPs in urine samples that can be used as potential biomarkers of right heart failure in PAH. Biotinylated β-blocker alprenolol was synthesized and validated as a βAR specific probe that was combined with immunophenotyping to quantify βAR density in circulating WBC subsets. Ec-MPs obtained from urine samples were stained for annexin-V and CD144, and analyzed by a micro flow cytometer. Flow cytometric detection of alprenolol showed that βAR density was decreased in most WBC subsets in PAH samples compared to healthy controls. Ec-MPs in urine was increased in PAH compared to controls. Furthermore, there was a direct correlation between Ec-MPs and Tricuspid annular plane systolic excursion (TAPSE) in PAH patients. Therefore, flow cytometric quantification of peripheral blood cell βAR density and urinary Ec-MPs may be useful as potential biomarkers of right ventricular function in PAH. PMID:27270458

A randomized controlled trial of electrocoagulation-enabled biopsy versus conventional biopsy in the diagnosis of endobronchial lesions.

PubMed

Khan, Ajmal; Aggarwal, Ashutosh N; Agarwal, Ritesh; Bal, Amanjit; Gupta, Dheeraj

2011-01-01

Although electrocoagulation at time of endobronchial biopsy can potentially reduce procedure-related bleeding during fiberoptic bronchoscopy (FOB), it can also impair quality of tissue specimen; credible data for either are lacking. To evaluate the impact of hot biopsy on the quality of tissue samples and to quantify the amount of procedure-related bleeding during endobronchial biopsy. In this single-center, prospective, single-blind, randomized controlled study we included adult patients referred for FOB and having endobronchial lesions. Patients were randomized to bronchial biopsy using an electrocoagulation-enabled biopsy forceps, with (EC+ group) or without (EC- group) application of electrocoagulation current (40 W for 10 s in a monopolar mode). Procedure-related bleeding was semi-quantified by observer description, as well as through a visual analogue scale. Overall quality of biopsy specimen and tissue damage were assessed and graded by a pulmonary pathologist blinded to FOB details. 160 patients were randomized to endobronchial biopsy with (n = 81) or without (n = 79) the application of electrocoagulation. There were no severe bleeding episodes in either group, and severity of bleeding in the EC+ and EC- groups was similar (median visual analogue scale scores of 14 and 16, respectively). Histopathological diagnosis was similar in the EC+ and EC- groups (77.8% and 82.3%, respectively). There was no significant difference in tissue quality between the two groups. Use of electrocoagulation-enabled endobronchial biopsy does not alter specimen quality and does not result in any significant reduction in procedure-related bleeding. Copyright © 2010 S. Karger AG, Basel.

Joint Contributions of Negative Emotionality, Positive Emotionality, and Effortful Control on Depressive Symptoms in Youth.

PubMed

Van Beveren, Marie-Lotte; Mezulis, Amy; Wante, Laura; Braet, Caroline

2016-11-02

From a clinical developmental perspective, temperament has been shown to confer vulnerability to depression among youth. High negative emotionality (NE), low positive emotionality (PE), and low effortful control (EC) have repeatedly been independently associated with youth depressive symptoms. However, far less research has examined the joint contributions of NE, PE, and EC on such symptoms. The present study builds upon previous research by examining how NE, PE, and EC jointly predict change in depressive symptoms over time among 211 youngsters (7-14 years, M = 10.7, SD = 1.81) who participated in an 8-month prospective study. Self-reported temperament and symptoms were assessed at baseline; self-reported symptoms were measured again at follow-up. Results suggest that all 3 temperamental traits need to be considered jointly in predicting change in depressive symptoms. Furthermore, results provide further support for the "best two out of three" principle. Surprisingly, results reveal that high EC might be maladaptive in the context of high emotional reactivity. Last, results show that the combination of high NE and low EC could be a possible pathway to the development of symptoms. The current study clarified how NE, PE, and EC may jointly confer risk-or protection for developing depressive symptoms during adolescence. The results highlight the need of taking into account all three temperamental traits in order to provide a more nuanced understanding of the risk for developing depressive symptoms at an early stage, as well as to provide customized care targeting temperamental vulnerability in depressed youth.

Cardiac transient outward potassium current: a pulse chemistry model of frequency-dependent properties.

PubMed

Liu, L; Krinsky, V I; Grant, A O; Starmer, C F

1996-01-01

Recent voltage-clamp studies of isolated myocytes have demonstrated widespread occurrence of a transient outward current (I(to)) carried by potassium ions. In the canine ventricle, this current is well developed in epicardial cells but not in endocardial cells. The resultant spatial dispersion of refractoriness is potentially proarrhythmic and may be amplified by channel blockade. The inactivation and recovery time constants of this channel are in excess of several hundred milliseconds, and consequently channel availability is frequency dependent at physiological stimulation rates. When the time constants associated with transitions between different channel conformations are rapid relative to drug binding kinetics, the interactions between drugs and an ion channel can be approximated by a sequence of first-order reactions, in which binding occurs in pulses in response to pulse train stimulation (pulse chemistry). When channel conformation transition time constants do not meet this constraint, analytical characterizations of the drug-channel interaction must then be modified to reflect the channel time-dependent properties. Here we report that the rate and steady-state amount of frequency-dependent inactivation of I(to) are consistent with a generalization of the channel blockade model: channel availability is reduced in a pulsatile exponential pattern as the stimulation frequency is increased, and the rate of reduction is a linear function of the pulse train depolarizing and recovery intervals. I(to) was reduced in the presence of quinidine. After accounting for the use-dependent availability of I(to) channels, we found little evidence of an additional use-dependent component of block after exposure to quinidine, suggesting that quinidine reacts with both open and closed I(to) channels as though the binding site is continuously accessible. The model provides a useful tool for assessing drug-channel interactions when the reaction cannot be continuously monitored.

Differences in transient outward currents of feline endocardial and epicardial myocytes.

PubMed

Furukawa, T; Myerburg, R J; Furukawa, N; Bassett, A L; Kimura, S

1990-11-01

Whole-cell voltage-clamp experiments were performed on enzymatically dissociated single ventricular myocytes harvested from feline endocardial and epicardial surfaces. The studies were designed to test the hypothesis that the differences in the amplitude of transient outward current (Ito) contribute to the difference in action potential configuration between endocardial and epicardial myocytes. In the control state, action potentials recorded from epicardial cells demonstrated a prominent notch between phases 1 and 2, and membrane current recordings displayed a prominent Ito, whereas in endocardial cells the notch in action potentials and Ito were small. External application of 4-aminopyridine (2 mM) reduced the amplitudes of notch and Ito in epicardial cells but not in endocardial cells. After application of 4-aminopyridine (2 mM) and caffeine (5 mM), the notch and Ito were abolished completely in both endocardial and epicardial cells. The first component of Ito (Ito1) was present in all epicardial cells studied (n = 20); it was absent in 12 of the 20 endocardial cells, and a small Ito1 was present in the remaining eight endocardial cells. The mean amplitude of Ito1 was significantly greater in epicardial than in endocardial cells. At a test voltage of +80 mV, the amplitude of Ito1 was 102.0 +/- 47.7 pA/pF in epicardial cells and 3.3 +/- 3.3 pA/pF in endocardial cells (p less than 0.01). The second component of Ito (Ito2) was present in all endocardial (n = 30) and epicardial (n = 30) cells studied. The amplitude of Ito2 was significantly greater in epicardial than in endocardial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Cooling arrangement for a superconducting coil

DOEpatents

Herd, K.G.; Laskaris, E.T.

1998-06-30

A superconducting device is disclosed, such as a superconducting rotor for a generator or motor. A vacuum enclosure has an interior wall surrounding a cavity containing a vacuum. A superconductive coil is placed in the cavity. A generally-annularly-arranged, thermally-conductive sheet has an inward-facing surface contacting generally the entire outward-facing surface of the superconductive coil. A generally-annularly-arranged coolant tube contains a cryogenic fluid and contacts a generally-circumferential portion of the outward-facing surface of the sheet. A generally-annularly-arranged, thermally-insulative coil overwrap generally circumferentially surrounds the sheet. The coolant tube and the inward-facing surface of the coil overwrap together contact generally the entire outward-facing surface of the sheet. 3 figs.

Toxicity of marine pollutants on the ascidian oocyte physiology: an electrophysiological approach.

PubMed

Gallo, Alessandra

2018-02-01

In marine animals with external fertilization, gametes are released into seawater where fertilization and embryo development occur. Consequently, pollutants introduced into the marine environment by human activities may affect gametes and embryos. These xenobiotics can alter cell physiology with consequent reduction of fertilization success. Here the adverse effects on the reproductive processes of the marine invertebrate Ciona intestinalis (ascidian) of different xenobiotics: lead, zinc, an organic tin compound and a phenylurea herbicide were evaluated. By using the electrophysiological technique of whole-cell voltage clamping, the effects of these compounds on the mature oocyte plasma membrane electrical properties and the electrical events of fertilization were tested by calculating the concentration that induced 50% normal larval formation (EC50). The results demonstrated that sodium currents in mature oocytes were reduced in a concentration-dependent manner by all tested xenobiotics, with the lowest EC50 value for lead. In contrast, fertilization current frequencies were differently affected by zinc and organic tin compound. Toxicity tests on gametes demonstrated that sperm fertilizing capability and fertilization oocyte competence were not altered by xenobiotics, whereas fertilization was inhibited in zinc solution and underwent a reduction in organic tin compound solution (EC50 value of 1.7 µM). Furthermore, fertilized oocytes resulted in a low percentage of normal larvae with an EC50 value of 0.90 µM. This study shows that reproductive processes of ascidians are highly sensitive to xenobiotics suggesting that they may be considered a reliable biomarker and that ascidians are suitable model organisms to assess marine environmental quality.