KCNMA1 encoded cardiac BK channels afford protection against ischemia-reperfusion injury

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Soltysinska, Ewa; Bentzen, Bo Hjorth; Barthmes, Maria

2014-01-01

Mitochondrial potassium channels have been implicated in myocardial protection mediated through pre-/postconditioning. Compounds that open the Ca2+- and voltage-activated potassium channel of big-conductance (BK) have a pre-conditioning-like effect on survival of cardiomyocytes after ischemia/rep...

Chronic Prenatal Hypoxia Down-Regulated BK Channel Β1 Subunits in Mesenteric Artery Smooth Muscle Cells of the Offspring

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Bailin Liu

2018-02-01

Full Text Available Background/Aims: Chronic hypoxia in utero could impair vascular functions in the offspring, underlying mechanisms are unclear. This study investigated functional alteration in large-conductance Ca2+-activated K+ (BK channels in offspring mesenteric arteries following prenatal hypoxia. Methods: Pregnant rats were exposed to normoxic control (21% O2, Con or hypoxic (10.5% O2, Hy conditions from gestational day 5 to 21, their 7-month-old adult male offspring were tested for blood pressure, vascular BK channel functions and expression using patch clamp and wire myograh technique, western blotting, and qRT-PCR. Results: Prenatal hypoxia increased pressor responses and vasoconstrictions to phenylephrine in the offspring. Whole-cell currents density of BK channels and amplitude of spontaneous transient outward currents (STOCs, not the frequency, were significantly reduced in Hy vascular myocytes. The sensitivity of BK channels to voltage, Ca2+, and tamoxifen were reduced in Hy myocytes, whereas the number of channels per patch and the single-channel conductance were unchanged. Prenatal hypoxia impaired NS1102- and tamoxifen-mediated relaxation in mesenteric arteries precontracted with phenylephrine in the presence of Nω-nitro-L-arginine methyl ester. The mRNA and protein expression of BK channel β1, not the α-subunit, was decreased in Hy mesenteric arteries. Conclusions: Impaired BK channel β1-subunits in vascular smooth muscle cells contributed to vascular dysfunction in the offspring exposed to prenatal hypoxia.

Functional validation of Ca2+-binding residues from the crystal structure of the BK ion channel.

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Kshatri, Aravind S; Gonzalez-Hernandez, Alberto J; Giraldez, Teresa

2018-04-01

BK channels are dually regulated by voltage and Ca 2+ , providing a cellular mechanism to couple electrical and chemical signalling. Intracellular Ca 2+ concentration is sensed by a large cytoplasmic region in the channel known as "gating ring", which is formed by four tandems of regulator of conductance for K + (RCK1 and RCK2) domains. The recent crystal structure of the full-length BK channel from Aplysia californica has provided new information about the residues involved in Ca 2+ coordination at the high-affinity binding sites located in the RCK1 and RCK2 domains, as well as their cooperativity. Some of these residues have not been previously studied in the human BK channel. In this work we have investigated, through site directed mutagenesis and electrophysiology, the effects of these residues on channel activation by voltage and Ca 2+ . Our results demonstrate that the side chains of two non-conserved residues proposed to coordinate Ca 2+ in the A. californica structure (G523 and E591) have no apparent functional role in the human BK Ca 2+ sensing mechanism. Consistent with the crystal structure, our data indicate that in the human channel the conserved residue R514 participates in Ca 2+ coordination in the RCK1 binding site. Additionally, this study provides functional evidence indicating that R514 also interacts with residues E902 and Y904 connected to the Ca 2+ binding site in RCK2. Interestingly, it has been proposed that this interaction may constitute a structural correlate underlying the cooperative interactions between the two high-affinity Ca 2+ binding sites regulating the Ca 2+ dependent gating of the BK channel. This article is part of a Special Issue entitled: Beyond the Structure-Function Horizon of Membrane Proteins edited by Ute Hellmich, Rupak Doshi and Benjamin McIlwain. Copyright © 2017 Elsevier B.V. All rights reserved.

The BK(Ca) channels deficiency as a possible reason for radiation-induced vascular hypercontractility.

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Kyrychenko, Sergii; Tishkin, Sergey; Dosenko, Victor; Ivanova, Irina; Novokhatska, Tatiana; Soloviev, Anatoly

2012-01-01

It is likely that large-conductance Ca²⁺-activated K⁺ (BK(Ca)) channels channelopathy tightly involved in vascular malfunctions and arterial hypertension development. In the present study, we compared the results of siRNAs-induced α-BK(Ca) gene silencing and vascular abnormalities produced by whole-body ionized irradiation in rats. The experimental design comprised RT-PCR and patch clamp technique, thoracic aorta smooth muscle (SM) contractile recordings and arterial blood pressure (BP) measurements on the 30th day after whole body irradiation (6Gy) and following siRNAs KCNMA1 gene silencing in vivo. The expression profile of BK(Ca) mRNA transcripts in SM was significantly decreased in siRNAs-treated rats in a manner similar to irradiated SM. In contrast, the mRNA levels of K(v) and K(ATP) were significantly increased while L-type calcium channels mRNA transcripts demonstrated tendency to increment. The SMCs obtained from irradiated animals and after KCNMA1 gene silencing showed a significant decrease in total K⁺ current density amplitude. Paxilline (500 nM)-sensitive components of outward current were significantly decreased in both irradiated and gene silencing SMCs. KCNMA1 gene silencing increased SM sensitivity to norepinephrine while Ach-induced relaxation had decreased. The silencing of KCNMA1 had no significant effect on BP while radiation produced sustained arterial hypertension. Therefore, radiation alters the form and function of the BK(Ca) channel and this type of channelopathy may contribute to related vascular abnormalities. Nevertheless, it is unlikely that BK(Ca) can operate as a crucial factor for radiation-induced arterial hypertension. Copyright © 2012 Elsevier Inc. All rights reserved.

Double-Nanodomain Coupling of Calcium Channels, Ryanodine Receptors, and BK Channels Controls the Generation of Burst Firing.

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Irie, Tomohiko; Trussell, Laurence O

2017-11-15

Action potentials clustered into high-frequency bursts play distinct roles in neural computations. However, little is known about ionic currents that control the duration and probability of these bursts. We found that, in cartwheel inhibitory interneurons of the dorsal cochlear nucleus, the likelihood of bursts and the interval between their spikelets were controlled by Ca 2+ acting across two nanodomains, one between plasma membrane P/Q Ca 2+ channels and endoplasmic reticulum (ER) ryanodine receptors and another between ryanodine receptors and large-conductance, voltage- and Ca 2+ -activated K + (BK) channels. Each spike triggered Ca 2+ -induced Ca 2+ release (CICR) from the ER immediately beneath somatic, but not axonal or dendritic, plasma membrane. Moreover, immunolabeling demonstrated close apposition of ryanodine receptors and BK channels. Double-nanodomain coupling between somatic plasma membrane and hypolemmal ER cisterns provides a unique mechanism for rapid control of action potentials on the millisecond timescale. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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Pantazis, Antonios

2012-01-01

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

Differential expression of BK channel isoforms and beta-subunits in rat neuro-vascular tissues

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Poulsen, Asser Nyander; Wulf, Helle; Hay-Schmidt, Anders

2009-01-01

We investigated the expression of splice variants and beta-subunits of the BK channel (big conductance Ca(2+)-activated K(+) channel, Slo1, MaxiK, K(Ca)1.1) in rat cerebral blood vessels, meninges, trigeminal ganglion among other tissues. An alpha-subunit splice variant X1(+24) was found expresse...

Probing the Geometry of the Inner Vestibule of BK Channels with Sugars

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Brelidze, Tinatin I.; Magleby, Karl L.

2005-01-01

The geometry of the inner vestibule of BK channels was probed by examining the effects of different sugars in the intracellular solution on single-channel current amplitude (unitary current). Glycerol, glucose, and sucrose decreased unitary current through BK channels in a concentration- and size-dependent manner, in the order sucrose > glucose > glycerol, with outward currents being reduced more than inward currents. The fractional decrease of outward current was more directly related to the fractional hydrodynamic volume occupied by the sugars than to changes in osmolality. For concentrations of sugars ≤1 M, the i/V plots for outward currents in the presence and absence of sugar superimposed after scaling, and increasing K+ i from 150 mM to 2 M increased the magnitudes of the i/V plots with little effect on the shape of the scaled curves. These observations suggest that sugars ≤1 M reduce outward currents mainly by entering the inner vestibule and reducing the movement of K+ through the vestibule, rather than by limiting diffusion-controlled access of K+ to the vestibule. With 2 M sucrose, the movement of K+ into the inner vestibule became diffusion limited for 150 mM K+ i and voltages >+100 mV. Increasing K+ i then relieved the diffusion limitation. An estimate of the capture radius based on the 5 pA diffusion-limited current for channels without the ring of negative charge at the entrance to the inner vestibule was 2.2 Å. Adding the radius of a hydrated K+ (6–8 Å) then gave an effective radius for the entrance to the inner vestibule of 8–10 Å. Such a functionally wide entrance to the inner vestibule together with our observation that even small concentrations of sugar in the inner vestibule reduce unitary current suggest that a wide inner vestibule is required for the large conductance of BK channels. PMID:16043773

Overexpression of the Large-Conductance, Ca2+-Activated K+ (BK) Channel Shortens Action Potential Duration in HL-1 Cardiomyocytes.

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Stimers, Joseph R; Song, Li; Rusch, Nancy J; Rhee, Sung W

2015-01-01

Long QT syndrome is characterized by a prolongation of the interval between the Q wave and the T wave on the electrocardiogram. This abnormality reflects a prolongation of the ventricular action potential caused by a number of genetic mutations or a variety of drugs. Since effective treatments are unavailable, we explored the possibility of using cardiac expression of the large-conductance, Ca2+-activated K+ (BK) channel to shorten action potential duration (APD). We hypothesized that expression of the pore-forming α subunit of human BK channels (hBKα) in HL-1 cells would shorten action potential duration in this mouse atrial cell line. Expression of hBKα had minimal effects on expression levels of other ion channels with the exception of a small but significant reduction in Kv11.1. Patch-clamped hBKα expressing HL-1 cells exhibited an outward voltage- and Ca2+-sensitive K+ current, which was inhibited by the BK channel blocker iberiotoxin (100 nM). This BK current phenotype was not detected in untransfected HL-1 cells or in HL-1 null cells sham-transfected with an empty vector. Importantly, APD in hBKα-expressing HL-1 cells averaged 14.3 ± 2.8 ms (n = 10), which represented a 53% reduction in APD compared to HL-1 null cells lacking BKα expression. APD in the latter cells averaged 31.0 ± 5.1 ms (n = 13). The shortened APD in hBKα-expressing cells was restored to normal duration by 100 nM iberiotoxin, suggesting that a repolarizing K+ current attributed to BK channels accounted for action potential shortening. These findings provide initial proof-of-concept that the introduction of hBKα channels into a cardiac cell line can shorten APD, and raise the possibility that gene-based interventions to increase hBKα channels in cardiac cells may hold promise as a therapeutic strategy for long QT syndrome.

Neuronal fast activating and meningeal silent modulatory BK channel splice variants cloned from rat

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Poulsen, Asser Nyander; Jansen-Olesen, Inger; Olesen, Jes

2011-01-01

The big conductance calcium-activated K(+) channel (BK) is involved in regulating neuron and smooth muscle cell excitability. Functional diversity of BK is generated by alpha-subunit splice variation and co-expression with beta subunits. Here, we present six different splice combinations cloned...... and RCK2 (4 aa at SS1) and upstream of the calcium "bowl" (27 aa at SS4). Two other truncated variants, X2(92) and X2(188), lacking the intracellular C-terminal (stop downstream of S6), were cloned from cerebral vascular/meningeal tissue. They appear non-functional as no current expression was observed...

Mechanism of the modulation of BK potassium channel complexes with different auxiliary subunit compositions by the omega-3 fatty acid DHA.

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Hoshi, Toshinori; Tian, Yutao; Xu, Rong; Heinemann, Stefan H; Hou, Shangwei

2013-03-19

Large-conductance Ca(2+)- and voltage-activated K(+) (BK) channels are well known for their functional versatility, which is bestowed in part by their rich modulatory repertoire. We recently showed that long-chain omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) found in oily fish lower blood pressure by activating vascular BK channels made of Slo1+β1 subunits. Here we examined the action of DHA on BK channels with different auxiliary subunit compositions. Neuronal Slo1+β4 channels were just as well activated by DHA as vascular Slo1+β1 channels. In contrast, the stimulatory effect of DHA was much smaller in Slo1+β2, Slo1+LRRC26 (γ1), and Slo1 channels without auxiliary subunits. Mutagenesis of β1, β2, and β4 showed that the large effect of DHA in Slo1+β1 and Slo1+β4 is conferred by the presence of two residues, one in the N terminus and the other in the first transmembrane segment of the β1 and β4 subunits. Transfer of this amino acid pair from β1 or β4 to β2 introduces a large response to DHA in Slo1+β2. The presence of a pair of oppositely charged residues at the aforementioned positions in β subunits is associated with a large response to DHA. The Slo1 auxiliary subunits are expressed in a highly tissue-dependent fashion. Thus, the subunit composition-dependent stimulation by DHA demonstrates that BK channels are effectors of omega-3 fatty acids with marked tissue specificity.

The Role of Ca2+ and BK Channels of Locus Coeruleus (LC) Neurons as a Brake to the CO2 Chemosensitivity Response of Rats.

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Imber, Ann N; Patrone, Luis G A; Li, Ke-Yong; Gargaglioni, Luciane H; Putnam, Robert W

2018-06-15

The cellular mechanisms by which LC neurons respond to hypercapnia are usually attributed to an "accelerator" whereby hypercapnic acidosis causes an inhibition of K + channels or activation of Na + and Ca +2 channels to depolarize CO 2 -sensitive neurons. Nevertheless, it is still unknown if this "accelerator" mechanism could be controlled by a brake phenomenon. Whole-cell patch clamping, fluorescence imaging microscopy and plethysmography were used to study the chemosensitive response of the LC neurons. Hypercapnic acidosis activates L-type Ca 2+ channels and large conductance Ca-activated K + (BK) channels, which function as a "brake" on the chemosensitive response of LC neurons. Our findings indicate that both Ca 2+ and BK currents develop over the first 2 weeks of postnatal life in rat LC slices and that this brake pathway may cause the developmental decrease in the chemosensitive firing rate response of LC neurons to hypercapnic acidosis. Inhibition of this brake by paxilline (BK channel inhibitor) returns the magnitude of the chemosensitive firing rate response from LC neurons in rats older than P10 to high values similar to those in LC neurons from younger rats. Inhibition of BK channels in LC neurons by bilateral injections of paxilline into the LC results in a significant increase in the hypercapnic ventilatory response of adult rats. Our findings indicate that a BK channel-based braking system helps to determine the chemosensitive respiratory drive of LC neurons and contributes to the hypercapnic ventilatory response. Perhaps, abnormalities of this braking system could result in hypercapnia-induced respiratory disorders and panic responses. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Differential contribution of Ca2+ sources to day and night BK current activation in the circadian clock.

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Whitt, Joshua P; McNally, Beth A; Meredith, Andrea L

2018-02-05

Large conductance K + (BK) channels are expressed widely in neurons, where their activation is regulated by membrane depolarization and intracellular Ca 2+ (Ca 2+ i ). To enable this regulation, BK channels functionally couple to both voltage-gated Ca 2+ channels (VGCCs) and channels mediating Ca 2+ release from intracellular stores. However, the relationship between BK channels and their specific Ca 2+ source for particular patterns of excitability is not well understood. In neurons within the suprachiasmatic nucleus (SCN)-the brain's circadian clock-BK current, VGCC current, and Ca 2+ i are diurnally regulated, but paradoxically, BK current is greatest at night when VGCC current and Ca 2+ i are reduced. Here, to determine whether diurnal regulation of Ca 2+ is relevant for BK channel activation, we combine pharmacology with day and night patch-clamp recordings in acute slices of SCN. We find that activation of BK current depends primarily on three types of channels but that the relative contribution changes between day and night. BK current can be abrogated with nimodipine during the day but not at night, establishing that L-type Ca 2+ channels (LTCCs) are the primary daytime Ca 2+ source for BK activation. In contrast, dantrolene causes a significant decrease in BK current at night, suggesting that nighttime BK activation is driven by ryanodine receptor (RyR)-mediated Ca 2+ i release. The N- and P/Q-type Ca 2+ channel blocker ω-conotoxin MVIIC causes a smaller reduction of BK current that does not differ between day and night. Finally, inhibition of LTCCs, but not RyRs, eliminates BK inactivation, but the BK β2 subunit was not required for activation of BK current by LTCCs. These data reveal a dynamic coupling strategy between BK channels and their Ca 2+ sources in the SCN, contributing to diurnal regulation of SCN excitability. © 2018 Whitt et al.

Pharmacological investigation of the role of ion channels in salivary secretion

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Stummann, Tina C; Poulsen, Jørgen H; Hay-Schmidt, Anders

2003-01-01

The role of K+ and Cl- channels in salivary secretion was investigated, with emphasis on the potential role of Ca2+ -activated K+ channels. Ligand saturation kinetic assays and autoradiography showed large-conductance (BK) K+ channels to be highly expressed in rat submandibular and parotid glands...

Statin therapy exacerbates alcohol-induced constriction of cerebral arteries via modulation of ethanol-induced BK channel inhibition in vascular smooth muscle.

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Simakova, Maria N; Bisen, Shivantika; Dopico, Alex M; Bukiya, Anna N

2017-12-01

Statins constitute the most commonly prescribed drugs to decrease cholesterol (CLR). CLR is an important modulator of alcohol-induced cerebral artery constriction (AICAC). Using rats on a high CLR diet (2% CLR) we set to determine whether atorvastatin administration (10mg/kg daily for 18-23weeks) modified AICAC. Middle cerebral arteries were pressurized in vitro at 60mmHg and AICAC was evoked by 50mM ethanol, that is within the range of blood alcohol detected in humans following moderate-to-heavy drinking. AICAC was evident in high CLR+atorvastatin group but not in high CLR diet+placebo. Statin exacerbation of AICAC persisted in de-endothelialized arteries, and was blunted by CLR enrichment in vitro. Fluorescence imaging of filipin-stained arteries showed that atorvastatin decreased vascular smooth muscle (VSM) CLR when compared to placebo, this difference being reduced by CLR enrichment in vitro. Voltage- and calcium-gated potassium channels of large conductance (BK) are known VSM targets of ethanol, with their beta1 subunit being necessary for ethanol-induced channel inhibition and resulting AICAC. Ethanol-induced BK inhibition in excised membrane patches from freshly isolated myocytes was exacerbated in the high CLR diet+atorvastatin group when compared to high CLR diet+placebo. Unexpectedly, atorvastatin decreased the amount and function of BK beta1 subunit as documented by immunofluorescence imaging and functional patch-clamp studies. Atorvastatin exacerbation of ethanol-induced BK inhibition disappeared upon artery CLR enrichment in vitro. Our study demonstrates for the first time statin's ability to exacerbate the vascular effect of a widely consumed drug of abuse, this exacerbation being driven by statin modulation of ethanol-induced BK channel inhibition in the VSM via CLR-mediated mechanism. Copyright © 2017 Elsevier Inc. All rights reserved.

Expression of BK_Ca channels and the modulatory ß-subunits in the rat and porcine trigeminal ganglion

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Wulf-Johansson, Helle; Hay-Schmidt, Anders; Poulsen, Asser Nyander

2009-01-01

Large conductance calcium-activated potassium (BK(Ca)) channels contribute to electrical impulses, proper signal transmission of information and regulation of neurotransmitter release. Migraine has been proposed to be a trigeminovascular disease involving the sensory trigeminal pathways and the c...

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

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

2012-01-01

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

Compartmentalized beta subunit distribution determines characteristics and ethanol sensitivity of somatic, dendritic, and terminal large-conductance calcium-activated potassium channels in the rat central nervous system.

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Wynne, P M; Puig, S I; Martin, G E; Treistman, S N

2009-06-01

Neurons are highly differentiated and polarized cells, whose various functions depend upon the compartmentalization of ion channels. The rat hypothalamic-neurohypophysial system (HNS), in which cell bodies and dendrites reside in the hypothalamus, physically separated from their nerve terminals in the neurohypophysis, provides a particularly powerful preparation in which to study the distribution and regional properties of ion channel proteins. Using electrophysiological and immunohistochemical techniques, we characterized the large-conductance calcium-activated potassium (BK) channel in each of the three primary compartments (soma, dendrite, and terminal) of HNS neurons. We found that dendritic BK channels, in common with somatic channels but in contrast to nerve terminal channels, are insensitive to iberiotoxin. Furthermore, analysis of dendritic BK channel gating kinetics indicates that they, like somatic channels, have fast activation kinetics, in contrast to the slow gating of terminal channels. Dendritic and somatic channels are also more sensitive to calcium and have a greater conductance than terminal channels. Finally, although terminal BK channels are highly potentiated by ethanol, somatic and dendritic channels are insensitive to the drug. The biophysical and pharmacological properties of somatic and dendritic versus nerve terminal channels are consistent with the characteristics of exogenously expressed alphabeta1 versus alphabeta4 channels, respectively. Therefore, one possible explanation for our findings is a selective distribution of auxiliary beta1 subunits to the somatic and dendritic compartments and beta4 to the terminal compartment. This hypothesis is supported immunohistochemically by the appearance of distinct punctate beta1 or beta4 channel clusters in the membrane of somatic and dendritic or nerve terminal compartments, respectively.

Cholesterol tuning of BK ethanol response is enantioselective, and is a function of accompanying lipids.

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Chunbo Yuan

Full Text Available In the search to uncover ethanol's molecular mechanisms, the calcium and voltage activated, large conductance potassium channel (BK has emerged as an important molecule. We examine how cholesterol content in bilayers of 1,2-dioleoyl-3-phosphatidylethanolamine (DOPE/sphingomyelin (SPM and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylethanolamine (POPE/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylserine (POPS affect the function and ethanol sensitivity of BK. In addition, we examine how manipulation of cholesterol in biological membranes modulates ethanol's actions on BK. We report that cholesterol levels regulate the change in BK channel open probability elicited by 50 mM ethanol. Low levels of cholesterol (<20%, molar ratio supports ethanol activation, while high levels of cholesterol leads to ethanol inhibition of BK. To determine if cholesterol affects BK and its sensitivity to ethanol through a direct cholesterol-protein interaction or via an indirect action on the lipid bilayer, we used the synthetic enantiomer of cholesterol (ent-CHS. We found that 20% and 40% ent-CHS had little effect on the ethanol sensitivity of BK, when compared with the same concentration of nat-CHS. We accessed the effects of ent-CHS and nat-CHS on the molecular organization of DOPE/SPM monolayers at the air/water interface. The isotherm data showed that ent-CHS condensed DOPE/SPM monolayer equivalently to nat-CHS at a 20% concentration, but slightly less at a 40% concentration. Atomic force microscopy (AFM images of DOPE/SPM membranes in the presence of ent-CHS or nat-CHS prepared with LB technique or vesicle deposition showed no significant difference in topographies, supporting the interpretation that the differences in actions of nat-CHS and ent-CHS on BK channel are not likely from a generalized action on bilayers. We conclude that membrane cholesterol influences ethanol's modulation of BK in a complex manner, including an interaction with the channel protein

Astaxanthin and Docosahexaenoic Acid Reverse the Toxicity of the Maxi-K (BK Channel Antagonist Mycotoxin Penitrem A

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Amira A. Goda

2016-11-01

Full Text Available Penitrem A (PA is a food mycotoxin produced by several terrestrial and few marine Penicillium species. PA is a potent tremorgen through selective antagonism of the calcium-dependent potassium BK (Maxi-K channels. Discovery of natural products that can prevent the toxic effects of PA is important for food safety. Astaxanthin (AST is a marine natural xanthophyll carotenoid with documented antioxidant activity. Unlike other common antioxidants, AST can cross blood brain barriers (BBBs, inducing neuroprotective effects. Docosahexaenoic acid (DHA is polyunsaturated ω-3 fatty acid naturally occurring in fish and algae. DHA is essential for normal neurological and cellular development. This study evaluated the protective activity of AST and DHA against PA-induced toxicity, in vitro on Schwann cells CRL-2765 and in vivo in the worm Caenorhbitidis elegans and Sprague Dawley rat models. PA inhibited the viability of Schwann cells, with an IC50 of 22.6 μM. Dose-dependent treatments with 10–100 μM DHA significantly reversed the PA toxicity at its IC50 dose, and improved the survival of Schwann cells to 70.5%–98.8%. Similarly, dose-dependent treatments with 10–20 μM AST reversed the PA toxicity at its IC50 dose and raised these cells’ survival to 61.7%–70.5%. BK channel inhibition in the nematode C. elegans is associated with abnormal reversal locomotion. DHA and AST counteracted the in vivo PA BK channel antagonistic activity in the C. elegans model. Rats fed a PA-contaminated diet showed high levels of glutamate (GLU, aspartate (ASP, and gamma amino butyric acid (GABA, with observed necrosis or absence of Purkinjie neurons, typical of PA-induced neurotoxicity. Dopamine (DA, serotonin (5-HT, and norepinephrine (NE levels were abnormal, Nitric Oxide (NO and Malondialdehyde (MDA levels were significantly increased, and total antioxidant capacity (TAC level in serum and brain homogenates was significantly decreased in PA-treated rats. DHA and AST

[β-estradiol activates BK(Ca) in mesenteric artery smooth muscle cells of post-menopause women].

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Cheng, Jun; Zeng, Xiao-Rong; Li, Peng-Yun; Lu, Ting-Ting; Tan, Xiao-Qiu; Wen, Jing; Yang, Yan

2012-04-25

The aim of the present study was to study the effect of β-estradiol (β-E(2)) on the large-conductance Ca(2+)-activated potassium (BK(Ca)) channel in mesenteric artery smooth muscle cells (SMCs). The mesenteric arteries were obtained from post-menopause female patients with abdominal surgery, and the SMCs were isolated from the arteries using an enzymatic disassociation. According to the sources, the SMCs were divided into non-hypertension (NH) and essential hypertension (EH) groups. Single channel patch clamp technique was used to investigate the effect of β-E(2) and ICI 182780 (a specific blocker of estrogen receptor) on BK(Ca) in the SMCs. The results showed the opening of BK(Ca) in the SMCs was voltage and calcium dependent, and could be blocked by IbTX. β-E(2) (100 μmol/L) significantly increased open probability (Po) of BK(Ca) in both NH and EH groups. After β-E(2) treatment, NH group showed higher Po of BK(Ca) compared with EH group. ICI 182780 could inhibit the activating effect of β-E(2) on BK(Ca) in no matter NH or EH groups. These results suggest β-E(2) activates BK(Ca) in mesenteric artery SMCs from post-menopause women via estrogen receptor, but hypertension may decline the activating effect of β-E(2) on BK(Ca).

Up-Regulatory Effects of Curcumin on Large Conductance Ca2+-Activated K+ Channels

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Hei, Hongya; Li, Fangping; Wang, Yunman; Peng, Wen; Zhang, Xuemei

2015-01-01

Large conductance Ca2+-activated potassium channels (BK) are targets for research that explores therapeutic means to various diseases, owing to the roles of the channels in mediating multiple physiological processes in various cells and tissues. We investigated the pharmacological effects of curcumin, a compound isolated from the herb Curcuma longa, on BK channels. As recorded by whole-cell patch-clamp, curcumin increased BK (α) and BK (α+β1) currents in transfected HEK293 cells as well as the current density of BK in A7r5 smooth muscle cells in a dose-dependent manner. By incubating with curcumin for 24 hours, the current density of exogenous BK (α) in HEK293 cells and the endogenous BK in A7r5 cells were both enhanced notably, though the steady-state activation of the channels did not shift significantly, except for BK (α+β1). Curcumin up-regulated the BK protein expression without changing its mRNA level in A7r5 cells. The surface expression and the half-life of BK channels were also increased by curcumin in HEK293 cells. These effects of curcumin were abolished by MG-132, a proteasome inhibitor. Curcumin also increased ERK 1/2 phosphorylation, while inhibiting ERK by U0126 attenuated the curcumin-induced up-regulation of BK protein expression. We also observed that the curcumin-induced relaxation in the isolated rat aortic rings was significantly attenuated by paxilline, a BK channel specific blocker. These results show that curcumin enhances the activity of the BK channels by interacting with BK directly as well as enhancing BK protein expression through inhibiting proteasomal degradation and activating ERK signaling pathway. The findings suggest that curcumin is a potential BK channel activator and provide novel insight into its complicated pharmacological effects and the underlying mechanisms. PMID:26672753

Up-Regulatory Effects of Curcumin on Large Conductance Ca2+-Activated K+ Channels.

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Qijing Chen

Full Text Available Large conductance Ca2+-activated potassium channels (BK are targets for research that explores therapeutic means to various diseases, owing to the roles of the channels in mediating multiple physiological processes in various cells and tissues. We investigated the pharmacological effects of curcumin, a compound isolated from the herb Curcuma longa, on BK channels. As recorded by whole-cell patch-clamp, curcumin increased BK (α and BK (α+β1 currents in transfected HEK293 cells as well as the current density of BK in A7r5 smooth muscle cells in a dose-dependent manner. By incubating with curcumin for 24 hours, the current density of exogenous BK (α in HEK293 cells and the endogenous BK in A7r5 cells were both enhanced notably, though the steady-state activation of the channels did not shift significantly, except for BK (α+β1. Curcumin up-regulated the BK protein expression without changing its mRNA level in A7r5 cells. The surface expression and the half-life of BK channels were also increased by curcumin in HEK293 cells. These effects of curcumin were abolished by MG-132, a proteasome inhibitor. Curcumin also increased ERK 1/2 phosphorylation, while inhibiting ERK by U0126 attenuated the curcumin-induced up-regulation of BK protein expression. We also observed that the curcumin-induced relaxation in the isolated rat aortic rings was significantly attenuated by paxilline, a BK channel specific blocker. These results show that curcumin enhances the activity of the BK channels by interacting with BK directly as well as enhancing BK protein expression through inhibiting proteasomal degradation and activating ERK signaling pathway. The findings suggest that curcumin is a potential BK channel activator and provide novel insight into its complicated pharmacological effects and the underlying mechanisms.

Quantification and distribution of big conductance Ca2+-activated K+ channels in kidney epithelia

DEFF Research Database (Denmark)

Grunnet, Morten; Hay-Schmidt, Anders; Klaerke, Dan A

2005-01-01

and immunohistochemical studies. In cortical collecting ducts, BK channels were exclusively located in principal cells while no channels could be found in intercalated cells. The abundant and distinct distribution in kidney epithelia talks in favor for BK channels being important contributors in maintaining salt......Big conductance Ca2+ activated K+ channels (BK channels) is an abundant channel present in almost all kind of tissue. The accurate quantity and especially the precise distribution of this channel in kidney epithelia are, however, still debated. The aim of the present study has therefore been...... to examine the presence of BK channels in kidney epithelia and determine the actual number and distribution of these channels. For this purpose, a selective peptidyl ligand for BK channels called iberiotoxin or the radiolabeled double mutant analog 125I-IbTX-D19Y/Y36F has been employed. The presence of BK...

Structure of the (0+,1+) mesons Bs0 and Bs1, and the strong coupling constant gBs0BK and gBs1B*K

International Nuclear Information System (INIS)

Wang, Z. G.

2008-01-01

In this article, we take the point of view that the bottomed (0 + ,1 + ) mesons B s0 and B s1 are the conventional bs meson and calculate the strong coupling constants g B s0 BK and g B s1 B*K with the light-cone QCD sum rules. The numerical values of strong coupling constants g B s1 B*K and g B s0 BK are very large and support the hadronic dressing mechanism. Just like the scalar mesons f 0 (980), a 0 (980), D s0 and axial-vector meson D s1 , the (0 + ,1 + ) bottomed mesons B s0 and B s1 may have small bs kernels of the typical bs meson size. The strong couplings to the hadronic channels (or the virtual mesons loops) may result in smaller masses than the conventional bs mesons in the potential quark models and enrich the pure bs states with other components.

Large-conductance Ca2+-activated K+ channel β1-subunit knockout mice are not hypertensive

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Garver, Hannah; Galligan, James J.; Fink, Gregory D.

2011-01-01

Large-conductance Ca2+-activated K+ (BK) channels are composed of pore-forming α-subunits and accessory β1-subunits that modulate Ca2+ sensitivity. BK channels regulate arterial myogenic tone and renal Na+ clearance/K+ reabsorption. Previous studies using indirect or short-term blood pressure measurements found that BK channel β1-subunit knockout (BK β1-KO) mice were hypertensive. We evaluated 24-h mean arterial pressure (MAP) and heart rate in BK β1-KO mice using radiotelemetry. BK β1-KO mice did not have a higher 24-h average MAP when compared with wild-type (WT) mice, although MAP was ∼10 mmHg higher at night. The dose-dependent peak declines in MAP by nifedipine were only slightly larger in BK β1-KO mice. In BK β1-KO mice, giving 1% NaCl to mice to drink for 7 days caused a transient (5 days) elevation of MAP (∼5 mmHg); MAP returned to pre-saline levels by day 6. BK β1-KO mesenteric arteries in vitro demonstrated diminished contractile responses to paxilline, increased reactivity to Bay K 8644 and norepinephrine (NE), and maintained relaxation to isoproterenol. Paxilline and Bay K 8644 did not constrict WT or BK β1-KO mesenteric veins (MV). BK β1-subunits are not expressed in MV. The results indicate that BK β1-KO mice are not hypertensive on normal or high-salt intake. BK channel deficiency increases arterial reactivity to NE and L-type Ca2+ channel function in vitro, but the L-type Ca2+ channel modulation of MAP is not altered in BK β1-KO mice. BK and L-type Ca2+ channels do not modulate murine venous tone. It appears that selective loss of BK channel function in arteries only is not sufficient to cause sustained hypertension. PMID:21131476

Local calcium signalling is mediated by mechanosensitive ion channels in mesenchymal stem cells

International Nuclear Information System (INIS)

Chubinskiy-Nadezhdin, Vladislav I.; Vasileva, Valeria Y.; Pugovkina, Natalia A.; Vassilieva, Irina O.; Morachevskaya, Elena A.; Nikolsky, Nikolay N.; Negulyaev, Yuri A.

2017-01-01

Mechanical forces are implicated in key physiological processes in stem cells, including proliferation, differentiation and lineage switching. To date, there is an evident lack of understanding of how external mechanical cues are coupled with calcium signalling in stem cells. Mechanical reactions are of particular interest in adult mesenchymal stem cells because of their promising potential for use in tissue remodelling and clinical therapy. Here, single channel patch-clamp technique was employed to search for cation channels involved in mechanosensitivity in mesenchymal endometrial-derived stem cells (hMESCs). Functional expression of native mechanosensitive stretch-activated channels (SACs) and calcium-sensitive potassium channels of different conductances in hMESCs was shown. Single current analysis of stretch-induced channel activity revealed functional coupling of SACs and BK channels in plasma membrane. The combination of cell-attached and inside-out experiments have indicated that highly localized Ca 2+ entry via SACs triggers BK channel activity. At the same time, SK channels are not coupled with SACs despite of high calcium sensitivity as compared to BK. Our data demonstrate novel mechanism controlling BK channel activity in native cells. We conclude that SACs and BK channels are clusterized in functional mechanosensitive domains in the plasma membrane of hMESCs. Co-clustering of ion channels may significantly contribute to mechano-dependent calcium signalling in stem cells. - Highlights: • Stretch-induced channel activity in human mesenchymal stem cells was analyzed. • Functional expression of SACs and Ca 2+ -sensitive BK and SK channels was shown. • Local Ca 2+ influx via stretch-activated channels triggers BK channel activity. • SK channels are not coupled with SACs despite higher sensitivity to [Ca 2+ ] i . • Functional clustering of SACs and BK channels in stem cell membrane is proposed.

Cell volume and membrane stretch independently control K+ channel activity

DEFF Research Database (Denmark)

Bomholtz, Sofia Hammami; Willumsen, Niels J; Olsen, Hervør L

2009-01-01

A number of potassium channels including members of the KCNQ family and the Ca(2+) activated IK and SK, but not BK, are strongly and reversibly regulated by small changes in cell volume. It has been argued that this general regulation is mediated through sensitivity to changes in membrane stretch...... was not affected by membrane stretch. The results indicate that (1) activation of BK channels by local membrane stretch is not mimicked by membrane stress induced by cell swelling, and (2) activation of KCNQ1 channels by cell volume increase is not mediated by local tension in the cell membrane. We conclude....... To test this hypothesis we have studied the regulation of KCNQ1 and BK channels after expression in Xenopus oocytes. Results from cell-attached patch clamp studies (approximately 50 microm(2) macropatches) in oocytes expressing BK channels demonstrate that the macroscopic volume-insensitive BK current...

Potassium channels in brain mitochondria.

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Bednarczyk, Piotr

2009-01-01

Potassium channels are the most widely distributed class of ion channels. These channels are transmembrane proteins known to play important roles in both normal and pathophysiological functions in all cell types. Various potassium channels are recognised as potential therapeutic targets in the treatment of Parkinson's disease, Alzheimer's disease, brain/spinal cord ischaemia and sepsis. In addition to their importance as therapeutic targets, certain potassium channels are known for their beneficial roles in anaesthesia, cardioprotection and neuroprotection. Some types of potassium channels present in the plasma membrane of various cells have been found in the inner mitochondrial membrane as well. Potassium channels have been proposed to regulate mitochondrial membrane potential, respiration, matrix volume and Ca(+) ion homeostasis. It has been proposed that mitochondrial potassium channels mediate ischaemic preconditioning in various tissues. However, the specificity of a pharmacological agents and the mechanisms underlying their effects on ischaemic preconditioning remain controversial. The following potassium channels from various tissues have been identified in the inner mitochondrial membrane: ATP-regulated (mitoK(ATP)) channel, large conductance Ca(2+)-regulated (mitoBK(Ca)) channel, intermediate conductance Ca(2+)-regulated (mitoIK(Ca)) channel, voltage-gated (mitoKv1.3 type) channel, and twin-pore domain (mitoTASK-3) channel. It has been shown that increased potassium flux into brain mitochondria induced by either the mitoK(ATP) channel or mitoBK(Ca) channel affects the beneficial effects on neuronal cell survival under pathological conditions. Recently, differential distribution of mitoBK(Ca) channels has been observed in neuronal mitochondria. These findings may suggest a neuroprotective role for the mitoBK(Ca) channel in specific brain structures. This minireview summarises current data on brain mitochondrial potassium channels and the efforts to identify

Molecular and functional expression of high conductance Ca 2+ activated K+ channels in the eel intestinal epithelium

DEFF Research Database (Denmark)

Lionetto, Maria G; Rizzello, Antonia; Giordano, Maria E

2008-01-01

Several types of K(+) channels have been identified in epithelial cells. Among them high conductance Ca(2+)-activated K(+) channels (BK channels) are of relevant importance for their involvement in regulatory volume decrease (RVD) response following hypotonic stress. The aim of the present work...... was to investigate the functional and molecular expression of BK in the eel intestine, which is a useful experimental model for cell volume regulation research. In the present paper using rat BK channel-specific primer, a RT-PCR signal of 696 pb cDNA was detected in eel intestine, whole nucleotide sequence showed...... high similarity (83%) to the alpha subunit of BK channel family. BK channel protein expression was verified by immunoblotting and confocal microscopy, while the functional role of BK channels in epithelial ion transport mechanisms and cell volume regulation was examined by electrophysiological...

Large-conductance calcium-dependent potassium channels prevent dendritic excitability in neocortical pyramidal neurons.

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Benhassine, Narimane; Berger, Thomas

2009-03-01

Large-conductance calcium-dependent potassium channels (BK channels) are homogeneously distributed along the somatodendritic axis of layer 5 pyramidal neurons of the rat somatosensory cortex. The relevance of this conductance for dendritic calcium electrogenesis was studied in acute brain slices using somatodendritic patch clamp recordings and calcium imaging. BK channel activation reduces the occurrence of dendritic calcium spikes. This is reflected in an increased critical frequency of somatic spikes necessary to activate the distal initiation zone. Whilst BK channels repolarise the somatic spike, they dampen it only in the distal dendrite. Their activation reduces dendritic calcium influx via glutamate receptors. Furthermore, they prevent dendritic calcium electrogenesis and subsequent somatic burst discharges. However, the time window for coincident somatic action potential and dendritic input to elicit dendritic calcium events is not influenced by BK channels. Thus, BK channel activation in layer 5 pyramidal neurons affects cellular excitability primarily by establishing a high threshold at the distal action potential initiation zone.

The Kinetics and the Permeation Properties of Piezo Channels.

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Gnanasambandam, R; Gottlieb, P A; Sachs, F

2017-01-01

Piezo channels are eukaryotic, cation-selective mechanosensitive channels (MSCs), which show rapid activation and voltage-dependent inactivation. The kinetics of these channels are largely consistent across multiple cell types and different stimulation paradigms with some minor variability. No accessory subunits that associate with Piezo channels have been reported. They are homotrimers and each ∼300kD monomer has an N-terminal propeller blade-like mechanosensing module, which can confer mechanosensing capabilities on ASIC-1 (the trimeric non-MSC, acid-sensing ion channel-1) and a C-terminal pore module, which influences conductance, selectivity, and channel inactivation. Repeated stimulation can cause domain fracture and diffusion of these channels leading to synchronous loss of inactivation. The reconstituted channels spontaneously open only in asymmetric bilayers but lack inactivation. Mutations that cause hereditary xerocytosis alter PIEZO1 kinetics. The kinetics of the wild-type PIEZO1 and alterations thereof in mutants (M2225R, R2456K, and DhPIEZO1) are summarized in the form of a quantitative model and hosted online. The pore is permeable to alkali ions although Li + permeates poorly. Divalent cations, notably Ca 2+ , traverse the channel and inhibit the flux of monovalents. The large monovalent organic cations such as tetramethyl ammonium and tetraethyl ammonium can traverse the channel, but slowly, suggesting a pore diameter of ∼8Å, and the estimated in-plane area change upon opening is around 6-20nm 2 . Ruthenium red can enter the channel only from the extracellular side and seems to bind in a pocket close to residue 2496. Copyright © 2017 Elsevier Inc. All rights reserved.

Homogeneous distribution of large-conductance calcium-dependent potassium channels on soma and apical dendrite of rat neocortical layer 5 pyramidal neurons.

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Benhassine, Narimane; Berger, Thomas

2005-02-01

Voltage-gated conductances on dendrites of layer 5 pyramidal neurons participate in synaptic integration and output generation. We investigated the properties and the distribution of large-conductance calcium-activated potassium channels (BK channels) in this cell type using excised patches in acute slice preparations of rat somatosensory cortex. BK channels were characterized by their large conductance and sensitivity to the specific blockers paxilline and iberiotoxin. BK channels showed a pronounced calcium-dependence with a maximal opening probability of 0.69 at 10 microm and 0.42 at 3 microm free calcium. Their opening probability and transition time constants between open and closed states are voltage-dependent. At depolarized potentials, BK channel gating is described by two open and one closed states. Depolarization increases the opening probability due to a prolongation of the open time constant and a shortening of the closed time constant. Calcium-dependence and biophysical properties of somatic and dendritic BK channels were identical. The presence of BK channels on the apical dendrite of layer 5 pyramidal neurons was shown by immunofluorescence. Patch-clamp recordings revealed a homogeneous density of BK channels on the soma and along the apical dendrite up to 850 microm with a mean density of 1.9 channels per microm(2). BK channels are expressed either isolated or in clusters containing up to four channels. This study shows the presence of BK channels on dendrites. Their activation might modulate the shape of sodium and calcium action potentials, their propagation along the dendrite, and thereby the electrotonic distance between the somatic and dendritic action potential initiation zones.

Membrane potential and cation channels in rat juxtaglomerular cells

DEFF Research Database (Denmark)

Friis, U G; Jørgensen, F; Andreasen, D

2004-01-01

The relationship between membrane potential and cation channels in juxtaglomerular (JG) cells is not well understood. Here we review electrophysiological and molecular studies of JG cells demonstrating the presence of large voltage-sensitive, calcium-activated potassium channels (BK(Ca)) of the Z......The relationship between membrane potential and cation channels in juxtaglomerular (JG) cells is not well understood. Here we review electrophysiological and molecular studies of JG cells demonstrating the presence of large voltage-sensitive, calcium-activated potassium channels (BK...

Localization of Ca2+ -activated big-conductance K+ channels in rabbit distal colon

DEFF Research Database (Denmark)

Hay-Schmidt, Anders; Grunnet, Morten; Abrahamse, Salomon L

2003-01-01

Big-conductance Ca(2+)-activated K(+) channels (BK channels) may play an important role in the regulation of epithelial salt and water transport, but little is known about the expression level and the precise localization of BK channels in epithelia. The aim of the present study was to quantify a...

Regulation of cloned, Ca2+-activated K+ channels by cell volume changes

DEFF Research Database (Denmark)

Grunnet, Morten; MacAulay, Nanna; Jorgensen, Nanna K

2002-01-01

Ca2+-activated K+ channels of big (hBK), intermediate (hIK) or small (rSK3) conductance were co-expressed with aquaporin 1 (AQP1) in Xenopus laevis oocytes. hBK channels were activated by depolarization, whereas hIK and rSK3 channels were activated by direct injection of Ca2+ or Cd2+ into the ooc...

Molecular studies of BKCa channels in intracranial arteries

DEFF Research Database (Denmark)

Wulf, Helle; Hay-Schmidt, Anders; Poulsen, Asser Nyander

2008-01-01

expression of the BK(Ca) channel in rat basilar, middle cerebral, and middle meningeal arteries by reverse transcription polymerase chain reaction (RT-PCR), quantitative real-time PCR, and Western blotting. Distribution patterns were investigated using in situ hybridization and immunofluorescence studies. RT......  Large conductance calcium-activated potassium channels (BK(ca)) are crucial for the regulation of cerebral vascular basal tone and might be involved in cerebral vasodilation relevant to migraine and stroke. We studied the differential gene expression of mRNA transcript levels and protein......-PCR and quantitative real-time PCR detected the expression of the BK(Ca) channel mRNA transcript in rat basilar, middle cerebral, and middle meningeal arteries, with the transcript being expressed more abundantly in rat basilar arteries than in middle cerebral and middle meningeal arteries. Western blotting detected...

Polyomavirus specific cellular immunity: from BK-virus-specific cellular immunity to BK-virus-associated nephropathy ?

Directory of Open Access Journals (Sweden)

manon edekeyser

2015-06-01

Full Text Available In renal transplantation, BK-virus-associated nephropathy has emerged as a major complication, with a prevalence of 5–10% and graft loss in >50% of cases. BK-virus is a member of the Polyomavirus family and rarely induces apparent clinical disease in the general population. However, replication of polyomaviruses, associated with significant organ disease, is observed in patients with acquired immunosuppression, which suggests a critical role for virus-specific cellular immunity to control virus replication and prevent chronic disease. Monitoring of specific immunity combined with viral load could be used to individually assess the risk of viral reactivation and virus control. We review the current knowledge on BK-virus specific cellular immunity and, more specifically, in immunocompromised patients. In the future, immune-based therapies could allow us to treat and prevent BK-virus-associated nephropathy.

Levels of 250Cf populated in the decay of 250Bk

International Nuclear Information System (INIS)

Uecke, J.W.

1975-06-01

The nuclide 250 Bk undergoes β-decay with a half-life of 3.2 h to 13.1 y 250 Cf. A study is undertaken of the excited states in 250 Cf populated by 250 Bk decay which results from the α-decay of 276d 254 Es. The general features of published level schemes for these nuclei are consistent with predictions of the Nilsson and collective models; however, there remain many undiscovered transitions and ambiguous or uncertain level assignments. In an attempt to confirm predictions of current theoretical models which account for nuclear level assignments in this nucleus, these gamma transitions and their levels have been studied. Twenty-eight new γ-rays were determined. The decay of 250 Bk is investigated primarily by high resolution gamma-ray singles spectrometry and supported in part by two-parameter gamma-gamma coincidence spectrometry. The equipment, comprised of a Ge(HP) and a large volume Ge(Li) detector, a 4096-channel two-parameter analyzer, and a PDP-8/e computer system, permitted significant improvement in sensitivity and accuracy over previous investigations on this nucleus. (11 figures, 2 tables) (U.S.)

Melatonin mediates vasodilation through both direct and indirect activation of BKCa channels.

Science.gov (United States)

Zhao, T; Zhang, H; Jin, C; Qiu, F; Wu, Y; Shi, L

2017-10-01

Melatonin, synthesized primarily by the pineal gland, is a neuroendocrine hormone with high membrane permeability. The vascular effects of melatonin, including vasoconstriction and vasodilation, have been demonstrated in numerous studies. However, the mechanisms underlying these effects are not fully understood. Large-conductance Ca 2+ -activated K + (BK Ca ) channels are expressed broadly on smooth muscle cells and play an important role in vascular tone regulation. This study explored the mechanisms of myocyte BK Ca channels and endothelial factors underlying the action of melatonin on the mesenteric arteries (MAs). Vascular contractility and patch-clamp studies were performed on myocytes of MAs from Wistar rats. Melatonin induced significant vasodilation on MAs. In the presence of N ω -nitro-l-arginine methyl ester (l-NAME), a potent endothelial oxide synthase (eNOS) inhibitor, melatonin elicited concentration-dependent relaxation, with lowered pIC 50 The effect of melatonin was significantly attenuated in the presence of BK Ca channel blocker iberiotoxin or MT1/MT2 receptor antagonist luzindole in both (+) l-NAME and (-) l-NAME groups. In the (+) l-NAME group, iberiotoxin caused a parallel rightward shift of the melatonin concentration-relaxation curve, with pIC 50 lower than that of luzindole. Both inside-out and cell-attached patch-clamp recordings showed that melatonin significantly increased the open probability, mean open time and voltage sensitivity of BK Ca channels. In a cell-attached patch-clamp configuration, the melatonin-induced enhancement of BK Ca channel activity was significantly suppressed by luzindole. These findings indicate that in addition to the activation of eNOS, melatonin-induced vasorelaxation of MAs is partially attributable to its direct (passing through the cell membrane) and indirect (via MT1/MT2 receptors) activation of the BK Ca channels on mesenteric arterial myocytes. © 2017 Society for Endocrinology.

Neurogenic detrusor overactivity is associated with decreased expression and function of the large conductance voltage- and Ca(2+-activated K(+ channels.

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Kiril L Hristov

Full Text Available Patients suffering from a variety of neurological diseases such as spinal cord injury, Parkinson's disease, and multiple sclerosis often develop neurogenic detrusor overactivity (NDO, which currently lacks a universally effective therapy. Here, we tested the hypothesis that NDO is associated with changes in detrusor smooth muscle (DSM large conductance Ca(2+-activated K(+ (BK channel expression and function. DSM tissue samples from 33 patients were obtained during open bladder surgeries. NDO patients were clinically characterized preoperatively with pressure-flow urodynamics demonstrating detrusor overactivity, in the setting of a clinically relevant neurological condition. Control patients did not have overactive bladder and did not have a clinically relevant neurological disease. We conducted quantitative polymerase chain reactions (qPCR, perforated patch-clamp electrophysiology on freshly-isolated DSM cells, and functional studies on DSM contractility. qPCR experiments revealed that DSM samples from NDO patients showed decreased BK channel mRNA expression in comparison to controls. Patch-clamp experiments demonstrated reduced whole cell and transient BK currents (TBKCs in freshly-isolated DSM cells from NDO patients. Functional studies on DSM contractility showed that spontaneous phasic contractions had a decreased sensitivity to iberiotoxin, a selective BK channel inhibitor, in DSM strips isolated from NDO patients. These results reveal the novel finding that NDO is associated with decreased DSM BK channel expression and function leading to increased DSM excitability and contractility. BK channel openers or BK channel gene transfer could be an alternative strategy to control NDO. Future clinical trials are needed to evaluate the value of BK channel opening drugs or gene therapies for NDO treatment and to identify any possible adverse effects.

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

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

2015-01-01

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

Molecular studies of BKCa channels in intracranial arteries: presence and localization

DEFF Research Database (Denmark)

Johansson, Helle Wulf; Hay-Schmidt, Anders; Poulsen, Asser Nyander

2008-01-01

of the BK(Ca) channel in rat basilar, middle cerebral, and middle meningeal arteries by reverse transcription polymerase chain reaction (RT-PCR), quantitative real-time PCR, and Western blotting. Distribution patterns were investigated using in situ hybridization and immunofluorescence studies. RT......Large conductance calcium-activated potassium channels (BK(ca)) are crucial for the regulation of cerebral vascular basal tone and might be involved in cerebral vasodilation relevant to migraine and stroke. We studied the differential gene expression of mRNA transcript levels and protein expression......-PCR and quantitative real-time PCR detected the expression of the BK(Ca) channel mRNA transcript in rat basilar, middle cerebral, and middle meningeal arteries, with the transcript being expressed more abundantly in rat basilar arteries than in middle cerebral and middle meningeal arteries. Western blotting detected...

Calcium Activated K+ Channels in The Electroreceptor of the Skate Confirmed by Cloning. Details of Subunits and Splicing

Science.gov (United States)

King, Benjamin L.; Shi, Ling Fang; Kao, Peter; Clusin, William T.

2015-01-01

Elasmobranchs detect small potentials using excitable cells of the ampulla of Lorenzini which have calcium-activated K+ channels, first described in l974. A distinctive feature of the outward current in voltage clamped ampullae is its apparent insensitivity to voltage. The sequence of a BK channel α isoform expressed in the ampulla of the skate was characterized. A signal peptide is present at the beginning of the gene. When compared to human isoform 1 (the canonical sequence), the largest difference was absence of a 59 amino acid region from the S8-S9 intracellular linker that contains the strex regulatory domain. The ampulla isoform was also compared with the isoform predicted˜ in late skate embryos where strex was also absent. The BK voltage sensors were conserved in both skate isoforms. Differences between the skate and human BK channel included alternative splicing. Alternative splicing occurs at seven previously defined sites that are characteristic for BK channels in general and hair cells in particular. Skate BK sequences were highly similar to the Australian ghost shark and several other vertebrate species. Based on alignment of known BK sequences with the skate genome and transcriptome, there are at least two isoforms of Kcnma1α expressed in the skate. One of the β subunits (β4), which is known to decrease voltage sensitivity, was also identified in the skate genome and transcriptome and in the ampulla. These studies advance our knowledge of BK channels and suggest further studies in the ampulla and other excitable tissues. PMID:26687710

Distribution, expression and functional effects of small conductance Ca-activated potassium (SK) channels in rat myometrium.

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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.

Hydralazine-induced vasodilation involves opening of high conductance Ca2+-activated K+ channels

DEFF Research Database (Denmark)

Bang, Lone; Nielsen-Kudsk, J E; Gruhn, N

1998-01-01

The purpose of this study was to investigate whether high conductance Ca2+-activated K+ channels (BK(Ca)) are mediating the vasodilator action of hydralazine. In isolated porcine coronary arteries, hydralazine (1-300 microM), like the K+ channel opener levcromakalim, preferentially relaxed......M) suppressed this response by 82% (P opening of BK(Ca) takes part in the mechanism whereby...

Kinetic studies on purification capability of channel flow type wastewater treatment plant

Energy Technology Data Exchange (ETDEWEB)

Hashimoto, S [Fukui Institute of Technology, Fukui (Japan); Furukawa, K; Kim, J [Osaka Univ., Osaka (Japan). Faculty of Engineering

1990-10-01

In order to develop a wastewater treatment process of secondary effluent and a wastewater treatment process of a farm village, some experiments have been carried out using bench scale and full scale hydroponic type wastewater treatment plant. This wastewater treatment system mainly consists of water channels and hydroponic water tanks. The authors carried out of a kinetic study for purification capability of the water channels while assuring the growth of microorganism in the treatment scheme. It was shown experimentally that the channel flow type wastewater treatment plant had a high TOC removal capability regardless of the kind of contact material and treatment time. Activated sludge microorganism concentration in water channels was obtained by kinetic estimation from the measured effluent suspended solid concentration. Estimated amount of activated sludge in water channels comprised only 11.5-37.4 percent of the measured amounts of withdrawn sludge, indicating high photosynthesis production of algae in water channels. 8 refs., 4 figs., 5 tabs.

Calcium activated K⁺ channels in the electroreceptor of the skate confirmed by cloning. Details of subunits and splicing.

Science.gov (United States)

King, Benjamin L; Shi, Ling Fang; Kao, Peter; Clusin, William T

2016-03-01

Elasmobranchs detect small potentials using excitable cells of the ampulla of Lorenzini which have calcium-activated K(+) channels, first described in 1974. A distinctive feature of the outward current in voltage clamped ampullae is its apparent insensitivity to voltage. The sequence of a BK channel α isoform expressed in the ampulla of the skate was characterized. A signal peptide is present at the beginning of the gene. When compared to human isoform 1 (the canonical sequence), the largest difference was absence of a 59 amino acid region from the S8-S9 intra-cellular linker that contains the strex regulatory domain. The ampulla isoform was also compared with the isoform predicted in late skate embryos where strex was also absent. The BK voltage sensors were conserved in both skate isoforms. Differences between the skate and human BK channel included alternative splicing. Alternative splicing occurs at seven previously defined sites that are characteristic for BK channels in general and hair cells in particular. Skate BK sequences were highly similar to the Australian ghost shark and several other vertebrate species. Based on alignment of known BK sequences with the skate genome and transcriptome, there are at least two isoforms of Kcnma1α expressed in the skate. One of the β subunits (β4), which is known to decrease voltage sensitivity, was also identified in the skate genome and transcriptome and in the ampulla. These studies advance our knowledge of BK channels and suggest further studies in the ampulla and other excitable tissues. Copyright © 2015 Elsevier B.V. All rights reserved.

Sinusoidal voltage protocols for rapid characterisation of ion channel kinetics.

Science.gov (United States)

Beattie, Kylie A; Hill, Adam P; Bardenet, Rémi; Cui, Yi; Vandenberg, Jamie I; Gavaghan, David J; de Boer, Teun P; Mirams, Gary R

2018-03-24

Ion current kinetics are commonly represented by current-voltage relationships, time constant-voltage relationships and subsequently mathematical models fitted to these. These experiments take substantial time, which means they are rarely performed in the same cell. Rather than traditional square-wave voltage clamps, we fitted a model to the current evoked by a novel sum-of-sinusoids voltage clamp that was only 8 s long. Short protocols that can be performed multiple times within a single cell will offer many new opportunities to measure how ion current kinetics are affected by changing conditions. The new model predicts the current under traditional square-wave protocols well, with better predictions of underlying currents than literature models. The current under a novel physiologically relevant series of action potential clamps is predicted extremely well. The short sinusoidal protocols allow a model to be fully fitted to individual cells, allowing us to examine cell-cell variability in current kinetics for the first time. Understanding the roles of ion currents is crucial to predict the action of pharmaceuticals and mutations in different scenarios, and thereby to guide clinical interventions in the heart, brain and other electrophysiological systems. Our ability to predict how ion currents contribute to cellular electrophysiology is in turn critically dependent on our characterisation of ion channel kinetics - the voltage-dependent rates of transition between open, closed and inactivated channel states. We present a new method for rapidly exploring and characterising ion channel kinetics, applying it to the hERG potassium channel as an example, with the aim of generating a quantitatively predictive representation of the ion current. We fitted a mathematical model to currents evoked by a novel 8 second sinusoidal voltage clamp in CHO cells overexpressing hERG1a. The model was then used to predict over 5 minutes of recordings in the same cell in response to

Absorption of 249Bk from the gastrointestinal tract

International Nuclear Information System (INIS)

Zalikin, G.A.; Nisimov, P.G.

1988-01-01

In experimets with albino mongrel female rats a study was made of the absorption of 249 Bk from the gastrointestinal tract after a single per os administration. The bulk of 249 Bk (96 per cent) administered either intravenously or per os was mainly deposited in the skeleton and liver. The value of 249 Bk absorption from the gastrointestinal trat by days 4 and 8 following administration was 0.05 per cent

Dynamics of Db isotopes formed in reactions induced by 238U, 248Cm, and 249Bk across the Coulomb barrier

Science.gov (United States)

Kaur, Gurjit; Sandhu, Kirandeep; Kaur, Amandeep; Sharma, Manoj K.

2018-05-01

The dynamical cluster decay model is employed to investigate the decay of *265Db and *267Db nuclei, formed in the 27Al+238U , 18O+249Bk , and 19F+248Cm hot fusion reactions at energies around the Coulomb barrier. First, the fission dynamics of the 27Al+238U reaction is explored by investigating the fragmentation and preformation yield of the reaction. The symmetric mass distribution of the fission fragments is observed for *265Db nucleus, when static β2 i deformations are used within hot optimum orientation approach. However, the mass split gets broaden for the use of β2 i-dynamical hot configuration of the fragments and becomes clearly asymmetric for the cold-static-deformed approach. Within the application of cold orientations of fragments, a new fission channel is observed at mass asymmetry η =0.29 . In addition to 238U-induced reaction, the work is carried out to address the fission and neutron evaporation cross sections of *267Db nucleus formed via 19F+248Cm and 18O+249Bk reactions, besides a comprehensive analysis of fusion and capture processes. Higher fusion cross sections and compound nucleus formation probabilities (PCN) are obtained for the 18O+249Bk reaction, as larger mass asymmetry in the entrance channel leads to reduced Coulomb factor. Finally, the role of sticking (IS) and nonsticking (INS) moments of inertia is analyzed for the 4 n and 5 n channels of *267Db nuclear system.

Agnoprotein Is an Essential Egress Factor during BK Polyomavirus Infection

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Margarita-Maria Panou

2018-03-01

Full Text Available BK polyomavirus (BKPyV; hereafter referred to as BK causes a lifelong chronic infection and is associated with debilitating disease in kidney transplant recipients. Despite its importance, aspects of the virus life cycle remain poorly understood. In addition to the structural proteins, the late region of the BK genome encodes for an auxiliary protein called agnoprotein. Studies on other polyomavirus agnoproteins have suggested that the protein may contribute to virion infectivity. Here, we demonstrate an essential role for agnoprotein in BK virus release. Viruses lacking agnoprotein fail to release from host cells and do not propagate to wild-type levels. Despite this, agnoprotein is not essential for virion infectivity or morphogenesis. Instead, agnoprotein expression correlates with nuclear egress of BK virions. We demonstrate that the agnoprotein binding partner α-soluble N-ethylmaleimide sensitive fusion (NSF attachment protein (α-SNAP is necessary for BK virion release, and siRNA knockdown of α-SNAP prevents nuclear release of wild-type BK virions. These data highlight a novel role for agnoprotein and begin to reveal the mechanism by which polyomaviruses leave an infected cell.

Localization of large conductance calcium-activated potassium channels and their effect on calcitonin gene-related peptide release in the rat trigemino-neuronal pathway

DEFF Research Database (Denmark)

Wulf-Johansson, H.; Amrutkar, D.V.; Hay-Schmidt, Anders

2010-01-01

Large conductance calcium-activated potassium (BK(Ca)) channels are membrane proteins contributing to electrical propagation through neurons. Calcitonin gene-related peptide (CGRP) is a neuropeptide found in the trigeminovascular system (TGVS). Both BK(Ca) channels and CGRP are involved in migrai...

BK Virus-Associated Nephropathy without Viremia in an Adolescent Kidney Transplant Recipient

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Kraisoon Lomjansook, M.D.

2017-09-01

Full Text Available BK virus can reactivate in kidney transplant recipients leading to BK virus-associated nephropathy (BKVAN and allograft dysfunction. Pathogenesis begins with viral replication, follows by viruria, viremia and nephropathy. Screening tools recommended for viral detection are urine and blood BK viral load. Viremia has higher positive predictive value than viruria, thus several guidelines recommend using viremia to determine whether renal biopsy, a gold standard for diagnosis of BKVAN is needed. We present a 16-year-old boy who developed BKVAN five months after deceased donor kidney transplantation. He had increased serum creatinine with negative blood BK viral load. BK nephropathy was diagnosed in kidney graft biopsy. The urine showed BK viruria. Immunosuppressant was reduced and ciprofloxacin given. Viruria disappeared and repeated graft biopsy was normal 4 months later. BK viremia was negative through 1 year follow up. We conclude that BKVAN may occur even without viremia and BK viruria may be considered for screening tool.

Reactivation of BK polyomavirus in patients with multiple sclerosis receiving natalizumab therapy.

LENUS (Irish Health Repository)

Lonergan, Roisin M

2012-02-01

Natalizumab therapy in multiple sclerosis has been associated with JC polyomavirus-induced progressive multifocal leucoencephalopathy. We hypothesized that natalizumab may also lead to reactivation of BK, a related human polyomavirus capable of causing morbidity in immunosuppressed groups. Patients with relapsing remitting multiple sclerosis treated with natalizumab were prospectively monitored for reactivation of BK virus in blood and urine samples, and for evidence of associated renal dysfunction. In this cohort, JC and BK DNA in blood and urine; cytomegalovirus (CMV) DNA in blood and urine; CD4 and CD8 T-lymphocyte counts and ratios in peripheral blood; and renal function were monitored at regular intervals. BK subtyping and noncoding control region sequencing was performed on samples demonstrating reactivation. Prior to commencement of natalizumab therapy, 3 of 36 patients with multiple sclerosis (8.3%) had BK viruria and BK reactivation occurred in 12 of 54 patients (22.2%). BK viruria was transient in 7, continuous in 2 patients, and persistent viruria was associated with transient viremia. Concomitant JC and CMV viral loads were undetectable. CD4:CD8 ratios fluctuated, but absolute CD4 counts did not fall below normal limits. In four of seven patients with BK virus reactivation, transient reductions in CD4 counts were observed at onset of BK viruria: these resolved in three of four patients on resuppression of BK replication. No renal dysfunction was observed in the cohort. BK virus reactivation can occur during natalizumab therapy; however, the significance in the absence of renal dysfunction is unclear. We propose regular monitoring for BK reactivation or at least for evidence of renal dysfunction in patients receiving natalizumab.

Activation gating kinetics of GIRK channels are mediated by cytoplasmic residues adjacent to transmembrane domains.

Science.gov (United States)

Sadja, Rona; Reuveny, Eitan

2009-01-01

G-protein-coupled inwardly rectifying potassium channels (GIRK/Kir3.x) are involved in neurotransmission-mediated reduction of excitability. The gating mechanism following G protein activation of these channels likely proceeds from movement of inner transmembrane helices to allow K(+) ions movement through the pore of the channel. There is limited understanding of how the binding of G-protein betagamma subunits to cytoplasmic regions of the channel transduces the signal to the transmembrane regions. In this study, we examined the molecular basis that governs the activation kinetics of these channels, using a chimeric approach. We identified two regions as being important in determining the kinetics of activation. One region is the bottom of the outer transmembrane helix (TM1) and the cytoplasmic domain immediately adjacent (the slide helix); and the second region is the bottom of the inner transmembrane helix (TM2) and the cytoplasmic domain immediately adjacent. Interestingly, both of these regions are sufficient in mediating the kinetics of fast activation gating. This result suggests that there is a cooperative movement of either one of these domains to allow fast and efficient activation gating of GIRK channels.

Apelin-13 inhibits large-conductance Ca2+-activated K+ channels in cerebral artery smooth muscle cells via a PI3-kinase dependent mechanism.

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Amit Modgil

Full Text Available Apelin-13 causes vasoconstriction by acting directly on APJ receptors in vascular smooth muscle (VSM cells; however, the ionic mechanisms underlying this action at the cellular level remain unclear. Large-conductance Ca(2+-activated K(+ (BKCa channels in VSM cells are critical regulators of membrane potential and vascular tone. In the present study, we examined the effect of apelin-13 on BK(Ca channel activity in VSM cells, freshly isolated from rat middle cerebral arteries. In whole-cell patch clamp mode, apelin-13 (0.001-1 μM caused concentration-dependent inhibition of BK(Ca in VSM cells. Apelin-13 (0.1 µM significantly decreased BK(Ca current density from 71.25 ± 8.14 pA/pF to 44.52 ± 7.10 pA/pF (n=14 cells, P<0.05. This inhibitory effect of apelin-13 was confirmed by single channel recording in cell-attached patches, in which extracellular application of apelin-13 (0.1 µM decreased the open-state probability (NPo of BK(Ca channels in freshly isolated VSM cells. However, in inside-out patches, extracellular application of apelin-13 (0.1 µM did not alter the NPo of BK(Ca channels, suggesting that the inhibitory effect of apelin-13 on BKCa is not mediated by a direct action on BK(Ca. In whole cell patches, pretreatment of VSM cells with LY-294002, a PI3-kinase inhibitor, markedly attenuated the apelin-13-induced decrease in BK(Ca current density. In addition, treatment of arteries with apelin-13 (0.1 µM significantly increased the ratio of phosphorylated-Akt/total Akt, indicating that apelin-13 significantly increases PI3-kinase activity. Taken together, the data suggest that apelin-13 inhibits BK(Ca channel via a PI3-kinase-dependent signaling pathway in cerebral artery VSM cells, which may contribute to its regulatory action in the control of vascular tone.

Physiological role of Kv1.3 channel in T lymphocyte cell investigated quantitatively by kinetic modeling.

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Panpan Hou

Full Text Available Kv1.3 channel is a delayed rectifier channel abundant in human T lymphocytes. Chronic inflammatory and autoimmune disorders lead to the over-expression of Kv1.3 in T cells. To quantitatively study the regulatory mechanism and physiological function of Kv1.3 in T cells, it is necessary to have a precise kinetic model of Kv1.3. In this study, we firstly established a kinetic model capable to precisely replicate all the kinetic features for Kv1.3 channels, and then constructed a T-cell model composed of ion channels including Ca2+-release activated calcium (CRAC channel, intermediate K+ (IK channel, TASK channel and Kv1.3 channel for quantitatively simulating the changes in membrane potentials and local Ca2+ signaling messengers during activation of T cells. Based on the experimental data from current-clamp recordings, we successfully demonstrated that Kv1.3 dominated the membrane potential of T cells to manipulate the Ca2+ influx via CRAC channel. Our results revealed that the deficient expression of Kv1.3 channel would cause the less Ca2+ signal, leading to the less efficiency in secretion. This was the first successful attempt to simulate membrane potential in non-excitable cells, which laid a solid basis for quantitatively studying the regulatory mechanism and physiological role of channels in non-excitable cells.

Perbedaan Pemahaman Guru BK Tentang Konseling Kelompok antara Alumni Unnes dan Non-Unnes

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Desta Rizky Budiarti

2014-10-01

Full Text Available Tujuan penelitian ini untuk mengetahui gambaran pemahaman guru BK alumni Unnes dan guru BK alumni non-Unnes tentang konseling kelompok, dan perbedaan pemahaman diantara keduanya. Jenis penelitian adalah penelitian survey komparatif. Populasi penelitian ini yaitu guru BK di SMP Negeri se-Kota Semarang. Teknik sampling yang digunakan adalah Cluster Proportional Random Sampling. Metode pengumpulan data menggunakan tes tentang pemahaman konseling kelompok. Analisis datanya menggunakan analisis kuantitatif yang mencakup deskriptif prosentase dan uji beda t-test polled varian. Hasil penelitian menunjukkan bahwa ada perbedaan yang signifikan, dimana pemahaman guru BK alumni Unnes tentang konseling kelompok berada pada kategori sangat tinggi dengan persentase 84,26% dibandingkan dengan guru BK alumni non-Unnes yang memiliki persentase 63,9% berada pada kategori sedang. Simpulan dari penelitian ini, pemahaman guru BK tentang konseling kelompok antara alumni Unnes lebih tinggi daripada guru BK alumni non-Unnes. The purpose of this study to describe the understanding of BK teacher Unnes graduate and BK teacher non - Unnes graduates about group counseling, and understanding the differences between them . This type of research is a comparative survey research. The population of this study are in Junior High School teacher BK as the city of Semarang. The sampling technique used is proportional cluster random sampling. Methods of data collection using test on understanding group counseling. Analysis of the data using descriptive quantitative analysis that includes the percentage and t - test different test variants polled. The results showed that there were significant differences, where the understanding of BK teacher Unnes graduate  abaout  the counseling group in the category with a very high percentage of 84.26 % compared to a BK teacher non - Unnes graduates who have a percentage only 63.9 % are in the medium category. The conclusions of this study

Evaluation of fluoroquinolones for the prevention of BK viremia after renal transplantation.

Science.gov (United States)

Gabardi, Steven; Waikar, Sushrut S; Martin, Spencer; Roberts, Keri; Chen, Jie; Borgi, Lea; Sheashaa, Hussein; Dyer, Christine; Malek, Sayeed K; Tullius, Stefan G; Vadivel, Nidyanandh; Grafals, Monica; Abdi, Reza; Najafian, Nader; Milford, Edgar; Chandraker, Anil

2010-07-01

Nearly 30% of renal transplant recipients develops BK viremia, a prerequisite for BK nephropathy. Case reports have evaluated treatment options for BK virus, but no controlled studies have assessed prophylactic therapies. Fluoroquinolone antibiotics were studied for prevention of BK viremia after renal transplantation. This retrospective analysis evaluated adult renal transplant recipients with at least one BK viral load (blood) between 90 and 400 days after transplantation. Six to 12 months of co-trimoxazole was used for Pneumocystis prophylaxis. In sulfa-allergic/-intolerant patients, 6 to 12 months of atovaquone with 1 month of a fluoroquinolone was used. Fluoroquinolones can inhibit BK DNA topoisomerase. The two groups studied were those that received 30 days of levofloxacin or ciprofloxacin after transplantation and those that did not. The primary endpoint was BK viremia rates at 1 year. Of note, of the 160 patients not receiving fluoroquinolone prophylaxis, 40 received a fluoroquinolone for treatment of a bacterial infection within 3 months after transplantation. Subgroup analysis evaluating these 40 patients against the 120 who had no exposure to fluoroquinolones was completed. A 1-month fluoroquinolone course after transplantation was associated with significantly lower rates of BK viremia at 1 year compared with those with no fluoroquinolone. In the subgroup analysis, exposure to fluoroquinolone for treatment of bacterial infections within 3 months after transplantation was associated with significantly lower 1-year rates of BK viremia. This analysis demonstrates that fluoroquinolones are effective at preventing BK viremia after renal transplantation.

BK channel activators and their therapeutic perspectives

DEFF Research Database (Denmark)

Bentzen, Bo Hjorth; Olesen, Søren-Peter; Rønn, Lars C B

2014-01-01

in intracellular calcium to outward hyperpolarizing potassium currents. Consequently, the channel has many important physiological roles including regulation of smooth muscle tone, neurotransmitter release and neuronal excitability. Additionally, cardioprotective roles have been revealed in recent years. After...

Inhibition of CUG-binding protein 1 and activation of caspases are critically involved in piperazine derivative BK10007S induced apoptosis in hepatocellular carcinoma cells.

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Ju-Ha Kim

Full Text Available Though piperazine derivative BK10007S was known to induce apoptosis in pancreatic cancer xenograft model as a T-type CaV3.1 a1G isoform calcium channel blocker, its underlying antitumor mechanism still remains unclear so far. Thus, in the present study, the antitumor mechanism of BK10007S was elucidated in hepatocellular carcinoma cells (HCCs. Herein, BK10007S showed significant cytotoxicity by 3-[4,5-2-yl]-2,5-diphenyltetra-zolium bromide (MTT assay and anti-proliferative effects by colony formation assay in HepG2 and SK-Hep1 cells. Also, apoptotic bodies and terminal deoxynucleotidyl transferase (TdT dUTP Nick End Labeling (TUNEL positive cells were observed in BK10007S treated HepG2 and SK-Hep1 cells by 4',6-diamidino-2-phenylinodole (DAPI staining and TUNEL assay, respectively. Consistently, BK10007S increased sub G1 population in HepG2 and SK-Hep1 cells by cell cycle analysis. Furthermore, Western blotting revealed that BK10007S activated the caspase cascades (caspase 8, 9 and 3, cleaved poly (ADP-ribose polymerase (PARP, and downregulated the expression of cyclin D1, survivin and for CUG-binding protein 1 (CUGBP1 or CELF1 in HepG2 and SK-Hep1 cells. Conversely, overexpression of CUGBP1 reduced cleavages of PARP and caspase 3, cytotoxicity and subG1 population in BK10007S treated HepG2 cells. Overall, these findings provide scientific evidences that BK10007S induces apoptosis via inhibition of CUGBP1 and activation of caspases in hepatocellular carcinomas as a potent anticancer candidate.

Analogies between colored Lévy noise and random channel approach to disordered kinetics

Science.gov (United States)

Vlad, Marcel O.; Velarde, Manuel G.; Ross, John

2004-02-01

We point out some interesting analogies between colored Lévy noise and the random channel approach to disordered kinetics. These analogies are due to the fact that the probability density of the Lévy noise source plays a similar role as the probability density of rate coefficients in disordered kinetics. Although the equations for the two approaches are not identical, the analogies can be used for deriving new, useful results for both problems. The random channel approach makes it possible to generalize the fractional Uhlenbeck-Ornstein processes (FUO) for space- and time-dependent colored noise. We describe the properties of colored noise in terms of characteristic functionals, which are evaluated by using a generalization of Huber's approach to complex relaxation [Phys. Rev. B 31, 6070 (1985)]. We start out by investigating the properties of symmetrical white noise and then define the Lévy colored noise in terms of a Langevin equation with a Lévy white noise source. We derive exact analytical expressions for the various characteristic functionals, which characterize the noise, and a functional fractional Fokker-Planck equation for the probability density functional of the noise at a given moment in time. Second, by making an analogy between the theory of colored noise and the random channel approach to disordered kinetics, we derive fractional equations for the evolution of the probability densities of the random rate coefficients in disordered kinetics. These equations serve as a basis for developing methods for the evaluation of the statistical properties of the random rate coefficients from experimental data. Special attention is paid to the analysis of systems for which the observed kinetic curves can be described by linear or nonlinear stretched exponential kinetics.

Measuring kinetics of complex single ion channel data using mean-variance histograms.

Science.gov (United States)

Patlak, J B

1993-07-01

The measurement of single ion channel kinetics is difficult when those channels exhibit subconductance events. When the kinetics are fast, and when the current magnitudes are small, as is the case for Na+, Ca2+, and some K+ channels, these difficulties can lead to serious errors in the estimation of channel kinetics. I present here a method, based on the construction and analysis of mean-variance histograms, that can overcome these problems. A mean-variance histogram is constructed by calculating the mean current and the current variance within a brief "window" (a set of N consecutive data samples) superimposed on the digitized raw channel data. Systematic movement of this window over the data produces large numbers of mean-variance pairs which can be assembled into a two-dimensional histogram. Defined current levels (open, closed, or sublevel) appear in such plots as low variance regions. The total number of events in such low variance regions is estimated by curve fitting and plotted as a function of window width. This function decreases with the same time constants as the original dwell time probability distribution for each of the regions. The method can therefore be used: 1) to present a qualitative summary of the single channel data from which the signal-to-noise ratio, open channel noise, steadiness of the baseline, and number of conductance levels can be quickly determined; 2) to quantify the dwell time distribution in each of the levels exhibited. In this paper I present the analysis of a Na+ channel recording that had a number of complexities. The signal-to-noise ratio was only about 8 for the main open state, open channel noise, and fast flickers to other states were present, as were a substantial number of subconductance states. "Standard" half-amplitude threshold analysis of these data produce open and closed time histograms that were well fitted by the sum of two exponentials, but with apparently erroneous time constants, whereas the mean

Study of the properties of the superheavy nuclei Z=117 produced in the 249Bk + 48Ca reaction

International Nuclear Information System (INIS)

Oganessian, Y.T.; Abdullin, F.S.; Dmitriev, S.N.; Itkis, M.G.; Polyakov, A.N.; Sagaidak, R.N.; Shirokovsky, I.V.; Shumeiko, M.V.; Subbotin, V.G.; Sukhov, A.M.; Tsyganov, Y.S.; Utyonkov, V.K.; Voinov, A.A.; Vostokin, G.K.; Alexander, C.; Binder, J.; Boll, R.A.; Ezold, J.; Felker, K.; Miernik, K.; Roberto, J.B.; Rykaczewski, K.P.; Gostic, J.M.; Henderson, R.A.; Moody, K.J.; Shaughnessy, D.H.; Stoyer, M.A.; Stoyer, N.J.; Grzywacz, R.K.; Miller, D.; Hamilton, J.H.; Ramayya, A.V.; Ryabinin, M.A.

2014-01-01

The reaction of 249 Bk with 48 Ca have been reinvestigated to provide new evidence for the discovery of element 117 on a larger number of events. The experiments were performed at five projectile energies and with a total beam dose of 48 Ca of about 4.6*10 19 . Two isotopes 293,294 117 were synthesized in the 249 Bk+ 48 Ca reaction, providing excitation functions and α-decay spectra of the produced isotopes that establishes these nuclei to be the products of the 4n- and 3n-evaporation channels, respectively. Decay properties of 293,294 117 and of all the daughter products agree with the data of the experiment in which these nuclei were synthesized for the first time in 2010. The new 289 115 events, populated by a decay of 293 117, demonstrate the same decay properties as those observed for 289 115 produced in the 243 Am( 48 Ca,2n) reaction thus providing cross-bombardment evidence. In addition, a single decay of 294 118 was observed from the reaction with 249 Cf - a result of the in-growth of 249 Cf in the 249 Bk target. (authors)

THEORETICAL RESEARCH ON THE MULTI-CHANNEL REACTION MECHANISM AND KINETICS OF HNCS WITH OH-

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Li-Jie Hou

Full Text Available We presented a theoretical study on the detailed reaction mechanism and kinetics of the HNCS molecule with the OH-. The barrierless minimum energy path and the most favorable entrance channel have been determined by study the thermodynamic and kinetic characters of the channel with low energy barrier. The B3LYP/6-311++G** method was employed for all the geometrical optimizations and a multi-level extrapolation method based on the G3 energies was employed for further energy refinements. In addition, the analysis of the combining interaction between hydroxide ion and HNCS was performed by natural bond orbitals (NBO analysis. The calculation results indicated that the reaction of OH- with HNCS had four channels, and the channel of H-atom in HNCS direct extraction to OH- (OH-+HNCS→IM1→TS3→IM4→P2(SCN- +H2O in singlet state was the main channel with the low potential energy and high equilibrium constant and reaction rate constant. SCN- and H2O were main products.

Kinetic Theory and Simulation of Single-Channel Water Transport

Science.gov (United States)

Tajkhorshid, Emad; Zhu, Fangqiang; Schulten, Klaus

Water translocation between various compartments of a system is a fundamental process in biology of all living cells and in a wide variety of technological problems. The process is of interest in different fields of physiology, physical chemistry, and physics, and many scientists have tried to describe the process through physical models. Owing to advances in computer simulation of molecular processes at an atomic level, water transport has been studied in a variety of molecular systems ranging from biological water channels to artificial nanotubes. While simulations have successfully described various kinetic aspects of water transport, offering a simple, unified model to describe trans-channel translocation of water turned out to be a nontrivial task.

Infección por virus BK en paciente pediátrico trasplantado renal BK virus infection in a pediatric renal transplant recipient

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R. Bonaventura

2005-09-01

Full Text Available El poliomavirus humano BK causa infección primaria asintomática en la niñez, estableciendo latencia principalmente en el tracto urinario. En individuos con alteración en la inmunidad celular se puede producir su reactivación desencadenando patología a nivel renal. Por estas razones es particularmente importante en la población pediátrica trasplantada renal, en la que puede producir la infección primaria cuando el paciente está inmunosuprimido. En nuestro trabajo se realizó el seguimiento de un paciente de 5 años trasplantado renal en octubre de 2003 que 45 días post-trasplante sufrió un deterioro del órgano injertado. Desde la fecha del trasplante hasta junio de 2004 se produjeron 3 episodios de alteración en la función renal, durante los cuales se analizaron muestras de sangre, orina, biopsia renal y líquido de linfocele. Para el diagnóstico difererencial entre rechazo agudo versus causa infecciosa se emplearon técnicas de detección para los virus BK, CMV y ADV, además del estudio citológico del tejido renal. Los resultados obtenidos junto con la clínica del paciente indican un probable caso de infección por BK. La importancia de realizar el diagnóstico diferencial entre rechazo agudo y la infección por BK radica en que la conducta en cuanto a la terapia inmunosupresora es opuesta en cada caso.BK Human Polyomavirus causes an asymptomatic primary infection in children, then establishing latency mainly in the urinary tract. Viral reactivation can lead to renal pathology in individuals with impaired cellular immune response. This is particularly important in pediatric transplant recipients, who can suffer a primary infection when immunosupressed. We followed up the case of a 5 years old patient who received a renal transplant in October 2003, and presented damaged graft 45 days after the intervention. The patient suffered 3 episodes of renal function failure between October 2003 and June 2004. Blood, urine, renal biopsy

A conserved residue cluster that governs kinetics of ATP-dependent gating of Kir6.2 potassium channels

DEFF Research Database (Denmark)

Zhang, Roger S; Wright, Jordan; Pless, Stephan Alexander

2015-01-01

modest effects on gating kinetics despite significant changes in ATP sensitivity and open probability. However, we identified a pair of highly conserved neighboring amino acids (Trp68, Lys170) that control the rate of channel opening and inhibition in response to ATP. Paradoxically, mutations of Trp68...... or Lys170 markedly slow the kinetics of channel opening (500 ms and 700 ms for Trp68Leu and Lys170Asn, respectively), while increasing channel open probability. Examining the functional effects of these residues using phi-value analysis revealed a steep negative slope. This finding implies...

Drosophila QVR/SSS modulates the activation and C-type inactivation kinetics of Shaker K+ channels

Science.gov (United States)

Dean, Terry; Xu, Rong; Joiner, William; Sehgal, Amita; Hoshi, Toshinori

2011-01-01

The quiver/sleepless (qvr/sss) gene encodes a small, glycosylphosphatidylinositol-anchored protein that plays a critical role in the regulation of sleep in Drosophila. Loss-of-function mutations in qvr/sss severely suppress sleep and effect multiple changes in in situ Shaker K+ currents, including decreased magnitude, slower time-to-peak, and cumulative inactivation. Recently, we demonstrated that SLEEPLESS (SSS) protein modulates Shaker channel activity, possibly through a direct interaction at the plasma membrane. We show here that SSS accelerates the activation of heterologously expressed Shaker channels with no effect on deactivation or fast N-type inactivation. Furthermore, this SSS-induced acceleration is sensitive to the pharmacological disruption of lipid rafts and sufficiently accounts for the slower time-to-peak of in situ Shaker currents seen in qvr/sss mutants. We also find that SSS decreases the rate of C-type inactivation of heterologously expressed Shaker channels, providing a potential mechanism for the cumulative inactivation phenotype induced by qvr/sss loss of function mutations. Kinetic modeling based on the in vitro results suggests that the SSS-dependent regulation of channel kinetics accounts for nearly 40% of the decrease in Shaker current magnitude in flies lacking SSS. Sleep duration in qvr/sss null mutants is restored to normal by a qvr/sss transgene that fully rescues the Shaker kinetic phenotypes but only partially rescues the decrease in current magnitude. Together, these results suggest that the role of SSS in the regulation of sleep in Drosophila correlates more strongly with the effects of SSS on Shaker kinetics than current magnitude. PMID:21813698

Drosophila QVR/SSS modulates the activation and C-type inactivation kinetics of Shaker K(+) channels.

Science.gov (United States)

Dean, Terry; Xu, Rong; Joiner, William; Sehgal, Amita; Hoshi, Toshinori

2011-08-03

The quiver/sleepless (qvr/sss) gene encodes a small, glycosylphosphatidylinositol-anchored protein that plays a critical role in the regulation of sleep in Drosophila. Loss-of-function mutations in qvr/sss severely suppress sleep and effect multiple changes in in situ Shaker K(+) currents, including decreased magnitude, slower time-to-peak, and cumulative inactivation. Recently, we demonstrated that SLEEPLESS (SSS) protein modulates Shaker channel activity, possibly through a direct interaction at the plasma membrane. We show here that SSS accelerates the activation of heterologously expressed Shaker channels with no effect on deactivation or fast N-type inactivation. Furthermore, this SSS-induced acceleration is sensitive to the pharmacological disruption of lipid rafts and sufficiently accounts for the slower time-to-peak of in situ Shaker currents seen in qvr/sss mutants. We also find that SSS decreases the rate of C-type inactivation of heterologously expressed Shaker channels, providing a potential mechanism for the cumulative inactivation phenotype induced by qvr/sss loss-of-function mutations. Kinetic modeling based on the in vitro results suggests that the SSS-dependent regulation of channel kinetics accounts for nearly 40% of the decrease in Shaker current magnitude in flies lacking SSS. Sleep duration in qvr/sss-null mutants is restored to normal by a qvr/sss transgene that fully rescues the Shaker kinetic phenotypes but only partially rescues the decrease in current magnitude. Together, these results suggest that the role of SSS in the regulation of sleep in Drosophila correlates more strongly with the effects of SSS on Shaker kinetics than current magnitude.

Low-Dose Ethanol Preconditioning Protects Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Neuronal Injury By Activating Large Conductance, Ca2+-Activated K+ Channels In Vitro.

Science.gov (United States)

Su, Fang; Guo, An-Chen; Li, Wei-Wei; Zhao, Yi-Long; Qu, Zheng-Yi; Wang, Yong-Jun; Wang, Qun; Zhu, Yu-Lan

2017-02-01

Increasing evidence suggests that low to moderate ethanol ingestion protects against the deleterious effects of subsequent ischemia/reperfusion; however, the underlying mechanism has not been elucidated. In the present study, we showed that expression of the neuronal large-conductance, Ca 2+ -activated K + channel (BK Ca ) α-subunit was upregulated in cultured neurons exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) compared with controls. Preconditioning with low-dose ethanol (10 mmol/L) increased cell survival rate in neurons subjected to OGD/R, attenuated the OGD/R-induced elevation of cytosolic Ca 2+ levels, and reduced the number of apoptotic neurons. Western blots revealed that ethanol preconditioning upregulated expression of the anti-apoptotic protein Bcl-2 and downregulated the pro-apoptotic protein Bax. The protective effect of ethanol preconditioning was antagonized by a BK Ca channel inhibitor, paxilline. Inside-out patches in primary neurons also demonstrated the direct activation of the BK Ca channel by 10 mmol/L ethanol. The above results indicated that low-dose ethanol preconditioning exerts its neuroprotective effects by attenuating the elevation of cytosolic Ca 2+ and preventing neuronal apoptosis, and this is mediated by BK Ca channel activation.

Outcomes of renal transplant recipients with BK virus infection and BK virus surveillance in the Auckland region from 2006 to 2012.

Science.gov (United States)

Hsiao, Chun-Yuan; Pilmore, Helen L; Zhou, Lifeng; de Zoysa, Janak R

2016-11-06

To evaluate incidence, risk factors and treatment outcome of BK polyomavirus nephropathy (BKVN) in a cohort of renal transplant recipients in the Auckland region without a formal BK polyomavirus (BKV) surveillance programme. A cohort of 226 patients who received their renal transplants from 2006 to 2012 was retrospectively reviewed. Seventy-six recipients (33.6%) had a BK viral load (BKVL) test and 9 patients (3.9%) developed BKVN. Cold ischaemia time (HR = 1.18, 95%CI: 1.04-1.35) was found to be a risk factor for BKVN. Four recipients with BKVN had complete resolution of their BKV infection; 1 recipient had BKVL less than 625 copies/mL; 3 recipients had BKVL more than 1000 copies/mL and 1 had graft failure from BKVN. BKVN has a negative impact on graft function [median estimated glomerular filtration rate (eGFR) 22.5 (IQR 18.5-53.0) mL/min per 1.73 m 2 , P = 0.015), but no statistically significant difference ( P = 0.374) in renal allograft function was found among negative BK viraemia group [median eGFR 60.0 (IQR 48.5-74.2) mL/min per 1.73 m 2 ), positive BK viraemia without BKVN group [median eGFR 55.0 (IQR 47.0-76.0) mL/min per 1.73 m 2 ] and unknown BKV status group [median eGFR 54.0 (IQR 43.8-71.0) mL/min per 1.73 m 2 ]. The incidence and treatment outcomes of BKVN were similar to some centres with BKV surveillance programmes. Recipients with BVKN have poorer graft function. Although active surveillance for BKV has been shown to be effective in reducing incidence of BKVN, it should be tailored specifically to that transplant centre based on its epidemiology and outcomes of BKVN, particularly in centres with limited resources.

Numerical solution of incompressible flow through branched channels

Czech Academy of Sciences Publication Activity Database

Louda, Petr; Kozel, K.; Příhoda, Jaromír; Beneš, L.; Kopáček, T.

2011-01-01

Roč. 46, č. 1 (2011), s. 318-324 ISSN 0045-7930 R&D Projects: GA ČR GA103/09/0977; GA ČR GAP101/10/1230 Institutional research plan: CEZ:AV0Z20760514 Keywords : channel flow * branched channel * EARSM turbulence model Subject RIV: BK - Fluid Dynamics Impact factor: 1.810, year: 2011 http://www.sciencedirect.com/science/article/pii/S0045793010003506

Pelaksanaan Asas-Asas BK dalam Pelayanan BK (Ditinjau dari Persepsi Siswa

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Yasinta Nur Miftakhul Jannah

2015-09-01

Full Text Available Penelitian ini didasarkan pada data dan fenomena yang ditemukan di lapangan yang menunjukkan rendahnya pelaksanaan asas-asas bimbingan dan konseling oleh konselor di sekolah. Penelitian ini bertujuan untuk mengetahui gambaran pelaksanaan asas-asas BK dalam pelayanan BK di SMA Negeri se-Kabupaten Pati (ditinjau dari persepsi siswa kelas XI Tahun Ajaran 2014/2015. Populasi penelitian ini adalah siswa kelas XI di SMA Negeri se-Kabupaten Pati. Pengambilan sampel penelitian dilakukan dengan menggunakan teknik proportionale homogen random sampling dengan sampel sebesar 307 siswa kelas XI. Metode pengumpulan data menggunakan skala psikologis dalam bentuk skala persepsi. Metode analisis data menggunakan statistik deskriptif persentase. Hasil dari penelitian menunjukkan, gambaran pelaksanaan asas-asas BK secara umum sudah masuk pada kategori baik dengan persentase sebesar 73,45%. Asas yang paling tinggi pelaksanaannya yaitu asas kegiatan dengan persentase sebesar 79,80%. Asas yang masih tergolong rendah persentase pelaksanaannya yaitu asas kekinian dengan persentase sebesar 68,80% dan asas alih tangan dengan persentase sebesar 69,10%. This research is based on data and phenomena found in a field that shows low  implementation of guidance and counseling principles by counselor at school. This research aims to find out the implementation of guidance and counseling principles in counseling services toward public senior high school throughout Pati Regency (reviewed from grade XI students’ perceptions Academic Year 2014/2015. Population of this research are grade XI public senior high school students throughout Pati Regency. Sampling in this research is done by using proportionale homogen random sampling technique with the number of samples 307 of grade IX. Collecting data method using psychological scale in the form of scale perception. Data analysis method which used is descriptive percentage. The result shows description of the implementation of

Bk and Cf chromatographic separation and 249Bk/248Cm and 249Cf/248Cm elemental ratios determination by inductively coupled plasma quadrupole mass spectrometry

International Nuclear Information System (INIS)

Gourgiotis, A.; Isnard, H.; Nonell, A.; Aubert, M.; Stadelmann, G.; Dupont, E.; AlMahamid, I.; Tiang, G.; Rao, L.; Lukens, W.; Cassette, P.; Panebianco, S.; Letourneau, A.; Chartier, F.

2013-01-01

The French Atomic Energy Commission has carried out several experiments for the study of minor-actinide transmutation processes in high intensity thermal neutron flux. In this context a Cm sample enriched in 248 Cm (97%) was irradiated in a thermal neutron flux at the High Flux Reactor (HFR) of the Laue-Langevin Institute (ILL). The precise and accurate determination of Cf isotope ratios and of 249 Bk/ 248 Cm and 249 Cf/ 248 Cm elemental ratios in the 248 Cm irradiated sample is crucial for the calculation of actinide neutron capture cross-sections.This work describes an analytical procedure for the separation and the isotope ratio measurement of Bk and Cf in the irradiated sample.The Bk and Cf separation is based on a lanthanides separation protocol previously developed by the laboratory. Well-defined retention times for Bk and Cf were obtained by coupling the Ionic Chromatography (IC) with an ICP-QMS. All conditions of element separation by IC and the different steps of the analytical protocol in order to obtain the isotopic and elemental ratios are presented. Relative uncertainties of Cf isotopic ratios range from 0.3% to 0.5% and the uncertainty of the 249 Bk/ 248 Cm and 249 Cf/ 248 Cm elemental ratios are respectively 6.1% and 3.2%.This level of uncertainty for both isotopic and elemental ratios is in perfect agreement with the requirement for transmutation studies. (authors)

Urinary BK virus excretion in children newly diagnosed with acute lymphoblastic leukemia

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Nahid Raeesi

2012-01-01

Conclusion: To demonstrate the role of BK virus in inducing ALL or increasing the number of relapses, prospective studies on larger scale of population and evaluating both serum and urine for BK virus are recommended.

Molecular mapping of qBK1 WD , a major QTL for bakanae disease resistance in rice.

Science.gov (United States)

Lee, Sais-Beul; Hur, Yeon-Jae; Cho, Jun-Hyeon; Lee, Jong-Hee; Kim, Tae-Heon; Cho, Soo-Min; Song, You-Chun; Seo, Young-Su; Lee, Jungkwan; Kim, Tae-Sung; Park, Yong-Jin; Oh, Myung-Kyu; Park, Dong-Soo

2018-01-10

Bakanae or foot rot disease is a prominent disease of rice caused by Gibberella fujikuroi. This disease may infect rice plants from the pre-emergence stage to the mature stage. In recent years, raising rice seedlings in seed boxes for mechanical transplanting has increased the incidence of many seedling diseases; only a few rice varieties have been reported to exhibit resistance to bakanae disease. In this study, we attempted to identify quantitative trait loci (QTLs) conferring bakanae disease resistance from the highly resistant japonica variety Wonseadaesoo. A primary QTL study using the genotypes/phenotypes of the recombinant inbred lines (RILs) indicated that the locus qBK1 WD conferring resistance to bakanae disease from Wonseadaesoo was located in a 1.59 Mb interval delimited on the physical map between chr01_13542347 (13.54 Mb) and chr01_15132528 (15.13 Mb). The log of odds (LOD) score of qBK1 WD was 8.29, accounting for 20.2% of the total phenotypic variation. We further identified a gene pyramiding effect of two QTLs, qBK WD and previously developed qBK1. The mean proportion of healthy plant for 31 F 4 RILs that had no resistance genes was 35.3%, which was similar to that of the susceptible check variety Ilpum. The proportion of healthy plants for the lines with only qBK WD or qBK1 was 66.1% and 55.5%, respectively, which was significantly higher than that of the lines without resistance genes and that of Ilpum. The mean proportion of the healthy plant for 15 F 4 RILs harboring both qBK WD and qBK1 was 80.2%, which was significantly higher than that of the lines with only qBK WD or qBK1. Introducing qBK WD or pyramiding the QTLs qBK WD and qBK1 could provide effective tools for breeding rice with bakanae disease resistance. To our knowledge, this is the first report on a gene pyramiding effect that provides higher resistance against bakanae disease.

Vascular ATP-sensitive potassium channels are over-expressed and partially regulated by nitric oxide in experimental septic shock.

Science.gov (United States)

Collin, Solène; Sennoun, Nacira; Dron, Anne-Gaëlle; de la Bourdonnaye, Mathilde; Montemont, Chantal; Asfar, Pierre; Lacolley, Patrick; Meziani, Ferhat; Levy, Bruno

2011-05-01

To study the activation and expression of vascular (aorta and small mesenteric arteries) potassium channels during septic shock with or without modulation of the NO pathway. Septic shock was induced in rats by peritonitis. Selective inhibitors of vascular K(ATP) (PNU-37883A) or BK(Ca) [iberiotoxin (IbTX)] channels were used to demonstrate their involvement in vascular hyporeactivity. Vascular response to phenylephrine was measured on aorta and small mesenteric arteries mounted on a wire myograph. Vascular expression of potassium channels was studied by PCR and Western blot, in the presence or absence of 1400W, an inducible NO synthase (iNOS) inhibitor. Aortic activation of the transcriptional factor nuclear factor-kappaB (NF-κB) was assessed by electrophoretic mobility shift assay. Arterial pressure as well as in vivo and ex vivo vascular reactivity were reduced by sepsis and improved by PNU-37883A but not by IbTX. Sepsis was associated with an up-regulation of mRNA and protein expression of vascular K(ATP) channels, while expression of vascular BK(Ca) channels remained unchanged. Selective iNOS inhibition blunted the sepsis-induced increase in aortic NO, decreased NF-κB activation, and down-regulated vascular K(ATP) channel expression. Vascular K(ATP) but not BK(Ca) channels are activated, over-expressed, and partially regulated by NO via NF-κB activation during septic shock. Their selective inhibition restores arterial pressure and vascular reactivity and decreases lactate concentration. The present data suggest that selective vascular K(ATP) channel inhibitors offer potential therapeutic perspectives for septic shock.

The transport kinetics and selectivity of HpUreI, the urea channel from Helicobacter pylori†

Science.gov (United States)

Gray, Lawrence R; Gu, Sean X; Quick, Matthias; Khademi, Shahram

2017-01-01

Helicobacter pylori’s unique ability to colonize and survive in the acidic environment of the stomach is critically dependent on uptake of urea through the urea channel, HpUreI. Hence, HpUreI may represent a promising target for the development of specific drugs against this human pathogen. To obtain insight into the structure/function relationship of this channel, we have developed conditions for the high-yield expression and purification of stable recombinant HpUreI that allowed its detailed kinetic characterization in solubilized form and reconstituted into liposomes. Detergent-solubilized HpUreI forms homo-trimer, as determined by chemical cross-linking. Urea dissociation kinetics of purified HpUreI were determined by means of the scintillation proximity assay (SPA), whereas urea efflux was measured in HpUreI-containing proteoliposomes using stopped-flow spectrometry to determine the kinetics and selectivity of the urea channel. The kinetic analyses revealed that urea conduction in HpUreI is pH sensitive and saturable with a half-saturation concentration (or K0.5) of ~163 mM. Binding of urea by HpUreI was increased at lower pH; however, the apparent affinity of urea binding (~150 mM) was not significantly pH dependent. The solute selectivity analysis indicated that HpUreI is highly selective for urea and hydroxyurea. Removing either amino group of urea molecules diminishes their permeability through HpUreI. Similar to urea conduction, water diffusion through HpUreI is pH-dependent with low water permeability at neutral pH. PMID:21877689

Impact of two different commercial DNA extraction methods on BK virus viral load

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Massimiliano Bergallo

2016-03-01

Full Text Available Background and aim: BK virus, a member of human polyomavirus family, is a worldwide distributed virus characterized by a seroprevalence rate of 70-90% in adult population. Monitoring of viral replication is made by evaluation of BK DNA by quantitative polymerase chain reaction. Many different methods can be applied for extraction of nucleic acid from several specimens. The aim of this study was to assess the impact of two different DNA extraction procedure on BK viral load. Materials and methods: DNA extraction procedure including the Nuclisens easyMAG platform (bioMerieux, Marcy l’Etoile, France and manual QIAGEN extraction (QIAGEN Hilden, Germany. BK DNA quantification was performed by Real Time TaqMan PCR using a commercial kit. Result and discussion: The samples capacity, cost and time spent were compared for both systems. In conclusion our results demonstrate that automated nucleic acid extraction method using Nuclisense easyMAG was superior to manual protocol (QIAGEN Blood Mini kit, for the extraction of BK virus from serum and urine specimens.

Determinants of Isoform-Specific Gating Kinetics of hERG1 Channel: Combined Experimental and Simulation Study

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Laura L. Perissinotti

2018-04-01

Full Text Available IKr is the rapidly activating component of the delayed rectifier potassium current, the ion current largely responsible for the repolarization of the cardiac action potential. Inherited forms of long QT syndrome (LQTS (Lees-Miller et al., 1997 in humans are linked to functional modifications in the Kv11.1 (hERG ion channel and potentially life threatening arrhythmias. There is little doubt now that hERG-related component of IKr in the heart depends on the tetrameric (homo- or hetero- channels formed by two alternatively processed isoforms of hERG, termed hERG1a and hERG1b. Isoform composition (hERG1a- vs. the b-isoform has recently been reported to alter pharmacologic responses to some hERG blockers and was proposed to be an essential factor pre-disposing patients for drug-induced QT prolongation. Very little is known about the gating and pharmacological properties of two isoforms in heart membranes. For example, how gating mechanisms of the hERG1a channels differ from that of hERG1b is still unknown. The mechanisms by which hERG 1a/1b hetero-tetramers contribute to function in the heart, or what role hERG1b might play in disease are all questions to be answered. Structurally, the two isoforms differ only in the N-terminal region located in the cytoplasm: hERG1b is 340 residues shorter than hERG1a and the initial 36 residues of hERG1b are unique to this isoform. In this study, we combined electrophysiological measurements for HEK cells, kinetics and structural modeling to tease out the individual contributions of each isoform to Action Potential formation and then make predictions about the effects of having various mixture ratios of the two isoforms. By coupling electrophysiological data with computational kinetic modeling, two proposed mechanisms of hERG gating in two homo-tetramers were examined. Sets of data from various experimental stimulation protocols (HEK cells were analyzed simultaneously and fitted to Markov-chain models (M

Identification of the new isotope sup 2 sup 4 sup 1 Bk

CERN Document Server

Asai, M; Ichikawa, S; Nagame, Y; Nishinaka, I; Akiyama, K; Toyoshima, A; Kaneko, T; Sakama, M; Haba, H; Oura, Y; Kojima, Y; Shibata, M

2003-01-01

A new neutron-deficient berkelium isotope sup 2 sup 4 sup 1 Bk produced in the sup 2 sup 3 sup 9 Pu( sup 6 Li, 4n) reaction has been identified using a gas-jet coupled on-line isotope separator. Cm K and L X-rays associated with the EC decay of sup 2 sup 4 sup 1 Bk were observed in the mass-241 fraction, and three gamma transitions were attributed to the EC decay of sup 2 sup 4 sup 1 Bk through X-gamma coincidences. The half-life of sup 2 sup 4 sup 1 Bk was determined to be 4.6+-0.4 min which is 1/2-1/4 of that of theoretical predictions. The half-life value and the observed gamma transitions can be consistently explained as a consequence of the allowed EC transition of pi 7/2 sup + [633] -> nu 7/2 sup + [624]. (orig.)

Bifurcating channels supplying "numbered-up" microreactors

Czech Academy of Sciences Publication Activity Database

Tesař, Václav

2011-01-01

Roč. 89, č. 12A (2011), s. 2507-2020 ISSN 0263-8762 R&D Projects: GA ČR(CZ) GCP101/11/J019 Institutional research plan: CEZ:AV0Z20760514 Keywords : microfluidics * branched channels * geometric self-similarity Subject RIV: BK - Fluid Dynamics Impact factor: 1.968, year: 2011 http://www.sciencedirect.com/science/article/pii/S0263876211001821

Mitochondrial BK Channel Openers CGS7181 and CGS7184 Exhibit Cytotoxic Properties

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Bartłomiej Augustynek

2018-01-01

Full Text Available Potassium channel openers (KCOs have been shown to play a role in cytoprotection through the activation of mitochondrial potassium channels. Recently, in several reports, a number of data has been described as off-target actions for KCOs. In the present study, we investigated the effects of BKCa channel openers CGS7181, CGS7184, NS1619, and NS004 in neuronal cells. For the purpose of this research, we used a rat brain, the mouse hippocampal HT22 cells, and the human astrocytoma U-87 MG cell line. We showed that CGS7184 activated the mitochondrial BKCa (mitoBKCa channel in single-channel recordings performed on astrocytoma mitoplasts. Moreover, when applied to the rat brain homogenate or isolated rat brain mitochondria, CGS7184 increased the oxygen consumption rate, and can thus be considered a potentially cytoprotective agent. However, experiments on intact neuronal HT22 cells revealed that both CGS7181 and CGS7184 induced HT22 cell death in a concentration- and time-dependent manner. By contrast, we did not observe cell death when NS1619 or NS004 was applied. CGS7184 toxicity was not abolished by BKCa channel inhibitors, suggesting that the observed effects were independent of a BKCa-type channel activity. CGS7184 treatment resulted in an increase of cytoplasmic Ca2+ concentration that likely involved efflux from internal calcium stores and the activation of calpains (calcium-dependent proteases. The cytotoxic effect of the channel opener was partially reversed by a calpain inhibitor. Our data show that KCOs under study not only activate mitoBKCa channels from brain tissue, but also induce cell death when used in cellular models.

Coupling of unidimensional neutron kinetics to thermal hydraulics in parallel channels

International Nuclear Information System (INIS)

Cecenas F, M.; Campos G, R.M.

2003-01-01

In this work the dynamic behavior of a consistent system in fifteen channels in parallel that represent the reactor core of a BWR type, coupled of a kinetic neutronic model in one dimension is studied by means of time series. The arrangement of channels is obtained collapsing the assemblies that it consists the core to an arrangement of channels prepared in straight lines, and it is coupled to the unidimensional solution of the neutron diffusion equation. This solution represents the radial power distribution, and initially the static solution is obtained to verify that the one modeling core is critic. The coupled set nuclear-thermal hydraulics it is solved numerically by means of a net of CPUs working in the outline teacher-slave by means of Parallel Virtual Machine (PVM), subject to the restriction that the pressure drop is equal for each channel, which is executed iterating on the refrigerant distribution. The channels are dimensioned according to the one Stability Benchmark of the Ringhals swedish plant, organized by the Nuclear Energy Agency in 1994. From the information of this benchmark it is obtained the axial power profile for each channel, which is assumed as invariant in the time. To obtain the time series, the system gets excited with white noise (sequence that statistically obeys to a normal distribution with zero media), so that the power generated in each channel it possesses the same ones characteristics of a typical signal obtained by means of the acquisition of those signals of neutron flux in a BWR reactor. (Author)

Efficacy of levofloxacin in the treatment of BK viremia: a multicenter, double-blinded, randomized, placebo-controlled trial.

Science.gov (United States)

Lee, Belinda T; Gabardi, Steven; Grafals, Monica; Hofmann, R Michael; Akalin, Enver; Aljanabi, Aws; Mandelbrot, Didier A; Adey, Deborah B; Heher, Eliot; Fan, Pang-Yen; Conte, Sarah; Dyer-Ward, Christine; Chandraker, Anil

2014-03-01

BK virus reactivation in kidney transplant recipients can lead to progressive allograft injury. Reduction of immunosuppression remains the cornerstone of treatment for active BK infection. Fluoroquinolone antibiotics are known to have in vitro antiviral properties, but the evidence for their use in patients with BK viremia is inconclusive. The objective of the study was to determine the efficacy of levofloxacin in the treatment of BK viremia. Enrollment in this prospective, multicenter, double-blinded, placebo-controlled trial occurred from July 2009 to March 2012. Thirty-nine kidney transplant recipients with BK viremia were randomly assigned to receive levofloxacin, 500 mg daily, or placebo for 30 days. Immunosuppression in all patients was adjusted on the basis of standard clinical practices at each institution. Plasma BK viral load and serum creatinine were measured monthly for 3 months and at 6 months. At the 3-month follow-up, the percentage reductions in BK viral load were 70.3% and 69.1% in the levofloxacin group and the placebo group, respectively (P=0.93). The percentage reductions in BK viral load were also equivalent at 1 month (58% versus and 67.1%; P=0.47) and 6 months (82.1% versus 90.5%; P=0.38). Linear regression analysis of serum creatinine versus time showed no difference in allograft function between the two study groups during the follow-up period. A 30-day course of levofloxacin does not significantly improve BK viral load reduction or allograft function when used in addition to overall reduction of immunosuppression.

Rapid detection of urinary polyomavirus BK by heterodyne-based surface plasmon resonance biosensor

Science.gov (United States)

Su, Li-Chen; Tian, Ya-Chung; Chang, Ying-Feng; Chou, Chien; Lai, Chao-Sung

2014-01-01

In renal transplant patients, immunosuppressive therapy may result in the reactivation of polyomavirus BK (BKV), leading to polyomavirus-associated nephropathy (PVAN), which inevitably causes allograft failure. Since the treatment outcomes of PVAN remain unsatisfactory, early identification and continuous monitoring of BKV reactivation and reduction of immunosuppressants are essential to prevent PVAN development. The present study demonstrated that the developed dual-channel heterodyne-based surface plasmon resonance (SPR) biosensor is applicable for the rapid detection of urinary BKV. The use of a symmetrical reference channel integrated with the poly(ethylene glycol)-based low-fouling self-assembled monolayer to reduce the environmental variations and the nonspecific noise was proven to enhance the sensitivity in urinary BKV detection. Experimentally, the detection limit of the biosensor for BKV detection was estimated to be around 8500 copies/mL. In addition, urine samples from five renal transplant patients were tested to rapidly distinguish PVAN-positive and PVAN-negative renal transplant patients. By virtue of its simplicity, rapidity, and applicability, the SPR biosensor is a remarkable potential to be used for continuous clinical monitoring of BKV reactivation.

An ERG channel inhibitor from the scorpion Buthus eupeus

DEFF Research Database (Denmark)

Korolkova, Y.V.; Kozlov, S.A.; Lipkin, A.V.

2001-01-01

and the three mutants partly inhibited the native M-like current in NG108-15 at 100 nm. The effect of the recombinant BeKm-1 on different K(+) channels was also studied. BeKm-1 inhibited hERG1 channels with an IC(50) of 3.3 nm, but had no effect at 100 nm on hEAG, hSK1, rSK2, hIK, hBK, KCNQ1/KCNE1, KCNQ2/KCNQ3......, KCNQ4 channels, and minimal effect on rELK1. Thus, BeKm-1 was shown to be a novel specific blocker of hERG1 potassium channels....

Diagnosis of BK viral nephropathy in the renal allograft biopsy: role of fluorescence in situ hybridization.

Science.gov (United States)

Wang, Zhen; Portier, Bryce P; Hu, Bo; Chiesa-Vottero, Andres; Myles, Jonathan; Procop, Gary W; Tubbs, Raymond R

2012-09-01

Early recognition of BK viral nephropathy is essential for successful management. Our aim in this study was to evaluate a novel fluorescence in situ hybridization (FISH) assay for detection of BK virus in renal transplant biopsies in the context of standard detection methods. Renal allograft biopsies (n = 108) were analyzed via H&E, immunohistochemistry (IHC) for simian virus 40, and FISH for BK virus. BK virus was detected in 16 (14.8%) cases by H&E, 13 (12%) cases by IHC, 18 (16.6%) cases by FISH, and 19 (17.6%) cases by real-time PCR; 24 of 108 showed a discrepancy in ≥1 testing modalities. Comparison of H&E, IHC, and FISH showed no statistical difference in detection of BK virus. However, performing comparisons between the different tissue-based assays in the context of plasma or urine real-time PCR results showed significant improvement in detection of BK by FISH over H&E (P = 0.02) but not IHC (P = 0.07). This novel FISH-based approach for BK virus identification in renal allograft biopsy tissue mirrored real-time PCR results and showed superior performance to detection of inclusions by H&E. Therefore, use of FISH for BK virus detection in the setting of renal allograft biopsy is a useful and sensitive detection method and could be adopted in any laboratory that currently performs FISH analysis. Copyright © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Identification of pyrolysis products of the new psychoactive substance 2-amino-1-(4-bromo-2,5-dimethoxyphenyl)ethanone hydrochloride (bk-2C-B) and its iodo analogue bk-2C-I.

Science.gov (United States)

Texter, Kelly B; Waymach, Rachel; Kavanagh, Pierce V; O'Brien, John E; Talbot, Brian; Brandt, Simon D; Gardner, Elizabeth A

2018-01-01

2-Amino-1-(4-bromo-2,5-dimethoxyphenyl)ethanone hydrochloride (bk-2C-B) has recently emerged as a new psychoactive substance (NPS). It is most commonly consumed orally, although there are indications that it might also be ingested by inhalation or 'smoking'. Information about the stability of bk-2C-B when exposed to heat is unavailable and the potential for pyrolytic degradation and formation of unknown substances available for inhalation prompted an investigation using a simulated 'meth pipe' scenario. Twelve products following pyrolysis of bk-2C-B were detected and verified by organic synthesis of the corresponding standards. In addition, 2-amino-1-(4-iodo-2,5-dimethoxyphenyl)ethanone hydrochloride (bk-2C-I) was characterized for the first time and subjected to pyrolysis as well. Similar products were formed, which indicated that the replacement of the bromo with the iodo substituent did not affect the pyrolysis pattern under the conditions used. Two additional products were detected in the bk-2C-I pyrolates, namely 1-(2,5-dimethoxyphenyl)-ethanone and 1-iodo-4-ethenyl-5-methoxyphenol. The potential ingestion of pyrolysis products with unknown toxicity adds an element of concern. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

The role of voltage-gated potassium channels in the regulation of mouse uterine contractility

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Abel Peter W

2007-11-01

Full Text Available Abstract Background Uterine smooth muscle cells exhibit ionic currents that appear to be important in the control of uterine contractility, but how these currents might produce the changes in contractile activity seen in pregnant myometrium has not been established. There are conflicting reports concerning the role of voltage-gated potassium (Kv channels and large-conductance, calcium-activated potassium (BK channels in the regulation of uterine contractility. In this study we provide molecular and functional evidence for a role for Kv channels in the regulation of spontaneous contractile activity in mouse myometrium, and also demonstrate a change in Kv channel regulation of contractility in pregnant mouse myometrium. Methods Functional assays which evaluated the effects of channel blockers and various contractile agonists were accomplished by quantifying contractility of isolated uterine smooth muscle obtained from nonpregnant mice as well as mice at various stages of pregnancy. Expression of Kv channel proteins in isolated uterine smooth muscle was evaluated by Western blots. Results The Kv channel blocker 4-aminopyridine (4-AP caused contractions in nonpregnant mouse myometrium (EC50 = 54 micromolar, maximal effect at 300 micromolar but this effect disappeared in pregnant mice; similarly, the Kv4.2/Kv4.3 blocker phrixotoxin-2 caused contractions in nonpregnant, but not pregnant, myometrium. Contractile responses to 4-AP were not dependent upon nerves, as neither tetrodotoxin nor storage of tissues at room temperature significantly altered these responses, nor were responses dependent upon the presence of the endometrium. Spontaneous contractions and contractions in response to 4-AP did not appear to be mediated by BK, as the BK channel-selective blockers iberiotoxin, verruculogen, or tetraethylammonium failed to affect either spontaneous contractions or 4-AP-elicited responses. A number of different Kv channel alpha subunit proteins were

Production and decay of the heaviest odd-Z nuclei in the 249Bk + 48Ca reaction

International Nuclear Information System (INIS)

Oganessian, Yu Ts; Abdullin, F Sh; Dmitriev, S N; Itkis, M G; Polyakov, A N; Alexander, C; Binder, J; Boll, R A; Ezold, J; Felker, K; Grzywacz, R K; Miernik, K; Roberto, J B; Gostic, J M; Henderson, R A; Moody, K J; Hamilton, J H; Ramayya, A V; Miller, D; Ryabinin, M A

2015-01-01

The reaction of 249 Bk with 48 Ca has been investigated with an aim of synthesizing and studying the decay properties of isotopes of the new element 117. The experiments were performed at five projectile energies (in two runs, in 2009-2010 and 2012) and with a total beam dose of 48 Ca ions of about 9x10 19 The experiments yielded data on a-decay characteristics and excitation functions of the produced nuclei that establish these to be 293 117 and 294 117 – the products of the 4n- and 3n-evaporation channels, respectively. In total, we have observed 20 decay chains of Z=117 nuclides. The cross sections were measured to be 1.1 pb for the 3n and 2.4 pb for the 4n-reaction channel. The new 289 115 events, populated by α decay of 117, demonstrate the same decay properties as those observed for 115 produced in the 243 Am( 48 Ca,2n) reaction thus providing cross-bombardment evidence. In addition, a single decay of 294 118 was observed from the reaction with 249 Cf – a result of the in-growth of 249 Cf in the 249 Bk target. The observed decay chain of 294 118 is in good agreement with decay properties obtained in 2002-2005 in the experiments with the reaction 249 Cf( 48 Ca,3n) 294 118. The energies and half-lives of the odd-Z isotopes observed in the 117 decay chains together with the results obtained for lower-Z superheavy nuclei demonstrate enhancement of nuclear stability with increasing neutron number towards the predicted new magic number N=184

Time-resolved resonance Raman spectroscopy of intermediates of bacteriorhodopsin: The bK(590) intermediate.

Science.gov (United States)

Terner, J; Hsieh, C L; Burns, A R; El-Sayed, M A

1979-07-01

We have combined microbeam and flow techniques with computer subtraction methods to obtain the resonance Raman spectrum of the short lived batho-intermediate (bK(590)) of bacteriorhodopsin. Comparison of the spectra obtained in (1)H(2)O and (2)H(2)O, as well as the fact that the bK(590) intermediate shows large optical red shifts, suggests that the Schiff base linkage of this intermediate is protonated. The fingerprint region of the spectrum of bK(590), sensitive to the isomeric configuration of the retinal chromophore, does not resemble the corresponding region of the parent bR(570) form. The resonance Raman spectrum of bK(590) as well as the spectra of all of the other main intermediates in the photoreaction cycle of bacteriorhodopsin are discussed and compared with resonance Raman spectra of published model compounds.

Surveillance of polyomavirus BK in relation to immunosuppressive therapy in kidney transplantation

Directory of Open Access Journals (Sweden)

Cristina Costa

2012-03-01

Full Text Available Introduction. Reactivation of polyomavirus BK in kidney transplant recipients has been associated to the development of nephropathy (polyomavirus-associated nephropathy, PVAN, possibly leading to the loss of the transplanted organ. Immunosuppression is the condicio sine qua non for the onset of PVAN; however, a lower incidence of BK viremia has been reported with low-level tacrolimus based immunosuppressive protocols in comparison to cyclosporine A.Aim of this study was to compare the two immunosuppressive protocols. Methods. Virological monitoring of BK was performed in 468 consecutive renal transplant patients over a period of 3 years (2370 urine e 2370 serum specimens: in particular, 1780 specimens from 362 patients treated with tacrolimus and 590 from 106 treated with cyclosporine A. Results. BK viremia was evidenced in 124 (7.0% and 12 (2.0% specimens from 40 (11.0% and 11 (10.4% patients treated with tacrolimus and cyclosporine A, respectively; similarly, BK viruria in 289 (16.2% and 58 (9.8% specimens from 67 (18.5% and 27 (25.5% patients, being the difference of incidence highly significant (p <0.0001 for both viremia and viruria at comparison between specimens and not significant for patients. No case of PVAN was diagnosed at histophatology evaluation. Conclusions. The incidence of viremia and viruria was similar to that previously reported. Our results evidenced that with low-level tacrolimus-based protocols the overall incidence of reactivation in renal transplant patients is not significantly different and there is no increased risk of PVAN, nevertheless the higher incidence of episodes of reactivation.

Kinetic description of a wiggler pumped ion-channel free electron laser

International Nuclear Information System (INIS)

Mehdian, H; Raghavi, A

2006-01-01

The wiggler pumped ion-channel free electron laser (WPIC-FEL) is treated and the classes of possible single-particle electron trajectories in this configuration are discussed in the paper. A new region of orbital stability is seen in the negative mass regime. A kinetic description of WPIC-FEL is given. Vlasov-Maxwell equations are solved to get the linear gain in a tenuous-beam limit, where the beam plasma frequency is much less than the radiation frequency and the self-field effects can be ignored

Modelling of supercritical turbulent flow over transversal ribs in an open channel

Czech Academy of Sciences Publication Activity Database

Příhoda, Jaromír; Šulc, J.; Sedlář, M.; Zubík, P.

2009-01-01

Roč. 16, č. 1 (2009), s. 65-74 ISSN 1802-1484 R&D Projects: GA ČR GA103/06/0461 Institutional research plan: CEZ:AV0Z20760514 Keywords : turbulent flow in open channels * flow over obstacles Subject RIV: BK - Fluid Dynamics

Fragile X mental retardation protein controls ion channel expression and activity.

Science.gov (United States)

Ferron, Laurent

2016-10-15

Fragile X-associated disorders are a family of genetic conditions resulting from the partial or complete loss of fragile X mental retardation protein (FMRP). Among these disorders is fragile X syndrome, the most common cause of inherited intellectual disability and autism. FMRP is an RNA-binding protein involved in the control of local translation, which has pleiotropic effects, in particular on synaptic function. Analysis of the brain FMRP transcriptome has revealed hundreds of potential mRNA targets encoding postsynaptic and presynaptic proteins, including a number of ion channels. FMRP has been confirmed to bind voltage-gated potassium channels (K v 3.1 and K v 4.2) mRNAs and regulates their expression in somatodendritic compartments of neurons. Recent studies have uncovered a number of additional roles for FMRP besides RNA regulation. FMRP was shown to directly interact with, and modulate, a number of ion channel complexes. The sodium-activated potassium (Slack) channel was the first ion channel shown to directly interact with FMRP; this interaction alters the single-channel properties of the Slack channel. FMRP was also shown to interact with the auxiliary β4 subunit of the calcium-activated potassium (BK) channel; this interaction increases calcium-dependent activation of the BK channel. More recently, FMRP was shown to directly interact with the voltage-gated calcium channel, Ca v 2.2, and reduce its trafficking to the plasma membrane. Studies performed on animal models of fragile X syndrome have revealed links between modifications of ion channel activity and changes in neuronal excitability, suggesting that these modifications could contribute to the phenotypes observed in patients with fragile X-associated disorders. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Persepsi Guru BK Tentang Kompetensi Konselor di Sekolah Dasar Swasta Kota Semarang

Directory of Open Access Journals (Sweden)

Restu Setyoningtyas

2014-10-01

Full Text Available Tujuan penelitian ini adalah untuk mengetahui tentang persepsi guru BK tentang kompetensi konselor di sekolah dasar swasta Kota Semarang. Penelitian ini bersifat kuantitatif, responden penelitian adalah guru BK sekolah dasar swasta, teknik pengumpulan data berupa skala psikologi dan dokumentasi. Analisis data menggunakan Analisis Deskriptif Persentase. Hasil penelitian menunjukkan persepsi guru BK tentang kompetensi konselor mendapatkan hasil yang positif. Kompetensi pedagogik yaitu positif, kepribadian yaitu kurang positif, sosial yaitu kurang positif, profesional yaitu cukup positif. Kesimpulan dari penelitian ini adalah persepsi guru BK tentang kompetensi konselor di sekolah dasar swasta Kota Semarang pada umumnya positif. The purpose of this research is determine perception guidance and counseling teacher about counselor competence in private elementary school on Semarang city. This research is quantitative. Respondens is guidance and counseling teacher from private elementary school, techniques of data collection are psychology scale and documentation. The data analysis using Analysis Descriptive Percentage. Result showed that research is perception  guidance and counseling teacher about counselor competence is positive. Pedagogic competence is positive, personality is not positive enough, social is not positive enough, professional is positive enough. The conclusion of this research is perception guidance and counseling teacher about counselor competence in private elementary school on Semarang city in general is positive.

Molecular cloning of a K+ channel from the malaria parasite Plasmodium falciparum

DEFF Research Database (Denmark)

Ellekvist, Peter; Ricke, Christina Høier; Litman, Thomas

2004-01-01

In most living cells, K(+) channels are important for the generation of the membrane potential and for volume regulation. The parasite Plasmodium falciparum, which causes malignant malaria, must be able to deal with large variations in the ambient K(+) concentration: it is exposed to high...... concentrations of K(+) when inside the erythrocyte and low concentrations when in plasma. In the recently published genome of P. falciparum, we have identified a gene, pfkch1, encoding a potential K(+) channel, which to some extent resembles the big-conductance (BK) K(+) channel. We have cloned the approximately...

Pemahaman Guru BK Tentang Pelaksanaan Layanan Peminatan pada Kurikulum 2013

Directory of Open Access Journals (Sweden)

Finda Marsetyana

2015-04-01

Full Text Available Penelitian ini dilakukan berdasar fenomena yaitu belum adanya kesiapan tentang program peminatan di SMK Negeri se-Kota Semarang. Tujuan penelitian secara umum untuk mengetahui pemahaman guru BK tentang pelaksanaan layanan peminatan pada kurikulum 2013 di SMK Negeri se-Kota Semarang. Medote pengumpulan data yaitu angket tertutup yang diberikan kepada 44 orang guru BK SMK Negeri se Kota Semarang. Analisis data menggunakan analisis deskriptif persentase. Hasil penelitian dari Pemahaman Guru BK Tentang Pelaksanaan Layanan Peminatan Pada Kurikulum 2013 Di SMK Negeri Se-Kota Semarang termasuk dalam kategori tinggi (71.59% dengan perincian indikator variabel yaitu pemahaman guru BK tentang kurikulum 2013 persentase sebesar 75.04% (tinggi, konsep dan strategi pelayanan bimbingan dan konseling pada kurikulum 2013 sebesar 69.31% (sedang, lingkup layanan peminatan sebesar 70.57% (tinggi, dan pelaksanaan layanan peminatan 72.22% (tinggi. Simpulan penelitian ini yakni guru BK SMK Negeri se-Kota Semarang telah mempunyai pemahaman tentang pelaksanaan layanan peminatan pada kurikulum 2013 dengan kriteria tinggi. This research was conducted based on the phenomenon that is there was no readiness about the students’ interest program vocational high schools in around Semarang.The general objective of this research was to know the counseling’s teachers deals with the implementation of students’ interest service towards the 2013 curriculum vocational high schools in around Semarang. Method of data collection is used closed questionnaire and it was given to 44 students vocational high schools in around Semarang in which the data obtained was analysed trough descriptive percentages. The research finding from counseling’s teachers about the implementation of students’ interest in the 2013 curriculum vocational high schools in around Semarang are in a high category (71.59%, with the details of the indicator variable are as follows; the understanding of

Faktor-Faktor Hambatan Profesionalisasi Guru BK di SMA Negeri se- Kota Purwokerto

Directory of Open Access Journals (Sweden)

Cahya Dewi Rizkiwati

2014-10-01

Full Text Available Tujuan penelitian ini yaitu untuk mendeskripsikan tentang faktor-faktor hambatan yang terjadi dalam profesionalisasi guru BK. Jenis penelitian ini merupakan penelitian survey. Penelitian ini dilaksanakan di SMA Negeri se-Kota Purwokerto. Penelitian ini adalah penelitian populasi atau sensus karena populasi guru BK berjumlah 25 orang. Metode yang digunakan dalam penelitian ini adalah  inventori dalam bentuk daftar cek masalah. Instrumen tersebut telah diuji validitasnya menggunakan rumus point biserial, sedangkan reliabilitas instrumen digunakan rumus KR-20. Data yang telah diperoleh dianalisis dengan menggunakan teknik deskriptif prosentase. Hasil dari penelitian ini menunjukkan hambatan yang berasal dari faktor internal mendapat prosentase lebih tinggi daripada faktor eksternal. Faktor internal yang paling mempengaruhi profesionalisasi guru BK antara lain latar belakang pendidikan, pengalaman kerja, motivasi kerja, kompetensi guru BK. Sedangkan faktor eksternal yang paling mempengaruhi profesionalisasi guru BK adalah sarana dan prasarana. The purpose of this research is to describe problems  occur in the professionalization of guidance and counseling teachers. The type of the research is survey research . This research was conducted in all of Senior High School in Purwokerto. Population research or census were used as sampling method, since  the population of guidance and counseling teachers were 25 people. Data collection technique was  using inventory with list of issues. The instrument validity has been tested using point biserial formula, whilst its reliability was tested using KR-20 formula. The data was analyzed using descriptive percentage techniques. The results of this research indicate that internal factors get higher percentage than external factors. Internal factors that have the most influence in the professionalization of guidance and counseling teachers include educational background, working experience , motivation, teacher�

Diagnóstico y clasificación molecular del virus BK en receptores de trasplante renal

OpenAIRE

Riva, Omar; Cobos, Marisa; Raimondi, J. Clemente

2010-01-01

La infección primaria por virus BK ocurre durante la infancia permaneciendo latente en el tracto urogenital. En individuos que presentan alteraciones en la inmunidad celular, el virus se reactiva haciendo posible su detección en orina y sangre. En receptores de trasplante renal, la nefropatía producida por el virus BK puede llevar a la pérdida de la función del injerto. El virus BK es miembro de la familia Polyomaviridae, presenta un genoma de ADN circular doble cadena unido en forma covalent...

Inflammatory mediator bradykinin increases population of sensory neurons expressing functional T-type Ca(2+) channels.

Science.gov (United States)

Huang, Dongyang; Liang, Ce; Zhang, Fan; Men, Hongchao; Du, Xiaona; Gamper, Nikita; Zhang, Hailin

2016-04-29

T-type Ca(2+) channels are important regulators of peripheral sensory neuron excitability. Accordingly, T-type Ca(2+) currents are often increased in various pathological pain conditions, such as inflammation or nerve injury. Here we investigated effects of inflammation on functional expression of T-type Ca(2+) channels in small-diameter cultured dorsal root ganglion (DRG) neurons. We found that overnight treatment of DRG cultures with a cocktail of inflammatory mediators bradykinin (BK), adenosine triphosphate (ATP), norepinephrine (NE) and prostaglandin E2 (PGE2) strongly increased the population size of the small-diameter neurons displaying low-voltage activated (LVA, T-type) Ca(2+) currents while having no effect on the peak LVA current amplitude. When applied individually, BK and ATP also increased the population size of LVA-positive neurons while NE and PGE2 had no effect. The PLC inhibitor U-73122 and B2 receptor antagonist, Hoe-140, both abolished the increase of the population of LVA-positive DRG neurons. Inflammatory treatment did not affect CaV3.2 mRNA or protein levels in DRG cultures. Furthermore, an ubiquitination inhibitor, MG132, did not increase the population of LVA-positive neurons. Our data suggest that inflammatory mediators BK and ATP increase the abundance of LVA-positive DRG neurons in total neuronal population by stimulating the recruitment of a 'reserve pool' of CaV3.2 channels, particularly in neurons that do not display measurable LVA currents under control conditions. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Experimental and numerical modelling of turbulent flow over an inclined backward-facing step in an open channel

Czech Academy of Sciences Publication Activity Database

Příhoda, Jaromír; Zubík, P.; Šulc, J.; Sedlář, M.

2012-01-01

Roč. 14, 4a (2012), s. 6-12 ISSN 1335-4205 R&D Projects: GA ČR GA103/09/0977 Institutional support: RVO:61388998 Keywords : open channel flow * inclined backward-facing step Subject RIV: BK - Fluid Dynamics

Deactivation kinetics of acid-sensing ion channel 1a are strongly pH-sensitive.

Science.gov (United States)

MacLean, David M; Jayaraman, Vasanthi

2017-03-21

Acid-sensing ion channels (ASICs) are trimeric cation-selective ion channels activated by protons in the physiological range. Recent reports have revealed that postsynaptically localized ASICs contribute to the excitatory postsynaptic current by responding to the transient acidification of the synaptic cleft that accompanies neurotransmission. In response to such brief acidic transients, both recombinant and native ASICs show extremely rapid deactivation in outside-out patches when jumping from a pH 5 stimulus to a single resting pH of 8. Given that the resting pH of the synaptic cleft is highly dynamic and depends on recent synaptic activity, we explored the kinetics of ASIC1a and 1a/2a heteromers to such brief pH transients over a wider [H + ] range to approximate neuronal conditions better. Surprisingly, the deactivation of ASICs was steeply dependent on the pH, spanning nearly three orders of magnitude from extremely fast (pH 8 to very slow (>300 ms) at pH 7. This study provides an example of a ligand-gated ion channel whose deactivation is sensitive to agonist concentrations that do not directly activate the receptor. Kinetic simulations and further mutagenesis provide evidence that ASICs show such steeply agonist-dependent deactivation because of strong cooperativity in proton binding. This capacity to signal across such a large synaptically relevant bandwidth enhances the response to small-amplitude acidifications likely to occur at the cleft and may provide ASICs with the ability to shape activity in response to the recent history of the synapse.

Characterization of self-assembled virus-like particles of human polyomavirus BK generated by recombinant baculoviruses

International Nuclear Information System (INIS)

Li, T.-C.; Takeda, Naokazu; Kato, Kenzo; Nilsson, Josefina; Xing Li; Haag, Lars; Cheng, R. Holland; Miyamura, Tatsuo

2003-01-01

The major structural protein of the human polyomavirus BK (BKV), VP1, was expressed by using recombinant baculoviruses. A large amount of protein with a molecular mass of about 42 kDa was synthesized and identified by Western blotting. The protein was detected exclusively in the nuclei by immunofluorescent analysis and it was released into culture medium. The expressed BKV VP1 protein was self-assembled into virus-like particles (BK-VLPs) with two different sizes (50 and 26 nm in diameter), which migrated into four different bands in CsCl gradient with buoyant densities of 1.29, 1.30, 1.33, and 1.35 g/cm 3 . The immunological studies on the BK-VLPs suggested that they have similar antigenicity with those of authentic BKV particles. Cryoelectron microscopy and 3D image analysis further revealed that the larger BK-VLPs were composed of 72 capsomers which all were pentamers arranged in a T = 7 surface lattice. This system provides useful information for detailed studies of viral morphogenesis and the structural basis for the antigenicity of BKV

Activation of human IK and SK Ca2+ -activated K+ channels by NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime)

DEFF Research Database (Denmark)

Strøbaek, Dorte; Teuber, Lene; Jørgensen, Tino D

2004-01-01

We have identified and characterized the compound NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime) as a potent activator of human Ca2+ -activated K+ channels of SK and IK types, whereas it is devoid of effect on BK type channels. IK- and SK-channels have previously been reported to be activated...

A single Markov-type kinetic model accounting for the macroscopic currents of all human voltage-gated sodium channel isoforms.

Science.gov (United States)

Balbi, Pietro; Massobrio, Paolo; Hellgren Kotaleski, Jeanette

2017-09-01

Modelling ionic channels represents a fundamental step towards developing biologically detailed neuron models. Until recently, the voltage-gated ion channels have been mainly modelled according to the formalism introduced by the seminal works of Hodgkin and Huxley (HH). However, following the continuing achievements in the biophysical and molecular comprehension of these pore-forming transmembrane proteins, the HH formalism turned out to carry limitations and inconsistencies in reproducing the ion-channels electrophysiological behaviour. At the same time, Markov-type kinetic models have been increasingly proven to successfully replicate both the electrophysiological and biophysical features of different ion channels. However, in order to model even the finest non-conducting molecular conformational change, they are often equipped with a considerable number of states and related transitions, which make them computationally heavy and less suitable for implementation in conductance-based neurons and large networks of those. In this purely modelling study we develop a Markov-type kinetic model for all human voltage-gated sodium channels (VGSCs). The model framework is detailed, unifying (i.e., it accounts for all ion-channel isoforms) and computationally efficient (i.e. with a minimal set of states and transitions). The electrophysiological data to be modelled are gathered from previously published studies on whole-cell patch-clamp experiments in mammalian cell lines heterologously expressing the human VGSC subtypes (from NaV1.1 to NaV1.9). By adopting a minimum sequence of states, and using the same state diagram for all the distinct isoforms, the model ensures the lightest computational load when used in neuron models and neural networks of increasing complexity. The transitions between the states are described by original ordinary differential equations, which represent the rate of the state transitions as a function of voltage (i.e., membrane potential). The

Two-channel recoder for magnetometer with energy-independent mass memory device

International Nuclear Information System (INIS)

Korzinin, V.N.; Selivanov, A.M.

1993-01-01

The paper describes a two-channel digit-to-analog recorder designed for converting the sequence of pulses from proton magnetometer (MMH-203) outlet; the device enables processing of the pulses and their recording in RAM and on the tape of the analog recorder. The availability of nonvolotile RAM allows to transmit digit information to a computer (BK-0010) for its further processing

Effect of temperature on surface error and laser damage threshold for self-healing BK7 glass.

Science.gov (United States)

Wang, Chu; Wang, Hongxiang; Shen, Lu; Hou, Jing; Xu, Qiao; Wang, Jian; Chen, Xianhua; Liu, Zhichao

2018-03-20

Cracks caused during the lapping and polishing process can decrease the laser-induced damage threshold (LIDT) of the BK7 glass optical elements, which would shorten the lifetime and limit the output power of the high-energy laser system. When BK7 glass is heated under appropriate conditions, the surface cracks can exhibit a self-healing phenomenon. In this paper, based on thermodynamics and viscous fluid mechanics theory, the mechanisms of crack self-healing are explained. The heat-healing experiment was carried out, and the effect of water was analyzed. The multi-spatial-frequency analysis was used to investigate the effect of temperature on surface error for self-healing BK7 glass, and the lapped BK7 glass specimens before and after heat healing were detected by an interferometer and atomic force microscopy. The low-spatial-frequency error was analyzed by peak to valley and root mean square, the mid-spatial-frequency error was analyzed by power spectral density, and the high-spatial-frequency error was analyzed by surface roughness. The results showed that the optimal heating temperature for BK7 was 450°C, and when the heating temperature was higher than the glass transition temperature (555°C), the surface quality decreased a lot. The laser damage test was performed, and the specimen heated at 450°C showed an improvement in LIDT.

Universal features of JIMWLK and BK evolution at small x

CERN Document Server

Rummukainen, K; Rummukainen, Kari; Weigert, Heribert

2004-01-01

In this paper we present the results of numerical studies of the JIMWLK and BK equations with a particular emphasis on the universal scaling properties and phase space structure involved. The results are valid for near zero impact parameter in DIS. We demonstrate IR safety due to the occurrence of a rapidity dependent saturation scale Q_s(\\tau). Within the set of initial conditions chosen both JIMWLK and BK equations show remarkable agreement. We point out the crucial importance of running coupling corrections to obtain consistency in the UV. Despite the scale breaking induced by the running coupling we find that evolution drives correlators towards an asymptotic form with near scaling properties. We discuss asymptotic features of the evolution, such as the \\tau- and A-dependence of Q_s away from the initial condition.

Analýza marketingové komunikace sportovního klubu BK Lokomotiva Karlovy Vary

OpenAIRE

Houdková, Jana

2012-01-01

ANALYSIS OF MARKETING COMMUNICATIONS BK LOKOMOTIVA KARLOVY VARY SPORTS CLUB Objectives: The aim of this work is to analyze the current state of marketing communication with the audience and sponsors for women's basketball club BK Lokomotiva Karlovy Vary and propose a strategy for improving marketing communications. Methods: In this thesis were performed using the methods of observation and personal interviews examined subjects Results: An analysis of marketing communication club, thanks to wh...

Hydronephrosis Resulting from Bilateral Ureteral Stenosis: A Late Complication of Polyoma BK Virus Cystitis?

OpenAIRE

Basara, N.; Rasche, F.-M.; Schwalenberg, T.; Wickenhauser, C.; Maier, M.; Ivovic, J.; Niederwieser, D.; Lindner, T. H.

2010-01-01

We report here a case of acute lymphoblastic leukemia in remission presenting a late-onset bilateral hydronephrosis probably due to polyoma BK virus-induced proliferation of bladder endothelium on both ostii. The diagnosis was made virologically by BK virus Polymerase Chain Reaction (PCR) detection in the absence of any other bladder disease. Awareness of this late complication is necessary not only in patients after renal transplantation but also in patients after hematopoietic stem cell tra...

BK/TD models for analyzing in vitro impedance data on cytotoxicity.

Science.gov (United States)

Teng, S; Barcellini-Couget, S; Beaudouin, R; Brochot, C; Desousa, G; Rahmani, R; Pery, A R R

2015-06-01

The ban of animal testing has enhanced the development of new in vitro technologies for cosmetics safety assessment. Impedance metrics is one such technology which enables monitoring of cell viability in real time. However, analyzing real time data requires moving from static to dynamic toxicity assessment. In the present study, we built mechanistic biokinetic/toxicodynamic (BK/TD) models to analyze the time course of cell viability in cytotoxicity assay using impedance. These models account for the fate of the tested compounds during the assay. BK/TD models were applied to analyze HepaRG cell viability, after single (48 h) and repeated (4 weeks) exposures to three hepatotoxic compounds (coumarin, isoeugenol and benzophenone-2). The BK/TD models properly fit the data used for their calibration that was obtained for single or repeated exposure. Only for one out of the three compounds, the models calibrated with a single exposure were able to predict repeated exposure data. We therefore recommend the use of long-term exposure in vitro data in order to adequately account for chronic hepatotoxic effects. The models we propose here are capable of being coupled with human biokinetic models in order to relate dose exposure and human hepatotoxicity. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

The oncogenic potential of BK-polyomavirus is linked to viral integration into the human genome.

Science.gov (United States)

Kenan, Daniel J; Mieczkowski, Piotr A; Burger-Calderon, Raquel; Singh, Harsharan K; Nickeleit, Volker

2015-11-01

It has been suggested that BK-polyomavirus is linked to oncogenesis via high expression levels of large T-antigen in some urothelial neoplasms arising following kidney transplantation. However, a causal association between BK-polyomavirus, large T-antigen expression and oncogenesis has never been demonstrated in humans. Here we describe an investigation using high-throughput sequencing of tumour DNA obtained from an urothelial carcinoma arising in a renal allograft. We show that a novel BK-polyomavirus strain, named CH-1, is integrated into exon 26 of the myosin-binding protein C1 gene (MYBPC1) on chromosome 12 in tumour cells but not in normal renal cells. Integration of the BK-polyomavirus results in a number of discrete alterations in viral gene expression, including: (a) disruption of VP1 protein expression and robust expression of large T-antigen; (b) preclusion of viral replication; and (c) deletions in the non-coding control region (NCCR), with presumed alterations in promoter feedback loops. Viral integration disrupts one MYBPC1 gene copy and likely alters its expression. Circular episomal BK-polyomavirus gene sequences are not found, and the renal allograft shows no productive polyomavirus infection or polyomavirus nephropathy. These findings support the hypothesis that integration of polyomaviruses is essential to tumourigenesis. It is likely that dysregulation of large T-antigen, with persistent over-expression in non-lytic cells, promotes cell growth, genetic instability and neoplastic transformation. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

A Precise determination of B(K) in quenched QCD

CERN Document Server

Dimopoulos, P.; Palombi, F.; Pena, C.; Sint, S.; Vladikas, A.

2006-01-01

The $B_K$ parameter is computed in quenched lattice QCD with Wilson twisted mass fermions. Two variants of tmQCD are used; in both of them the relevant $\\Delta S = 2$ four-fermion operator is renormalised multiplicatively. The renormalisation adopted is non-perturbative, with a Schroedinger functional renormalisation condition. Renormalisation group running is also non-perturbative, up to very high energy scales. In one of the two tmQCD frameworks the computations have been performed at the physical $K$-meson mass, thus eliminating the need of mass extrapolations. Simulations have been performed at several lattice spacings and the continuum limit was reached by combining results from both tmQCD regularisations. Finite volume effects have been partially checked and turned out to be small. Exploratory studies have also been performed with non-degenerate valence flavours. The final result for the RGI bag parameter, with all sources of uncertainty (except quenching) under control, is $\\hat B_K =0.789 \\pm 0.046$.

Hydronephrosis Resulting from Bilateral Ureteral Stenosis: A Late Complication of Polyoma BK Virus Cystitis?

Science.gov (United States)

Basara, N; Rasche, F-M; Schwalenberg, T; Wickenhauser, C; Maier, M; Ivovic, J; Niederwieser, D; Lindner, T H

2010-01-01

We report here a case of acute lymphoblastic leukemia in remission presenting a late-onset bilateral hydronephrosis probably due to polyoma BK virus-induced proliferation of bladder endothelium on both ostii. The diagnosis was made virologically by BK virus Polymerase Chain Reaction (PCR) detection in the absence of any other bladder disease. Awareness of this late complication is necessary not only in patients after renal transplantation but also in patients after hematopoietic stem cell transplantation from matched unrelated donor.

Hydronephrosis Resulting from Bilateral Ureteral Stenosis: A Late Complication of Polyoma BK Virus Cystitis?

Science.gov (United States)

Basara, N.; Rasche, F.-M.; Schwalenberg, T.; Wickenhauser, C.; Maier, M.; Ivovic, J.; Niederwieser, D.; Lindner, T. H.

2010-01-01

We report here a case of acute lymphoblastic leukemia in remission presenting a late-onset bilateral hydronephrosis probably due to polyoma BK virus-induced proliferation of bladder endothelium on both ostii. The diagnosis was made virologically by BK virus Polymerase Chain Reaction (PCR) detection in the absence of any other bladder disease. Awareness of this late complication is necessary not only in patients after renal transplantation but also in patients after hematopoietic stem cell transplantation from matched unrelated donor. PMID:20936157

Hydronephrosis Resulting from Bilateral Ureteral Stenosis: A Late Complication of Polyoma BK Virus Cystitis?

Directory of Open Access Journals (Sweden)

N. Basara

2010-01-01

Full Text Available We report here a case of acute lymphoblastic leukemia in remission presenting a late-onset bilateral hydronephrosis probably due to polyoma BK virus-induced proliferation of bladder endothelium on both ostii. The diagnosis was made virologically by BK virus Polymerase Chain Reaction (PCR detection in the absence of any other bladder disease. Awareness of this late complication is necessary not only in patients after renal transplantation but also in patients after hematopoietic stem cell transplantation from matched unrelated donor.

Coupling tests of parallel channels to modal neutronic kinetics; Pruebas de acoplamiento de canales paralelos a cinetica neutronica modal

Energy Technology Data Exchange (ETDEWEB)

Cecenas F, M.; Campos G, R.M. [IIE, 62490 Cuernavaca, Morelos (Mexico)]. e-mail: mcf@iie.org.mx

2007-07-01

In this work the initial results of the joining of an arrangement of 36 channels in parallel are studied to a modal neutronic kinetic model to represent the core of a BWR type reactor. The set of channels is obtained group the assemblies of that it consists the core in an arrangement of concentric rings, for later on to subdivide each ring in four parts to assign each segment to a quadrant of the core. The obtained channels are coupled to a modal kinetics model that considers the fundamental way and the first harmonic. The obtained solution represents the radial distribution and power azimuthal, the one which is feedback to the channels to update the thermohydraulic variables. The restriction that the pressure drop is same for each channel it is only imposed as initial condition, like part of the stationary state, and it is allowed that the pressure drop in the assemblies them it is different in each channel during a reactivity interference. For the tests to the system, it is convenient to select a relatively big core and that it operates near their stability frontier, for that the channels are dimensioning according to the case 9 of the Stability Benchmark of the Ringhals Swedish plant, organized by the Nuclear Energy Agency in 1994. In general, they reproduce the results of this benchmark, when reproducing oscillations outside of phase, with the additional results that the quadrants 1 and 2 of the core present oscillations of more width that the quadrants 3 and 4. The set group nuclear-thermohydraulics it is solved numerically by means of the outline master-slave of distributed calculation implemented by means of Parallel Virtual Machine (PVM). (Author)

BK virus has tropism for human salivary gland cells in vitro: Implications for transmission

International Nuclear Information System (INIS)

Jeffers, Liesl K.; Madden, Vicki; Webster-Cyriaque, Jennifer

2009-01-01

Background: In this study, it was determined that BKV is shed in saliva and an in vitro model system was developed whereby BKV can productively infect both submandibular (HSG) and parotid (HSY) salivary gland cell lines. Results: BKV was detected in oral fluids using quantitative real-time PCR (QRTPCR). BKV infection was determined using quantitative RT-PCR, immunofluorescence and immunoblotting assays. The infectivity of BKV was inhibited by pre-incubation of the virus with gangliosides that saturated the major capsid protein, VP1, halting receptor mediated BKV entry into salivary gland cells. Examination of infected cultures by transmission electron microscopy revealed 45-50 nm BK virions clearly visible within the cells. Subsequent to infection, encapsidated BK virus was detected in the supernatant. Conclusion: We thus demonstrated that BKV was detected in oral fluids and that BK infection and replication occur in vitro in salivary gland cells. These data collectively suggest the potential for BKV oral route of transmission and oral pathogenesis.

BK Virus-Associated Nephropathy: Current Situation in a Resource-Limited Country.

Science.gov (United States)

Yooprasert, P; Rotjanapan, P

Data on BK virus-associated nephropathy (BKVAN) and treatment strategy in a resource-limited country are scarce. This study aimed to evaluate epidemiology of BKVAN and its situation in Thailand. A retrospective analysis was conducted among adult kidney transplant recipients at Ramathibodi Hospital from October 2011 to September 2016. Patients' demographic data, information on kidney transplantation, immunosuppressive therapy, cytomegalovirus and BK virus infections, and allograft outcomes were retrieved and analyzed. This study included 623 kidney transplant recipients. Only 327 patients (52.49%) received BK virus infection screening, and 176 of 327 patients had allograft dysfunction as a trigger for screening. BKVAN was identified in 39 of 327 patients (11.93%). Deceased donor transplantation and cytomegalovirus infection were associated with a higher risk of BKVAN (odds ratio = 2.2, P = .024, 95% confidence intervals [1.1, 4.43], and odds ratio = 2.6, P = .006, 95% confidence intervals [1.29, 5.26], respectively). BKVAN patients were at significantly higher risk for allograft rejection (P < .001) and allograft failure (P = .036). At the end of the study, 4 graft losses were documented (12.12%). BKVAN was associated with high rate of allograft rejection and failure. However, surveillance of its complications has been underperformed at our facility. Implementing a formal practice guideline may improve allograft outcome in resource-limited countries. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Tungstate-targeting of BKαβ1 channels tunes ERK phosphorylation and cell proliferation in human vascular smooth muscle.

Directory of Open Access Journals (Sweden)

Ana Isabel Fernández-Mariño

Full Text Available Despite the substantial knowledge on the antidiabetic, antiobesity and antihypertensive actions of tungstate, information on its primary target/s is scarce. Tungstate activates both the ERK1/2 pathway and the vascular voltage- and Ca2+-dependent large-conductance BKαβ1 potassium channel, which modulates vascular smooth muscle cell (VSMC proliferation and function, respectively. Here, we have assessed the possible involvement of BKαβ1 channels in the tungstate-induced ERK phosphorylation and its relevance for VSMC proliferation. Western blot analysis in HEK cell lines showed that expression of vascular BKαβ1 channels potentiates the tungstate-induced ERK1/2 phosphorylation in a Gi/o protein-dependent manner. Tungstate activated BKαβ1 channels upstream of G proteins as channel activation was not altered by the inhibition of G proteins with GDPβS or pertussis toxin. Moreover, analysis of Gi/o protein activation measuring the FRET among heterologously expressed Gi protein subunits suggested that tungstate-targeting of BKαβ1 channels promotes G protein activation. Single channel recordings on VSMCs from wild-type and β1-knockout mice indicated that the presence of the regulatory β1 subunit was essential for the tungstate-mediated activation of BK channels in VSMCs. Moreover, the specific BK channel blocker iberiotoxin lowered tungstate-induced ERK phosphorylation by 55% and partially reverted (by 51% the tungstate-produced reduction of platelet-derived growth factor (PDGF-induced proliferation in human VSMCs. Our observations indicate that tungstate-targeting of BKαβ1 channels promotes activation of PTX-sensitive Gi proteins to enhance the tungstate-induced phosphorylation of ERK, and inhibits PDGF-stimulated cell proliferation in human vascular smooth muscle.

Decay properties of ${}_{97}{}^{243}\mathrm{<span\; class="hlt">Bk</span>}$ and ${}_{97}{}^{244}\mathrm{<span\; class="hlt">Bk</span>}$

Energy Technology Data Exchange (ETDEWEB)

Ahmad, I.; Kondev, F. G.; Greene, J. P.; Zhu, S.

2018-01-01

Electron capture decays of Bk-243 and Bk-244 have been studied by measuring the gamma-ray spectra of mass-separated sources and level structures of Cm-243 and Cm-244 have been deduced. In Cm-243, the electron capture population to the ground state, 1/2(+)[631], and 1/2(+)[620] Nilsson states have been observed. The octupole K-pi = 2(-) band was identified in Cm-244 at 933.6 keV. In addition, spins and parities were deduced for several other states and two-quasiparticle configurations have been tentatively assigned to them

Flow over back-facing step in a narrow channel

Czech Academy of Sciences Publication Activity Database

Uruba, Václav; Jonáš, Pavel

2012-01-01

Roč. 12, č. 1 (2012), s. 501-502 ISSN 1617-7061. [Annual Meeting of the International Association of Applied Mathematics and Mechanics /83./. Darmstadt, 26.03.2012-30.03.2012] R&D Projects: GA ČR GAP101/10/1230; GA ČR GA101/08/1112 Institutional research plan: CEZ:AV0Z20760514 Keywords : channel flow * backward facing step * PIV Subject RIV: BK - Fluid Dynamics http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1617-7061

Dynamics of reattachment region behind backward-facing step in a narrow channel

Czech Academy of Sciences Publication Activity Database

Uruba, Václav

2014-01-01

Roč. 14, č. 1 (2014), s. 641-642 ISSN 1617-7061. [Annual Meeting of the International Association of Applied Mathematics and Mechanics /85./. Erlangen, 10.03.2014-14.03.2014] R&D Projects: GA ČR GAP101/10/1230 Institutional support: RVO:61388998 Keywords : backward facing step * reattachment * channel flow Subject RIV: BK - Fluid Dynamics http://onlinelibrary.wiley.com/doi/10.1002/pamm.201410305/abstract

BK virus infection in a renal transplant Saudi child

International Nuclear Information System (INIS)

Maghrabi, M.; Marwan, D.; Osoba, Abimbola O.

2007-01-01

BK human polyomavirus (BKV) causes an asymptomatic primary infection in children, but later, establishes latency mainly in the urinary tract. Virus-host interactions influencing persistence and pathogenicity are not well-understood. We present here a 12-year-old Saudi boy, who had renal transplant in Egypt. Seven months later, he was admitted to our Pediatric Nephrology Unit as a case of renal impairment. He developed BKV infection, diagnosed and successfully managed in our hospital. This case demonstrates the expanding clinical importance of BKV in a post renal transplant patient. This virus can be detected in transitional cells in the urine (decoy cells) using cytology. Testing for BKV deoxyribonucleic acid in urine and blood is an early detection assay, and can be used as a screening test in the early stages. The early reduction of immunosuppression can improve the prognosis. No specific antiviral treatment has been established yet. This is the first report of detecting BK virus in a Saudi post-transplant child in urine and blood specimens by using polymerase chain reaction. (author)

Mārketinga komunikācijas pielietojums atjaunotā BK "VEF Rīga" zīmola virzīšanā

OpenAIRE

Līcis, Mārtiņš

2014-01-01

Darba tēma ir „Mārketinga komunikācijas pielietojums atjaunotā BK „VEF Rīga” zīmola virzīšanā”. Darba mērķis ir noskaidrot mārketinga komunikācijas pielietojumu atjaunotā BK „VEF Rīga” zīmola virzīšanā. Uzdevumi ir izstudēt nepieciešamo teoriju, izanalizēt mārketinga komunikācijas instrumentu pielietojumu, noskaidrot BK „VEF Rīga”, sporta mārketinga speciālista un sabiedrības viedokli par BK „VEF Rīga” zīmolu. Teoriju veido: zīmols, zīmolvedība, mārketinga komunikācija, sociālo mediju mārketi...

NS19504

DEFF Research Database (Denmark)

Nausch, Bernhard; Rode, Frederik; Jørgensen, Susanne

2014-01-01

channel activators and identified a small-molecule positive modulator, NS19504 (5-[(4-bromophenyl)methyl]-1,3-thiazol-2-amine), which activated the BK channel with an EC50 value of 11.0 ± 1.4 µM. Hit validation was performed using high-throughput electrophysiology (QPatch), and further characterization......19504 activated BK channels in native smooth muscle cells from guinea pig urinary bladder. In guinea pig urinary bladder strips, NS19504 (1 µM) reduced spontaneous phasic contractions, an effect that was significantly inhibited by the specific BK channel blocker iberiotoxin. In contrast, NS19504 (1 µ......M) only modestly inhibited nerve-evoked contractions and had no effect on contractions induced by a high K(+) concentration consistent with a K(+) channel-mediated action. Collectively, these results show that NS19504 is a positive modulator of BK channels and provide support for the role of BK channels...

Dwarf Elliptical Galaxies in the M81 Group: The Structure and Stellar Populations of BK5N and F8D1

OpenAIRE

Caldwell, Nelson; Armandroff, Taft E.; Da Costa, G. S.; Seitzer, Patrick

1997-01-01

We have obtained HST WFPC2 images through the F555W and F814W filters of two M81 group dE's: BK5N and a new system, designated F8D1. The resulting color-magnitude diagrams show the upper two magnitudes of the red giant branch. Surface brightness and total magnitude measurements indicate that BK5N and F8D1 have similar central surface brightness (24.5 and 25.4 mag/arcsec^2 in V, respectively), but F8D1's larger length scale results in it being 3 magnitudes more luminous than BK5N. BK5N lies on...

Some experimental results on flow in a diverging 2D channel

Czech Academy of Sciences Publication Activity Database

Antoš, Pavel; Hladík, Ondřej; Jonáš, Pavel; Uruba, Václav

2013-01-01

Roč. 13, č. 1 (2013), s. 297-298 ISSN 1617-7061. [Annual Meeting of the International Association of Applied Mathematics and Mechanics /84./. Novi Sad, 18.03.2013-22.03.2013] R&D Projects: GA ČR GAP101/12/1271 Institutional support: RVO:61388998 Keywords : free stream turbulence * negative pressure gradient * diverging 2D channel Subject RIV: BK - Fluid Dynamics http://onlinelibrary.wiley.com/doi/10.1002/pamm.201310144/pdf

Rectified motion in an asymmetrically structured channel due to induced-charge electrokinetic and thermo-kinetic phenomena

International Nuclear Information System (INIS)

Sugioka, Hideyuki

2016-01-01

It would be advantageous to move fluid by the gradient of random thermal noises that are omnipresent in the natural world. To achieve this motion, we propose a rectifier that uses a thermal noise along with induced-charge electroosmosis and electrophoresis (ICEO and ICEP) around a metal post cylinder in an asymmetrically structured channel and numerically examine its rectification performance. By the boundary element method combined with the thin double layer approximation, we find that rectified motion occurs in the asymmetrically structured channel due to ICEO and ICEP. Further, by thermodynamical and equivalent circuit methods, we discuss a thermal voltage that drives a rectifier consisting of a fluidic channel of an electrolyte and an impedance as a noise source. Our calculations show that fluid can be moved in the asymmetrically structured channel by the fluctuation of electric fields due to a thermal noise only when there is a temperature difference. In addition, our simple noise argument provides a different perspective for the thermo-kinetic phenomena (around a metal post) which was predicted based on the electrolyte Seebeck effect in our previous paper [H. Sugioka, “Nonlinear thermokinetic phenomena due to the Seebeck effect,” Langmuir 30, 8621 (2014)

Rectified motion in an asymmetrically structured channel due to induced-charge electrokinetic and thermo-kinetic phenomena

Energy Technology Data Exchange (ETDEWEB)

Sugioka, Hideyuki, E-mail: hsugioka@shinshu-u.ac.jp [Frontier Research Center, Canon Inc. 30-2, Shimomaruko 3-chome, Ohta-ku, Tokyo 146-8501, Japan and Department of Mechanical Systems Engineering, Shinshu University 4-17-1 Wakasato, Nagano 380-8553 (Japan)

2016-02-15

It would be advantageous to move fluid by the gradient of random thermal noises that are omnipresent in the natural world. To achieve this motion, we propose a rectifier that uses a thermal noise along with induced-charge electroosmosis and electrophoresis (ICEO and ICEP) around a metal post cylinder in an asymmetrically structured channel and numerically examine its rectification performance. By the boundary element method combined with the thin double layer approximation, we find that rectified motion occurs in the asymmetrically structured channel due to ICEO and ICEP. Further, by thermodynamical and equivalent circuit methods, we discuss a thermal voltage that drives a rectifier consisting of a fluidic channel of an electrolyte and an impedance as a noise source. Our calculations show that fluid can be moved in the asymmetrically structured channel by the fluctuation of electric fields due to a thermal noise only when there is a temperature difference. In addition, our simple noise argument provides a different perspective for the thermo-kinetic phenomena (around a metal post) which was predicted based on the electrolyte Seebeck effect in our previous paper [H. Sugioka, “Nonlinear thermokinetic phenomena due to the Seebeck effect,” Langmuir 30, 8621 (2014)].

Kinetic Study of the Chemical Vapor Deposition of Tantalum in Long Narrow Channels

DEFF Research Database (Denmark)

Mugabi, James Atwoki; Eriksen, Søren; Petrushina, Irina

2016-01-01

A kinetic study of the chemical vapor deposition of tantalum in long narrow channels is done to optimize the industrial process for the manufacture of tantalum coated plate heat exchangers. The developed model fits well at temperatures between 750 and 850 °C, and in the pressure range of25–990 mbar....... According to the model, the predominant tantalum growth species is TaCl3. The temperature is shown to have a pronounced effect onthe morphology and rate of deposition of the tantalum and an apparent change in deposition mechanism occurs between 850–900 °C, resulting in the deposition rate at 900 °C being...

Intermittent losartan administration triggers cardiac post-conditioning in isolated rat hearts: role of BK2 receptors.

Directory of Open Access Journals (Sweden)

Luca Sgarra

Full Text Available The angiotensin (Ang and bradykinin (BK tissue-system plays a pivotal role in post-conditioning, but the efficacy of angiotensin type 1 receptor (AT1R blockers (ARBs in post-ischemic strategies is still under investigation. We evaluated functional and morphological outcomes, together with activation of cytosolic RISK pathway kinases, in rat hearts subjected to losartan (LOS or irbesartan (IRB post-ischemic administration.Isolated rat hearts underwent 30 min ischemia and 120 min reperfusion. Post-conditioning was obtained by intermittent (10 s/each or continuous drug infusion during the first 3 min of reperfusion. Left ventricular end-diastolic pressure (LVEDP, left ventricular developed pressure (dLVP, coronary flow (CF, and left ventricular infarct mass (IM were measured together with the activation status of RISK kinases Akt, p42/44 MAPK and GSK3β.When compared to hearts subjected to ischemia/reperfusion (iI/R alone, continuous IRB or LOS administration did not significantly reduce total infarct mass (cIRB or cLOS vs. iI/R, p = 0.2. Similarly, intermittent IRB (iIRB was not able to enhance cardioprotection. Conversely, intermittent LOS administration (iLOS significantly ameliorated cardiac recovery (iLOS vs iI/R, p<0.01. Differences between iLOS and iIRB persisted under continuous blockade of AT2R (iLOS+cPD vs. iIRB+cPD, p<0.05. Interestingly, iLOS cardioprotection was lost when BK2R was simultaneously blocked (iLOS+cHOE vs. iI/R, p = 0.6, whereas concurrent administration of iBK and iIRB replicated iLOS effects (iIRB+iBK vs. iLOS, p = 0.7. At the molecular level, iIRB treatment did not significantly activate RISK kinases, whereas both iLOS and iBK treatments were associated with activation of the Akt/GSK3β branch of the RISK pathways (p<0.05 vs. iI/R, for both.Our results suggest that intermittent losartan is effective in mediating post-conditioning cardioprotection, whereas irbesartan is not. The infarct mass reduction by intermittent

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

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Xiaohui eSun

2012-04-01

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

Towards saturation of the electron-capture delayed fission probability: The new isotopes 240Es and 236Bk

Directory of Open Access Journals (Sweden)

J. Konki

2017-01-01

Full Text Available The new neutron-deficient nuclei 240Es and 236Bk were synthesised at the gas-filled recoil separator RITU. They were identified by their radioactive decay chains starting from 240Es produced in the fusion–evaporation reaction 209Bi(34S,3n240Es. Half-lives of 6(2s and 22−6+13s were obtained for 240Es and 236Bk, respectively. Two groups of α particles with energies Eα=8.19(3MeV and 8.09(3MeV were unambiguously assigned to 240Es. Electron-capture delayed fission branches with probabilities of 0.16(6 and 0.04(2 were measured for 240Es and 236Bk, respectively. These new data show a continuation of the exponential increase of ECDF probabilities in more neutron-deficient isotopes.

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

Science.gov (United States)

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

2016-06-01

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

On the Operator ⨁Bk Related to Bessel Heat Equation

Directory of Open Access Journals (Sweden)

Wanchak Satsanit

2010-01-01

Full Text Available We study the equation (∂/∂tu(x,t=c2⊕Bku(x,t with the initial condition u(x,0=f(x for x∈Rn+. The operator ⊕Bk is the operator iterated k-times and is defined by ⊕Bk=((∑i=1pBxi4-(∑j=p+1p+qBxi4k, where p+q=n is the dimension of the Rn+, Bxi=∂2/∂xi2+(2vi/xi(∂/∂xi, 2vi=2αi+1, αi>-1/2, i=1,2,3,…,n, and k is a nonnegative integer, u(x,t is an unknown function for (x,t=(x1,x2,…,xn,t∈Rn+×(0,∞, f(x is a given generalized function, and c is a positive constant. We obtain the solution of such equation, which is related to the spectrum and the kernel, which is so called Bessel heat kernel. Moreover, such Bessel heat kernel has interesting properties and also related to the kernel of an extension of the heat equation.

BK Virus Load Associated with Serum Levels of sCD30 in Renal Transplant Recipients

Science.gov (United States)

Malik, Salma N.; Al-Saffer, Jinan M.; Jawad, Rana S.

2016-01-01

Background. Rejection is the main drawback facing the renal transplant operations. Complicated and overlapping factors, mainly related to the immune system, are responsible for this rejection. Elevated serum levels of sCD30 were frequently recorded as an indicator for renal allograft rejection, while BV virus is considered as one of the most serious consequences for immunosuppressive treatment of renal transplant recipients (RTRs). Aims. This study aimed to determine the association of BK virus load with serum levels of sCD30 in RTRs suffering from nephropathy. Patients and Methods. A total of 50 RTRs with nephropathy and 30 age-matched apparently healthy individuals were recruited for this study. Serum samples were obtained from each participant. Real-time PCR was used to quantify BK virus load in RTRs serum, while ELISA technique was employed to estimate serum levels of sCD30. Results. Twenty-two percent of RTRs had detectable BKV with mean viral load of 1.094E + 06 ± 2.291E + 06. RTRs showed higher mean serum level of sCD30 (20.669 ± 18.713 U/mL) than that of controls (5.517 ± 5.304 U/mL) with significant difference. BK virus load had significant positive correlation with the serum levels of sCD30 in RTRs group. Conclusion. These results suggest that serum levels of sCD30 could be used as an indicator of BK viremia, and accordingly the immunosuppressive regime should be adjusted. PMID:27051424

Comprehensive benchmarking reveals H2BK20 acetylation as a distinctive signature of cell-state-specific enhancers and promoters.

Science.gov (United States)

Kumar, Vibhor; Rayan, Nirmala Arul; Muratani, Masafumi; Lim, Stefan; Elanggovan, Bavani; Xin, Lixia; Lu, Tess; Makhija, Harshyaa; Poschmann, Jeremie; Lufkin, Thomas; Ng, Huck Hui; Prabhakar, Shyam

2016-05-01

Although over 35 different histone acetylation marks have been described, the overwhelming majority of regulatory genomics studies focus exclusively on H3K27ac and H3K9ac. In order to identify novel epigenomic traits of regulatory elements, we constructed a benchmark set of validated enhancers by performing 140 enhancer assays in human T cells. We tested 40 chromatin signatures on this unbiased enhancer set and identified H2BK20ac, a little-studied histone modification, as the most predictive mark of active enhancers. Notably, we detected a novel class of functionally distinct enhancers enriched in H2BK20ac but lacking H3K27ac, which was present in all examined cell lines and also in embryonic forebrain tissue. H2BK20ac was also unique in highlighting cell-type-specific promoters. In contrast, other acetylation marks were present in all active promoters, regardless of cell-type specificity. In stimulated microglial cells, H2BK20ac was more correlated with cell-state-specific expression changes than H3K27ac, with TGF-beta signaling decoupling the two acetylation marks at a subset of regulatory elements. In summary, our study reveals a previously unknown connection between histone acetylation and cell-type-specific gene regulation and indicates that H2BK20ac profiling can be used to uncover new dimensions of gene regulation. © 2016 Kumar et al.; Published by Cold Spring Harbor Laboratory Press.

On the influence of plasma DBD actuator on the flow in a rectangular channel

Czech Academy of Sciences Publication Activity Database

Procházka, Pavel P.; Uruba, Václav

2014-01-01

Roč. 14, č. 1 (2014), s. 727-728 ISSN 1617-7061. [Annual Meeting of the International Association of Applied Mathematics and Mechanics /85./. Erlangen, 10.03.2014-14.03.2014] R&D Projects: GA ČR(CZ) GP14-25354P Institutional support: RVO:61388998 Keywords : plasma DBD * boundary layer * channel flow Subject RIV: BK - Fluid Dynamics http://onlinelibrary.wiley.com/doi/10.1002/pamm.201410346/abstract

Flow-Induced New Channels of Energy Exchange in Multi-Scale Plasma Dynamics - Revisiting Perturbative Hybrid Kinetic-MHD Theory.

Science.gov (United States)

Shiraishi, Junya; Miyato, Naoaki; Matsunaga, Go

2016-05-10

It is found that new channels of energy exchange between macro- and microscopic dynamics exist in plasmas. They are induced by macroscopic plasma flow. This finding is based on the kinetic-magnetohydrodynamic (MHD) theory, which analyses interaction between macroscopic (MHD-scale) motion and microscopic (particle-scale) dynamics. The kinetic-MHD theory is extended to include effects of macroscopic plasma flow self-consistently. The extension is realised by generalising an energy exchange term due to wave-particle resonance, denoted by δ WK. The first extension is generalisation of the particle's Lagrangian, and the second one stems from modification to the particle distribution function due to flow. These extensions lead to a generalised expression of δ WK, which affects the MHD stability of plasmas.

A single-center epidemiological study of BK virus infection and analysis of risk factors in patients with renal transplantation

Directory of Open Access Journals (Sweden)

Ji-gang LI

2014-10-01

Full Text Available Objective　To investigate the epidemiological characteristics of BK virus (BKV infection in living renal transplantation patients, and analyze the risk factors of BKV infection and BKV nephropathy (BKVN. Methods　The BKV DNA load in urine and blood samples of 43 renal transplant recipients, who had received renal transplantation in 309 Hospital from Feb. 2012 to Feb. 2013, was determined at preoperative period and 0.5, 1, 3, 6, 9, 12 and 15 months after transplantation. Meanwhile, the biopsy of grafted kidney was performed in those patients with continuously elevated serum creatinine and those with higher BKV DNA load. Patients were divided into 3 groups as follows according to the test results: BK viruria group, BK viremia group and pathologically diagnosed BKVN group. Data of each group were then recorded, including gender, age, postoperative diabetes (PTDM, acute rejection (AR, delayed recovery of graft function (DGF, postoperative pulmonary infection, preoperative immune induction therapy, postoperative immunosuppressive regimen, and other information. The risk factors for postoperative BKV infection and BKVN were analyzed. Results　After an average of 15-month follow-up, it was found that the incidence of BKV viruria was 46.5%, that of BKV viremia was 14.0%, and that of BKVN was 2.3%. Sixth month after transplantation was found to be the peak time of viruria and viremia. FK506 was significantly associated with viremia in living donor renal transplantation. The immunosuppressive regimen was the immune related independent risk factor for BK viremia developing BKVN after living renal transplantation. Conclusion　The incidence of BK viremia and BKVN is lower in living donor renal transplantation than in cadaver renal transplantation, but that of viruria is similar in both groups. Immunosuppressive scheme based on FK506 is an immune related independent risk factor leading to BK viremia proceeding to BKVN in living donor kidney

Phase 1b randomized trial and follow-up study in Uganda of the blood-stage malaria vaccine candidate BK-SE36.

Science.gov (United States)

Palacpac, Nirianne Marie Q; Ntege, Edward; Yeka, Adoke; Balikagala, Betty; Suzuki, Nahoko; Shirai, Hiroki; Yagi, Masanori; Ito, Kazuya; Fukushima, Wakaba; Hirota, Yoshio; Nsereko, Christopher; Okada, Takuya; Kanoi, Bernard N; Tetsutani, Kohhei; Arisue, Nobuko; Itagaki, Sawako; Tougan, Takahiro; Ishii, Ken J; Ueda, Shigeharu; Egwang, Thomas G; Horii, Toshihiro

2013-01-01

Up to now a malaria vaccine remains elusive. The Plasmodium falciparum serine repeat antigen-5 formulated with aluminum hydroxyl gel (BK-SE36) is a blood-stage malaria vaccine candidate that has undergone phase 1a trial in malaria-naive Japanese adults. We have now assessed the safety and immunogenicity of BK-SE36 in a malaria endemic area in Northern Uganda. We performed a two-stage, randomized, single-blinded, placebo-controlled phase 1b trial (Current Controlled trials ISRCTN71619711). A computer-generated sequence randomized healthy subjects for 2 subcutaneous injections at 21-day intervals in Stage1 (21-40 year-olds) to 1-mL BK-SE36 (BKSE1.0) (n = 36) or saline (n = 20) and in Stage2 (6-20 year-olds) to BKSE1.0 (n = 33), 0.5-mL BK-SE36 (BKSE0.5) (n = 33), or saline (n = 18). Subjects and laboratory personnel were blinded. Safety and antibody responses 21-days post-second vaccination (Day42) were assessed. Post-trial, to compare the risk of malaria episodes 130-365 days post-second vaccination, Stage2 subjects were age-matched to 50 control individuals. Nearly all subjects who received BK-SE36 had induration (Stage1, n = 33, 92%; Stage2, n = 63, 96%) as a local adverse event. No serious adverse event related to BK-SE36 was reported. Pre-existing anti-SE36 antibody titers negatively correlated with vaccination-induced antibody response. At Day42, change in antibody titers was significant for seronegative adults (1.95-fold higher than baseline [95% CI, 1.56-2.43], p = 0.004) and 6-10 year-olds (5.71-fold [95% CI, 2.38-13.72], p = 0.002) vaccinated with BKSE1.0. Immunogenicity response to BKSE0.5 was low and not significant (1.55-fold [95% CI, 1.24-1.94], p = 0.75). In the ancillary analysis, cumulative incidence of first malaria episodes with ≥5000 parasites/µL was 7 cases/33 subjects in BKSE1.0 and 10 cases/33 subjects in BKSE0.5 vs. 29 cases/66 subjects in the control group. Risk ratio for BKSE1.0 was 0.48 (95% CI, 0

Chemical consequences of radioactive decay. 1. Study of 249Cf ingrowth into crystalline 249BkBr3: a new crystalline phase of CfBr3

International Nuclear Information System (INIS)

Young, J.P.; Haire, R.G.; Peterson, J.R.; Ensor, D.D.; Fellows, R.L.

1980-01-01

Spectrophotometric and x-ray powder diffraction methods have been applied to a study of the ingrowth of californium-249 by β - decay of berkelium-249 in crystalline 249 BkBr 3 . It was found that the Cf daughter grows in with the same oxidation state and crystal structure as the parent. Thus, six-coordinate BkBr 3 (AlCl 3 -type monoclinic structure) generates six-coordinate CfBr 3 , and eight-coordinate BkBr 3 (PuBr 3 -type orthorhombic structure) generates eight-coordinate CfBr 3 , a previously unknown form of CfBr 3 . It was also found that the daughter Cf(III) in the BkBr 3 parent compound can be reduced to Cf(II) by treatment with H 2 , as it can in pure CfBr 3 . 5 figures

Modification of sodium and potassium channel kinetics by diethyl ether and studies on sodium channel inactivation in the crayfish giant axon membrane

Energy Technology Data Exchange (ETDEWEB)

Bean, Bruce Palmer [Univ. of Rochester, NY (United States)

1979-01-01

The effects of ether and halothane on membrane currents in the voltage clamped crayfish giant axon membrane were investigated. Concentrations of ether up to 300 mM and of halothane up to 32 mM had no effect on resting potential or leakage conductance. Ether and halothane reduced the size of sodium currents without changing the voltage dependence of the peak currents or their reversal potential. Ether and halothane also produced a reversible, dose-dependent speeding of sodium current decay at all membrane potentials. Ether reduced the time constants for inactivation, and also shifted the midpoint of the steady-state inactivation curve in the hyperpolarizing direction. Potassium currents were smaller with ether present, with no change in the voltage dependence of steady-state currents. The activation of potassium channels was faster with ether present. There was no apparent change in the capacitance of the crayfish giant axon membrane with ether concentrations of up to 100 mM. Experiments on sodium channel inactivation kinetics were performed using 4-aminopyridine to block potassium currents. Sodium currents decayed with a time course generally fit well by a single exponential. The time constant of decay was a steep function of voltage, especially in the negative resistance region of the peak current vs voltage relation.The time course of inactivation was very similar to that of the decay of the current at the same potential. The measurement of steady-state inactivation curves with different test pulses showed no shifts along the voltage asix. The voltage-dependence of the integral of sodium conductance was measured to test models of sodium channel inactivation in which channels must open before inactivating; the results appear inconsistent with some of the simplest cases of such models.

Simulation of A Main Steam Line Break Accident Using the Coupled 'System Thermal-Hydraulics, 3D reactor Kinetics, and Hot Channel' Analysis Capability of MARS 3.0

International Nuclear Information System (INIS)

Jeong, Jae Jun; Chung, Bub Dong

2005-09-01

For realistic analysis of thermal-hydraulics (T-H) transients in light water reactors, KAERI has developed the best-estimate T-H system code, MARS. The code has been improved from the consolidated version of the RELAP5/MOD3 and COBRA-TF codes. Then, the MARS code was coupled with a three-dimensional (3-D) reactor kinetics code, MASTER. This coupled calculation feature, in conjunction with the existing hot channel analysis capabilities of the MARS and MASTER codes, allows for more realistic simulations of nuclear system transients. In this work, a main steam line break (MSLB) accident is simulated using the coupled 'system T-H, 3-D reactor kinetics, and hot channel analysis' feature of the MARS code. Two coupled calculations are performed for demonstration. First, a coupled calculation of the 'system T-H and 3-D reactor kinetics' with a refined core T-H nodalization is carried out to obtain global core power and local departure from nucleate boiling (DNB) ratio (DNBR) behaviors. Next, for a more accurate DNBR prediction, another coupled calculation with subchannel meshes for the hot channels is performed. The results of the coupled calculations are very reasonable and consistent so that these can be used to remove the excessive conservatism in the conventional safety analysis

Preliminary study on rotary ultrasonic machining of Bk-7 optical glass rod

International Nuclear Information System (INIS)

Hamzah, E.; Izman, S.; Khoo, C.Y.; Zainal Abidin, N.N.

2007-01-01

This paper presents an experimental observation on rotary ultrasonic machining (RUM) of BK7 optical glass rod. BK7 is a common technical optical glass for high quality optical components due to its high linear optical transmission in the visible range and is chemically stable. RUM is a hybrid machining process that combines the material removal mechanisms of diamond grinding and ultrasonic machining (USM) and it is non-thermal, non-chemical, creates no change in the microstructure, chemical or physical properties of the work piece. In the RUM, a controlled static load is applied to the rotating core drill with metal bonded diamond abrasive and is ultrasonically vibrated in the axial direction. A water-soluble coolant was used to cool the tool and sample during machining processes. By using DOE (Design of Experiment) approach, the effect of spindle speed and feed rate to the ultrasonic machinability had been developed. The main effects and two-factor interactions of process parameters (spindle speed) and feed rate) on output variables (MRR, surface roughness, opaqueness, chipping thickness and chipping size) are studied. (author)

High-level viruria as a screening tool for BK virus nephropathy in renal transplant recipients

Directory of Open Access Journals (Sweden)

W. James Chon

2016-09-01

Conclusion: The presence of high-grade viruria is an early marker for developing BK viremia/BKVN. Detection of high-grade viruria should prompt early allograft biopsy and/or preemptive reduction in immunosuppression.

Dechanneling function for relativistic axially channeled electrons

International Nuclear Information System (INIS)

Muralev, V.A.; Telegin, V.I.

1981-01-01

Behaviour of the x(t) dechanneling function depending on the depth is theoretically studied. Theoretical consideration of x(t) for axial channeled relativistic electrons in anisotropic medium results in two-dimensional kinetic equation with mixed derivatives of the parabolic type. The kinetic equation in the approximation of the continuous Lindchard model for relativistic axial channeled electrons is numerically solved. The depth dependence of the x(t) dechanneling function is obtained [ru

Development of the coupled 'system thermal-hydraulics, 3D reactor kinetics, and hot channel' analysis capability of the MARS code

Energy Technology Data Exchange (ETDEWEB)

Jeong, J. J.; Chung, B. D.; Lee, W.J

2005-02-01

The subchannel analysis capability of the MARS 3D module has been improved. Especially, the turbulent mixing and void drift models for flow mixing phenomena in rod bundles have been assessed using some well-known rod bundle test data. Then, the subchannel analysis feature was combined to the existing coupled 'system Thermal-Hydraulics (T/H) and 3D reactor kinetics' calculation capability of MARS. These features allow the coupled 'system T/H, 3D reactor kinetics, and hot channel' analysis capability and, thus, realistic simulations of hot channel behavior as well as global system T/H behavior. In this report, the MARS code features for the coupled analysis capability are described first. The code modifications relevant to the features are also given. Then, a coupled analysis of the Main Steam Line Break (MSLB) is carried out for demonstration. The results of the coupled calculations are very reasonable and realistic, and show these methods can be used to reduce the over-conservatism in the conventional safety analysis.

Effects of Nonlinear Absorption in BK7 and Color Glasses at 355 nm

International Nuclear Information System (INIS)

Adams, J J; McCarville, T; Bruere, J; McElroy, J; Peterson, J

2003-01-01

We have demonstrated a simple experimental technique that can be used to measure the nonlinear absorption coefficients in glasses. We determine BK7, UG1, and UG11 glasses to have linear absorption coefficients of 0.0217 ± 10% cm -1 , 1.7 ± 10% cm -1 , and 0.82 ± 10% cm -1 , respectively, two-photon absorption cross-sections of 0.025 ± 20% cm/GW, 0.035 ± 20% cm/GW, and 0.047 ± 20% cm/GW, respectively, excited-state absorption cross-sections of 8.0 x 10 -18 ± 20% cm 2 , 2.8 x 10 -16 ± 20% cm 2 , and 5 x 10 -17 ± 20% cm 2 , respectively, and solarization coefficients of 8.5 x 10 -20 ± 20% cm 2 , 2.5 x 10 -18 ± 20% cm 2 , and 1.3 x 10 -19 ± 20% cm 2 , respectively. For our application, nonlinear effects in 10-cm of BK7 are small ((le) 2%) for 355-nm fluences 2 for flat-top pulses. However, nonlinear effects are noticeable for 355-nm fluences at 0.8 J/cm 2 . In particular, we determine a 20% increase in the instantaneous absorption from linear, a solarization rate of 4% per 100 shots, and a 10% temporal droop introduced in the pulse, for 355-nm flat-top pulses at a fluence of 0.8 J/cm 2 . For 0.5-cm of UG1 absorbing glass the non-linear absorption has a similar effect as that from 10-cm of BK7 on the pulse shape; however, the effects in UG11 are much smaller

Vaccine for BK Polyomavirus-associated Infections in Transplant Recipients | NCI Technology Transfer Center | TTC

Science.gov (United States)

NCI researches identified a BK polyomavirus (BKV) virulent strain that causes chronic urinary tract infections, and the development of vaccine and therapeutic methods that would block BKV pathogenesis. The NCI Laboratory of Cellular Oncology, seek parties to license or co-develop this technology.

Unraveling hominin behavior at another anthropogenic site from Olduvai Gorge (Tanzania): new archaeological and taphonomic research at BK, Upper Bed II.

Science.gov (United States)

Domínguez-Rodrigo, M; Mabulla, A; Bunn, H T; Barba, R; Diez-Martín, F; Egeland, C P; Espílez, E; Egeland, A; Yravedra, J; Sánchez, P

2009-09-01

New archaeological excavations and research at BK, Upper Bed II (Olduvai Gorge, Tanzania) have yielded a rich and unbiased collection of fossil bones. These new excavations show that BK is a stratified deposit formed in a riverine setting close to an alluvial plain. The present taphonomic study reveals the second-largest collection of hominin-modified bones from Olduvai, with abundant cut marks found on most of the anatomical areas preserved. Meat and marrow exploitation is reconstructed using the taphonomic signatures left on the bones by hominins. Highly cut-marked long limb shafts, especially those of upper limb bones, suggest that hominins at BK were actively engaged in acquiring small and middle-sized animals using strategies other than passive scavenging. The exploitation of large-sized game (Pelorovis) by Lower Pleistocene hominins, as suggested by previous researchers, is supported by the present study.

Simulation of A Main Steam Line Break Accident Using the Coupled 'System Thermal-Hydraulics, 3D reactor Kinetics, and Hot Channel' Analysis Capability of MARS 3.0

Energy Technology Data Exchange (ETDEWEB)

Jeong, Jae Jun; Chung, Bub Dong

2005-09-15

For realistic analysis of thermal-hydraulics (T-H) transients in light water reactors, KAERI has developed the best-estimate T-H system code, MARS. The code has been improved from the consolidated version of the RELAP5/MOD3 and COBRA-TF codes. Then, the MARS code was coupled with a three-dimensional (3-D) reactor kinetics code, MASTER. This coupled calculation feature, in conjunction with the existing hot channel analysis capabilities of the MARS and MASTER codes, allows for more realistic simulations of nuclear system transients. In this work, a main steam line break (MSLB) accident is simulated using the coupled 'system T-H, 3-D reactor kinetics, and hot channel analysis' feature of the MARS code. Two coupled calculations are performed for demonstration. First, a coupled calculation of the 'system T-H and 3-D reactor kinetics' with a refined core T-H nodalization is carried out to obtain global core power and local departure from nucleate boiling (DNB) ratio (DNBR) behaviors. Next, for a more accurate DNBR prediction, another coupled calculation with subchannel meshes for the hot channels is performed. The results of the coupled calculations are very reasonable and consistent so that these can be used to remove the excessive conservatism in the conventional safety analysis.

Adrenaline-induced colonic K+ secretion is mediated by KCa1.1 (BK) channels

DEFF Research Database (Denmark)

Sørensen, Mads Vaarby; Sausbier, Matthias; Ruth, Peter

2010-01-01

. However, the secretory K(+) channel responsible for cAMP-induced K(+) secretion remains to be defined. In this study we used the Ussing chamber to identify adrenaline-induced electrogenic K(+) secretion. We found that the adrenaline-induced electrogenic ion secretion is a compound effect dominated...... variants in colonic enterocytes (STREX and ZERO). Importantly, the ZERO variant known to be activated by cAMP is differentially up-regulated in enterocytes from animals on a high K(+) diet. In summary, these results strongly suggest that the adrenaline-induced distal colonic K(+) secretion is mediated...

Surface channeling

International Nuclear Information System (INIS)

Sizmann, R.; Varelas, C.

1976-01-01

There is experimental evidence that swift light ions incident at small angles towards single crystalline surfaces can lose an appreciable fraction of their kinetic energy during reflection. It is shown that these projectiles penetrate into the bulk surface region of the crystal. They can travel as channeled particles along long paths through the solid (surface channeling). The angular distribution and the depth history of the re-emerged projectiles are investigated by computer simulations. A considerable fraction of the penetrating projectiles re-emerges from the crystal with constant transverse energy if the angle of incidence is smaller than the critical angle for axial channeling. Analytical formulae are derived based on a diffusion model for surface channeling. A comparison with experimental data exhibits the relevance of the analytical solutions. (Auth.)

Differential T cell response against BK virus regulatory and structural antigens: A viral dynamics modelling approach.

Directory of Open Access Journals (Sweden)

Arturo Blazquez-Navarro

2018-05-01

Full Text Available BK virus (BKV associated nephropathy affects 1-10% of kidney transplant recipients, leading to graft failure in about 50% of cases. Immune responses against different BKV antigens have been shown to have a prognostic value for disease development. Data currently suggest that the structural antigens and regulatory antigens of BKV might each trigger a different mode of action of the immune response. To study the influence of different modes of action of the cellular immune response on BKV clearance dynamics, we have analysed the kinetics of BKV plasma load and anti-BKV T cell response (Elispot in six patients with BKV associated nephropathy using ODE modelling. The results show that only a small number of hypotheses on the mode of action are compatible with the empirical data. The hypothesis with the highest empirical support is that structural antigens trigger blocking of virus production from infected cells, whereas regulatory antigens trigger an acceleration of death of infected cells. These differential modes of action could be important for our understanding of BKV resolution, as according to the hypothesis, only regulatory antigens would trigger a fast and continuous clearance of the viral load. Other hypotheses showed a lower degree of empirical support, but could potentially explain the clearing mechanisms of individual patients. Our results highlight the heterogeneity of the dynamics, including the delay between immune response against structural versus regulatory antigens, and its relevance for BKV clearance. Our modelling approach is the first that studies the process of BKV clearance by bringing together viral and immune kinetics and can provide a framework for personalised hypotheses generation on the interrelations between cellular immunity and viral dynamics.

Differential T cell response against BK virus regulatory and structural antigens: A viral dynamics modelling approach.

Science.gov (United States)

Blazquez-Navarro, Arturo; Schachtner, Thomas; Stervbo, Ulrik; Sefrin, Anett; Stein, Maik; Westhoff, Timm H; Reinke, Petra; Klipp, Edda; Babel, Nina; Neumann, Avidan U; Or-Guil, Michal

2018-05-01

BK virus (BKV) associated nephropathy affects 1-10% of kidney transplant recipients, leading to graft failure in about 50% of cases. Immune responses against different BKV antigens have been shown to have a prognostic value for disease development. Data currently suggest that the structural antigens and regulatory antigens of BKV might each trigger a different mode of action of the immune response. To study the influence of different modes of action of the cellular immune response on BKV clearance dynamics, we have analysed the kinetics of BKV plasma load and anti-BKV T cell response (Elispot) in six patients with BKV associated nephropathy using ODE modelling. The results show that only a small number of hypotheses on the mode of action are compatible with the empirical data. The hypothesis with the highest empirical support is that structural antigens trigger blocking of virus production from infected cells, whereas regulatory antigens trigger an acceleration of death of infected cells. These differential modes of action could be important for our understanding of BKV resolution, as according to the hypothesis, only regulatory antigens would trigger a fast and continuous clearance of the viral load. Other hypotheses showed a lower degree of empirical support, but could potentially explain the clearing mechanisms of individual patients. Our results highlight the heterogeneity of the dynamics, including the delay between immune response against structural versus regulatory antigens, and its relevance for BKV clearance. Our modelling approach is the first that studies the process of BKV clearance by bringing together viral and immune kinetics and can provide a framework for personalised hypotheses generation on the interrelations between cellular immunity and viral dynamics.

Characterization of an extracellular lipase by Pseudomonas koreensis BK-L07 isolated from soil.

Science.gov (United States)

Anbu, Periasamy

2014-01-01

Screening using spirit blue agar revealed that strain BK-L07 had the highest lipase activity. Furthermore, the isolated strain was identified as Pseudomonas sp. based on morphological, physiological, biochemical, and molecular analyses. The 16S rRNA gene sequence of strain BK-L07 shared a high similarity with that of Pseudomonas koreensis (99%). The nutritional conditions and physicochemical properties were influenced by P. koreensis BK-L07. The maximum lipase production was obtained in tryptic soy broth medium at pH 8.0 and a temperature of 25°C after 36 hr of incubation. In addition, the lipase activity was determined using different carbon sources and lipase inducers. The lipase production was greatest when 1% maltose was used as the carbon source and olive oil was used as the lipase inducer. The lipase production was significantly increased approximately threefold in the optimized medium when compared with the original medium. Further, the lipase was purified by ammonium sulfate precipitation and gel filtration chromatography with a purification yield of 10.8%. The molecular mass of lipase was 45 kDa. The optimum temperature and pH were 40°C and 8.0, respectively. The enzyme was stable up to 50°C and at pH from 7 to 9. In addition, the enzyme activity was stimulated by MgSO4 and completely inhibited by ethylenediamine tetraacetic acid (EDTA), indicating the metalloenzyme type. The lipase activity was toward medium to long chain length of fatty acids (C10 to C18). Supplemental materials are available for this article. Go to the publisher's online edition of Preparative Biochemistry and Biotechnology to view the supplemental file.

Saffman-Taylor fingers with kinetic undercooling

KAUST Repository

Gardiner, Bennett P. J.

2015-02-23

© 2015 American Physical Society. The mathematical model of a steadily propagating Saffman-Taylor finger in a Hele-Shaw channel has applications to two-dimensional interacting streamer discharges which are aligned in a periodic array. In the streamer context, the relevant regularization on the interface is not provided by surface tension but instead has been postulated to involve a mechanism equivalent to kinetic undercooling, which acts to penalize high velocities and prevent blow-up of the unregularized solution. Previous asymptotic results for the Hele-Shaw finger problem with kinetic undercooling suggest that for a given value of the kinetic undercooling parameter, there is a discrete set of possible finger shapes, each analytic at the nose and occupying a different fraction of the channel width. In the limit in which the kinetic undercooling parameter vanishes, the fraction for each family approaches 1/2, suggesting that this "selection" of 1/2 by kinetic undercooling is qualitatively similar to the well-known analog with surface tension. We treat the numerical problem of computing these Saffman-Taylor fingers with kinetic undercooling, which turns out to be more subtle than the analog with surface tension, since kinetic undercooling permits finger shapes which are corner-free but not analytic. We provide numerical evidence for the selection mechanism by setting up a problem with both kinetic undercooling and surface tension and numerically taking the limit that the surface tension vanishes.

Saffman-Taylor fingers with kinetic undercooling

KAUST Repository

Gardiner, Bennett P. J.; McCue, Scott W.; Dallaston, Michael C.; Moroney, Timothy J.

2015-01-01

© 2015 American Physical Society. The mathematical model of a steadily propagating Saffman-Taylor finger in a Hele-Shaw channel has applications to two-dimensional interacting streamer discharges which are aligned in a periodic array. In the streamer context, the relevant regularization on the interface is not provided by surface tension but instead has been postulated to involve a mechanism equivalent to kinetic undercooling, which acts to penalize high velocities and prevent blow-up of the unregularized solution. Previous asymptotic results for the Hele-Shaw finger problem with kinetic undercooling suggest that for a given value of the kinetic undercooling parameter, there is a discrete set of possible finger shapes, each analytic at the nose and occupying a different fraction of the channel width. In the limit in which the kinetic undercooling parameter vanishes, the fraction for each family approaches 1/2, suggesting that this "selection" of 1/2 by kinetic undercooling is qualitatively similar to the well-known analog with surface tension. We treat the numerical problem of computing these Saffman-Taylor fingers with kinetic undercooling, which turns out to be more subtle than the analog with surface tension, since kinetic undercooling permits finger shapes which are corner-free but not analytic. We provide numerical evidence for the selection mechanism by setting up a problem with both kinetic undercooling and surface tension and numerically taking the limit that the surface tension vanishes.

Pore dimensions and the role of occupancy in unitary conductance of Shaker K channels

Science.gov (United States)

Díaz-Franulic, Ignacio; Sepúlveda, Romina V.; Navarro-Quezada, Nieves; González-Nilo, Fernando

2015-01-01

conductance of the large conductance K (BK) channel (the K channel of highest conductance), reducing the energy gap between their K+ transport rates to ∼1 kT. Thus, although Shaker’s pore sustains ion translocation as the BK channel’s does, higher energetic costs of ion stabilization or higher friction with the ion’s rigid hydration cage in its narrower aqueous cavity may entail higher resistance. PMID:26216859

哈维氏弧菌黑鲷分离株BK-1培养条件优化研究%Studies on the Optimal Culture Conditions of Vibrio harveyi BK-1 from Sparus macrocephalus

Institute of Scientific and Technical Information of China (English)

潘晓艺; 沈锦玉; 尹文林; 曹铮; 马海其; 常抗美

2005-01-01

从患病黑鲷Sparus macrocephalus 的肾脏分离到一致病菌株BK-1,经鉴定为哈维氏弧菌.对哈维氏弧菌BK-1株的最佳生长条件及培养基优化进行了测定.结果表明:不同的培养条件和培养基成份均会影响其产量.哈维氏弧菌最适宜生长条件为:盐度为2%、pH8、温度为30℃;最佳培养基成份为:蛋白胨0.5%,牛肉膏0.75%,甘油0.05%,CuSO40.15 mg/L,CaCl2 0.01 g/L.

Properties of optical breakdown in BK7 glass induced by an extended-cavity femtosecond laser oscillator.

Science.gov (United States)

Do, Binh T; Phillips, Mark C; Miller, Paul A; Kimmel, Mark W; Britsch, Justin; Cho, Seong-Ho

2009-02-16

Using an extended-cavity femtosecond oscillator, we investigated optical breakdown in BK7 glass caused by the accumulated action of many laser pulses. By using a pump-probe experiment and collecting the transmitted pump along with the reflected pump and the broadband light generated by the optical breakdown, we measured the build-up time to optical breakdown as a function of the pulse energy, and we also observed the instability of the plasma due to the effect of defocusing and shielding created by the electron gas. The spectrum of the broadband light emitted by the optical breakdown and the origin of the material modification in BK7 glass was studied. We developed a simple model of electromagnetic wave propagation in plasma that is consistent with the observed behavior of the reflection, absorption, and transmission of the laser light.

Coupling of unidimensional neutron kinetics to thermal hydraulics in parallel channels; Acoplamiento de cinetica neutronica unidimensional a canales termohidraulicos en paralelo

Energy Technology Data Exchange (ETDEWEB)

Cecenas F, M.; Campos G, R.M. [IIE, Av. Reforma 113, Col. Palmira, Cuernavaca, Morelos (Mexico)]. e-mail: mcf@iie.org.mx

2003-07-01

In this work the dynamic behavior of a consistent system in fifteen channels in parallel that represent the reactor core of a BWR type, coupled of a kinetic neutronic model in one dimension is studied by means of time series. The arrangement of channels is obtained collapsing the assemblies that it consists the core to an arrangement of channels prepared in straight lines, and it is coupled to the unidimensional solution of the neutron diffusion equation. This solution represents the radial power distribution, and initially the static solution is obtained to verify that the one modeling core is critic. The coupled set nuclear-thermal hydraulics it is solved numerically by means of a net of CPUs working in the outline teacher-slave by means of Parallel Virtual Machine (PVM), subject to the restriction that the pressure drop is equal for each channel, which is executed iterating on the refrigerant distribution. The channels are dimensioned according to the one Stability Benchmark of the Ringhals swedish plant, organized by the Nuclear Energy Agency in 1994. From the information of this benchmark it is obtained the axial power profile for each channel, which is assumed as invariant in the time. To obtain the time series, the system gets excited with white noise (sequence that statistically obeys to a normal distribution with zero media), so that the power generated in each channel it possesses the same ones characteristics of a typical signal obtained by means of the acquisition of those signals of neutron flux in a BWR reactor. (Author)

[Occupational Hearing Loss (BK-No. 2301) - A Retrospective Analysis of 100 Consecutive Cases].

Science.gov (United States)

Reiter, R; Brosch, S

2016-10-01

Introduction: In order for a diagnosis of Occupational Hearing Loss (BK-no. 2301) to be made certain criteria must be fulfilled to establish that the hearing loss is occupational in origin. This work compares 2 groups, those who fulfil the criteria (BKE) and those who do not (BKNE). Methods: A 100 consecutive reports ("Lärmgutachten BK-no. 2301") written by the authors were examined retrospectively. These recorded audiometric examination, an analysis of any tinnitus and noise exposure plus use of hearing protection. Pre- and post-noise exposure status together with an expert assessment of work limitations was made to produce a 7 point score. Results: 67% of the group fulfilled the conditions for occupational hearing loss (9% were entitled to compensation). In the BKE group 82% showed typical audiometric signs of noise damage with 75% of them fulfilling at least 6 criteria of occupational disease no. 2301. Tinnitus typical for noise exposure was found in 26%. Discussion: A 7 point score could be useful in the future as a method of helping distinguish hearing loss and tinnitus from occupational as opposed to other causes. © Georg Thieme Verlag KG Stuttgart · New York.

Kinetics of a Migration－Driven Aggregation－Fragmentation Process

Institute of Scientific and Technical Information of China (English)

ZHUANGYou-Yi; LINZhen-Quan; KEJian-Hon~

2003-01-01

We propose a reversible model of the migration-driven aggregation-fragmentation process with the symmetric migration rate kernels K (k; j) = K′(k; j) =λkjv and the constant aggregation rates I1, I2 and fragmentation rates Jl, J2. Based on the mean-field theory, we investigate the evolution behavior of the aggregate size distributions in several cases with different values of index v. We find that the fragmentation reaction plays a more important role in the kinetic behaviors of the system than the aggregation and migration. When Jl = 0 and J2 = O, the aggregate size distributions αk(t) and bk(t) obey the conventional scaling law, while when Jl > 0 and J2 > O, they obey the modified scaling law with an exponential scaling function. The total mass of either species remains conserved.

Kinetics of a Migration-Driven Aggregation-Fragmentation Process

Institute of Scientific and Technical Information of China (English)

ZHUANG You-Yi; LIN Zhen-Quan; KE Jian-Hong

2003-01-01

We propose a reversible model of the migration-driven aggregation-fragmentation process with the sym-metric migration rate kernels K(k;j) = K'(k;j) = λkjv and the constant aggregation rates I1, I2 and fragmentationrates J1, J2. Based on the mean-field theory, we investigate the evolution behavior of the aggregate size distributions inseveral cases with different values of index v. We find that the fragmentation reaction plays a more important role in the kinetic behaviors of the system than the aggregation and migration. When J1 = 0 and J2 = 0, the aggregate sizedistributions ak(t) and bk(t) obey the conventional scaling law, while when J1 ＞ 0 and J2 ＞ 0, they obey the modifiedscaling law with an exponential scaling function. The total mass of either species remains conserved.

Electronic structure and spectral properties of heavy actinides Pu, Am, Cm and Bk

International Nuclear Information System (INIS)

Shick, Alexander B; Kolorenc, Jindrich; Lichtenstein, Alexander I; Havela, Ladislav

2010-01-01

Selected electronic properties of Pu, Am, Cm and Bk are calculated with the aid of charge self-consistent LDA + Hubbard I method. Presented all-electron calculations are performed in the full-potential LAPW basis and incorporate spin-orbit interaction. The results are found to be in good agreement with experimental valence photoelectron spectra as well as with core XAS/EELS spectra of heavy actinides.

PENGEMBANGAN INSTRUMEN ASESMEN KEBUTUHAN PERKEMBANGAN UNTUK PENYUSUNAN KURIKULUM DAN EVALUASI PROGRAM BK

Directory of Open Access Journals (Sweden)

Gendon Barus

2013-01-01

Full Text Available Penelitian pengembangan ini bertujuan menghasilkan instrumen asesmen kebutuhan peserta didik, disebut Invantori Kebutuhan Perkembangan Murid (IKPM. Penelitian mengikuti model Plomp (1999 dengan lima fase. Reliabilitas instrumen diestimasi dengan teknik Alpha Cronbach, validitas isi diperiksa oleh pakar dan telaah praktisi melalui FGD. Validitas empirik dan kecocokan model pengukuran dibuktikan dengan analisis faktor konfirmatori (CFA dengan program Lisrel 8.30. Telaah praktisi melibatkan 60 orang guru kelas V dan VI SD dalam dua tahap FGD, sedangkan uji coba empirik dan implementasi melibatkan murid kelas V dan VI. Hasil penelitian pengembang-an ini adalah: 1 IKPM dapat digunakan untuk menghimpun data kebutuhan perkembangan sebagai dasar penyusunan kurikulum bimbingan dan melaksanakan evaluasi program, bimbingan dan alat ukur evaluasi program bimbingan klasikal di sekolah dasar dan 2 teridentifikasi butir-butir kebutuhan per-kembangan murid yang intens dan sangat intens untuk dipenuhi melalui layanan bimbingan klasikal. Kata kunci: instrumen asesmen kebutuhan, kurikulum bimbingan, instrument evaluasi program BK ______________________________________________________________ DEVELOPMENT OF DEVELOPMENTAL NEEDS ASSESSMENT INSTRUMENT FOR CURRICULUM ARRANGEMENT AND EVALUATION OF BK PROGRAM Abstract The goal of this research is to produce a developmental needs assessment instrument, called Student’s Developmental Needs Inventory, which can be use to reveal the needs of students in elementary school. The research method follows the model of Research and Development (R & D by Plomp (1999 with five phases. The instrument which is developed in this study guidance and counseling (Bimbingan Konseling, BK in elementary school. Instrument reliability is estimated using by Alpha Cronbach technique, it content validity is checked by experts judgment and practitioner’s assessment with FGD technique. Furthermore, empirical validity and the goodness of fit

Experimental study of the reactions of limonene with OH and OD radicals: kinetics and products.

Science.gov (United States)

Braure, Tristan; Bedjanian, Yuri; Romanias, Manolis N; Morin, Julien; Riffault, Véronique; Tomas, Alexandre; Coddeville, Patrice

2014-10-09

The kinetics of the reactions of limonene with OH and OD radicals has been studied using a low-pressure flow tube reactor coupled with a quadrupole mass spectrometer: OH + C10H16 → products (1), OD + C10H16 → products (2). The rate constants of the title reactions were determined using four different approaches: either monitoring the kinetics of OH (OD) radicals or limonene consumption in excess of limonene or of the radicals, respectively (absolute method), and by the relative rate method using either the reaction OH (OD) + Br2 or OH (OD) + DMDS (dimethyl disulfide) as the reference one and following HOBr (DOBr) formation or DMDS and limonene consumption, respectively. As a result of the absolute and relative measurements, the overall rate coefficients, k1 = (3.0 ± 0.5) × 10(-11) exp((515 ± 50)/T) and k2 = (2.5 ± 0.6) × 10(-11) exp((575 ± 60)/T) cm(3) molecule(-1) s(-1), were determined at a pressure of 1 Torr of helium over the temperature ranges 220-360 and 233-353 K, respectively. k1 was found to be pressure independent over the range 0.5-5 Torr. There are two possible pathways for the reaction between OH (OD) and limonene: addition of the radical to one of the limonene double bonds (reactions 1a and 2a ) and abstraction of a hydrogen atom (reactions 1b and 2b ), resulting in the formation of H2O (HOD). Measurements of the HOD yield as a function of temperature led to the following branching ratio of the H atom abstraction channel: k2b/k2 = (0.07 ± 0.03) × exp((460 ± 140)/T) for T = (253-355) K.

Molecular and kinetic determinants of local anaesthetic action on sodium channels.

Science.gov (United States)

French, R J; Zamponi, G W; Sierralta, I E

1998-11-23

(1) Local anaesthetics (LA) rely for their clinical actions on state-dependent inhibition of voltage-dependent sodium channels. (2) Single, batrachoxin-modified sodium channels in planar lipid bilayers allow direct observation of drug-channel interactions. Two modes of inhibition of single-channel current are observed: fast block of the open channels and prolongation of a long-lived closed state, some of whose properties resemble those of the inactivated state of unmodified channels. (3) Analogues of different parts of the LA molecule separately mimic each blocking mode: amines--fast block, and water-soluble aromatics--closed state prolongation. (4) Interaction between a mu-conotoxin derivative and diethylammonium indicate an intrapore site of fast, open-state block. (5) Site-directed mutagenesis studies suggest that hydrophobic residues in transmembrane segment 6 of repeat domain 4 of sodium channels are critical for both LA binding and stabilization of the inactivated state.

Design of micro distribution systems consisting of long channels with arbitrary cross sections

International Nuclear Information System (INIS)

Misdanitis, S; Valougeorgis, D

2012-01-01

Gas flows through long micro-channels of various cross sections have been extensively investigated over the years both numerically and experimentally. In various technological applications including microfluidics, these micro-channels are combined together in order to form a micro-channel network. Computational algorithms for solving gas pipe networks in the hydrodynamic regime are well developed. However, corresponding tools for solving networks consisting of micro-channels under any degree of gas rarefaction is very limited. Recently a kinetic algorithm has been developed to simulate gas distribution systems consisting of long circular channels under any vacuum conditions. In the present work this algorithm is generalized and extended into micro-channels of arbitrary cross-section etched by KOH in silicon (triangular and trapezoidal channels with acute angle of 54.74°). Since a kinetic approach is implemented, the analysis is valid and the results are accurate in the whole range of the Knudsen number, while the involved computational effort is very small. This is achieved by successfully integrating the kinetic results for the corresponding single channels into the general solver for designing the gas pipe network. To demonstrate the feasibility of the approach two typical systems consisting of long rectangular and trapezoidal micro-channels are solved.

Deviation from the kinetic law of mass action for reactions induced by binary encounters in liquid solutions

International Nuclear Information System (INIS)

Doktorov, Alexander B; Kipriyanov, Alexey A

2007-01-01

In considering the irreversible chemical reaction A+B→ C+B in liquid solutions two many-particle approaches to the derivation of binary non-Markovian kinetic equations are compared: simple superposition decoupling and a method of extracting 'pair' channels from three-particle correlation evolution. It is shown that both methods provide an almost identical description of this reaction. However, in studies of reversible reactions in liquid solutions only the channel extraction method gives a correct physically clear description of the reaction though it consists of a sequence of steps: the development of integral encounter theory (IET), effective pairs approximation (EPA), modified encounter theory (MET), and the final regular form (RF) of kinetic equations. It is shown that the rate equations often encountered in the literature correspond to the independence of transient channels of 'scattering' in the bimolecular reversible reaction (A+B -B), while the independent transient channel of 'decay' in the reversible reactionA+B -C is defined solely by time integral convolution. In the general case transient channels in non-Markovian theory are not independent, and their interference manifests itself as a non-Markovian inhomogeneous source in binary non-Markovian kinetic equations in regular form. Based on the derived equations new universal kinetics (independent of models) of chemical equilibrium attainment have been obtained. It is shown that these kinetics can differ essentially from the kinetics corresponding to the kinetic law of mass action of formal chemical kinetics

Mechanism of voltage-gated channel formation in lipid membranes.

Science.gov (United States)

Guidelli, Rolando; Becucci, Lucia

2016-04-01

Although several molecular models for voltage-gated ion channels in lipid membranes have been proposed, a detailed mechanism accounting for the salient features of experimental data is lacking. A general treatment accounting for peptide dipole orientation in the electric field and their nucleation and growth kinetics with ion channel formation is provided. This is the first treatment that explains all the main features of the experimental current-voltage curves of peptides forming voltage-gated channels available in the literature. It predicts a regime of weakly voltage-dependent conductance, followed by one of strong voltage-dependent conductance at higher voltages. It also predicts values of the parameters expressing the exponential dependence of conductance upon voltage and peptide bulk concentration for both regimes, in good agreement with those reported in the literature. Most importantly, the only two adjustable parameters involved in the kinetics of nucleation and growth of ion channels can be varied over broad ranges without affecting the above predictions to a significant extent. Thus, the fitting of experimental current-voltage curves stems naturally from the treatment and depends only slightly upon the choice of the kinetic parameters. Copyright © 2015 Elsevier B.V. All rights reserved.

[Compared Markov with fractal models by using single-channel experimental and simulation data].

Science.gov (United States)

Lan, Tonghan; Wu, Hongxiu; Lin, Jiarui

2006-10-01

The gating mechanical kinetical of ion channels has been modeled as a Markov process. In these models it is assumed that the channel protein has a small number of discrete conformational states and kinetic rate constants connecting these states are constant, the transition rate constants among the states is independent both of time and of the previous channel activity. It is assumed in Liebovitch's fractal model that the channel exists in an infinite number of energy states, consequently, transitions from one conductance state to another would be governed by a continuum of rate constants. In this paper, a statistical comparison is presented of Markov and fractal models of ion channel gating, the analysis is based on single-channel data from ion channel voltage-dependence K+ single channel of neuron cell and simulation data from three-states Markov model.

Depletion of intracellular calcium stores facilitates the influx of extracellular calcium in platelet derived growth factor stimulated A172 glioblastoma cells.

Science.gov (United States)

Vereb, G; Szöllösi, J; Mátyus, L; Balázs, M; Hyun, W C; Feuerstein, B G

1996-05-01

Calcium signaling in non-excitable cells is the consequence of calcium release from intracellular stores, at times followed by entry of extracellular calcium through the plasma membrane. To study whether entry of calcium depends upon the level of saturation of intracellular stores, we measured calcium channel opening in the plasma membrane of single confluent A172 glioblastoma cells stimulated with platelet derived growth factor (PDGF) and/or bradykinin (BK). We monitored the entry of extracellular calcium by measuring manganese quenching of Indo-1 fluorescence. PDGF raised intracellular calcium concentration ([Ca2+]i) after a dose-dependent delay (tdel) and then opened calcium channels after a dose-independent delay (tch). At higher doses (> 3 nM), BK increased [Ca2+]i after a tdel approximately 0 s, and tch decreased inversely with both dose and peak [Ca2+]i. Experiments with thapsigargin (TG), BK, and PDGF indicated that BK and PDGF share intracellular Ca2+ pools that are sensitive to TG. When these stores were depleted by treatment with BK and intracellular BAPTA, tdel did not change, but tch fell to almost 0 s in PDGF stimulated cells, indicating that depletion of calcium stores affects calcium channel opening in the plasma membrane. Our data support the capacitative model for calcium channel opening and the steady-state model describing quantal Ca2+ release from intracellular stores.

Draft Genome Sequence of an Invasive Multidrug-Resistant Strain, Pseudomonas aeruginosa BK1, Isolated from a Keratitis Patient

KAUST Repository

Jeganathan, Lakshmi Priya; Prakash, Logambiga; Neelamegam, Sivakumar; Antony, Aju; Alqarawi, Sami; Prajna, Lalitha; Devarajan, Bharanidharan; Mohankumar, Vidyarani

2014-01-01

Pseudomonas aeruginosa infections are difficult to treat due to the presence of a multitude of virulence factors and antibiotic resistance. Here, we report the draft genome sequence of P. aeruginosa BK1, an invasive and multidrug-resistant strain

Parametric study of the stability properties of a thermo hydraulic channel coupled to punctual kinetics

International Nuclear Information System (INIS)

Cecenas F, M.; Campos G, R.M.

2005-01-01

The reason of decay is the indicator of stability usually used in the literature to evaluate stability of boiling water reactors, however, in the operation of this type of reactors is considered the length of boiling like an auxiliary parameter for the evaluation of stability. In this work its are studied the variation of these two indicators when modifying a given an operation parameter in a model of a thermo hydraulic channel coupled to punctual kinetics, maintaining all the other input constant variables. The parameters selected for study are the axial profile of power, the subcooling, the flow of coolant and the thermal power. The study is supplemented by means of real data of plant using the one Benchmark of Ringhals, and the results for the case of the ratio of decay its are compared with the decay reasons obtained by means of autoregression models of the local instrumentation of neutron flux. (Author)

Profil Siswa Agresif dan Peranan Guru BK

Directory of Open Access Journals (Sweden)

Hafiz Hidayat

2013-06-01

Full Text Available Abstract: Teens have a positive and negative behavior. Negative behavior is not characteristic of normal adolescent development, adolescents are developing will exhibit positive behavior. One of the teens indicated negative behavior is aggressive behavior. It can be seen in SMA N 5 Padang is quarrelsome, like teasing, hitting, pinching her, saying rude, insulting. This study aimed to describe the type of aggressive behavior of students and the role of BK teachers to address students' aggressive behavior SMAN 5 Padang. This study used a descriptive approach. The study population was a high school student Padang N 5 340 people with a total sample amounted to 77 people. Questionnaire data collection techniques to use. Data were analyzed using Microsoft Office Excel 2007. The findings showed that students' views of the aggressive actions hurt people physically with a percentage of 35.32%, while the aggressive actions of the student views of hurting people verbally 41.30% and aggression seen from damaging and destroying property by 30 percent, 42%. This means that the presence of aggressive behavior in SMA N 5 Padang.

Ca2+ and voltage dependence of cardiac ryanodine receptor channel block by sphingosylphosphorylcholine.

Science.gov (United States)

Yasukochi, Midori; Uehara, Akira; Kobayashi, Sei; Berlin, Joshua R

2003-03-01

The effect of sphingosylphosphorylcholine (SPC) on the cytoplasmic Ca(2+) and voltage dependence of channel gating by cardiac ryanodine receptors (RyR) was examined in lipid bilayer experiments. Micromolar concentrations of the lysosphingolipid SPC added to cis solutions rapidly and reversibly decreased the single-channel open probability (P(o)) of reconstituted RyR channels. The SPC-induced decrease in P(o) was marked by an increase in mean closed time and burst-like channel gating. Gating kinetics during intraburst periods were unchanged from those observed in the absence of the sphingolipid, although SPC induced a long-lived closed state that appeared to explain the observed decrease in channel P(o). SPC effects were observed over a broad range of cis [Ca(2+)] but were not competitive with Ca(2+). Interestingly, the sphingolipid-induced, long-lived closed state displayed voltage-dependent kinetics, even though other channel gating kinetics were not sensitive to voltage. Assuming SPC effects represent channel blockade, these results suggest that the blocking rate is independent of voltage whereas the unblocking rate is voltage dependent. Together, these results suggest that SPC binds directly to the cytoplasmic side of the RyR protein in a location in or near the membrane dielectric, but distinct from cytoplasmic Ca(2+) binding sites on the protein.

Vasoinhibins Prevent Bradykinin-Stimulated Endothelial Cell Proliferation by Inactivating eNOS via Reduction of both Intracellular Ca2+ Levels and eNOS Phosphorylation at Ser1179

Directory of Open Access Journals (Sweden)

Carmen Clapp

2011-07-01

Full Text Available Vasoinhibins, a family of antiangiogenic peptides derived from prolactin proteolysis, inhibit the vascular effects of several proangiogenic factors, including bradykinin (BK. Here, we report that vasoinhibins block the BK-induced proliferation of bovine umbilical vein endothelial cells. This effect is mediated by the inactivation of endothelial nitric oxide synthase (eNOS, as the NO donor DETA-NONOate reverted vasoinhibin action. It is an experimentally proven fact that the elevation of intracellular Ca2+ levels ([Ca2+]i upon BK stimulation activates eNOS, and vasoinhibins blocked the BK-mediated activation of phospholipase C and the formation of inositol 1,4,5-triphosphate leading to a reduced release of Ca2+ from intracellular stores. The [Ca2+]i rise evoked by BK also involves the influx of extracellular Ca2+ via canonical transient receptor potential (TRPC channels. Vasoinhibins likely interfere with TRPC-mediated Ca2+ entry since La3+, which is an enhancer of TRPC4 and TRPC5 channel activity, prevented vasoinhibins from blocking the stimulation by BK of endothelial cell NO production and proliferation, and vasoinhibins reduced the BK-induced increase of TRPC5 mRNA expression. Finally, vasoinhibins prevented the BK-induced phosphorylation of eNOS at Ser1179, a post-translational modification that facilitates Ca2+-calmodulin activation of eNOS. Together, our data show that vasoinhibins, by lowering NO production through the inhibition of both [Ca2+]i mobilization and eNOS phosphorylation, prevent the BK-induced stimulation of endothelial cell proliferation. Thus, vasoinhibins help to regulate BK effects on angiogenesis and vascular homeostasis.

Nanosecond pulsed electric fields depolarize transmembrane potential via voltage-gated K+, Ca2+ and TRPM8 channels in U87 glioblastoma cells.

Science.gov (United States)

Burke, Ryan C; Bardet, Sylvia M; Carr, Lynn; Romanenko, Sergii; Arnaud-Cormos, Delia; Leveque, Philippe; O'Connor, Rodney P

2017-10-01

Nanosecond pulsed electric fields (nsPEFs) have a variety of applications in the biomedical and biotechnology industries. Cancer treatment has been at the forefront of investigations thus far as nsPEFs permeabilize cellular and intracellular membranes leading to apoptosis and necrosis. nsPEFs may also influence ion channel gating and have the potential to modulate cell physiology without poration of the membrane. This phenomenon was explored using live cell imaging and a sensitive fluorescent probe of transmembrane voltage in the human glioblastoma cell line, U87 MG, known to express a number of voltage-gated ion channels. The specific ion channels involved in the nsPEF response were screened using a membrane potential imaging approach and a combination of pharmacological antagonists and ion substitutions. It was found that a single 10ns pulsed electric field of 34kV/cm depolarizes the transmembrane potential of cells by acting on specific voltage-sensitive ion channels; namely the voltage and Ca2 + gated BK potassium channel, L- and T-type calcium channels, and the TRPM8 transient receptor potential channel. Copyright © 2017 Elsevier B.V. All rights reserved.

Electrostatics at the membrane define MscL channel mechanosensitivity and kinetics.

Science.gov (United States)

Zhong, Dalian; Blount, Paul

2014-12-01

The bacterial mechanosensitive channel of large conductance (MscL) serves as a biological emergency release valve, preventing the occurrence of cell lysis caused by acute osmotic stress. Its tractable nature allows it to serve as a paradigm for how a protein can directly sense membrane tension. Although much is known of the importance of the hydrophobicity of specific residues in channel gating, it has remained unclear whether electrostatics at the membrane plays any role. We studied MscL chimeras derived from functionally distinct orthologues: Escherichia coli and Staphylococcus aureus. Dissection of one set led to an observation that changing the charge of a single residue, K101, of E. coli (Ec)-MscL, effects a channel phenotype: when mutated to a negative residue, the channel is less mechanosensitive and has longer open dwell times. Assuming electrostatic interactions, we determined whether they are due to protein-protein or protein-lipid interactions by performing site-directed mutagenesis elsewhere in the protein and reconstituting channels into defined lipids, with and without negative head groups. We found that although both interactions appear to play some role, the primary determinant of the channel phenotype seems to be protein-lipid electrostatics. The data suggest a model for the role of electrostatic interactions in the dynamics of MscL gating. © FASEB.

Course on Ionic Channels

CERN Document Server

1986-01-01

This book is based on a series of lectures for a course on ionic channels held in Santiago, Chile, on November 17-20, 1984. It is intended as a tutorial guide on the properties, function, modulation, and reconstitution of ionic channels, and it should be accessible to graduate students taking their first steps in this field. In the presentation there has been a deliberate emphasis on the spe­ cific methodologies used toward the understanding of the workings and function of channels. Thus, in the first section, we learn to "read" single­ channel records: how to interpret them in the theoretical frame of kinetic models, which information can be extracted from gating currents in re­ lation to the closing and opening processes, and how ion transport through an open channel can be explained in terms of fluctuating energy barriers. The importance of assessing unequivocally the origin and purity of mem­ brane preparations and the use of membrane vesicles and optical tech­ niques in the stUGY of ionic channels a...

[Synopsis about the hypothesis of "information channel" of channel-collateral system].

Science.gov (United States)

Chang, Xi-Lang

2008-10-01

The author of the present paper founded a theorem about the "incompleteness of single channel structure" (nerve, blood vessel, lymphatic, interspace, aperture, etc.) through quantitative and qualitative analysis about the economic information channel in the human body, which eliminates the probability of single channel structure in the information channel of channel (meridian)-collateral system. After comprehensive analysis on the current researches, the author puts forward a neodoxy, i.e., the body "information channel" structure of the channel-collateral system, mainly follows the distribution regularity of systemic statistics, and is not a single specific entity; various layers of the information channel in the main stems of the channel-collaterals are composed of optimized structure tissues. Hence, the structure of this information channel of channel-collateral system is an overall-optimized, sequential and compatible systemic structure. From this neodoxy, the author brings forward a working principle of channel-collaterals, which is supported theoretically by bio-auxology. The longitudinal distribution of the main stems of meridian-collaterals is considered to result from that in the process of the animal evolution, in the animals moving forward, the microscopic complicated movement of intracorporeal information and energy molecules is related to the forward macroscopic and non-uniform movement of organism in trans-measure. Its impulse and kinetic momentum forms a main vector in the longitudinal direction of the body (the direction of the main stem of channel-collaterals). In order to adapt to and utilize natural regularities, the main stems of the channel-collaterals gradually differentiate and evolve in the living organism, forming a whole system. The "hypothesis of biological origin of channel-collateral system" and "that of information channel of the channel-collaterals in the body" constitute a relatively complete theoretical system framework.

Conversion from tacrolimus-mycophenolate mofetil to tacrolimus-mTOR immunosuppression after kidney-pancreas transplantation reduces the incidence of both BK and CMV viremia.

Science.gov (United States)

Knight, Richard J; Graviss, Edward A; Nguyen, Duc T; Kuten, Samantha A; Patel, Samir J; Gaber, Lillian; Gaber, A Osama

2018-04-19

We sought to determine whether conversion from tacrolimus/mycophenolate mofetil (TAC-MMF) into tacrolimus/mTOR inhibitor (TAC-mTOR) immunosuppression would reduce the incidences of BK and CMV viremia after kidney/pancreas (KP) transplantation. In this single-center review, the TAC-mTOR cohort (n = 39) was converted at 1 month post-transplant to an mTOR inhibitor and reduced-dose tacrolimus. Outcomes were compared to a cohort of KP recipients (n = 40) maintained on TAC-MMF. At 3 years post-transplant, KP survivals and incidences of kidney/pancreas rejection were equivalent between mTOR and MMF-treated cohorts. (P = ns). BK viremia-free survival was better for the mTOR vs MMF-treated group (P = .004). In multivariate analysis, MMF vs mTOR immunosuppression was an independent risk factor for BK viremia (hazard ratio 12.27, P = .02). Similarly, mTOR-treated recipients displayed better CMV infection-free survival compared to the MMF-treated cohort (P = .01). MMF vs mTOR immunosuppression (hazard ratio 18.77, P = .001) and older recipient age (hazard ratio 1.13 per year, P = .006) were independent risk factors for CMV viremia. Mean estimated GFR and HgbA1c levels were equivalent between groups at 1, 2, and 3 years post-transplantation. Conversion from TAC/MMF into TAC/mTOR immunosuppression after KP transplantation reduced the incidences of BK and CMV viremia with an equivalent risk of acute rejection and similar renal/pancreas function. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Perilaku Bullying dan Peranan Guru BK/Konselor dalam Pengentasannya (Studi Deskriptif terhadap Siswa SMP Negeri 3 Lubuk Basung

Directory of Open Access Journals (Sweden)

Ilfajri Yenes

2016-06-01

Full Text Available Bullying merupakan suatu situasi di mana terjadinya penyalahgunaan kekuatan/kekuasaan yang dilakukan oleh seseorang/kelompok. Perilaku bullying merupakan  salah satu bentuk kekerasan dan agresif siswa di sekolah. Penelitian ini adalah penelitian deskriptif yang bertujuan untuk mendeskripsikan perilaku bullying yang ditampilkan siswa SMPN 3 Lubuk Basung dan peranan guru BK/konselor dalam pengentasannya. Populasi penelitian adalah siswa di SMP Negeri 3 Lubuk Basung berjumlah  564 orang dengan sampel 138 orang diambil dengan menggunakan teknik propotonal stratified random. Teknik pengumpulan data dengan menggunakan angket. Temuan penelitian menunjukkan bahwa jenis perilaku bullying yang dominan terjadi yaitu menyakiti secara verbal dilanjutkan dengan menyakiti secara fisik kemudian menyakiti secara mental dengan faktor keluarga. Faktor teman sebaya merupakan faktor yang lebih dominan sebagai penyebab perilaku bullying siswa. Secara umum guru BK/konselor cukup berperan mengatasi perilaku bullyingdengan memberikan  layanan informasi sebagai layanan yang lebih dominan diberikan dilanjutkan dengan layanan bimbingan kelompok dan konseling kelompok serta pemberian layanan konseling individual.

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

Science.gov (United States)

Chowdhury, Sandipan

2013-01-01

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

Functional modifications of acid-sensing ion channels by ligand-gated chloride channels.

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Xuanmao Chen

Full Text Available Together, acid-sensing ion channels (ASICs and epithelial sodium channels (ENaC constitute the majority of voltage-independent sodium channels in mammals. ENaC is regulated by a chloride channel, the cystic fibrosis transmembrane conductance regulator (CFTR. Here we show that ASICs were reversibly inhibited by activation of GABA(A receptors in murine hippocampal neurons. This inhibition of ASICs required opening of the chloride channels but occurred with both outward and inward GABA(A receptor-mediated currents. Moreover, activation of the GABA(A receptors modified the pharmacological features and kinetic properties of the ASIC currents, including the time course of activation, desensitization and deactivation. Modification of ASICs by open GABA(A receptors was also observed in both nucleated patches and outside-out patches excised from hippocampal neurons. Interestingly, ASICs and GABA(A receptors interacted to regulate synaptic plasticity in CA1 hippocampal slices. The activation of glycine receptors, which are similar to GABA(A receptors, also modified ASICs in spinal neurons. We conclude that GABA(A receptors and glycine receptors modify ASICs in neurons through mechanisms that require the opening of chloride channels.

Role of KCNMA1 gene in breast cancer invasion and metastasis to brain

International Nuclear Information System (INIS)

Khaitan, Divya; Sankpal, Umesh T; Weksler, Babette; Meister, Edward A; Romero, Ignacio A; Couraud, Pierre-Olivier; Ningaraj, Nagendra S

2009-01-01

The prognosis for patients with breast tumor metastases to brain is extremely poor. Identification of prognostic molecular markers of the metastatic process is critical for designing therapeutic modalities for reducing the occurrence of metastasis. Although ubiquitously present in most human organs, large-conductance calcium- and voltage-activated potassium channel (BK Ca ) channels are significantly upregulated in breast cancer cells. In this study we investigated the role of KCNMA1 gene that encodes for the pore-forming α-subunit of BK Ca channels in breast cancer metastasis and invasion. We performed Global exon array to study the expression of KCNMA1 in metastatic breast cancer to brain, compared its expression in primary breast cancer and breast cancers metastatic to other organs, and validated the findings by RT-PCR. Immunohistochemistry was performed to study the expression and localization of BK Ca channel protein in primary and metastatic breast cancer tissues and breast cancer cell lines. We performed matrigel invasion, transendothelial migration and membrane potential assays in established lines of normal breast cells (MCF-10A), non-metastatic breast cancer (MCF-7), non-brain metastatic breast cancer cells (MDA-MB-231), and brain-specific metastatic breast cancer cells (MDA-MB-361) to study whether BK Ca channel inhibition attenuates breast tumor invasion and metastasis using KCNMA1 knockdown with siRNA and biochemical inhibition with Iberiotoxin (IBTX). The Global exon array and RT-PCR showed higher KCNMA1 expression in metastatic breast cancer in brain compared to metastatic breast cancers in other organs. Our results clearly show that metastatic breast cancer cells exhibit increased BK Ca channel activity, leading to greater invasiveness and transendothelial migration, both of which could be attenuated by blocking KCNMA1. Determining the relative abundance of BK Ca channel expression in breast cancer metastatic to brain and the mechanism of its

Draft Genome Sequence of an Invasive Multidrug-Resistant Strain, Pseudomonas aeruginosa BK1, Isolated from a Keratitis Patient

KAUST Repository

Jeganathan, Lakshmi Priya

2014-03-27

Pseudomonas aeruginosa infections are difficult to treat due to the presence of a multitude of virulence factors and antibiotic resistance. Here, we report the draft genome sequence of P. aeruginosa BK1, an invasive and multidrug-resistant strain, isolated from a bacterial keratitis patient in southern India.

Reconstruction of Cell Surface Densities of Ion Pumps, Exchangers, and Channels from mRNA Expression, Conductance Kinetics, Whole-Cell Calcium, and Current-Clamp Voltage Recordings, with an Application to Human Uterine Smooth Muscle Cells.

Directory of Open Access Journals (Sweden)

Jolene Atia

2016-04-01

Full Text Available Uterine smooth muscle cells remain quiescent throughout most of gestation, only generating spontaneous action potentials immediately prior to, and during, labor. This study presents a method that combines transcriptomics with biophysical recordings to characterise the conductance repertoire of these cells, the 'conductance repertoire' being the total complement of ion channels and transporters expressed by an electrically active cell. Transcriptomic analysis provides a set of potential electrogenic entities, of which the conductance repertoire is a subset. Each entity within the conductance repertoire was modeled independently and its gating parameter values were fixed using the available biophysical data. The only remaining free parameters were the surface densities for each entity. We characterise the space of combinations of surface densities (density vectors consistent with experimentally observed membrane potential and calcium waveforms. This yields insights on the functional redundancy of the system as well as its behavioral versatility. Our approach couples high-throughput transcriptomic data with physiological behaviors in health and disease, and provides a formal method to link genotype to phenotype in excitable systems. We accurately predict current densities and chart functional redundancy. For example, we find that to evoke the observed voltage waveform, the BK channel is functionally redundant whereas hERG is essential. Furthermore, our analysis suggests that activation of calcium-activated chloride conductances by intracellular calcium release is the key factor underlying spontaneous depolarisations.

Abnormal differentiation, hyperplasia and embryonic/perinatal lethality in BK5-T/t transgenic mice

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Chen, Xin; Schneider-Broussard, Robin; Hollowell, Debra; McArthur, Mark; Jeter, Collene R.; Benavides, Fernando; DiGiovanni, John; Tang, Dean G.

2009-01-01

The cell-of-origin has a great impact on the types of tumors that develop and the stem/progenitor cells have long been considered main targets of malignant transformation. The SV40 large T and small t antigens (T/t), have been targeted to multiple differentiated cellular compartments in transgenic mice. In most of these studies, transgenic animals develop tumors without apparent defects in animal development. In this study, we used the bovine keratin 5 (BK5) promoter to target the T/t antigens to stem/progenitor cell-containing cytokeratin 5 (CK5) cellular compartment. A transgene construct, BK5-T/t, was made and microinjected into the male pronucleus of FVB/N mouse oocytes. After implanting ∼1700 embryos, only 7 transgenics were obtained, including 4 embryos (E9.5, E13, E15, and E20) and 3 postnatal animals, which died at P1, P2, and P18, respectively. Immunohistological analysis revealed aberrant differentiation and prominent hyperplasia in several transgenic CK5 tissues, especially the upper digestive organs (tongue, oral mucosa, esophagus, and forestomach) and epidermis, the latter of which also showed focal dysplasia. Altogether, these results indicate that constitutive expression of the T/t antigens in CK5 cellular compartment results in abnormal epithelial differentiation and leads to embryonic/perinatal animal lethality. PMID:19272531

Experimental Investigation on Cutting Characteristics in Nanometric Plunge-Cutting of BK7 and Fused Silica Glasses.

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An, Qinglong; Ming, Weiwei; Chen, Ming

2015-03-27

Ductile cutting are most widely used in fabricating high-quality optical glass components to achieve crack-free surfaces. For ultra-precision machining of brittle glass materials, critical undeformed chip thickness (CUCT) commonly plays a pivotal role in determining the transition point from ductile cutting to brittle cutting. In this research, cutting characteristics in nanometric cutting of BK7 and fused silica glasses, including machined surface morphology, surface roughness, cutting force and specific cutting energy, were investigated with nanometric plunge-cutting experiments. The same cutting speed of 300 mm/min was used in the experiments with single-crystal diamond tool. CUCT was determined according to the mentioned cutting characteristics. The results revealed that 320 nm was found as the CUCT in BK7 cutting and 50 nm was determined as the size effect of undeformed chip thickness. A high-quality machined surface could be obtained with the undeformed chip thickness between 50 and 320 nm at ductile cutting stage. Moreover, no CUCT was identified in fused silica cutting with the current cutting conditions, and brittle-fracture mechanism was confirmed as the predominant chip-separation mode throughout the nanometric cutting operation.

A combination of genistein and magnesium enhances the vasodilatory effect via an eNOS pathway and BK(Ca) current amplification.

Science.gov (United States)

Sun, Lina; Hou, Yunlong; Zhao, Tingting; Zhou, Shanshan; Wang, Xiaoran; Zhang, Liming; Yu, Guichun

2015-04-01

The phytoestrogen genistein (GST) and magnesium have been independently shown to regulate vascular tone; however, their individual vasodilatory effects are limited. The aim of this study was to examine the combined effects of GST plus magnesium on vascular tone in mesenteric arteries. The effects of pretreatment with GST (0-200 μmol/L), MgCl2 (0-4.8 mmol/L) and GST plus MgCl2 on 10 μmol/L phenylephrine (PE) precontracted mesenteric arteries in rats were assessed by measuring isometric force. BK(Ca) currents were detected by the patch clamp method. GST caused concentration- and partial endothelium-dependent relaxation. Magnesium resulted in dual adjustment of vascular tone. Magnesium-free solution eliminated the vasodilatation of GST in both endothelium-intact and denuded rings. GST (50 μmol/L) plus magnesium (4.8 mmol/L) caused stronger relaxation in both endothelium-intact and denuded rings. Pretreatment with the nitric oxide synthase (NOS) inhibitor L-N-nitroarginine methyl ester (L-NAME, 100 μmol/L) significantly inhibited the effects of GST, high magnesium, and the combination of GST and magnesium. BK(Ca) currents were amplified to a greater extent when GST (50 μmol/L) was combined with 4.8 versus 1.2 mmol/L Mg(2+). Our data suggest that GST plus magnesium provides enhanced vasodilatory effects in rat mesenteric arteries compared with that observed when either is used separately, which was related to an eNOS pathway and BK(Ca) current amplification.

Photodissociation dynamics of propene at 157.6 nm: Kinetic energy distributions and branching ratios

International Nuclear Information System (INIS)

Lee, S.-H.; Lee, Y.-Y.; Lee, Yuan T.; Yang Xueming

2003-01-01

Photodissociation dynamics of propene at 157.6 nm has been investigated in a molecular beam apparatus using the photofragment translational spectroscopic technique combined with the vacuum ultraviolet ionization method. Eleven photofragments have been successfully detected and ascribed to eight (five binary and three triple) dissociation channels: namely, C 3 H 5 +H, C 3 H 4 +H+H, C 3 H 4 +H 2 , C 3 H 3 +H 2 +H, C 2 H 4 +CH 2 , C 2 H 3 +CH 3 , C 2 H 2 +CH 4 , and C 2 H 2 +CH 3 +H. Their branching ratios have been determined to be 1%, 7%, 2 H 2 +CH 3 +H channel. In addition, the averaged kinetic energy releases and the fractions in translational energy have also been determined from the measured kinetic energy distributions. For the binary dissociation channels, the fractions in translational energy are less than 18% except the C 3 H 5 +H channel, whereas they are more than 42% for the triple dissociation channels. An intriguing finding indicates that the C 2 H 4 +CH 2 channel has a nearly identical kinetic energy distribution and a similar branching ratio to the C 2 H 3 +CH 3 channel, although the former undergoes a three-center elimination process different from the C-C bond rupture occurring in the latter

Increase in cortical pyramidal cell excitability accompanies depression-like behavior in mice: a transcranial magnetic stimulation study.

Science.gov (United States)

Sun, Peng; Wang, Furong; Wang, Li; Zhang, Yu; Yamamoto, Ryo; Sugai, Tokio; Zhang, Qing; Wang, Zhengda; Kato, Nobuo

2011-11-09

Clinical evidence suggests that cortical excitability is increased in depressives. We investigated its cellular basis in a mouse model of depression. In a modified version of forced swimming (FS), mice were initially forced to swim for 5 consecutive days and then were treated daily with repetitive transcranial magnetic stimulation (rTMS) or sham treatment for the following 4 weeks without swimming. On day 2 through day 5, the mice manifested depression-like behaviors. The next and last FS was performed 4 weeks later, which revealed a 4 week maintenance of depression-like behavior in the sham mice. In slices from the sham controls, excitability in cingulate cortex pyramidal cells was elevated in terms of membrane potential and frequencies of spikes evoked by current injection. Depolarized resting potential was shown to depend on suppression of large conductance calcium-activated potassium (BK) channels. This BK channel suppression was confirmed by measuring spike width, which depends on BK channels. Chronic rTMS treatment during the 4 week period significantly reduced the depression-like behavior. In slices obtained from the rTMS mice, normal excitability and BK channel activity were recovered. Expression of a scaffold protein Homer1a was reduced by the FS and reversed by rTMS in the cingulate cortex. Similar recovery in the same behavioral, electrophysiological, and biochemical features was observed after chronic imipramine treatment. The present study demonstrated that manifestation and disappearance of depression-like behavior are in parallel with increase and decrease in cortical neuronal excitability in mice and suggested that regulation of BK channels by Homer1a is involved in this parallelism.

Axial channeling of uttrarelativistic electrons

Energy Technology Data Exchange (ETDEWEB)

Telegin, V.I.; Khokonov, M.Kh. (Moskovskij Gosudarstvennyj Univ. (USSR). Nauchno-Issledovatel' skij Inst. Yadernoj Fiziki)

1982-07-01

The dynamics of motion of ultrarelativistic electrons under axial channeling conditions is investigated. The analysis is based on the solution of the kinetic equation obtained recently by Beloshitsky and Kumakhov. The particle dechanneling function is investigated as depending on the type of a crystal, particle energy and angle of entrance into the single crystal. It is found that for most of the beam the major diffusion mechanism is scattering by electrons. It is shown that an optimal depth range exists for which the fraction of channeled particles sharply increases at the expense of the quasi-channeled particles. In a number of cases the dechanneling length for crystals with high atomic numbers may be greater than that of light elements.

Axial channeling of uttrarelativistic electrons

International Nuclear Information System (INIS)

Telegin, V.I.; Khokonov, M.Kh.

1982-01-01

The dynamics of motion of ultrarelativistic electrons under axial channeling conditions is investigated. The analysis is based on the solution of the kinetic equation obtained recently by Beloshitsky and Kumakhov. The particle dechanneling function is investigated as depending on the type of a crystal, particle energy and angle of entrance into the single crystal. It is found that for most of the beam the major diffusion mechanism is scattering by electrons. It is shown that an optimal depth range exists for which the fraction of channeled particles sharply increases at the expense of the quasi-channeled particles. In a number of cases the dechanneling length for crystals with high atomic numbers may be greater than that of light elements

Coupled Model of channels in parallel and neutron kinetics in two dimensions

International Nuclear Information System (INIS)

Cecenas F, M.; Campos G, R.M.; Valle G, E. del

2004-01-01

In this work an arrangement of thermohydraulic channels is presented that represent those four quadrants of a nucleus of reactor type BWR. The channels are coupled to a model of neutronic in two dimensions that allow to generate the radial profile of power of the reactor. Nevertheless that the neutronic pattern is of two dimensions, it is supplemented with axial additional information when considering the axial profiles of power for each thermo hydraulic channel. The stationary state is obtained the one it imposes as frontier condition the same pressure drop for all the channels. This condition is satisfied to iterating on the flow of coolant in each channel to equal the pressure drop in all the channels. This stationary state is perturbed later on when modifying the values for the effective sections corresponding to an it assembles. The calculation in parallel of the neutronic and the thermo hydraulic is carried out with Vpm (Virtual parallel machine) by means of an outline teacher-slave in a local net of computers. (Author)

Spectroscopy and reaction kinetics of HCO

International Nuclear Information System (INIS)

Guo, Yili.

1989-01-01

The high-resolution infrared spectrum of the C-H stretching fundamental of HCO has been studied by means of infrared flash kinetic spectroscopy. HCO was generated by flash photolysis of acetaldehyde or formaldehyde using a 308 nm (XeCl) excimer laser. The transient absorption was probed with an infrared difference frequency laser system. The high resolution spectra obtained were assigned and fitted with rotational, spin-rotational, and centrifugal distortion constants. The ν 1 band origin is 2434.48 cm/sup /minus/1/. New ground state constants have been derived from a least-squares fit combining the ν 1 data with previous microwave and FIR LMR measurements. A new set of spectroscopic constants for the (1, 0, 0) state, the equilibrium rotational constants, and the orientation of the transition dipole moment are also reported. The kinetics and product branching ratios of the HCO + NO 2 reaction have been studied using visible and infrared laser flash kinetic spectroscopy. The rate constant for the disappearance of HCO radical at 296 K is (5.7 +- 0.9) /times/ 10/sup /minus/11/ cm 3 molec/sup /minus/1/ sec/sup /minus/1/, and it is independent of the pressure of SF 6 buffer gas up to 700 torr. Less than 10% of the reaction goes through the most exothermic product channel, HNO + CO 2 . The product channel, H + CO 2 + NO, is responsible for 52% of the reaction. HONO has been observed, though not quantitatively, as a reaction product corresponding to the HONO + CO channel. 51 refs., 21 figs., 8 tabs

Electron angular distribution axial channeling

International Nuclear Information System (INIS)

Khokonov, A.Kh.; Khokonov, M.Kh.

1989-01-01

Angular distributions of ultra-relativistic electrons are calculated in the assumption about presence of statistical equilibrium. Analysis is based on numerical solution of Fokker-Planck type kinetic equation. It is shown that in contrast to case of amorphous medium, the multiple scattering at axial channeling of negative particles results in self-focusing of the initial beam particles and due to it number of electrons moving at an angles to the chain, which are smaller, than critical angle of channeling, may increase by several times as compared to the initial one

Polyomavirus BK replication in renal transplant recipients: combined monitoring of viremia and VP1 mRNA in urine

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Sara Astegiano

2010-06-01

Full Text Available Introduction. Human polyomavirus BK (BKV is worldwide distributed, with a seroprevalence rate of 70–90% in the adults. Following primary infection, BK remains latent in the renourinary tract as the epidemiologically most relevant latency site, and in B cell, brain, spleen and probably other tissues. Reactivation may occur in both immunocompetent subjects and immunocompromised patients. In renal transplantation, in the context of intense immunosuppression, viral replication may determine BKV-associated nephropathy (BKVAN with interstitial nephritis and/or ureteral stenosis in 1–10% of the patients and leading to graft failure and return to haemodialysis in 30 to 80% of the cases (5. Screening of BKV replication represents the basic strategy to predict early the onset of BKVAN and may allow for earlier intervention with reduced allograft loss (3, 4. Nowadays, replication of BKV is monitored by quantification of BKV-DNA in serum and urine (2. The aim of this study was to evaluated the role of BKV VP1 mRNA in urine as a marker of viral replication in renal transplant recipients.

CONTRIBUTIONS OF INTRACELLULAR IONS TO Kv CHANNEL VOLTAGE SENSOR DYNAMICS.

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Samuel eGoodchild

2012-06-01

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

The polyomavirus BK agnoprotein co-localizes with lipid droplets

International Nuclear Information System (INIS)

Unterstab, Gunhild; Gosert, Rainer; Leuenberger, David; Lorentz, Pascal; Rinaldo, Christine H.; Hirsch, Hans H.

2010-01-01

Agnoprotein encoded by human polyomavirus BK (BKV) is a late cytoplasmic protein of 66 amino acids (aa) of unknown function. Immunofluorescence microscopy revealed a fine granular and a vesicular distribution in donut-like structures. Using BKV(Dunlop)-infected or agnoprotein-transfected cells, we investigated agnoprotein co-localization with subcellular structures. We found that agnoprotein co-localizes with lipid droplets (LD) in primary human renal tubular epithelial cells as well as in other cells supporting BKV replication in vitro (UTA, Vero cells). Using agnoprotein-enhanced green fluorescent protein (EGFP) fusion constructs, we demonstrate that agnoprotein aa 20-42 are required for targeting LD, whereas aa 1-20 or aa 42-66 were not. Agnoprotein aa 22-40 are predicted to form an amphipathic helix, and mutations A25D and F39E, disrupting its hydrophobic domain, prevented LD targeting. However, changing the phosphorylation site serine-11 to alanine or aspartic acid did not alter LD co-localization. Our findings provide new clues to unravel agnoprotein function.

Evaluation of stochastic differential equation approximation of ion channel gating models.

Science.gov (United States)

Bruce, Ian C

2009-04-01

Fox and Lu derived an algorithm based on stochastic differential equations for approximating the kinetics of ion channel gating that is simpler and faster than "exact" algorithms for simulating Markov process models of channel gating. However, the approximation may not be sufficiently accurate to predict statistics of action potential generation in some cases. The objective of this study was to develop a framework for analyzing the inaccuracies and determining their origin. Simulations of a patch of membrane with voltage-gated sodium and potassium channels were performed using an exact algorithm for the kinetics of channel gating and the approximate algorithm of Fox & Lu. The Fox & Lu algorithm assumes that channel gating particle dynamics have a stochastic term that is uncorrelated, zero-mean Gaussian noise, whereas the results of this study demonstrate that in many cases the stochastic term in the Fox & Lu algorithm should be correlated and non-Gaussian noise with a non-zero mean. The results indicate that: (i) the source of the inaccuracy is that the Fox & Lu algorithm does not adequately describe the combined behavior of the multiple activation particles in each sodium and potassium channel, and (ii) the accuracy does not improve with increasing numbers of channels.

The Activation Effect of Hainantoxin-I, a Peptide Toxin from the Chinese Spider, Ornithoctonus hainana, on Intermediate-Conductance Ca2+-Activated K+ Channels

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Pengfei Huang

2014-08-01

Full Text Available Intermediate-conductance Ca2+-activated K+ (IK channels are calcium/calmodulin-regulated voltage-independent K+ channels. Activation of IK currents is important in vessel and respiratory tissues, rendering the channels potential drug targets. A variety of small organic molecules have been synthesized and found to be potent activators of IK channels. However, the poor selectivity of these molecules limits their therapeutic value. Venom-derived peptides usually block their targets with high specificity. Therefore, we searched for novel peptide activators of IK channels by testing a series of toxins from spiders. Using electrophysiological experiments, we identified hainantoxin-I (HNTX-I as an IK-channel activator. HNTX-I has little effect on voltage-gated Na+ and Ca2+ channels from rat dorsal root ganglion neurons and on the heterologous expression of voltage-gated rapidly activating delayed rectifier K+ channels (human ether-à-go-go-related gene; human ERG in HEK293T cells. Only 35.2% ± 0.4% of the currents were activated in SK channels, and there was no effect on BK channels. We demonstrated that HNTX-I was not a phrenic nerve conduction blocker or acutely toxic. This is believed to be the first report of a peptide activator effect on IK channels. Our study suggests that the activity and selectivity of HNTX-I on IK channels make HNTX-I a promising template for designing new drugs for cardiovascular diseases.

(-)-Epicatechin-induced relaxation of isolated human saphenous vein: Roles of K+ and Ca2+ channels.

Science.gov (United States)

Marinko, Marija; Jankovic, Goran; Nenezic, Dragoslav; Milojevic, Predrag; Stojanovic, Ivan; Kanjuh, Vladimir; Novakovic, Aleksandra

2018-02-01

In this study, we aimed to investigate relaxant effect of flavanol (-)-epicatechin on the isolated human saphenous vein (HSV), as a part of its cardioprotective action, and to define the mechanisms underlying this vasorelaxation. (-)-Epicatechin induced a concentration-dependent relaxation of HSV pre-contracted by phenylephrine. Among K + channel blockers, 4-aminopyridine, margatoxin, and iberiotoxin significantly inhibited relaxation of HSV, while glibenclamide considerably reduced effects of the high concentrations of (-)-epicatechin. Additionally, (-)-epicatechin relaxed contraction induced by 80 mM K + , whereas in the presence of nifedipine produced partial relaxation of HSV rings pre-contracted by phenylephrine. In Ca 2+ -free solution, (-)-epicatechin relaxed contraction induced by phenylephrine, but had no effect on contraction induced by caffeine. A sarcoplasmic reticulum Ca 2+ -ATPase inhibitor, thapsigargin, significantly reduced relaxation of HSV produced by (-)-epicatechin. These results demonstrate that (-)-epicatechin produces endothelium-independent relaxation of isolated HSV rings. Vasorelaxation to (-)-epicatechin probably involves activation of 4-aminopyridine- and margatoxin-sensitive K V channels, BK Ca channels, and at least partly, K ATP channels. In addition, not only the inhibition of extracellular Ca 2+ influx, but regulation of the intracellular Ca 2+ release, via inositol-trisphosphate receptors and reuptake into sarcoplasmic reticulum, via stimulation of Ca 2+ -ATPase, as well, most likely participate in (-)-epicatechin-induced relaxation of HSV. Copyright © 2017 John Wiley & Sons, Ltd.

Voltage-Dependent Gating of hERG Potassium Channels

Science.gov (United States)

Cheng, Yen May; Claydon, Tom W.

2012-01-01

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

Voltage-dependent gating of hERG potassium channels

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Yen May eCheng

2012-05-01

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

Effects of potassium channel opener on the kinetics of thallium-201 in in-vitro and in-vivo

International Nuclear Information System (INIS)

Lee, J.; Kim, E. J.; Ahn, B. C.; Chae, S. C.; Lee, K. B.; Kim, C. K.

1997-01-01

Potassium channel opener (K-opener) opens membrane ATP-sensitive K + -channel and induces and increase in potassium efflux from cells. K-openers are powerful smooth muscle relaxants and currently used as antihypertensive, antianginal drugs or bronchodilators in clinic. Pharmacologic potency of newly synthesized K-opener is being evaluated with efflux capacity of preincubated Rb-83 from the isolated aortic vascular tissue preparation. Thallium has similar characteristics to those of rubidium and potassium in vivo. To evaluate the effect of pinacidil (a potent K-opener) on Tl-201 biokinetics, we have performed uptake/washout studies in cultured myocytes, and mice biodistribution study. Primary culture of spontaneous contracting myocytes was undertake from hearts of newborn Sprague-Dawley rat. Different concentration of pinacidil (100nM or 10uM) was co-incubated with Tl-201 in HBSS buffer to evaluate its effect on cellular uptake, or challenged to myocyte preparations pre-incubated with Tl-201 for washout study. Pinacidil was injected into mice simultaneous or 10-min after Tl-201 injection, and organ uptake and whole body retention ratio was measured using gamma counter or dose calibrator. Co-incubation of pinacidil with Tl-201 resulted in a decrease in Tl uptake into myocytes by 1.6 - 2.5 times, and an increase in washout by 1.6 - 3.1 times. Pinacidil injection resulted in mild decrease in blood, heart and liver uptake in mice, bur renal uptake was markedly decreased in a dose dependent manner. These results suggest that the pinacidil Tl-201 kinetics and may potentially affect the interpretation of Tl-201 myocardial imaging

Kinetic Study on Channelling of Protons in Metallic Carbon Nanotubes

International Nuclear Information System (INIS)

Dan, Zhao; Yuan-Hong, Song; You-Nian, Wang

2008-01-01

Based on the kinetic model and the dielectric response theory, a theoretical model is put forward to describe the transport of protons along nanotube axes. With the introduction of electron band structure for different nanotubes like zigzag and armchair nanotubes of metallic properties, the collective excitation of electrons on the cylinders induced by the incident ions is studied, showing several distinct peaks in the curves of the energy loss function. Furthermore, the stopping power and the self-energy are calculated as functions of ion velocities, especially taking into account the influence of damping coefficients. It is conceivable from the results that, in the kinetic formulation, plasmon excitation plays a major role in the stopping. And as the damping increases, the peaks of the stopping power shift to the lower velocities, with the broadening of the plasmon resonance. (condensed matter: structure, mechanical and thermal properties)

Potassium and ANO1/TMEM16A chloride channel profiles distinguish atypical and typical smooth muscle cells from interstitial cells in the mouse renal pelvis

Science.gov (United States)

Iqbal, Javed; Tonta, Mary A; Mitsui, Retsu; Li, Qun; Kett, Michelle; Li, Jinhua; Parkington, Helena C; Hashitani, Hikaru; Lang, Richard J

2012-01-01

BACKGROUND AND PURPOSE Although atypical smooth muscle cells (SMCs) in the proximal renal pelvis are thought to generate the pacemaker signals that drive pyeloureteric peristalsis, their location and electrical properties remain obscure. EXPERIMENTAL APPROACH Standard patch clamp, intracellular microelectrode and immunohistochemistry techniques were used. To unequivocally identify SMCs, transgenic mice with enhanced yellow fluorescent protein (eYFP) expressed in cells containing α-smooth muscle actin (α-SMA) were sometimes used. KEY RESULTS Atypical SMCs were distinguished from typical SMCs by the absence of both a transient 4-aminopyridine-sensitive K+ current (IKA) and spontaneous transient outward currents (STOCs) upon the opening of large-conductance Ca2+-activated K+ (BK) channels. Many typical SMCs displayed a slowly activating, slowly decaying Cl- current blocked by niflumic acid (NFA). Immunostaining for KV4.3 and ANO1/ TMEM16A Cl- channel subunits co-localized with α-SMA immunoreactive product predominately in the distal renal pelvis. Atypical SMCs fired spontaneous inward currents that were either selective for Cl- and blocked by NFA, or cation-selective and blocked by La3+. α-SMA- interstitial cells (ICs) were distinguished by the presence of a Xe991-sensitive KV7 current, BK channel STOCs and Cl- selective, NFA-sensitive spontaneous transient inward currents (STICs). Intense ANO1/ TMEM16A and KV7.5 immunostaining was present in Kit-α-SMA- ICs in the suburothelial and adventitial regions of the renal pelvis. CONCLUSIONS AND IMPLICATIONS We conclude that KV4.3+α-SMA+ SMCs are typical SMCs that facilitate muscle wall contraction, that ANO1/ TMEM16A and KV7.5 immunoreactivity may be selective markers of Kit- ICs and that atypical SMCs which discharge spontaneous inward currents are the pelviureteric pacemakers. PMID:22014103

BK polyomavirus genotypes Ia and Ib1 exhibit different biological properties in renal transplant recipients.

Science.gov (United States)

Varella, Rafael B; Zalona, Ana Carolina J; Diaz, Nuria C; Zalis, Mariano G; Santoro-Lopes, Guilherme

2018-01-02

BK polyomavirus (BKV) is an opportunist agent associated with nephropathy (BKVAN) in 1-10% of kidney transplant recipients. BKV is classified into genotypes or subgroups according to minor nucleotidic variations with unknown biological implications. Studies assessing the possible association between genotypes and the risk of BKVAN in kidney transplant patients have presented conflicting results. In these studies, genotype Ia, which is highly prevalent in Brazil, was less frequently found and, thus, comparative data on the biological properties of this genotype are lacking. In this study, BKV Ia and Ib1 genotypes were compared according to their viral load, genetic evolution (VP1 and NCCR) - in a cohort of renal transplant recipients. The patients infected with Ia (13/23; 56.5%) genotype exhibited higher viral loads in urine [>1.4 log over Ib1 (10/23; 43.5%); p=0.025]. In addition, genotype Ia was associated with diverse mutations at VP1 loops and sites under positive selection outside loops, which were totally absent in Ib1. Although the number of viremic patients was similar, the three patients who had BK nephropathy (BKVAN) were infected with Ia genotype. NCCR architecture (ww or rr) were not distinctive between Ia and Ib1 genotypes. Ia genotype, which is rare in other published BKV cohorts, presented some diverse biological properties in transplanted recipients in comparison to Ib1. Copyright © 2017 Elsevier B.V. All rights reserved.

Radiation at planar channeling of relativistic electrons in thick crystals

International Nuclear Information System (INIS)

Baier, V.N.; Katkov, V.M.; Strakhovenko, V.M.

1983-01-01

The distribution kinetics with respect to the transverse energy at electron channeling is discussed. The asymptotic expressions for the radiation intensity into a given collimator at electron channeling in thick crystals are derived. An optimal thickness at which the radiation output is maximal is found. The spectral distribution of the radiation intensity is analysed for the case of a single diamond crystal. (author)

Unsupervised Idealization of Ion Channel Recordings by Minimum Description Length

DEFF Research Database (Denmark)

Gnanasambandam, Radhakrishnan; Nielsen, Morten S; Nicolai, Christopher

2017-01-01

and characterize an idealization algorithm based on Rissanen's Minimum Description Length (MDL) Principle. This method uses minimal assumptions and idealizes ion channel recordings without requiring a detailed user input or a priori assumptions about channel conductance and kinetics. Furthermore, we demonstrate...... that correlation analysis of conductance steps can resolve properties of single ion channels in recordings contaminated by signals from multiple channels. We first validated our methods on simulated data defined with a range of different signal-to-noise levels, and then showed that our algorithm can recover...... channel currents and their substates from recordings with multiple channels, even under conditions of high noise. We then tested the MDL algorithm on real experimental data from human PIEZO1 channels and found that our method revealed the presence of substates with alternate conductances....

Detection of BK virus in urine from renal transplant subjects by mass spectrometry

Directory of Open Access Journals (Sweden)

Konietzny Rebecca

2012-04-01

Full Text Available Abstract Background The diagnosis and management of BK virus (BKV reactivation following renal transplantation continues to be a significant clinical problem. Following reactivation of latent virus, impaired cellular immunity enables sustained viral replication to occur in urothelial cells, which potentially leads to the development of BKV-associated nephropathy (BKVAN. Current guidelines recommend regular surveillance for BKV reactivation through the detection of infected urothelial cells in urine (decoy cells or viral nucleic acid in urine or blood. However, these methods have variable sensitivity and cannot routinely distinguish between different viral subtypes. We therefore asked whether mass spectrometry might be able to overcome these limitations and provide an additional non-invasive technique for the surveillance of BKV and identification of recipients at increased risk of BKVAN. Results Here we describe a mass spectrometry (MS-based method for the detection of BKV derived proteins directly isolated from clinical urine samples. Peptides detected by MS derived from Viral Protein 1 (VP1 allowed differentiation between subtypes I and IV. Using this approach, we observed an association between higher decoy cell numbers and the presence of the VP1 subtype Ib-2 in urine samples derived from a cohort of 20 renal transplant recipients, consistent with the hypothesis that certain viral subtypes may be associated with more severe BKVAN. Conclusions This is the first study to identify BK virus proteins in clinical samples by MS and that this approach makes it possible to distinguish between different viral subtypes. Further studies are required to establish whether this information could lead to stratification of patients at risk of BKVAN, facilitate distinction between BKVAN and acute rejection (AR, and ultimately improve patient treatment and outcomes.

Kinetic description of self-field effects on laser and betatron emission in wiggler-pumped ion-channel free electron lasers

International Nuclear Information System (INIS)

Alimohamadi, M; Mehdian, H; Hasanbeigi, A

2011-01-01

The effects of self-fields on the free electron lasers (FELs) with a helical wiggler and ion-channel guiding are considered. The steady-state orbits for a single electron in this configuration are obtained. The rate of change of axial velocity with energy, the characteristic function Φ, is derived and studied numerically. A kinetic approach has been used to get the effects of self-field on the FEL and betatron gain formula in the low-gain-pre-pass limit. It is shown that betatron gain is smaller than FEL gain. We also found a gain decrement (enhancement), arising from diamagnetism (paramagnetism) generated by the self-magnetic field for group I (group II) orbits. It is interesting that the gain enhancement is found for the non-relativistic part of group II orbits. The FEL gain and betatron gain have also been investigated for different relativistic factors γ.

Observation of diffraction effects in positron channeling

International Nuclear Information System (INIS)

Palathingal, J.C.; Peng, J.P.; Lynn, K.G.; Wu, X.Y.; Schultz, P.J.

1994-01-01

An experimental investigation of positron channeling was made with a high-angular resolution apparatus, employing positrons of kinetic energy 1 MeV, derived from the Brookhaven National Laboratory Dynamitron. The pattern of transmission through a Si (100) single crystal of thickness 0.245 μm was investigated for a number of major planes. The authors have observed for the first time, in excellent detail, the fine structure of the channeling pattern expected to arise from the particle diffraction effects, theoretically explainable in terms of the quantum-mechanical many-beam calculations

Enzyme Kinetics By Directly Imaging A Porous Silicon Microfluidic Reactor Using Desorption/Ionization on Silicon Mass Spectrometry

NARCIS (Netherlands)

Nichols, K.P.F.; Azoz, Seyla; Gardeniers, Johannes G.E.

2008-01-01

Enzyme kinetics were obtained in a porous silicon microfluidic channel by combining an enzyme and substrate droplet, allowing them to react and deposit a small amount of residue on the channel walls, and then analyzing this residue by directly ionizing the channel walls using a matrix assisted laser

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

Science.gov (United States)

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

2006-03-01

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

Solution of the Fokker-Planck equation for axially-channeled relativistic electrons

International Nuclear Information System (INIS)

Muralev, V.A.; Telegin, V.I.

1981-01-01

A method of the two dimensional kinetic equation of the Fokker-Planck type for axially-channeled electrons is proposed. This equation has been obtained recently by Beloshitsky and Kumakhov to describe the diffusion of channeling negative particles over the transverse energy and angular momentum. The results of computation of the dechanneling function of 1 GeV electrons in tungsten are presented. (author)

Toxin-antitoxin loci as stress-response-elements: ChpAK/MazF and ChpBK cleave translated RNAs and are counteracted by tmRNA

DEFF Research Database (Denmark)

Christensen, S.K.; Pedersen, K.; Hansen, Flemming G.

2003-01-01

Prokaryotic chromosomes encode toxin-antitoxin loci, often in multiple copies. In most cases, the function of these genes is not known. The chpA (mazEF) locus of Escherichia coli has been described as a cell killing module that induces bacterial apoptosis during nutritional stress. However, we...... found recently that ChpAK (MazF) does not confer cell killing but rather, induces a bacteriostatic condition from which the cells could be resuscitated. Results presented here yield a mechanistic explanation for the detrimental effect on cell growth exerted by ChpAK and the homologous ChpBK protein of E......AK cleaved tmRNA in its coding region. Thus, ChpAK and ChpBK inhibit translation by a mechanism very similar to that of E. coli RelE. On the basis of these results, we propose a model that integrates TA loci into general prokaryotic stress physiology....

Photodissociation dynamics of formyl fluoride (HFCO) at 193 nm: Branching ratios and distributions of kinetic energy

International Nuclear Information System (INIS)

Lee, H.; Wu, C.-Y.; Yang, S.K.; Lee, Y.-P.

2005-01-01

Following photodissociation of formyl fluoride (HFCO) at 193 nm, we detected products with fragmentation translational spectroscopy utilizing a tunable vacuum ultraviolet beam from a synchrotron for ionization. Among three primary dissociation channels observed in this work, the F-elimination channel HFCO→HCO+F dominates, with a branching ratio ∼0.66 and an average release of kinetic energy ∼55 kJ mol -1 ; about 17% of HCO further decomposes to H+CO. The H-elimination channel HFCO→FCO+H has a branching ratio ∼0.28 and an average release of kinetic energy ∼99 kJ mol -1 ; about 21% of FCO further decomposes to F+CO. The F-elimination channel likely proceeds via the S 1 surface whereas the H-elimination channel proceeds via the T 1 surface; both channels exhibit moderate barriers for dissociation. The molecular HF-elimination channel HFCO→HF+CO, correlating with the ground electronic surface, has a branching ratio of only ∼0.06; the average translational release of 93 kJ mol -1 , ∼15% of available energy, implies that the fragments are highly internally excited. Detailed mechanisms of photodissociation are discussed

Marketingová situační analýza BK Lions Jindřichův Hradec

OpenAIRE

Hron, Patrik

2014-01-01

The aim of this bachelor thesis is to carry out an analysis of each part of marketing mix and the environment in which the BK Lions Jindřichův Hradec basketball club is situated. Suitable and applicable recommendations are suggested to make the marketing mix more effective based on analysis of marketing situation. The first part is focused on describing the marketing mix and marketing situational analysis at a theoretical level. The practical part describes particular marketing tools which ar...

Clusters of Cl- channels in CFTR-expressing em>Sf>9 cells switch spontaneously between slow and fast gating modes

DEFF Research Database (Denmark)

Larsen, Erik Hviid; Price, E. M.; Gabriel, S. E.

1996-01-01

channel. Excised outside-out patches of CFTR-infected and forskolin-stimulated cells exhibited wave-like gating kinetics of well-resolved current transitions. All-point Gaussian distributions revealed contributions from several (five to nine) identical channels. Such channels, in excised outside...

cAMP-dependent kinase does not modulate the Slack sodium-activated potassium channel.

Science.gov (United States)

Nuwer, Megan O; Picchione, Kelly E; Bhattacharjee, Arin

2009-09-01

The Slack gene encodes a Na(+)-activated K(+) channel and is expressed in many different types of neurons. Like the prokaryotic Ca(2+)-gated K(+) channel MthK, Slack contains two 'regulator of K(+) conductance' (RCK) domains within its carboxy terminal, domains likely involved in Na(+) binding and channel gating. It also contains multiple consensus protein kinase C (PKC) and protein kinase A (PKA) phosphorylation sites and although regulated by protein kinase C (PKC) phosphorylation, modulation by PKA has not been determined. To test if PKA directly regulates Slack, nystatin-perforated patch whole-cell currents were recorded from a human embryonic kidney (HEK-293) cell line stably expressing Slack. Bath application of forskolin, an adenylate cyclase activator, caused a rapid and complete inhibition of Slack currents however, the inactive homolog of forskolin, 1,9-dideoxyforskolin caused a similar effect. In contrast, bath application of 8-bromo-cAMP did not affect the amplitude nor the activation kinetics of Slack currents. In excised inside-out patch recordings, direct application of the PKA catalytic subunit to patches did not affect the open probability of Slack channels nor was open probability affected by direct application of protein phosphatase 2B. Preincubation of cells with the protein kinase A inhibitor KT5720 also did not change current density. Finally, mutating the consensus phosphorylation site located between RCK domain 1 and domain 2 from serine to glutamate did not affect current activation kinetics. We conclude that unlike PKC, phosphorylation by PKA does not acutely modulate the function and gating activation kinetics of Slack channels.

Altered Potassium Ion Channel Function as a Possible Mechanism of Increased Blood Pressure in Rats Fed Thermally Oxidized Palm Oil Diets.

Science.gov (United States)

Nkanu, Etah E; Owu, Daniel U; Osim, Eme E

2017-12-27

Intake of thermally oxidized palm oil leads to cytotoxicity and alteration of the potassium ion channel function. This study investigated the effects of fresh and thermally oxidized palm oil diets on blood pressure and potassium ion channel function in blood pressure regulation. Male Wistar rats were randomly divided into three groups of eight rats. Control group received normal feed; fresh palm oil (FPO) and thermally oxidized palm oil (TPO) groups were fed a diet mixed with 15% (weight/weight) fresh palm oil and five times heated palm oil, respectively, for 16 weeks. Blood pressure was measured; blood samples, hearts, and aortas were collected for biochemical and histological analyses. Thermally oxidized palm oil significantly elevated basal mean arterial pressure (MAP). Glibenclamide (10 -5 mmol/L) and tetraethylammonium (TEA; 10 -3 mmol/L) significantly raised blood pressure in TPO compared with FPO and control groups. Levcromakalim (10 -6 mmol/L) significantly (p palm oil increases MAP probably due to the attenuation of adenosine triphosphate-sensitive potassium (K ATP ) and large-conductance calcium-dependent potassium (BK Ca ) channels, tissue peroxidation, and altered histological structures of the heart and blood vessels.

Incidence and Factors Associated with De Novo DSA After BK Viremia in Renal Transplant Recipients.

Science.gov (United States)

Patel, Samir J; Kuten, Samantha A; Knight, Richard J; Graviss, Edward A; Nguyen, Duc; Gaber, A Osama

2016-01-01

BK polyomavirus infection and de novo donor-human leukocyte antigen (HLA) specific antibodies (dnDSA) are two well-known and distinct complications occurring after kidney transplantation. Recent literature suggests an association between the two events. This study aims to examine the relationship between BK viremia (BKV) and dnDSA and to identify potential risk factors for dnDSA following BKV in kidney transplant recipients. A retrospective review of 1019 recipients from Houston Methodist Hospital was conducted. All patients underwent routine screening for BKV and dnDSA. Median follow-up was 44 months. BKV was detected in 186 (18%) patients at a median of 107 (82-205) days post-transplant. dnDSA occurred in 283 (28%) patients at a median of 272 (62-575) days post-transplant. Of the 69 dnDSA-positive/BKV-positive patients, dnDSA detection occurred after BKV onset in 46 patients. Thus, 46 (28%) previously DSA-negative patients later became dnDSA-positive following BKV, not significantly different from the rate seen in BKV-negative patients (26%; p=0.5). Median time to DSA detection following BKV onset was 232 days (interquartile range, 119-460) post-BKV detection. Multivariate analysis revealed a greater number of HLA mismatches and viral clearance as risk factors for development of dnDSA following BKV, whereas delayed graft function was associated with a lower risk of dnDSA. In conclusion, despite being considered a result of over-immunosuppression, BKV can still be followed by dnDSA in a substantial proportion of patients. Monitoring for dnDSA in patients being managed for BKV may be warranted. Copyright© 2017 by the Terasaki Research Institute.

Hidden Quantum Processes, Quantum Ion Channels, and 1/ f θ-Type Noise.

Science.gov (United States)

Paris, Alan; Vosoughi, Azadeh; Berman, Stephen A; Atia, George

2018-03-22

In this letter, we perform a complete and in-depth analysis of Lorentzian noises, such as those arising from [Formula: see text] and [Formula: see text] channel kinetics, in order to identify the source of [Formula: see text]-type noise in neurological membranes. We prove that the autocovariance of Lorentzian noise depends solely on the eigenvalues (time constants) of the kinetic matrix but that the Lorentzian weighting coefficients depend entirely on the eigenvectors of this matrix. We then show that there are rotations of the kinetic eigenvectors that send any initial weights to any target weights without altering the time constants. In particular, we show there are target weights for which the resulting Lorenztian noise has an approximately [Formula: see text]-type spectrum. We justify these kinetic rotations by introducing a quantum mechanical formulation of membrane stochastics, hidden quantum activated-measurement models, and prove that these quantum models are probabilistically indistinguishable from the classical hidden Markov models typically used for ion channel stochastics. The quantum dividend obtained by replacing classical with quantum membranes is that rotations of the Lorentzian weights become simple readjustments of the quantum state without any change to the laboratory-determined kinetic and conductance parameters. Moreover, the quantum formalism allows us to model the activation energy of a membrane, and we show that maximizing entropy under constrained activation energy yields the previous [Formula: see text]-type Lorentzian weights, in which the spectral exponent [Formula: see text] is a Lagrange multiplier for the energy constraint. Thus, we provide a plausible neurophysical mechanism by which channel and membrane kinetics can give rise to [Formula: see text]-type noise (something that has been occasionally denied in the literature), as well as a realistic and experimentally testable explanation for the numerical values of the spectral

Silicide/Silicon Heterointerfaces, Reaction Kinetics and Ultra-short Channel Devices

Science.gov (United States)

Tang, Wei

Nickel silicide is one of the electrical contact materials widely used on very large scale integration (VLSI) of Si devices in microelectronic industry. This is because the silicide/silicon interface can be formed in a highly controlled manner to ensure reproducibility of optimal structural and electrical properties of the metal-Si contacts. These advantages can be inherited to Si nanowire (NW) field-effect transistors (FET) device. Due to the technological importance of nickel silicides, fundamental materials science of nickel silicides formation (Ni-Si reaction), especially in nanoscale, has raised wide interest and stimulate new insights and understandings. In this dissertation, in-situ transmission electron microscopy (TEM) in combination with FET device characterization will be demonstrated as useful tools in nano-device fabrication as well as in gaining insights into the process of nickel silicide formation. The shortest transistor channel length (17 nm) fabricated on a vapor-liquid-solid (VLS) grown silicon nanowire (NW) has been demonstrated by controlled reaction with Ni leads on an in-situ transmission electron microscope (TEM) heating stage at a moderate temperature of 400 ºC. NiSi2 is the leading phase, and the silicide-silicon interface is an atomically sharp type-A interface. At such channel lengths, high maximum on-currents of 890 (microA/microm) and a maximum transconductance of 430 (microS/microm) were obtained, which pushes forward the performance of bottom-up Si NW Schottky barrier field-effect transistors (SB-FETs). Through accurate control over the silicidation reaction, we provide a systematic study of channel length dependent carrier transport in a large number of SB-FETs with channel lengths in the range of (17 nm -- 3.6 microm). Our device results corroborate with our transport simulations and reveal a characteristic type of short channel effects in SB-FETs, both in on- and off-state, which is different from that in conventional MOSFETs

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

Science.gov (United States)

Kourie, J I

1999-01-01

The understanding of the role of cytoplasmic pH in modulating sarcoplasmic reticulum (SR) ion channels involved in Ca2+ regulation is important for the understanding of the function of normal and adversely affected muscles. The dependency of the SR small chloride (SCl) channel from rabbit skeletal muscle on cytoplasmic pH (pHcis) and luminal pH (pHtrans) was investigated using the lipid bilayer-vesicle fusion technique. Low pHcis 6.75-4.28 modifies the operational mode of this multiconductance channel (conductance levels between 5 and 75 pS). At pHcis 7.26-7.37 the channel mode is dominated by the conductance and kinetics of the main conductance state (65-75 pS) whereas at low pHcis 6.75-4.28 the channel mode is dominated by the conductance and kinetics of subconductance states (5-40 pS). Similarly, low pHtrans 4.07, but not pHtrans 6.28, modified the activity of SCl channels. The effects of low pHcis are pronounced at 10(-3) and 10(-4) M [Ca2+]cis but are not apparent at 10(-5) M [Ca2+]cis, where the subconductances of the channel are already prominent. Low pHcis-induced mode shift in the SCl channel activity is due to modification of the channel proteins that cause the uncoupling of the subconductance states. The results in this study suggest that low pHcis can modify the functional properties of the skeletal SR ion channels and hence contribute, at least partly, to the malfunction in the contraction-relaxation mechanism in skeletal muscle under low cytoplasmic pH levels.

Should they team up to make your brain clock?

Czech Academy of Sciences Publication Activity Database

Weiss, Norbert

2015-01-01

Roč. 36, č. 6 (2015), s. 2184-2185 ISSN 0197-4580 R&D Projects: GA ČR GA15-13556S; GA MŠk 7AMB15FR015 Institutional support: RVO:61388963 Keywords : potassium channel * BK channel * circadian rhythm * calcium channel * T-type channel * SCN neuron * aging Subject RIV: CE - Biochemistry Impact factor: 5.153, year: 2015

Calcium current activation kinetics in isolated pyramidal neurones of the Ca1 region of the mature guinea-pig hippocampus.

Science.gov (United States)

Kay, A R; Wong, R K

1987-11-01

1. Neurones were isolated from the CA1 region of the guinea-pig hippocampus and subjected to the whole-cell mode of voltage clamping, to determine the kinetics of voltage-gated Ca2+ channel activation. 2. Isolated neurones had an abbreviated morphology, having lost most of the distal dendritic tree during the isolation procedure. The electrical compactness of the cells facilitates voltage clamp analysis. 3. Block of sodium and potassium currents revealed a persistent current activated on depolarization above -40 mV, which inactivated slowly when the intracellular medium contained EGTA. The current was blocked by Co2+ and Cd2+, augmented by increases in Ca2+ and could be carried by Ba2+, suggesting that the current is borne by Ca2+. 4. Steady-state activation of the Ca2+ current was found to be well described by the Boltzman equation raised to the second power. 5. The open channel's current-voltage (I-V) relationship rectified in the inward direction and was consistent with the constant-field equation. 6. The kinetics of Ca2+ current onset followed m2 kinetics throughout the range of its activation. Tail current kinetics were in accord with this model. A detailed Hodgkin-Huxley model was derived, defining the activation of this current. 7. The kinetics of the currents observed in this regionally and morphologically defined class of neurones were consistent with the existence of a single kinetic class of channels.

Dependence of equilibrium properties of channeled particles on transverse quasi temperature

International Nuclear Information System (INIS)

Kashlev, Yu.A.

2006-01-01

Quasi-equilibrium and kinetic characteristics of channeled particles are investigated by methods of nonequilibrium statistical thermodynamics. The equilibrium equation of the transverse energy of fast particles and the equilibrium equation of the transverse momentum of particles are derived. It is shown that equilibrium equations solution permits to obtain the expression for the transverse quasi-temperature of the channeled particle subsystem. The quasi-equilibrium angular distribution of particles after transmission through a thin monocrystal and the angular distribution at backscattering are studied. The evaluated data of the transverse quasi-temperature are presented for the case of iodine ion channeling through silver crystals [ru

Dissociative and molecular oxygen chemisorption channels on reduced rutile TiO2(110): A high-resolution STM study

DEFF Research Database (Denmark)

Lira, Estephania; Hansen, Jonas Ørbæk; Huo, Peipei

2010-01-01

High-resolution scanning tunneling microscopy (STM) and temperature-programmed desorption (TPD) were used to study the interaction of O2 with reduced TiO2(110)–(1 × 1) crystals. STM is the technique of choice to unravel the relation between vacancy and non-vacancy assisted O2 dissociation channel...... in the near-surface region of reduced TiO2(110) crystals, the kinetics of the two O2 dissociation channels as well as the kinetics of the diffusion and reaction of Ti interstitials....

I h and HCN channels in murine spiral ganglion neurons: tonotopic variation, local heterogeneity, and kinetic model.

Science.gov (United States)

Liu, Qing; Manis, Paul B; Davis, Robin L

2014-08-01

One of the major contributors to the response profile of neurons in the auditory pathways is the I h current. Its properties such as magnitude, activation, and kinetics not only vary among different types of neurons (Banks et al., J Neurophysiol 70:1420-1432, 1993; Fu et al., J Neurophysiol 78:2235-2245, 1997; Bal and Oertel, J Neurophysiol 84:806-817, 2000; Cao and Oertel, J Neurophysiol 94:821-832, 2005; Rodrigues and Oertel, J Neurophysiol 95:76-87, 2006; Yi et al., J Neurophysiol 103:2532-2543, 2010), but they also display notable diversity in a single population of spiral ganglion neurons (Mo and Davis, J Neurophysiol 78:3019-3027, 1997), the first neural element in the auditory periphery. In this study, we found from somatic recordings that part of the heterogeneity can be attributed to variation along the tonotopic axis because I h in the apical neurons have more positive half-activation voltage levels than basal neurons. Even within a single cochlear region, however, I h current properties are not uniform. To account for this heterogeneity, we provide immunocytochemical evidence for variance in the intracellular density of the hyperpolarization-activated cyclic nucleotide-gated channel α-subunit 1 (HCN1), which mediates I h current. We also observed different combinations of HCN1 and HCN4 α-subunits from cell to cell. Lastly, based on the physiological data, we performed kinetic analysis for the I h current and generated a mathematical model to better understand varied I h on spiral ganglion function. Regardless of whether I h currents are recorded at the nerve terminals (Yi et al., J Neurophysiol 103:2532-2543, 2010) or at the somata of spiral ganglion neurons, they have comparable mean half-activation voltage and induce similar resting membrane potential changes, and thus our model may also provide insights into the impact of I h on synaptic physiology.

Efficient uptake of blood-borne BK and JC polyomavirus-like particles in endothelial cells of liver sinusoids and renal vasa recta.

Directory of Open Access Journals (Sweden)

Jaione Simon-Santamaria

Full Text Available Liver sinusoidal endothelial cells (LSECs are specialized scavenger cells that mediate high-capacity clearance of soluble waste macromolecules and colloid material, including blood-borne adenovirus. To explore if LSECs function as a sink for other viruses in blood, we studied the fate of virus-like particles (VLPs of two ubiquitous human DNA viruses, BK and JC polyomavirus, in mice. Like complete virions, VLPs specifically bind to receptors and enter cells, but unlike complete virions, they cannot replicate. 125I-labeled VLPs were used to assess blood decay, organ-, and hepatocellular distribution of ligand, and non-labeled VLPs to examine cellular uptake by immunohisto- and -cytochemistry. BK- and JC-VLPs rapidly distributed to liver, with lesser uptake in kidney and spleen. Liver uptake was predominantly in LSECs. Blood half-life (∼1 min, and tissue distribution of JC-VLPs and two JC-VLP-mutants (L55F and S269F that lack sialic acid binding affinity, were similar, indicating involvement of non-sialic acid receptors in cellular uptake. Liver uptake was not mediated by scavenger receptors. In spleen, the VLPs localized to the red pulp marginal zone reticuloendothelium, and in kidney to the endothelial lining of vasa recta segments, and the transitional epithelium of renal pelvis. Most VLP-positive vessels in renal medulla did not express PV-1/Meca 32, suggesting location to the non-fenestrated part of vasa recta. The endothelial cells of these vessels also efficiently endocytosed a scavenger receptor ligand, formaldehyde-denatured albumin, suggesting high endocytic activity compared to other renal endothelia. We conclude that LSECs very effectively cleared a large fraction of blood-borne BK- and JC-VLPs, indicating a central role of these cells in early removal of polyomavirus from the circulation. In addition, we report the novel finding that a subpopulation of endothelial cells in kidney, the main organ of polyomavirus persistence, showed

The what and where of adding channel noise to the Hodgkin-Huxley equations.

Directory of Open Access Journals (Sweden)

Joshua H Goldwyn

2011-11-01

Full Text Available Conductance-based equations for electrically active cells form one of the most widely studied mathematical frameworks in computational biology. This framework, as expressed through a set of differential equations by Hodgkin and Huxley, synthesizes the impact of ionic currents on a cell's voltage--and the highly nonlinear impact of that voltage back on the currents themselves--into the rapid push and pull of the action potential. Later studies confirmed that these cellular dynamics are orchestrated by individual ion channels, whose conformational changes regulate the conductance of each ionic current. Thus, kinetic equations familiar from physical chemistry are the natural setting for describing conductances; for small-to-moderate numbers of channels, these will predict fluctuations in conductances and stochasticity in the resulting action potentials. At first glance, the kinetic equations provide a far more complex (and higher-dimensional description than the original Hodgkin-Huxley equations or their counterparts. This has prompted more than a decade of efforts to capture channel fluctuations with noise terms added to the equations of Hodgkin-Huxley type. Many of these approaches, while intuitively appealing, produce quantitative errors when compared to kinetic equations; others, as only very recently demonstrated, are both accurate and relatively simple. We review what works, what doesn't, and why, seeking to build a bridge to well-established results for the deterministic equations of Hodgkin-Huxley type as well as to more modern models of ion channel dynamics. As such, we hope that this review will speed emerging studies of how channel noise modulates electrophysiological dynamics and function. We supply user-friendly MATLAB simulation code of these stochastic versions of the Hodgkin-Huxley equations on the ModelDB website (accession number 138950 and http://www.amath.washington.edu/~etsb/tutorials.html.

Internal Diffusion-Controlled Enzyme Reaction: The Acetylcholinesterase Kinetics.

Science.gov (United States)

Lee, Sangyun; Kim, Ji-Hyun; Lee, Sangyoub

2012-02-14

Acetylcholinesterase is an enzyme with a very high turnover rate; it quenches the neurotransmitter, acetylcholine, at the synapse. We have investigated the kinetics of the enzyme reaction by calculating the diffusion rate of the substrate molecule along an active site channel inside the enzyme from atomic-level molecular dynamics simulations. In contrast to the previous works, we have found that the internal substrate diffusion is the determinant of the acetylcholinesterase kinetics in the low substrate concentration limit. Our estimate of the overall bimolecular reaction rate constant for the enzyme is in good agreement with the experimental data. In addition, the present calculation provides a reasonable explanation for the effects of the ionic strength of solution and the mutation of surface residues of the enzyme. The study suggests that internal diffusion of the substrate could be a key factor in understanding the kinetics of enzymes of similar characteristics.

Broadening of white-light continuum by filamentation in BK7 glass at its zero-dispersion point

International Nuclear Information System (INIS)

Jiang, Jiaming; Zhong, Yue; Zheng, Yinghui; Zeng, Zhinan; Ge, Xiaochun; Li, Ruxin

2015-01-01

Broadening of white-light continuum is observed by filamentation of near-infrared femtosecond laser pulses with peak power exceeding the megawatt level in BK7 glass with the presence of the zero-dispersion point. The simulated results show that, due to the low dispersion at the zero-dispersion point, the broadening of white-light continuum can be wider and the filament can persist in propagating stably longer distance. - Highlights: • We observed the white-light continuum by filamentation at the zero-dispersion point. • Peak power significantly exceeding the critical value of self-focusing was used. • Wider spectral broadening was obtained around the zero-dispersion point

Human BK Polyomavirus—The Potential for Head and Neck Malignancy and Disease

Directory of Open Access Journals (Sweden)

Raquel Burger-Calderon

2015-07-01

Full Text Available Members of the human Polyomaviridae family are ubiquitous and pathogenic among immune-compromised individuals. While only Merkel cell polyomavirus (MCPyV has conclusively been linked to human cancer, all members of the polyomavirus (PyV family encode the oncoprotein T antigen and may be potentially carcinogenic. Studies focusing on PyV pathogenesis in humans have become more abundant as the number of PyV family members and the list of associated diseases has expanded. BK polyomavirus (BKPyV in particular has emerged as a new opportunistic pathogen among HIV positive individuals, carrying harmful implications. Increasing evidence links BKPyV to HIV-associated salivary gland disease (HIVSGD. HIVSGD is associated with elevated risk of lymphoma formation and its prevalence has increased among HIV/AIDS patients. Determining the relationship between BKPyV, disease and tumorigenesis among immunosuppressed individuals is necessary and will allow for expanding effective anti-viral treatment and prevention options in the future.

Importance of glycosylation on function of a potassium channel in neuroblastoma cells.

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M K Hall

Full Text Available The Kv3.1 glycoprotein, a voltage-gated potassium channel, is expressed throughout the central nervous system. The role of N-glycans attached to the Kv3.1 glycoprotein on conducting and non-conducting functions of the Kv3.1 channel are quite limiting. Glycosylated (wild type, partially glycosylated (N220Q and N229Q, and unglycosylated (N220Q/N229Q Kv3.1 proteins were expressed and characterized in a cultured neuronal-derived cell model, B35 neuroblastoma cells. Western blots, whole cell current recordings, and wound healing assays were employed to provide evidence that the conducting and non-conducting properties of the Kv3.1 channel were modified by N-glycans of the Kv3.1 glycoprotein. Electrophoretic migration of the various Kv3.1 proteins treated with PNGase F and neuraminidase verified that the glycosylation sites were occupied and that the N-glycans could be sialylated, respectively. The unglycosylated channel favored a different whole cell current pattern than the glycoform. Further the outward ionic currents of the unglycosylated channel had slower activation and deactivation rates than those of the glycosylated Kv3.1 channel. These kinetic parameters of the partially glycosylated Kv3.1 channels were also slowed. B35 cells expressing glycosylated Kv3.1 protein migrated faster than those expressing partially glycosylated and much faster than those expressing the unglycosylated Kv3.1 protein. These results have demonstrated that N-glycans of the Kv3.1 glycoprotein enhance outward ionic current kinetics, and neuronal migration. It is speculated that physiological changes which lead to a reduction in N-glycan attachment to proteins will alter the functions of the Kv3.1 channel.

Deficit of Kcnma1 mRNA expression in the dentate gyrus of epileptic rats

Science.gov (United States)

Ermolinsky, Boris; Arshadmansab, Massoud F.; Pacheco Otalora, Luis F.; Zarei, Masoud M.; Garrido-Sanabria, Emilio R.

2008-01-01

Epileptogenesis in mesial temporal lobe epilepsy is determined by several factors including abnormalities in the expression and function of ion channels. Here, we report a long-lasting deficit in gene expression of Kcnma1 coding for the large-conductance calcium-activated potassium (BK, MaxiK) channel α-subunits after pilocarpine-induced status epilepticus. By using comparative real-time PCR, Taqman gene expression assays, and the delta-delta comparative threshold method we detected a significant reduction in Kcnma1 expression in microdissected dentate gyrus at different intervals after status epilepticus (24 h, 10 days, 1 month, and more than 2 months). BK channels are key regulators of neuronal excitability and transmitter release. Hence, defective Kcnma1 expression may play a critical role in the pathogenesis of mesial temporal lobe epilepsy. PMID:18695509

Kaempferol stimulates large conductance Ca2+-activated K+ (BKCa) channels in human umbilical vein endothelial cells via a cAMP/PKA-dependent pathway

Science.gov (United States)

Xu, Y C; Leung, G P H; Wong, P Y D; Vanhoutte, P M; Man, R Y K

2008-01-01

Background and purpose: Kaempferol has been shown to possess a vasodilator effect but its mechanism of action remains unclear. In this study, experiments were carried out to study the effect of kaempferol on K+ channels in endothelial cells. Experimental approach: K+ channel activities in human umbilical vein endothelial cells (HUVECs) were studied by conventional whole cell and cell-attached patch-clamp electrophysiology. Key results: Kaempferol stimulated an outward-rectifying current in HUVECs in a dose-dependent manner with an EC50 value of 2.5±0.02 μM. This kaempferol-induced current was abolished by large conductance Ca2+-activated K+ (BKCa) channel blockers, such as iberiotoxin (IbTX) and charybdotoxin (ChTX), whereas the small conductance Ca2+-activated K+ (SKCa) channel blocker, apamin, and the voltage-dependent K+ (KV) channel blocker, 4-aminopyridine, had no effect. Cell-attached patches demonstrated that kaempferol increased the open probability of BkCa channels in HUVECs. Clamping intracellular Ca2+ did not prevent kaempferol-induced increases in outward current. In addition, the kaempferol-induced current was diminished by the adenylyl cyclase inhibitor SQ22536, the cAMP antagonist Rp-8-Br-cAMP and the PKA inhibitor KT5720, but was not affected by the guanylyl cyclase inhibitor ODQ, the cGMP antagonist Rp-8-Br-cGMP and the PKG inhibitor KT5823. The activation of BKCa channels by kaempferol caused membrane hyperpolarization of HUVECs. Conclusion and implications: These results demonstrate that kaempferol activates the opening of BKCa channels in HUVECs via a cAMP/PKA-dependent pathway, resulting in membrane hyperpolarization. This mechanism may partly account for the vasodilator effects of kaempferol. PMID:18493242

Inhibition of Na+ channel currents in rat myoblasts by 4-aminopyridine

International Nuclear Information System (INIS)

Lu Boxun; Liu Linyun; Liao Lei; Zhang Zhihong; Mei Yanai

2005-01-01

Our previous study revealed that 4-aminopyridine (4-AP), a specific blocker of A-type current, could also inhibit inward Na + currents (I Na ) with a state-independent mechanism in rat cerebellar granule cells. In the present study, we report an inhibitory effect of 4-AP on voltage-gated and tetrodotoxin (TTX)-sensitive I Na recorded from cultured rat myoblasts. 4-AP inhibited I Na amplitude in a dose-dependent manner between the concentrations of 0.5 and 10 mM without significant alteration in the activation or inactivation kinetics of the channel. By comparison to the 4-AP-induced inhibitory effect on cerebellum neurons, the inhibitory effect on myoblasts was enhanced through repetitive pulse and inflected by changing frequency. Specifically, the lower the frequency of pulse, the higher the inhibition observed, suggesting that block manner is inversely use-dependent. Moreover, experiments adding 4-AP to the intracellular solution indicate that the inhibitory effects are localized inside the cell. Additionally, 4-AP significantly modifies the properties of steady-state activation and inactivation kinetics of the channel. Our data suggest that the K + channel blocker 4-AP inhibits both neuron and myoblast Na + channels via different mechanisms. These findings may also provide information regarding 4-AP-induced pharmacological and toxicological effects in clinical use and experimental research

Polypeptide Translocation Through the Mitochondrial TOM Channel: Temperature-Dependent Rates at the Single-Molecule Level.

Science.gov (United States)

Mahendran, Kozhinjampara R; Lamichhane, Usha; Romero-Ruiz, Mercedes; Nussberger, Stephan; Winterhalter, Mathias

2013-01-03

The TOM protein complex facilitates the transfer of nearly all mitochondrial preproteins across outer mitochondrial membranes. Here we characterized the effect of temperature on facilitated translocation of a mitochondrial presequence peptide pF1β. Ion current fluctuations analysis through single TOM channels revealed thermodynamic and kinetic parameters of substrate binding and allowed determining the energy profile of peptide translocation. The activation energy for the on-rate and off-rate of the presequence peptide into the TOM complex was symmetric with respect to the electric field and estimated to be about 15 and 22 kT per peptide. These values are above that expected for free diffusion of ions in water (6 kT) and reflect the stronger interaction in the channel. Both values are in the range for typical enzyme kinetics and suggest one process without involving large conformational changes within the channel protein.

Hemorrhagic Cystitis due to BK Reactivation in a Young Female Treated for Hodgkin-Disease

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R. Le Calloch

2011-01-01

Full Text Available Hodgkin's lymphoma is a disease with a high rate of curability under classic chemo-radiotherapy regimes. Complications due to chemotherapy could include viral reactivation due to chronic lymphopenia. BK virus (BKV is a polyoma virus belonging to the Papovaviridae family with antibody seroprevalences in healthy populations varying from 60% to 80%. Initial infections are asymptomatic usually occur in early childhood, after which the viruses remain latent in the kidneys or urothelium. Reactivation of BKV occurs in individuals with severe immunosuppression during HIV infections, transplantation or, exceptionally, after classical chemotherapy. BKV incidence is approximately 0% to 5% in immunocompetent individuals. Reactivation is associated with nephropathy and haemorrhagic cystitis. Herein, we present a case of a haemorrhagic cystitis due to BKV reactivation in a patient with Hodgkin's disease treated with chemotherapy.

Structure of the CLC-1 chloride channel from Homo sapiens.

Science.gov (United States)

Park, Eunyong; MacKinnon, Roderick

2018-05-29

CLC channels mediate passive Cl - conduction, while CLC transporters mediate active Cl - transport coupled to H + transport in the opposite direction. The distinction between CLC-0/1/2 channels and CLC transporters seems undetectable by amino acid sequence. To understand why they are different functionally we determined the structure of the human CLC-1 channel. Its 'glutamate gate' residue, known to mediate proton transfer in CLC transporters, adopts a location in the structure that appears to preclude it from its transport function. Furthermore, smaller side chains produce a wider pore near the intracellular surface, potentially reducing a kinetic barrier for Cl - conduction. When the corresponding residues are mutated in a transporter, it is converted to a channel. Finally, Cl - at key sites in the pore appear to interact with reduced affinity compared to transporters. Thus, subtle differences in glutamate gate conformation, internal pore diameter and Cl - affinity distinguish CLC channels and transporters. © 2018, Park & MacKinnon.

Reactor thermal behaviors under kinetics parameters variations in fast reactivity insertion

Energy Technology Data Exchange (ETDEWEB)

Abou-El-Maaty, Talal [Reactors Department, Atomic Energy Authority, Cairo 13759 (Egypt)], E-mail: talal22969@yahoo.com; Abdelhady, Amr [Reactors Department, Atomic Energy Authority, Cairo 13759 (Egypt)

2009-03-15

The influences of variations in some of the kinetics parameters affecting the reactivity insertion are considered in this study, it has been accomplished in order to acquire knowledge about the role that kinetic parameters play in prompt critical transients from the safety point of view. The kinetics parameters variations are limited to the effective delayed neutron fraction ({beta}{sub eff}) and the prompt neutron generation time ({lambda}). The reactor thermal behaviors under the variations in effective delayed neutron fraction and prompt neutron generation time included, the reactor power, maximum fuel temperature, maximum clad temperature, maximum coolant temperature and the mass flux variations at the hot channel. The analysis is done for a typical swimming pool, plate type research reactor with low enriched uranium. The scram system is disabled during the accidents simulations. Calculations were done using PARET code. As a result of simulations, it is concluded that, the reactor (ETRR2) thermal behavior is considerably more sensitive to the variation in the effective delayed neutron fraction than to the variation in prompt neutron generation time and the fast reactivity insertion in both cases causes a flow expansion and contraction at the hot channel exit. The amplitude of the oscillated flow is a qualitatively increases with the decrease in both {beta}{sub eff} and {lambda}.

Brownian dynamic study of an enzyme metabolon in the TCA cycle: Substrate kinetics and channeling.

Science.gov (United States)

Huang, Yu-Ming M; Huber, Gary A; Wang, Nuo; Minteer, Shelley D; McCammon, J Andrew

2018-02-01

Malate dehydrogenase (MDH) and citrate synthase (CS) are two pacemaking enzymes involved in the tricarboxylic acid (TCA) cycle. Oxaloacetate (OAA) molecules are the intermediate substrates that are transferred from the MDH to CS to carry out sequential catalysis. It is known that, to achieve a high flux of intermediate transport and reduce the probability of substrate leaking, a MDH-CS metabolon forms to enhance the OAA substrate channeling. In this study, we aim to understand the OAA channeling within possible MDH-CS metabolons that have different structural orientations in their complexes. Three MDH-CS metabolons from native bovine, wild-type porcine, and recombinant sources, published in recent work, were selected to calculate OAA transfer efficiency by Brownian dynamics (BD) simulations and to study, through electrostatic potential calculations, a possible role of charges that drive the substrate channeling. Our results show that an electrostatic channel is formed in the metabolons of native bovine and recombinant porcine enzymes, which guides the oppositely charged OAA molecules passing through the channel and enhances the transfer efficiency. However, the channeling probability in a suggested wild-type porcine metabolon conformation is reduced due to an extended diffusion length between the MDH and CS active sites, implying that the corresponding arrangements of MDH and CS result in the decrease of electrostatic steering between substrates and protein surface and then reduce the substrate transfer efficiency from one active site to another. © 2017 The Protein Society.

Plasma parameters in the channel of a long leader in air

International Nuclear Information System (INIS)

Aleksandrov, N.L.; Konchakov, A. M.; Bazelyan, E.M.

2001-01-01

The time evolution of the electric field in the leader channel and other characteristics of the leader plasma in long air gaps are simulated. Calculations are performed in the one-dimensional time-dependent model with allowance for the time-varying energy deposition in the channel, the channel expansion, and the nonequilibrium ionization kinetics in the leader plasma. The calculations show that, at a gas temperature of 4500-6000 K, associative ionization becomes a dominant ionization mechanism in the leader channel; as a result, the electric field decreases to 100-200 V/cm in 10 -4 -10 -3 s under the conditions typical of the leader discharge. The calculated electric field agrees well with the data from the experimental modeling of long leaders by a spark discharge in short gaps

Does calcium influx regulate melatonin production through the circadian pacemaker in chick pineal cells? Effects of nitrendipine, Bay K 8644, Co2+, Mn2+, and low external Ca2+.

Science.gov (United States)

Zatz, M; Mullen, D A

1988-11-01

We have recently described a system, using dispersed chick pineal cells in static culture, which displays a persistent, photosensitive, circadian rhythm of melatonin production and release. Here, we describe the effects of nitrendipine (NTR) (a dihydropyridine 'antagonist' of L-type calcium channels), Bay K 8644 (BK) (a dihydropyridine calcium channel 'agonist'), cobalt and manganese ions (both inorganic calcium channel blockers), and low external calcium concentrations, on the melatonin rhythm. NTR inhibited and BK stimulated melatonin output; they were potent and effective. Co2+, Mn2+, and low external Ca2+ markedly inhibited melatonin output. These results support a role for calcium influx through voltage-dependent calcium channels (L-type) in the regulation of melatonin production. Four or 8 h pulses of white light or darkness, in otherwise constant red light, cause, in addition to acute effects, phase-dependent phase shifts of the melatonin rhythm in subsequent cycles. Such phase shifts indicate an effect on (proximal to) the pacemaker generating the rhythm. Four or 8 h pulses of NTR, BK, Co2+, or low Ca2+, however, did not appreciably alter the phase of subsequent melatonin cycles. Neither did BK interfere with phase shifts induced by light pulses. Mn2+ pulses did induce phase-dependent phase shifts, but, unlike those evoked by light or dark pulses, these were all delays. Such effects of Mn2+ in other systems have been attributed to, and are characteristic of, 'metabolic inhibitors'. On balance, the results fail to support a prominent role for calcium influx in regulating the pacemaker underlying the circadian rhythm in chick pineal cells. Rather, calcium influx appears to regulate melatonin production primarily by acting on the melatonin-synthesizing apparatus, distal to the pacemaker.

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

Science.gov (United States)

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

2013-01-01

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

Diffusion-controlled interface kinetics-inclusive system-theoretic propagation models for molecular communication systems

Science.gov (United States)

Chude-Okonkwo, Uche A. K.; Malekian, Reza; Maharaj, B. T.

2015-12-01

Inspired by biological systems, molecular communication has been proposed as a new communication paradigm that uses biochemical signals to transfer information from one nano device to another over a short distance. The biochemical nature of the information transfer process implies that for molecular communication purposes, the development of molecular channel models should take into consideration diffusion phenomenon as well as the physical/biochemical kinetic possibilities of the process. The physical and biochemical kinetics arise at the interfaces between the diffusion channel and the transmitter/receiver units. These interfaces are herein termed molecular antennas. In this paper, we present the deterministic propagation model of the molecular communication between an immobilized nanotransmitter and nanoreceiver, where the emission and reception kinetics are taken into consideration. Specifically, we derived closed-form system-theoretic models and expressions for configurations that represent different communication systems based on the type of molecular antennas used. The antennas considered are the nanopores at the transmitter and the surface receptor proteins/enzymes at the receiver. The developed models are simulated to show the influence of parameters such as the receiver radius, surface receptor protein/enzyme concentration, and various reaction rate constants. Results show that the effective receiver surface area and the rate constants are important to the system's output performance. Assuming high rate of catalysis, the analysis of the frequency behavior of the developed propagation channels in the form of transfer functions shows significant difference introduce by the inclusion of the molecular antennas into the diffusion-only model. It is also shown that for t > > 0 and with the information molecules' concentration greater than the Michaelis-Menten kinetic constant of the systems, the inclusion of surface receptors proteins and enzymes in the models

Channel for Applied Investigations on Low Energy Ion Beams of Cyclotron DC-60

CERN Document Server

Gikal, B N; Borisenko, A N; Fateev, A A; Gulbekyan, G G; Kalagin, I V; Kazacha, V I; Kazarinov, N Yu; Kolesov, I V; Lebedev, N I; Lysukhin, S N; Melnikov, V N

2006-01-01

The channel intended for carrying out applied investigations on the low energy ion beams having the kinetic energy 25 $Z/A$ keV/a.u. and transported from the ECR-source to a target is worked out. The channel structure and parameters of all its optics elements are defined. The calculation results of different ion types transportation are given. It is shown that ions having the ratio of their mass to charge Z/A=2-20 can be transported in the worked out channel with enough high expected efficiency. At that the ion beam diameter on the target is $\\sim$40 mm. The characteristics of the basic optical elements of the channel are also given.

Comparison of BWR-6 pressurization transients with one-dimensional and point kinetics

International Nuclear Information System (INIS)

Serra, J.M.; Mata, P.; Cronin, J.T.

1992-01-01

This paper focuses on the differences between the results of core reload licensing calculations for the BWR-6 plant when performed with a one-dimensional (1-D) versus a point kinetics model. More specifically, the improvement in critical power ratio which would be expected from a change in methods from a point to a 1-D kinetics core wide transient calculation for pressurization transients is investigated. To qualitatively assess critical power ratio (CPR) improvement, core wide transient and hot channel calculations of a generator load rejection with failure of the steam by-pass system and a feedwater controller failure of maximum demand are performed with both, point and 1-D kinetics models in the core wide simulation. Additionally, a sensitivity study on the frequency of power shape function updating in the 1-D kinetics calculation is performed

A review on the analysis and experiment of fluid flow and mixing in micro-channels

International Nuclear Information System (INIS)

Kang, Sang Mo; Suh, Yong Kweon; Jayaraj, Simon

2007-01-01

The studies with respect to micro-channels and micro-mixers are expanding in many dimensions. Most significant area of micro-mixer study is the flow analysis in various micro-channel configurations. The flow phenomena in microchannel devices are quite different from that of the macro-scale devices. An attempt is made here to review the important recent literature available in the area of micro-channel flow analysis and mixing. The topics covered include the physics of flow in micro-channels and integrated simulation of the micro-channel flow. Also, the flow control models and electro-kinetically driven micro-channel flows are dealt in detail. A survey of important numerical methods, which are currently popular for micro-channel flow analysis, is carried out. Different options for mixing in microchannels are provided, in sufficient detail

Binding of ArgTX-636 in the NMDA receptor ion channel

DEFF Research Database (Denmark)

Poulsen, Mette H; Andersen, Jacob; Christensen, Rune

2015-01-01

of NMDAR activity and have therapeutic potential for treatment of a variety of brain diseases or as pharmacological tools for studies of the neurobiological role of NMDARs. We have performed a kinetic analysis of the blocking mechanism of the prototypical polyamine toxin NMDAR ion channel blocker...

Experimental Study of Tool Wear and Grinding Forces During BK-7 Glass Micro-grinding with Modified PCD Tool

Science.gov (United States)

Pratap, A.; Sahoo, P.; Patra, K.; Dyakonov, A. A.

2017-09-01

This study focuses on the improvement in grinding performance of BK-7 glass using polycrystalline diamond micro-tool. Micro-tools are modified using wire EDM and performance of modified tools is compared with that of as received tool. Tool wear of different types of tools are observed. To quantify the tool wear, a method based on weight loss of tool is introduced in this study. Modified tools significantly reduce tool wear in comparison to the normal tool. Grinding forces increase with machining time due to tool wear. However, modified tools produce lesser forces thus can improve life of the PCD micro-grinding tool.

Phosphorylation of rat brain purified mitochondrial Voltage-Dependent Anion Channel by c-Jun N-terminal kinase-3 modifies open-channel noise.

Science.gov (United States)

Gupta, Rajeev

2017-09-02

The drift kinetic energy of ionic flow through single ion channels cause vibrations of the pore walls which are observed as open-state current fluctuations (open-channel noise) during single-channel recordings. Vibration of the pore wall leads to transitions among different conformational sub-states of the channel protein in the open-state. Open-channel noise analysis can provide important information about the different conformational sub-state transitions and how biochemical modifications of ion channels would affect their transport properties. It has been shown that c-Jun N-terminal kinase-3 (JNK3) becomes activated by phosphorylation in various neurodegenerative diseases and phosphorylates outer mitochondrion associated proteins leading to neuronal apoptosis. In our earlier work, JNK3 has been reported to phosphorylate purified rat brain mitochondrial voltage-dependent anion channel (VDAC) in vitro and modify its conductance and opening probability. In this article we have compared the open-state noise profile of the native and the JNK3 phosphorylated VDAC using Power Spectral Density vs frequency plots. Power spectral density analysis of open-state noise indicated power law with average slope value α ≈1 for native VDAC at both positive and negative voltage whereas average α value open-state noise arises due to coupling of ionic transport and conformational sub-states transitions in open-state and this coupling is perturbed as a result of channel phosphorylation. Copyright © 2017 Elsevier Inc. All rights reserved.

Chimeras Reveal a Single Lipid-Interface Residue that Controls MscL Channel Kinetics as well as Mechanosensitivity

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Li-Min Yang

2013-02-01

Full Text Available MscL, the highly conserved bacterial mechanosensitive channel of large conductance, serves as an osmotic “emergency release valve,” is among the best-studied mechanosensors, and is a paradigm of how a channel senses and responds to membrane tension. Although all homologs tested thus far encode channel activity, many show functional differences. We tested Escherichia coli and Staphylococcus aureus chimeras and found that the periplasmic region of the protein, particularly E. coli I49 and the equivalent S. aureus F47 at the periplasmic lipid-aqueous interface of the first transmembrane domain, drastically influences both the open dwell time and the threshold of channel opening. One mutant shows a severe hysteresis, confirming the importance of this residue in determining the energy barriers for channel gating. We propose that this site acts similarly to a spring for a clasp knife, adjusting the resistance for obtaining and stabilizing an open or closed channel structure.

Multilevel fitting of 235U resonance data sensitive to Bohr-and Brosa-fission channels

International Nuclear Information System (INIS)

Moore, M.S.

1995-01-01

The recent determination of the K, J dependence of the neutron induced fission cross section of 235 U by the Dubna group has led to a renewed interest in the mechanism of fission from saddle to scission. The K quantum numbers designate the so-called Bohr fission channels, which describe the fission properties at the saddle point. Certain other fission properties, e.g., the fragment mass and kinetic-energy distribution, are related to the properties of the scission point. The neutron energy dependence of the fragment kinetic energies has been measured by Hambsch et al., who analyzed their data according to a channel description of Brosa et al. How these two channel descriptions, the saddle-point Bohr channels and the scission-point Brosa channels, relate to one another is an open question, and is the subject matter of the present paper. We use the correlation coefficient between various data sets, in which variations are reported from resonance to resonance, as a measure of both-the statistical reliability of the data and of the degree to which different scission variables relate to different Bohr channels. We have carried out an adjustment of the ENDF/B-VI multilevel evaluation of the fission cross section of 235 U, one that provides a reasonably good fit to the energy dependence of the fission, capture, and total cross sections below 100 eV, and to the Bohr-channel structure deduced from an earlier measurement by Pattenden and Postma. We have also further explored the possibility of describing the data of Hambsch et al. in the Brosa-channel framework with the same set of fission-width vectors, only in a different reference system. While this approach shows promise, it is clear that better data are also needed for the neutron energy variation of the scission-point variables

A single-phase model for liquid-feed DMFCs with non-Tafel kinetics

Energy Technology Data Exchange (ETDEWEB)

Vera, Marcos [Area de Mecanica de Fluidos, Universidad Carlos III de Madrid, Avda. de la Universidad 30, 28911 Leganes (Spain)

2007-09-27

An isothermal single-phase 3D/1D model for liquid-feed direct methanol fuel cells (DMFC) is presented. Three-dimensional (3D) mass, momentum and species transport in the anode channels and gas diffusion layer is modeled using a commercial, finite-volume based, computational fluid dynamics (CFD) software complemented with user supplied subroutines. The 3D model is locally coupled to a one-dimensional (1D) model accounting for the electrochemical reactions in both the anode and the cathode, which provides a physically sound boundary condition for the velocity and methanol concentration fields at the anode gas diffusion layer/catalyst interface. The 1D model - comprising the membrane-electrode assembly, cathode gas diffusion layer, and cathode channel - assumes non-Tafel kinetics to describe the complex kinetics of the multi-step methanol oxidation reaction at the anode, and accounts for the mixed potential associated with methanol crossover, induced both by diffusion and electro-osmotic drag. Polarization curves computed for various methanol feed concentrations, temperatures, and methanol feed velocities show good agreement with recent experimental results. The spatial distribution of methanol in the anode channels, together with the distributions of current density, methanol crossover and fuel utilization at the anode catalyst layer, are also presented for different opperating conditions. (author)

Channel of Axial Injection of DC-60 Cyclotron

CERN Document Server

Gikal, B N; Bogomolov, S L; Borisenko, A N; Borisov, O N; Gulbekyan, G G; Ivanenko, I A; Kalagin, I V; Kazacha, V I; Kazarinov, N Yu; Khabarov, M V; Lysukhin, S N; Melnikov, V N; Paschenko, S V; Tikhomirov, A V

2006-01-01

The design study and realization of the axial injection beam line of DC-60 cyclotron constructed at the Flerov Laboratory of Nuclear Reactions of the Joint Institute for Nuclear Research are given. The channel allows one to transport and to inject into the cyclotron ions with mass-to-charge ratio $A/Z$ being within interval A/Z=6-12 and kinetic energy up to 17 $Z/A$ keV/m.u.

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

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Chai Ann Ng

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

Improving flow distribution in influent channels using computational fluid dynamics.

Science.gov (United States)

Park, No-Suk; Yoon, Sukmin; Jeong, Woochang; Lee, Seungjae

2016-10-01

Although the flow distribution in an influent channel where the inflow is split into each treatment process in a wastewater treatment plant greatly affects the efficiency of the process, and a weir is the typical structure for the flow distribution, to the authors' knowledge, there is a paucity of research on the flow distribution in an open channel with a weir. In this study, the influent channel of a real-scale wastewater treatment plant was used, installing a suppressed rectangular weir that has a horizontal crest to cross the full channel width. The flow distribution in the influent channel was analyzed using a validated computational fluid dynamics model to investigate (1) the comparison of single-phase and two-phase simulation, (2) the improved procedure of the prototype channel, and (3) the effect of the inflow rate on flow distribution. The results show that two-phase simulation is more reliable due to the description of the free-surface fluctuations. It should first be considered for improving flow distribution to prevent a short-circuit flow, and the difference in the kinetic energy with the inflow rate makes flow distribution trends different. The authors believe that this case study is helpful for improving flow distribution in an influent channel.

An Extension of the Burridge-Knopoff Model for Friction

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Veturia Chiroiu

2015-09-01

Full Text Available The paper presents an extension of the Burridge-Knopoff (BK model with an additional kinetic equation for the friction force in order to reproduce the both the velocity weakening friction between the tire and the road and the increase of static friction with time when the car is not moving. The BK was initially proposed to investigate statistical properties of earthquakes. In this model the sliding force decreases monotonously from a reference value, and the static friction can have negative values to prevent back sliding. The stability of the system is affected and the sliding regime at small sliding velocities and large stiffness cannot be reproduced. The extended model BK assures the stability of the diagram sliding-stationary sliding, and correctly reproduces the stability diagram for sliding friction under various loading conditions.

On the mechanism of TBA block of the TRPV1 channel.

Science.gov (United States)

Oseguera, Andrés Jara; Islas, León D; García-Villegas, Refugio; Rosenbaum, Tamara

2007-06-01

The transient receptor potential vanilloid 1 (TRPV1) channel is a nonselective cation channel activated by capsaicin and responsible for thermosensation. To date, little is known about the gating characteristics of these channels. Here we used tetrabutylammonium (TBA) to determine whether this molecule behaves as an ion conduction blocker in TRPV1 channels and to gain insight into the nature of the activation gate of this protein. TBA belongs to a family of classic potassium channel blockers that have been widely used as tools for determining the localization of the activation gate and the properties of the pore of several ion channels. We found TBA to be a voltage-dependent pore blocker and that the properties of block are consistent with an open-state blocker, with the TBA molecule binding to multiple open states, each with different blocker affinities. Kinetics of channel closure and burst-length analysis in the presence of blocker are consistent with a state-dependent blocking mechanism, with TBA interfering with closing of an activation gate. This activation gate may be located cytoplasmically with respect to the binding site of TBA ions, similar to what has been observed in potassium channels. We propose an allosteric model for TRPV1 activation and block by TBA, which explains our experimental data.

In vitro inactivation of Chlamydia trachomatis and of a panel of DNA (HSV-2, CMV, adenovirus, BK virus) and RNA (RSV, enterovirus) viruses by the spermicide benzalkonium chloride.

Science.gov (United States)

Bélec, L; Tevi-Benissan, C; Bianchi, A; Cotigny, S; Beumont-Mauviel, M; Si-Mohamed, A; Malkin, J E

2000-11-01

Kinetics of inactivation by the detergent spermicide benzalkonium chloride (BZK) of Chlamydia trachomatis and of a panel of DNA viruses [herpes simplex virus hominis type 2 (HSV-2), cytomegalovirus (CMV), adenovirus (ADV) and BK virus (BKV)] and RNA [respiratory syncytial virus (RSV) and enterovirus (ENV)] were established in accordance with a standardized in vitro protocol. After a 5 min incubation, inactivation of >95% of HSV-2 and CMV was obtained at a concentration of 0.0025% (w/v) (25 Ig/L); concentrations as low as 0.0005%, 0.0050% and 0.0125%, induced a 3.0 log10 reduction in infectivity of HSV-2 and CMV, RSV and ADV, respectively. After a 60 min incubation, concentrations of 0.0125% and 0.050% provided a 3.0 log10 reduction in infectivity of ENV and BKV, respectively. These features indicate that sensitivity to BZK was very high (HSV-2 and CMV) or high (RSV) for enveloped viruses, intermediate (ADV) or low (ENV and BKV) for non-enveloped viruses. Furthermore, BZK had marked antichlamydial activity, showing >99% killing after only a 1 min incubation at a concentration of 0.00125%. BZK demonstrates potent in vitro activity against the majority of microorganisms causing sexually transmitted infectious diseases, including those acting as major genital cofactors of human immunodeficiency virus transmission. These attributes qualify BZK as a particularly attractive candidate for microbicide development.

Engineering of an E. coli outer membrane protein FhuA with increased channel diameter

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Dworeck Tamara

2011-08-01

Full Text Available Abstract Background Channel proteins like FhuA can be an alternative to artificial chemically synthesized nanopores. To reach such goals, channel proteins must be flexible enough to be modified in their geometry, i.e. length and diameter. As continuation of a previous study in which we addressed the lengthening of the channel, here we report the increasing of the channel diameter by genetic engineering. Results The FhuA Δ1-159 diameter increase has been obtained by doubling the amino acid sequence of the first two N-terminal β-strands, resulting in variant FhuA Δ1-159 Exp. The total number of β-strands increased from 22 to 24 and the channel surface area is expected to increase by ~16%. The secondary structure analysis by circular dichroism (CD spectroscopy shows a high β-sheet content, suggesting the correct folding of FhuA Δ1-159 Exp. To further prove the FhuA Δ1-159 Exp channel functionality, kinetic measurement using the HRP-TMB assay (HRP = Horse Radish Peroxidase, TMB = 3,3',5,5'-tetramethylbenzidine were conducted. The results indicated a 17% faster diffusion kinetic for FhuA Δ1-159 Exp as compared to FhuA Δ1-159, well correlated to the expected channel surface area increase of ~16%. Conclusion In this study using a simple "semi rational" approach the FhuA Δ1-159 diameter was enlarged. By combining the actual results with the previous ones on the FhuA Δ1-159 lengthening a new set of synthetic nanochannels with desired lengths and diameters can be produced, broadening the FhuA Δ1-159 applications. As large scale protein production is possible our approach can give a contribution to nanochannel industrial applications.

Development of a loop-mediated isothermal amplification assay for rapid detection of BK virus.

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Bista, Bipin Raj; Ishwad, Chandra; Wadowsky, Robert M; Manna, Pradip; Randhawa, Parmjeet Singh; Gupta, Gaurav; Adhikari, Meena; Tyagi, Rakhi; Gasper, Gina; Vats, Abhay

2007-05-01

Loop-mediated isothermal amplification (LAMP) is a novel method for rapid amplification of DNA. Its advantages include rapidity and minimal equipment requirement. The LAMP assay was developed for BK virus (BKV), which is a leading cause of morbidity in renal transplant recipients. The characteristics of the assay, including its specificity and sensitivity, were evaluated. BKV LAMP was performed using various incubation times with a variety of specimens, including unprocessed urine and plasma samples. A ladder pattern on gel electrophoresis, typical of successful LAMP reactions, was observed specifically only for BKV and not for other viruses. The sensitivity of the assay with 1 h of incubation was 100 copies/tube of a cloned BKV fragment. Additionally, a positive reaction was visually ascertained by a simple color reaction using SYBR green dye. BKV LAMP was also successful for urine and plasma specimens without the need for DNA extraction. Due to its simplicity and specificity, the LAMP assay can potentially be developed for "point of care" screening of BKV.

A comparison of HK-CONWIP and BK-CONWIP control strategies in a multi-product manufacturing system

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Chukwunonyelum Emmanuel Onyeocha

2015-12-01

Full Text Available This paper evaluates the performance of the Hybrid Kanban Constant Work-In-Process control strategy and Basestock Kanban Constant Work-In-Process control strategy operating Shared Kanban Allocation Policy (S-KAP and Dedicated Kanban Allocation Policy (D-KAP in a multi-product serial flow line. We explored the effect of an increase of product types on the WIP inventory in the system. A simulation-based optimisation technique was used in determining the optimal settings for the strategies. The strategies were compared via pairwise comparison technique and Nelson’s ranking and selection procedure. S-KAP responds quicker to demand than D-KAP. BK-CONWIP outperforms HK-CONWIP in a serial manufacturing system. It was shown that an increase in the number of product-type increases the number of PAC and WIP inventory.

Hydration properties of mechanosensitive channel pores define the energetics of gating

International Nuclear Information System (INIS)

Anishkin, A; Akitake, B; Kamaraju, K; Chiang, C-S; Sukharev, S

2010-01-01

Opening of ion channels directly by tension in the surrounding membrane appears to be the most ancient and simple mechanism of gating. Bacterial mechanosensitive channels MscL and MscS are the best-studied tension-gated nanopores, yet the key physical factors that define their gating are still hotly debated. Here we present estimations, simulations and experimental results showing that hydration of the pore might be one of the major parameters defining the thermodynamics and kinetics of mechanosensitive channel gating. We associate closing of channel pores with complete dehydration of the hydrophobic gate (occlusion by 'vapor lock') and formation of two water-vapor interfaces above and below the constriction. The opening path is the expansion of these interfaces, ultimately leading to wetting of the hydrophobic pore, which does not appear to be the exact reverse of the closing path, thus producing hysteresis. We discuss specifically the role of polar groups (glycines) buried in narrow closed conformations but exposed in the open states that change the wetting characteristics of the pore lining and stabilize conductive states of the channels.

Numerical simulation and decomposition of kinetic energy in the Central Mediterranean: insight on mesoscale circulation and energy conversion

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R. Sorgente

2011-08-01

Full Text Available The spatial and temporal variability of eddy and mean kinetic energy of the Central Mediterranean region has been investigated, from January 2008 to December 2010, by mean of a numerical simulation mainly to quantify the mesoscale dynamics and their relationships with physical forcing. In order to understand the energy redistribution processes, the baroclinic energy conversion has been analysed, suggesting hypotheses about the drivers of the mesoscale activity in this area. The ocean model used is based on the Princeton Ocean Model implemented at 1/32° horizontal resolution. Surface momentum and buoyancy fluxes are interactively computed by mean of standard bulk formulae using predicted model Sea Surface Temperature and atmospheric variables provided by the European Centre for Medium Range Weather Forecast operational analyses. At its lateral boundaries the model is one-way nested within the Mediterranean Forecasting System operational products.

The model domain has been subdivided in four sub-regions: Sardinia channel and southern Tyrrhenian Sea, Sicily channel, eastern Tunisian shelf and Libyan Sea. Temporal evolution of eddy and mean kinetic energy has been analysed, on each of the four sub-regions, showing different behaviours. On annual scales and within the first 5 m depth, the eddy kinetic energy represents approximately the 60 % of the total kinetic energy over the whole domain, confirming the strong mesoscale nature of the surface current flows in this area. The analyses show that the model well reproduces the path and the temporal behaviour of the main known sub-basin circulation features. New mesoscale structures have been also identified, from numerical results and direct observations, for the first time as the Pantelleria Vortex and the Medina Gyre.

The classical kinetic energy decomposition (eddy and mean allowed to depict and to quantify the permanent and fluctuating parts of the circulation in the region, and

Role of KCNMA1 in breast cancer.

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Martin Oeggerli

Full Text Available KCNMA1 encodes the α-subunit of the large conductance, voltage and Ca(2+-activated (BK potassium channel and has been reported as a target gene of genomic amplification at 10q22 in prostate cancer. To investigate the prevalence of the amplification in other human cancers, the copy number of KCNMA1 was analyzed by fluorescence-in-situ-hybridization (FISH in 2,445 tumors across 118 different tumor types. Amplification of KCNMA1 was restricted to a small but distinct fraction of breast, ovarian and endometrial cancer with the highest prevalence in invasive ductal breast cancers and serous carcinoma of ovary and endometrium (3-7%. We performed an extensive analysis on breast cancer tissue microarrays (TMA of 1,200 tumors linked to prognosis. KCNMA1 amplification was significantly associated with high tumor stage, high grade, high tumor cell proliferation, and poor prognosis. Immunofluorescence revealed moderate or strong KCNMA1 protein expression in 8 out of 9 human breast cancers and in the breast cancer cell line MFM223. KCNMA1-function in breast cancer cell lines was confirmed by whole-cell patch clamp recordings and proliferation assays, using siRNA-knockdown, BK channel activators such as 17ß-estradiol and the BK-channel blocker paxilline. Our findings revealed that enhanced expression of KCNMA1 correlates with and contributes to high proliferation rate and malignancy of breast cancer.

"Legal highs"--toxicity in the clinical and medico-legal aspect as exemplified by suicide with bk-MBDB administration.

Science.gov (United States)

Rojek, Sebastian; Kłys, Małgorzata; Strona, Marcin; Maciów, Martyna; Kula, Karol

2012-10-10

The easily available "legal highs", which are products containing psychoactive substances, such as cathinones, piperazines and synthetic cannabinoids, are abused by adolescents in Poland and in the world as alternatives to classic drugs, such as amphetamines or marijuana. The majority of these potentially dangerous substances are still legal and they are associated with a risk of severe poisoning or even death, and provide new challenges in clinical and forensic toxicological practice. Investigations in the field of "designer drugs" may be well illustrated by the case of a suicide of a 21-year old male who ingested a specified dose of a preparation called "Amphi-bi-a" that contains bk-MBDB, chemically 2-methylamino-1-(3,4-methylenedioxyphenyl) butan-1-one, which belongs to the cathinone group, as a synthetic euphoric empathogen and psychoactive stimulant that is chemically similar to MDMA. It is one of more common components of "legal highs" examined in Poland and other countries. The documentation of the case includes a clinical assessment of the patient's health status performed during his almost 4-h hospitalization before death, autopsy and histological examinations supported by toxicological findings revealing bk-MBDB at extremely high concentrations (at 20 mg/l in the blood and 33 mg/kg in the liver); hence, this body of evidence contributes to knowledge in the field of "designer drugs". Inventions of designers of new psychoactive xenobiotics, which are much in demand, especially in view of the dynamic Internet marketing, which drums up narcobusiness, must be balanced by a national strategy developed by medical, legal and educational circles in the modern civilized world in order to prevent the spreading of the phenomenon. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Elucidation of molecular kinetic schemes from macroscopic traces using system identification.

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Miguel Fribourg

2017-02-01

Full Text Available Overall cellular responses to biologically-relevant stimuli are mediated by networks of simpler lower-level processes. Although information about some of these processes can now be obtained by visualizing and recording events at the molecular level, this is still possible only in especially favorable cases. Therefore the development of methods to extract the dynamics and relationships between the different lower-level (microscopic processes from the overall (macroscopic response remains a crucial challenge in the understanding of many aspects of physiology. Here we have devised a hybrid computational-analytical method to accomplish this task, the SYStems-based MOLecular kinetic scheme Extractor (SYSMOLE. SYSMOLE utilizes system-identification input-output analysis to obtain a transfer function between the stimulus and the overall cellular response in the Laplace-transformed domain. It then derives a Markov-chain state molecular kinetic scheme uniquely associated with the transfer function by means of a classification procedure and an analytical step that imposes general biological constraints. We first tested SYSMOLE with synthetic data and evaluated its performance in terms of its rate of convergence to the correct molecular kinetic scheme and its robustness to noise. We then examined its performance on real experimental traces by analyzing macroscopic calcium-current traces elicited by membrane depolarization. SYSMOLE derived the correct, previously known molecular kinetic scheme describing the activation and inactivation of the underlying calcium channels and correctly identified the accepted mechanism of action of nifedipine, a calcium-channel blocker clinically used in patients with cardiovascular disease. Finally, we applied SYSMOLE to study the pharmacology of a new class of glutamate antipsychotic drugs and their crosstalk mechanism through a heteromeric complex of G protein-coupled receptors. Our results indicate that our methodology

Coinfection with Epstein–Barr Virus (EBV), Human Papilloma Virus (HPV) and Polyoma BK Virus (BKPyV) in Laryngeal, Oropharyngeal and Oral Cavity Cancer

OpenAIRE

Drop, Bartłomiej; Strycharz-Dudziak, Małgorzata; Kliszczewska, Ewa; Polz-Dacewicz, Małgorzata

2017-01-01

Most research providing evidence for the role of oncogenic viruses in head and neck squamous cell carcinoma (SCC) development is focused on one type of virus without analyzing possible interactions between two or more types of viruses. The aim of this study was to analyse the prevalence of co-infection with human papillomavirus (HPV), Epstein–Barr virus (EBV) and polyoma BK virus (BKPyV) in oral, oropharyngeal and laryngeal squamous cell carcinomas in Polish patients. The correlations between...

Estimating kinetic mechanisms with prior knowledge I: Linear parameter constraints.

Science.gov (United States)

Salari, Autoosa; Navarro, Marco A; Milescu, Mirela; Milescu, Lorin S

2018-02-05

To understand how ion channels and other proteins function at the molecular and cellular levels, one must decrypt their kinetic mechanisms. Sophisticated algorithms have been developed that can be used to extract kinetic parameters from a variety of experimental data types. However, formulating models that not only explain new data, but are also consistent with existing knowledge, remains a challenge. Here, we present a two-part study describing a mathematical and computational formalism that can be used to enforce prior knowledge into the model using constraints. In this first part, we focus on constraints that enforce explicit linear relationships involving rate constants or other model parameters. We develop a simple, linear algebra-based transformation that can be applied to enforce many types of model properties and assumptions, such as microscopic reversibility, allosteric gating, and equality and inequality parameter relationships. This transformation converts the set of linearly interdependent model parameters into a reduced set of independent parameters, which can be passed to an automated search engine for model optimization. In the companion article, we introduce a complementary method that can be used to enforce arbitrary parameter relationships and any constraints that quantify the behavior of the model under certain conditions. The procedures described in this study can, in principle, be coupled to any of the existing methods for solving molecular kinetics for ion channels or other proteins. These concepts can be used not only to enforce existing knowledge but also to formulate and test new hypotheses. © 2018 Salari et al.

Effects of the small molecule HERG activator NS1643 on Kv11.3 channels.

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Arne Bilet

Full Text Available NS1643 is one of the small molecule HERG (Kv11.1 channel activators and has also been found to increase erg2 (Kv11.2 currents. We now investigated whether NS1643 is also able to act as an activator of Kv11.3 (erg3 channels expressed in CHO cells. Activation of rat Kv11.3 current occurred in a dose-dependent manner and maximal current increasing effects were obtained with 10 µM NS1643. At this concentration, steady-state outward current increased by about 80% and the current increase was associated with a significant shift in the voltage dependence of activation to more negative potentials by about 15 mV. In addition, activation kinetics were accelerated, whereas deactivation was slowed. There was no significant effect on the kinetics of inactivation and recovery from inactivation. The strong current-activating agonistic effect of NS1643 did not result from a shift in the voltage dependence of Kv11.3 channel inactivation and was independent from external Na(+ or Ca(2+. At the higher concentration of 20 µM, NS1643 induced clearly less current increase. The left shift in the voltage dependence of activation reversed and the voltage sensitivity of activation dramatically decreased along with a slowing of Kv11.3 channel activation. These data show that, in comparison to other Kv11 family members, NS1643 exerts distinct effects on Kv11.3 channels with especially pronounced partial antagonistic effects at higher concentration.

Measurements for kinetic parameters estimation in the RA-0 research reactor

International Nuclear Information System (INIS)

Gomez, A; Bellino, P A

2012-01-01

In the present work, measurements based on the neutron noise technique and the inverse kinetic method were performed to estimate the different kinetic parameters of the reactor in its critical state. By means of the neutron noise technique, we obtained the current calibration factor of the ionization chamber M6 belonging to the power range channels of the reactor instrumentation. The maximum current allowed compatible with the maximum power authorized by the operation license was also obtained. Using the neutron noise technique, the reduced mean reproduction time (Λ*) was estimated. This parameter plays a fundamental role in the deterministic analysis of criticality accidents. Comparison with previous values justified performing new measurements to study systematic trends in the value of Λ*. Using the inverse kinetics method, the reactivity worth of the control rods was estimated, confirming the existence of spatial effects and trends previously observed (author)

Cytomegalovirus and BK-Virus co-infection of a clinically non-functioning adrenal adenoma: innocent bystanders or new pathogenetic agents?

Science.gov (United States)

Pomara, G; Cappello, F; Barzon, L; Morelli, G; Rappa, F; Benvegna, L; Giannarini, G; Palù, G; Selli, C

2006-01-01

We report a case of a 64-year-old woman who underwent left adrenalectomy with removal of a 8,5 cm clinically non-functioning adrenocortical adenoma and a 4-cm myelolipoma. Molecular testing for viral infection demonstrated the presence of cytomegalovirus (CMV) DNA sequences in the adrenal adenoma, but not in the myelolipoma (confirmed by immunohistochemistry). Moreover, the adrenal adenoma was also positive for parvovirus B19, and both adrenal tumor samples were positive for polyomavirus BK (BKV) and adenovirus DNA sequences. This is the first report of co-infection of an adrenocortical adenoma by CMV and BKV. The role of these viruses in adrenal tumorigenesis was postulated.

Cytomegalovirus and BK-Virus co-infection of a clinically non-functioning adrenal adenoma: innocent bystanders or new pathogenetic agents?

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G Pomara

2009-06-01

Full Text Available We report a case of a 64-year-old woman who underwent left adrenalectomy with removal of a 8,5 cm clinically non-functioning adrenocortical adenoma and a 4-cm myelolipoma. Molecular testing for viral infection demonstrated the presence of cytomegalovirus (CMV DNA sequences in the adrenal adenoma, but not in the myelolipoma (confirmed by immunohistochemistry. Moreover, the adrenal adenoma was also positive for parvovirus B19, and both adrenal tumor samples were positive for polyomavirus BK (BKV and adenovirus DNA sequences. This is the first report of co-infection of an adrenocortical adenoma by CMV and BKV. The role of these viruses in adrenal tumorigenesis was postulated.

Revealing kinetics and state-dependent binding properties of IKur-targeting drugs that maximize atrial fibrillation selectivity

Science.gov (United States)

Ellinwood, Nicholas; Dobrev, Dobromir; Morotti, Stefano; Grandi, Eleonora

2017-09-01

The KV1.5 potassium channel, which underlies the ultra-rapid delayed-rectifier current (IKur) and is predominantly expressed in atria vs. ventricles, has emerged as a promising target to treat atrial fibrillation (AF). However, while numerous KV1.5-selective compounds have been screened, characterized, and tested in various animal models of AF, evidence of antiarrhythmic efficacy in humans is still lacking. Moreover, current guidelines for pre-clinical assessment of candidate drugs heavily rely on steady-state concentration-response curves or IC50 values, which can overlook adverse cardiotoxic effects. We sought to investigate the effects of kinetics and state-dependent binding of IKur-targeting drugs on atrial electrophysiology in silico and reveal the ideal properties of IKur blockers that maximize anti-AF efficacy and minimize pro-arrhythmic risk. To this aim, we developed a new Markov model of IKur that describes KV1.5 gating based on experimental voltage-clamp data in atrial myocytes from patient right-atrial samples in normal sinus rhythm. We extended the IKur formulation to account for state-specificity and kinetics of KV1.5-drug interactions and incorporated it into our human atrial cell model. We simulated 1- and 3-Hz pacing protocols in drug-free conditions and with a [drug] equal to the IC50 value. The effects of binding and unbinding kinetics were determined by examining permutations of the forward (kon) and reverse (koff) binding rates to the closed, open, and inactivated states of the KV1.5 channel. We identified a subset of ideal drugs exhibiting anti-AF electrophysiological parameter changes at fast pacing rates (effective refractory period prolongation), while having little effect on normal sinus rhythm (limited action potential prolongation). Our results highlight that accurately accounting for channel interactions with drugs, including kinetics and state-dependent binding, is critical for developing safer and more effective pharmacological anti

Beta-keto amphetamines: studies on the metabolism of the designer drug mephedrone and toxicological detection of mephedrone, butylone, and methylone in urine using gas chromatography-mass spectrometry.

Science.gov (United States)

Meyer, Markus R; Wilhelm, Jens; Peters, Frank T; Maurer, Hans H

2010-06-01

In recent years, a new class of designer drugs has appeared on the drugs of abuse market in many countries, namely, the so-called beta-keto (bk) designer drugs such as mephedrone (bk-4-methylmethamphetamine), butylone (bk-MBDB), and methylone (bk-MDMA). The aim of the present study was to identify the metabolites of mephedrone in rat and human urine using GC-MS techniques and to include mephedrone, butylone, and methylone within the authors' systematic toxicological analysis (STA) procedure. Six phase I metabolites of mephedrone were detected in rat urine and seven in human urine suggesting the following metabolic steps: N-demethylation to the primary amine, reduction of the keto moiety to the respective alcohol, and oxidation of the tolyl moiety to the corresponding alcohols and carboxylic acid. The STA procedure allowed the detection of mephedrone, butylone, methylone, and their metabolites in urine of rats treated with doses corresponding to those reported for abuse of amphetamines. Besides macro-based data evaluation, an automated evaluation using the automated mass spectral deconvolution and identification system was performed. Mephedrone and butylone could be detected also in human urine samples submitted for drug testing. Assuming similar kinetics in humans, the described STA procedure should be suitable for proof of an intake of the bk-designer drugs in human urine.

A numerical study of the complex flow structure in a compound meandering channel

Science.gov (United States)

Moncho-Esteve, Ignacio J.; García-Villalba, Manuel; Muto, Yasu; Shiono, Koji; Palau-Salvador, Guillermo

2018-06-01

In this study, we report large eddy simulations of turbulent flow in a periodic compound meandering channel for three different depth conditions: one in-bank and two overbank conditions. The flow configuration corresponds to the experiments of Shiono and Muto (1998). The predicted mean streamwise velocities, mean secondary motions, velocity fluctuations, turbulent kinetic energy as well as mean flood flow angle to meandering channel are in good agreement with the experimental measurements. We have analyzed the flow structure as a function of the inundation level, with particular emphasis on the development of the secondary motions due to the interaction between the main channel and the floodplain flow. Bed shear stresses have been also estimated in the simulations. Floodplain flow has a significant impact on the flow structure leading to significantly different bed shear stress patterns within the main meandering channel. The implications of these results for natural compound meandering channels are also discussed.

ASAI ISOLAT BAKTERI KITINOLITIK BACILLUS SP. BK17 PADA MEDIA PEMBAWA TANAH GAMBUT DAN KOMPOS JANJANG KELAPA SAWIT DALAM MENGHAMBAT PERTUMBUHAN JAMUR PATOGEN SCLEROTIUM ROLFSII DAN FUSARIUM OXYSPORUM PADA KECAMBAH CABAI

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Deswidya Hutauruk

2016-10-01

Full Text Available Assay of chitinolytic bacterial isolate of Bacillus sp. Bk17 in peat and palm oil bunch compost as carrier media in inhibiting Sclerotium rolfsii and Fusarium oxysporum of chilli seedlings. Sclerotium rolfsii and Fusarium oxysporum have been known as causal agents of seedling-off of chilli. Biological control has been used as an alternative control to replace chemical control. This study was aimed to determine the viability and ability of chitinolityc bacteria Bacillus sp. BK17 in carrier media of peat and palm oil bunch compost and in growing media to control seedling-off caused by S. rolfsii dan F. oxysporum of chilli. Our previous study showed that Bacillus sp. BK17 could reduce disease severity and intensity. Bacterial viability was measured as colony number grown after 90 days of storage in minimum salt medium with colloidal chitin as sole C source. Reduction of disease infection was measured as seedling number infected by S. rolfsii dan F. oxysporum. Seedling performances were measured as seedling height, leaf number and dry-weight after 30-days of growth. The result showed that bacterial cell viability was still high in both peat and palm oil bunch compost both with and without colloidal chitin addition after 90 days of storage. It was also shown that during application bacterial cell could grow. Seedling performaces i.e. seedling height, leaf number and dry-weight showed to be normal or even increase compared to those of pathogenic fungal inoculation only and (- control.

Disease: H01258 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available H01258 Generalized epilepsy and paroxysmal dyskinesia (GEPD) Epilepsy is one of th...BK channel causes this syndrome. Nervous system disease; Epilepsy KCNMA1 [HSA:3778] [KO:K04936] ... ICD-10

Heteromeric ASIC channels composed of ASIC2b and ASIC1a display novel channel properties and contribute to acidosis-induced neuronal death

Science.gov (United States)

Sherwood, Thomas W.; Lee, Kirsten G.; Gormley, Matthew G.; Askwith, Candice C.

2011-01-01

Acid-sensing ion channel (ASIC) subunits associate to form homomeric or heteromeric proton-gated ion channels in neurons throughout the nervous system. The ASIC1a subunit plays an important role in establishing the kinetics of proton-gated currents in the central nervous system and activation of ASIC1a homomeric channels induces neuronal death following local acidosis that accompanies cerebral ischemia. The ASIC2b subunit is expressed in the brain in a pattern that overlaps ASIC1a, yet the contribution of ASIC2b has remained elusive. We find that co-expression of ASIC2b with ASIC1a in Xenopus oocytes results in novel proton-gated currents with properties distinct from ASIC1a homomeric channels. In particular, ASIC2b/1a heteromeric channels are inhibited by the non-selective potassium channel blockers tetraethylammonium (TEA) and barium. In addition, steady-state desensitization is induced at more basic pH values and Big Dynorphin sensitivity is enhanced in these unique heteromeric channels. Cultured hippocampal neurons show proton-gated currents consistent with ASIC2b contribution and these currents are lacking in neurons from mice with an ACCN1 (ASIC2) gene disruption. Finally, we find that these ASIC2b/1a heteromeric channels contribute to acidosis-induced neuronal death. Together, our results show that ASIC2b confers unique properties to heteromeric channels in central neurons. Further, these data indicate that ASIC2, like ASIC1, plays a role in acidosis-induced neuronal death and implicate the ASIC2b/1a subtype as a novel pharmacological target to prevent neuronal injury following stroke. PMID:21715637

Kinetic equilibrium of space charge dominated beams in a misaligned quadrupole focusing channel

International Nuclear Information System (INIS)

Goswami, A.; Sing Babu, P.; Pandit, V. S.

2013-01-01

The dynamics of intense beam propagation through the misaligned quadrupole focusing channel has been studied in a self-consistent manner using nonlinear Vlasov-Maxwell equations. The equations of motion of the beam centroid have been developed and found to be independent of any specific beam distribution. A Vlasov equilibrium distribution and beam envelope equations have been obtained, which provide us a theoretical tool to investigate the dynamics of intense beam propagating in a misaligned quadrupole focusing channel. It is shown that the displaced quadrupoles only cause the centroid of the beam to wander off axis. The beam envelope around the centroid obeys the familiar Kapchinskij-Vladimirskij envelope equation that is independent of the centroid motion. However, the rotation of the quadrupole about its optical axis affects the beam envelope and causes an increase in the projected emittances in the two transverse planes due to the inter-plane coupling

A prominent anchoring effect on the kinetic control of drug release from mesoporous silica nanoparticles (MSNs).

Science.gov (United States)

Tran, Vy Anh; Lee, Sang-Wha

2018-01-15

This work demonstrated kinetically controlled release of model drugs (ibuprofen, FITC) from well-tailored mesoporous silica nanoparticles (MSNs) depending on the surface charges and molecular sizes of the drugs. The molecular interactions between entrapped drugs and the pore walls of MSNs controlled the release of the drugs through the pore channels of MSNs. Also, polydopamine (PDA) layer-coated MSNs (MSNs@PDA) was quite effective to retard the release of large FITC, in contrast to a slight retardation effect on relatively small Ibuprofen. Of all things, FITC (Fluorescein isothiocyanate)-labeled APTMS (3-aminopropyltrimethoxysilane) (APTMS-FITC conjugates) grafted onto the MSNs generate a pinch-effect on the pore channel (so-called a prominent anchoring effect), which was highly effective in trapping (or blocking) drug molecules at the pore mouth of the MSNs. The anchored APTMS-FITC conjugates provided not only tortuous pathways to the diffusing molecules, but also sustained release of the ibuprofen over a long period of time (∼7days). The fast release kinetics was predicted by an exponential equation based on Fick's law, while the slow release kinetics was predicted by Higuchi model. Copyright © 2017 Elsevier Inc. All rights reserved.

Growth kinetics and morphology of plasma electrolytic oxidation coating on aluminum

International Nuclear Information System (INIS)

Erfanifar, Eliyas; Aliofkhazraei, Mahmood; Fakhr Nabavi, Houman; Sharifi, Hossein; Rouhaghdam, Alireza Sabour

2017-01-01

Plasma electrolytic oxidation (PEO) was carried out on AA1190 aluminum alloy in mixed silicate-phosphate-based electrolyte in order to fabricate ceramic coating under constant current density. The variations of PEO coating duration with kinetics, surface roughness, amount and size of discharge channels were studied with respect to PEO processing time. The growth mechanism of the ceramic coating was described considering a variation of volume and diameters of discharge channels and pancakes during the PEO. Scanning electron microscope (SEM), atomic force microscope (AFM), and roughness tester were used to study the plasma discharge channels of the PEO coatings. In addition, the effect of alumina nanoparticles in the electrolyte as the suspension was studied on the geometric parameters of discharge channels. It seems that the nanoparticles are adsorbed to the locations of erupted molten oxide, where the dielectric breakdown occurs. Nanoparticles were embedded in the dense oxide layer and were adsorbed at the walls of voids and coatings surface. As a result, they caused significant changes in roughness parameters of the samples containing nanoparticles compared to those without nanoparticles. The obtained results showed that growth kinetics followed a linear trend with respect to PEO coating duration. It was also observed that in the absence of alumina nanoparticles, the average volume of the pancakes is 150% greater than the ones fabricated in the suspension of nanoparticles. Besides, increasing the PEO coating duration leads to adsorbing more nanoparticles on the coating surface, filling the voids, and flattening the surface, and alterations in R v , R sk , and R lo parameters. Correlation between the diameter of discharge channel (d c ) and thickness of the pancake (h) also showed a linear relation. - Highlights: • Precise calculation of thickness of pancake with AFM. • Study of different roughness parameters for PEO coating. • Calculation the amount of

Growth kinetics and morphology of plasma electrolytic oxidation coating on aluminum

Energy Technology Data Exchange (ETDEWEB)

Erfanifar, Eliyas; Aliofkhazraei, Mahmood, E-mail: maliofkh@gmail.com; Fakhr Nabavi, Houman; Sharifi, Hossein; Rouhaghdam, Alireza Sabour

2017-01-01

Plasma electrolytic oxidation (PEO) was carried out on AA1190 aluminum alloy in mixed silicate-phosphate-based electrolyte in order to fabricate ceramic coating under constant current density. The variations of PEO coating duration with kinetics, surface roughness, amount and size of discharge channels were studied with respect to PEO processing time. The growth mechanism of the ceramic coating was described considering a variation of volume and diameters of discharge channels and pancakes during the PEO. Scanning electron microscope (SEM), atomic force microscope (AFM), and roughness tester were used to study the plasma discharge channels of the PEO coatings. In addition, the effect of alumina nanoparticles in the electrolyte as the suspension was studied on the geometric parameters of discharge channels. It seems that the nanoparticles are adsorbed to the locations of erupted molten oxide, where the dielectric breakdown occurs. Nanoparticles were embedded in the dense oxide layer and were adsorbed at the walls of voids and coatings surface. As a result, they caused significant changes in roughness parameters of the samples containing nanoparticles compared to those without nanoparticles. The obtained results showed that growth kinetics followed a linear trend with respect to PEO coating duration. It was also observed that in the absence of alumina nanoparticles, the average volume of the pancakes is 150% greater than the ones fabricated in the suspension of nanoparticles. Besides, increasing the PEO coating duration leads to adsorbing more nanoparticles on the coating surface, filling the voids, and flattening the surface, and alterations in R{sub v}, R{sub sk}, and R{sub lo} parameters. Correlation between the diameter of discharge channel (d{sub c}) and thickness of the pancake (h) also showed a linear relation. - Highlights: • Precise calculation of thickness of pancake with AFM. • Study of different roughness parameters for PEO coating. • Calculation

Modulation of Kir4.1 and Kir4.1-Kir5.1 channels by small changes in cell volume

DEFF Research Database (Denmark)

Soe, Rikke; Macaulay, Nanna; Klaerke, Dan Arne

2009-01-01

in Kir4.1 and Kir4.1-Kir5.1 currents upon swelling of the oocytes and a reduction in the current when the oocytes were shrunk. The volume-dependent changes in channel activity were not due to changes in the kinetics of the channels. These findings implicate a putative functional interaction between...... the Kir channels and aquaporins via small, fast cell volume changes in the glial cells....... channels and aquaporins is therefore debated. To test a possible volume-sensitivity of the Kir channels, the Kir4.1 or Kir4.1-Kir5.1 channels were expressed in Xenopus oocytes with or without co-expression of aquaporins and subsequently exposed to cell volume alterations. Our results show an increase...

Interaction of a dinoflagellate neurotoxin with voltage-activated ion channels in a marine diatom.

Science.gov (United States)

Kitchen, Sheila A; Bourdelais, Andrea J; Taylor, Alison R

2018-01-01

The potent neurotoxins produced by the harmful algal bloom species Karenia brevis are activators of sodium voltage-gated channels (VGC) in animals, resulting in altered channel kinetics and membrane hyperexcitability. Recent biophysical and genomic evidence supports widespread presence of homologous sodium (Na + ) and calcium (Ca 2+ ) permeable VGCs in unicellular algae, including marine phytoplankton. We therefore hypothesized that VGCs of these phytoplankton may be an allelopathic target for waterborne neurotoxins produced by K. brevis blooms that could lead to ion channel dysfunction and disruption of signaling in a similar manner to animal Na + VGCs. We examined the interaction of brevetoxin-3 (PbTx-3), a K. brevis neurotoxin, with the Na + /Ca 2+ VGC of the non-toxic diatom Odontella sinensi s using electrophysiology. Single electrode current- and voltage- clamp recordings from O. sinensis in the presence of PbTx-3 were used to examine the toxin's effect on voltage gated Na + /Ca 2+ currents. In silico analysis was used to identify the putative PbTx binding site in the diatoms. We identified Na + /Ca 2+ VCG homologs from the transcriptomes and genomes of 12 diatoms, including three transcripts from O. sinensis and aligned them with site-5 of Na + VGCs, previously identified as the PbTx binding site in animals. Up to 1 µM PbTx had no effect on diatom resting membrane potential or membrane excitability. The kinetics of fast inward Na + /Ca 2+ currents that underlie diatom action potentials were also unaffected. However, the peak inward current was inhibited by 33%, delayed outward current was inhibited by 25%, and reversal potential of the currents shifted positive, indicating a change in permeability of the underlying channels. Sequence analysis showed a lack of conservation of the PbTx binding site in diatom VGC homologs, many of which share molecular features more similar to single-domain bacterial Na + /Ca 2+ VGCs than the 4-domain eukaryote channels

Dual Regulation of Voltage-Sensitive Ion Channels by PIP2

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Aldo A Rodríguez Menchaca

2012-09-01

Full Text Available Over the past 16 years, there has been an impressive number of ion channels shown to be sensitive to the major phosphoinositide in the plasma membrane, phosphatidilinositol 4,5-bisphosphate (PIP2. Among them are voltage-gated channels, which are crucial for both neuronal and cardiac excitability. Voltage-gated calcium (Cav channels were shown to be regulated bidirectionally by PIP2. On one hand, PIP2 stabilized their activity by reducing current rundown but on the other hand it produced a voltage-dependent inhibition by shifting the activation curve to more positive voltages. For voltage-gated potassium (Kv channels PIP2 was first shown to prevent N-type inactivation. Careful examination of the effects of PIP2 on the activation mechanism of Kv1.2 has shown a similar bidirectional regulation as in the Cav channels. The two effects could be distinguished kinetically, in terms of their sensitivities to PIP2 and by distinct molecular determinants. The rightward shift of the Kv1.2 voltage dependence implicated basic residues in the S4-S5 linker and was consistent with stabilization of the inactive state of the voltage sensor. A third type of a voltage-gated ion channel modulated by PIP2 is the hyperpolarization-activated cyclic nucleotide-gated (HCN channel. PIP2 has been shown to enhance the opening of HCN channels by shifting their voltage-dependent activation toward depolarized potentials. The sea urchin HCN channel, SpIH, showed again a PIP2-mediated bidirectional effect but in reverse order than the depolarization-activated Cav and Kv channels: a voltage-dependent potentiation, like the mammalian HCN channels, but also an inhibition of the cGMP-induced current activation. Just like the Kv1.2 channels, distinct molecular determinants underlied the PIP2 dual effects on SpIH channels. The dual regulation of these very different ion channels, all of which are voltage dependent, points to conserved mechanisms of regulation of these channels by PIP2.

Clinical polyomavirus BK variants with agnogene deletion are non-functional but rescued by trans-complementation

International Nuclear Information System (INIS)

Myhre, Marit Renee; Olsen, Gunn-Hege; Gosert, Rainer; Hirsch, Hans H.; Rinaldo, Christine Hanssen

2010-01-01

High-level replication of polyomavirus BK (BKV) in kidney transplant recipients is associated with the emergence of BKV variants with rearranged (rr) non-coding control region (NCCR) increasing viral early gene expression and cytopathology. Cloning and sequencing revealed the presence of a BKV quasispecies which included non-functional variants when assayed in a recombinant virus assay. Here we report that the rr-NCCR of BKV variants RH-3 and RH-12, both bearing a NCCR deletion including the 5' end of the agnoprotein coding sequence, mediated early and late viral reporter gene expression in kidney cells. However, in a recombinant virus they failed to produce infectious progeny despite large T-antigen and VP1 expression and the formation of nuclear virus-like particles. Infectious progeny was generated when the agnogene was reconstructed in cis or agnoprotein provided in trans from a co-existing BKV rr-NCCR variant. We conclude that complementation can rescue non-functional BKV variants in vitro and possibly in vivo.

Kinetic properties and adrenergic control of TREK-2-like channels in rat medial prefrontal cortex (mPFC) pyramidal neurons.

Science.gov (United States)

Ładno, W; Gawlak, M; Szulczyk, P; Nurowska, E

2017-06-15

TREK-2-like channels were identified on the basis of electrophysiological and pharmacological tests performed on freshly isolated and enzymatically/mechanically dispersed pyramidal neurons of the rat medial prefrontal cortex (mPFC). Single-channel currents were recorded in cell-attached configuration and the impact of adrenergic receptors (α 1 , α 2 , β) stimulation on spontaneously appearing TREK-2-like channel activity was tested. The obtained results indicate that noradrenaline decreases the mean open probability of TREK-2-like channel currents by activation of β 1 but not of α 1 - and α 2 -adrenergic receptors. Mean open time and channel conductance were not affected. The system of intracellular signaling pathways depends on the activation of protein kinase A. We also show that adrenergic control of TREK-2-like channel currents by adrenergic receptors was similar in pyramidal neurons isolated from young, adolescent, and adult rats. Immunofluorescent confocal scans of mPFC slices confirmed the presence of the TREK-2 protein, which was abundant in layer V pyramidal neurons. The role of TREK-2-like channel control by adrenergic receptors is discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Water in the physiology of plant: thermodynamics and kinetic

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Maurizio Cocucci

2011-02-01

Full Text Available Molecular properties of water molecule determine its role in plant physiology. At molecular level the properties of water molecules determine the behaviour of other plant molecules; in particular its physic characteristics are important in the operativeness of macromolecules and in plant thermoregulation. Plant water supply primarily dependent on thermodynamics properties in particular water chemical potential and its components, more recently there are evidences that suggest an important role in the water kinetic characteristics, depending, at cell membrane level, in particular plasmalemma, on the presence of specific water channel, the aquaporines controlled in its activity by a number of physiological and biochemical factors. Thermodynamics and kinetic factors controlled by physiological, biochemical properties and molecular effectors, control water supply and level in plants to realize their survival, growth and differentiation and the consequent plant production.

Fragmentation and mean kinetic energy release of the nitrogen molecule

International Nuclear Information System (INIS)

Santos, A.C.F.; Melo, W.S.; Sant'Anna, M.M.; Sigaud, G.M.; Montenegro, E.C.

2007-01-01

Ionization and fragmentation of the N 2 molecule in coincidence with the final projectile charge state have been measured for the impact of 0.188-0.875 MeV/amu He + projectiles. The average kinetic energy release (KER) of the target ionic fragments is derived from the peak widths of their time-of-flight distributions. It is shown that the KER's for singly-charged products follow scaling laws irrespectively to the collision channel

Modeling the concentration-dependent permeation modes of the KcsA potassium ion channel.

Science.gov (United States)

Nelson, Peter Hugo

2003-12-01

The potassium channel from Streptomyces lividans (KcsA) is an integral membrane protein with sequence similarity to all known potassium channels, particularly in the selectivity filter region. A recently proposed model for ion channels containing either n or (n-1) single-file ions in their selectivity filters [P. H. Nelson, J. Chem. Phys. 177, 11396 (2002)] is applied to published KcsA channel K+ permeation data that exhibit a high-affinity process at low concentrations and a low-affinity process at high concentrations [M. LeMasurier et al., J. Gen. Physiol. 118, 303 (2001)]. The kinetic model is shown to provide a reasonable first-order explanation for both the high- and low-concentration permeation modes observed experimentally. The low-concentration mode ([K+]200 mM) has a 200-mV dissociation constant of 1100 mM and a conductance of 500 pS. Based on the permeation model, and x-ray analysis [J. H. Morais-Cabral et al., Nature (London) 414, 37 (2001)], it is suggested that the experimentally observed K+ permeation modes correspond to an n=3 mechanism at high concentrations and an n=2 mechanism at low concentrations. The ratio of the electrical dissociation distances for the high- and low-concentration modes is 3:2, also consistent with the proposed n=3 and n=2 modes. Model predictions for K+ channels that exhibit asymmetric current-voltage (I-V) curves are presented, and further validation of the kinetic model via molecular simulation and experiment is discussed. The qualitatively distinct I-V characteristics exhibited experimentally by Tl+, NH+4, and Rb+ ions at 100 mM concentration can also be explained using the model, but more extensive experimental tests are required for quantitative validation of the model predictions.

No evidence for infection of UK prostate cancer patients with XMRV, BK virus, Trichomonas vaginalis or human papilloma viruses.

Science.gov (United States)

Groom, Harriet C T; Warren, Anne Y; Neal, David E; Bishop, Kate N

2012-01-01

The prevalence of specific infections in UK prostate cancer patients was investigated. Serum from 84 patients and 62 controls was tested for neutralisation of xenotropic murine leukaemia virus-related virus (XMRV) Envelope. No reactivity was found in the patient samples. In addition, a further 100 prostate DNA samples were tested for XMRV, BK virus, Trichomonas vaginalis and human papilloma viruses by nucleic acid detection techniques. Despite demonstrating DNA integrity and assay sensitivity, we failed to detect the presence of any of these agents in DNA samples, bar one sample that was weakly positive for HPV16. Therefore we conclude that these infections are absent in this typical cohort of men with prostate cancer.

No evidence for infection of UK prostate cancer patients with XMRV, BK virus, Trichomonas vaginalis or human papilloma viruses.

Directory of Open Access Journals (Sweden)

Harriet C T Groom

Full Text Available The prevalence of specific infections in UK prostate cancer patients was investigated. Serum from 84 patients and 62 controls was tested for neutralisation of xenotropic murine leukaemia virus-related virus (XMRV Envelope. No reactivity was found in the patient samples. In addition, a further 100 prostate DNA samples were tested for XMRV, BK virus, Trichomonas vaginalis and human papilloma viruses by nucleic acid detection techniques. Despite demonstrating DNA integrity and assay sensitivity, we failed to detect the presence of any of these agents in DNA samples, bar one sample that was weakly positive for HPV16. Therefore we conclude that these infections are absent in this typical cohort of men with prostate cancer.

KINETIC ALGORITHMS FOR HARBOUR MANAGEMENT

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C. M. Gold

2012-07-01

Full Text Available Modern harbour management for a busy port needs to resolve a variety of simultaneous problems. Harbour traffic may be busy and the waterways congested, both by the major shipping and by the attendant harbour tugs. The harbour channel may be narrow and tortuous, and rapidly changing tides may require frequent course adjustments. Navigation aids must be clearly specified and immediately identifiable, in order to permit safe passage for the vessels. This requires a GIS with attributes not easily available with traditional products. The GeoVS system is a kinetic GIS with full three-dimensional visualisation, so that ships, bathymetry and landscape may be viewed in a form that is immediately understandable to both harbour pilots and the harbour authority. The system is kinetic because the data structures used to preserve the topological relationships between ships, seafloor and coastline are able to be maintained on a real-time basis, taking account of ship movement recorded on the compulsory AIS (Automatic Information System beacons. Maintenance of this real-time topology allows for easy detection of potential collisions, as well as real-time bathymetric estimations, necessary to prevent ship grounding in highly tidal environments. The system, based on previous research into kinetic Voronoi diagrams, as well as development of a completely new graphical engine, is now in commercial production, where its advantages over simpler twodimensional models without automatic collision and grounding detection are becoming evident. Other applications are readily envisaged, and will be addressed in the near future.

P-waves imaging of the FRI and BK zones at the Grimsel Rock Laboratory

International Nuclear Information System (INIS)

Majer, E.L.; Peterson, J.E. Jr.; Blueming, P.; Sattel, G.

1990-08-01

This report is one of a series documenting the results of the Nagra-DOE Cooperative (NDC-I) research program in which the cooperating scientists explore the geological, geophysical, hydrological, geochemical, and structural effects anticipated from the use of a rock mass as a geological repository for nuclear waste. Tomographic imaging studies using a high frequency (10 Khz.) piezoelectric source and a three component receiver were carried out in two different regions of the underground Nagra Grimsel test facility in Switzerland. Both sites were in fractured granite, one being in a strongly foliated granite (FRI site), and the other being in a relatively homogeneous granite (BK zone). The object of the work was to determine if the seismic techniques could be useful in imaging the fracture zones and provide information on the hydrologic conditions. Both amplitude and velocity tomograms were obtained from the Data. The results indicate that the fracture zones strongly influenced the seismic wave propagation, thus imaging the fracture zones that were hydrologically important. 11 refs., 24 figs

Development of a Loop-Mediated Isothermal Amplification Assay for Rapid Detection of BK Virus▿

Science.gov (United States)

Bista, Bipin Raj; Ishwad, Chandra; Wadowsky, Robert M.; Manna, Pradip; Randhawa, Parmjeet Singh; Gupta, Gaurav; Adhikari, Meena; Tyagi, Rakhi; Gasper, Gina; Vats, Abhay

2007-01-01

Loop-mediated isothermal amplification (LAMP) is a novel method for rapid amplification of DNA. Its advantages include rapidity and minimal equipment requirement. The LAMP assay was developed for BK virus (BKV), which is a leading cause of morbidity in renal transplant recipients. The characteristics of the assay, including its specificity and sensitivity, were evaluated. BKV LAMP was performed using various incubation times with a variety of specimens, including unprocessed urine and plasma samples. A ladder pattern on gel electrophoresis, typical of successful LAMP reactions, was observed specifically only for BKV and not for other viruses. The sensitivity of the assay with 1 h of incubation was 100 copies/tube of a cloned BKV fragment. Additionally, a positive reaction was visually ascertained by a simple color reaction using SYBR green dye. BKV LAMP was also successful for urine and plasma specimens without the need for DNA extraction. Due to its simplicity and specificity, the LAMP assay can potentially be developed for “point of care” screening of BKV. PMID:17314224

Kinetics of the Dynamical Information Shannon Entropy for Complex Systems

International Nuclear Information System (INIS)

Yulmetyev, R.M.; Yulmetyeva, D.G.

1999-01-01

Kinetic behaviour of dynamical information Shannon entropy is discussed for complex systems: physical systems with non-Markovian property and memory in correlation approximation, and biological and physiological systems with sequences of the Markovian and non-Markovian random noises. For the stochastic processes, a description of the information entropy in terms of normalized time correlation functions is given. The influence and important role of two mutually dependent channels of the entropy change, correlation (creation or generation of correlations) and anti-correlation (decay or annihilation of correlation) is discussed. The method developed here is also used in analysis of the density fluctuations in liquid cesium obtained from slow neutron scattering data, fractal kinetics of the long-range fluctuation in the short-time human memory and chaotic dynamics of R-R intervals of human ECG. (author)

The N-terminal tail of hERG contains an amphipathic α-helix that regulates channel deactivation.

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Chai Ann Ng

Full Text Available The cytoplasmic N-terminal domain of the human ether-a-go-go related gene (hERG K+ channel is critical for the slow deactivation kinetics of the channel. However, the mechanism(s by which the N-terminal domain regulates deactivation remains to be determined. Here we show that the solution NMR structure of the N-terminal 135 residues of hERG contains a previously described Per-Arnt-Sim (PAS domain (residues 26-135 as well as an amphipathic α-helix (residues 13-23 and an initial unstructured segment (residues 2-9. Deletion of residues 2-25, only the unstructured segment (residues 2-9 or replacement of the α-helix with a flexible linker all result in enhanced rates of deactivation. Thus, both the initial flexible segment and the α-helix are required but neither is sufficient to confer slow deactivation kinetics. Alanine scanning mutagenesis identified R5 and G6 in the initial flexible segment as critical for slow deactivation. Alanine mutants in the helical region had less dramatic phenotypes. We propose that the PAS domain is bound close to the central core of the channel and that the N-terminal α-helix ensures that the flexible tail is correctly orientated for interaction with the activation gating machinery to stabilize the open state of the channel.

SALLY, Dynamic Behaviour of Reactor Cooling Channel by Point Model

International Nuclear Information System (INIS)

Reiche, Chr.; Ziegenbein, D.

1981-01-01

1 - Nature of the physical problem solved: The dynamical behaviour of a cooling channel is calculated. Starting from an equilibrium state a perturbation is introduced into the system. That may be an outer reactivity perturbation or a change in the coolant velocity or in the coolant temperature. The neutron kinetics is treated in the framework of the one-point model. The cooling channel consists of a cladded and cooled fuel rod. The temperature distribution is taken into account as an array above a mesh of radial zones and axial layers. Heat transfer is considered in radial direction only, the thermodynamical coupling of the different layers is obtained by the coolant flow. The thermal material parameters are considered to be temperature independent. Reactivity feedback is introduced by means of reactivity coefficients for fuel, canning, and coolant. Doppler broadening is included. The first cooling cycle can be taken into account by a simple model. 2 - Method of solution: The integration of the point kinetics equations is done numerically by the P11 scheme. The system of temperature equations with constant heat resistance coefficients is solved by the method of factorization. 3 - Restrictions on the complexity of the problem: Given limits are: 10 radial fuel zones, 25 axial layers, 6 groups of delayed neutrons

From pan-reactive KV7 channel opener to subtype selective opener/inhibitor by addition of a methyl group.

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Sigrid Marie Blom

Full Text Available The voltage-gated potassium channels of the KV7 family (KV7.1-5 play important roles in controlling neuronal excitability and are therefore attractive targets for treatment of CNS disorders linked to hyperexcitability. One of the main challenges in developing KV7 channel active drugs has been to identify compounds capable of discriminating between the neuronally expressed subtypes (KV7.2-5, aiding the identification of the subunit composition of KV7 currents in various tissues, and possessing better therapeutic potential for particular indications. By taking advantage of the structure-activity relationship of acrylamide KV7 channel openers and the effects of these compounds on mutant KV7 channels, we have designed and synthesized a novel KV7 channel modulator with a unique profile. The compound, named SMB-1, is an inhibitor of KV7.2 and an activator of KV7.4. SMB-1 inhibits KV7.2 by reducing the current amplitude and increasing the time constant for the slow component of the activation kinetics. The activation of KV7.4 is seen as an increase in the current amplitude and a slowing of the deactivation kinetics. Experiments studying mutant channels with a compromised binding site for the KV7.2-5 opener retigabine indicate that SMB-1 binds within the same pocket as retigabine for both inhibition of KV7.2 and activation of KV7.4. SMB-1 may serve as a valuable tool for KV7 channel research and may be used as a template for further design of better subtype selective KV7 channel modulators. A compound with this profile could hold novel therapeutic potential such as the treatment of both positive and cognitive symptoms in schizophrenia.

Anomaly in the Kumakhov radiation temperature dependence at axial channeling of electrons

Energy Technology Data Exchange (ETDEWEB)

Komarov, F.F.; Telegin, V.I.; Khokonov, M.Kh.

1983-01-01

The results of numerical solution of a kinetic equation for distribution function of axially channelled electrons obtained by Belostritsky and Kumakhov at different temperatures of crystals and calculated for the determined electron distributions spectral density of radiation are given. Analysis of the obtained dependence of the number of channelled 5 GeV electrons in tungsten along the <111> axis on depth Z has revealed that 2% of incidence beam electrons have anomalously large depths of dechannelling. Ratio of electrons with large by modulus cross section energies grows at decreasing crystal temperature from 293 to 40 K and, therefore, radiation intensity increases. Two-fold increase of radiation intensity can be attained at axial channelling of 1 GeV electrons in tungsten <111> at the temperatures of the crystal equal to 40 and 293 K and its thickness equal to 220 ..mu..m.

Kinetics of proton transport into influenza virions by the viral M2 channel.

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Tijana Ivanovic

Full Text Available M2 protein of influenza A viruses is a tetrameric transmembrane proton channel, which has essential functions both early and late in the virus infectious cycle. Previous studies of proton transport by M2 have been limited to measurements outside the context of the virus particle. We have developed an in vitro fluorescence-based assay to monitor internal acidification of individual virions triggered to undergo membrane fusion. We show that rimantadine, an inhibitor of M2 proton conductance, blocks the acidification-dependent dissipation of fluorescence from a pH-sensitive virus-content probe. Fusion-pore formation usually follows internal acidification but does not require it. The rate of internal virion acidification increases with external proton concentration and saturates with a pK(m of ∼4.7. The rate of proton transport through a single, fully protonated M2 channel is approximately 100 to 400 protons per second. The saturating proton-concentration dependence and the low rate of internal virion acidification derived from authentic virions support a transporter model for the mechanism of proton transfer.

Osmotic stress regulates the strength and kinetics of sugar binding to the maltoporin channel

International Nuclear Information System (INIS)

Gurnev, Philip A; Bezrukov, Sergey M; Harries, Daniel; Adrian Parsegian, V

2010-01-01

We study the effect of osmotic stress, exerted by salts, on carbohydrate binding to the sugar-specific bacterial channel maltoporin. When the channel is reconstituted into planar lipid bilayers, single events of its occlusion by sugar are seen as transient interruptions in the flow of small ions. We find that, for most salts, changes in the free energy of maltoporin-sugar binding vary linearly with solution osmotic pressure. Such a change in binding with solution osmolarity indicates that for each salt a constant number of salt-excluding water molecules is released upon sugar-maltoporin association at all salt concentrations. We find that larger numbers of water molecules are released upon binding of the cyclic carbohydrate β-cyclodextrin (CD) than upon binding of the corresponding linear homologue maltoheptaose (m7). Remarkably, the extent to which salts affect the binding constants and rates depends sensitively on the type of salt; dehydration in solutions of different anions corresponds to the Hofmeister series. In sodium sulfate solutions, CD and m7 respectively release about 120 and 35 salt-excluding water molecules; in sodium chloride solutions, 35 and 15 waters. No water release is observed with sodium bromide. Finally, by adding adamantane, known to form an inclusion complex with CD, we can infer that CD not only dehydrates but also undergoes a conformational change upon binding to the channel. As a practical outcome, our results also demonstrate how osmotic stress can improve single-molecule detection of different solutes using protein-based nanopores.

Long-Term Protection of Genetically Ablated Rabbit Retinal Degeneration by Sustained Transscleral Unoprostone Delivery.

Science.gov (United States)

Nagai, Nobuhiro; Koyanagi, Eri; Izumida, Yasuko; Liu, Junjun; Katsuyama, Aya; Kaji, Hirokazu; Nishizawa, Matsuhiko; Osumi, Noriko; Kondo, Mineo; Terasaki, Hiroko; Mashima, Yukihiko; Nakazawa, Toru; Abe, Toshiaki

2016-12-01

To evaluate the long-term protective effects of transscleral unoprostone (UNO) against retinal degeneration in transgenic (Tg) rabbits (Pro347Leu rhodopsin mutation). The UNO release devices (URDs) were implanted into the sclerae of Tg rabbits and ERG, optical coherence tomography (OCT), and ophthalmic examinations were conducted for 40 weeks. Unoprostone metabolites in retina, choroid/RPE, aqueous humor, and plasma from wild-type (Wt) rabbits were measured using liquid chromatography-tandem mass spectrometry. In situ hybridization and immunohistochemistry evaluated the retinal distribution of big potassium (BK) channels, and RT-PCR evaluated the expressions of BK channels and m-opsin at 1 week after URD treatment. The URD released UNO at a rate of 10.2 ±1.0 μg/d, and the release rate and amount of UNO decreased during 32 weeks. Higher ERG amplitudes were observed in the URD-treated Tg rabbits compared with the placebo-URD, or nontreated controls. At 24 weeks after implantation into the URD-treated Tg rabbits, OCT images showed preservation of retinal thickness, and histologic examinations (44 weeks) showed greater thickness of outer nuclear layers. Unoprostone was detected in the retina, choroid, and plasma of Wt rabbits. Retina/plasma ratio of UNO levels were 38.0 vs. 0.68 ng UNO*hour/mL in the URD-treated group versus control (topical UNO), respectively. Big potassium channels were observed in cone, cone ON-bipolar, and rod bipolar cells. Reverse-transcriptase PCR demonstrated BK channels and m-opsins increased in URD-treated eyes. In Tg rabbits, URD use slowed the decline of retinal function for more than 32 weeks, and therefore provides a promising tool for long-term treatment of RP.

Mechanisms of Gain Control by Voltage-Gated Channels in Intrinsically-Firing Neurons

Science.gov (United States)

Patel, Ameera X.; Burdakov, Denis

2015-01-01

Gain modulation is a key feature of neural information processing, but underlying mechanisms remain unclear. In single neurons, gain can be measured as the slope of the current-frequency (input-output) relationship over any given range of inputs. While much work has focused on the control of basal firing rates and spike rate adaptation, gain control has been relatively unstudied. Of the limited studies on gain control, some have examined the roles of synaptic noise and passive somatic currents, but the roles of voltage-gated channels present ubiquitously in neurons have been less explored. Here, we systematically examined the relationship between gain and voltage-gated ion channels in a conductance-based, tonically-active, model neuron. Changes in expression (conductance density) of voltage-gated channels increased (Ca2+ channel), reduced (K+ channels), or produced little effect (h-type channel) on gain. We found that the gain-controlling ability of channels increased exponentially with the steepness of their activation within the dynamic voltage window (voltage range associated with firing). For depolarization-activated channels, this produced a greater channel current per action potential at higher firing rates. This allowed these channels to modulate gain by contributing to firing preferentially at states of higher excitation. A finer analysis of the current-voltage relationship during tonic firing identified narrow voltage windows at which the gain-modulating channels exerted their effects. As a proof of concept, we show that h-type channels can be tuned to modulate gain by changing the steepness of their activation within the dynamic voltage window. These results show how the impact of an ion channel on gain can be predicted from the relationship between channel kinetics and the membrane potential during firing. This is potentially relevant to understanding input-output scaling in a wide class of neurons found throughout the brain and other nervous systems

Urological management (medical and surgical of BK-virus associated haemorrhagic cystitis in children following haematopoietic stem cell transplantation

Directory of Open Access Journals (Sweden)

Nikhil Vasdev

2013-10-01

Full Text Available Aim: Haemorrhagic cystitis (HC is uncommon and in its severe form potentially life threatening complication of Haematopoietic stem cell transplantation (HSCT in children. We present our single centre experience in the urological management of this clinically challenging condition. Patients and Methods: Fourteen patients were diagnosed with BK-Virus HC in our centre. The mean age at diagnosis was 8.8 years (range, 3.2-18.4 years. The mean number of days post-BMT until onset of HC was 20.8 (range, 1 – 51. While all patients tested urine positive for BKV at the clinical onset of HC, only four patients had viral quantification, with viral loads ranging from 97,000 to >1 billion/ml. 8 patients had clinical HC. Ten patients experienced acute GVHD (grade I: 6 patients, grade II: 3 patients, grade 4: 1 patient.Results: Four patients received medical management for their HC. Treatments included hyperhydration, MESNA, blood and platelet transfusion, premarin and oxybutynin (Table 6.  Two patients received both medical and surgical management which included cystoscopy with clot evacuation, bladder irrigation and supra-pubic catheter insertion. One patient received exclusive surgical management. Seven patients were treated conservatively. Conclusion: There is limited available evidence for other potential therapeutic strategies highlighting the need for more research into the pathophysiology of HSCT-associated HC. Commonly used interventions with possible clinical benefit (e.g. cidofovir, ciprofloxacin still require to be evaluated in multi-centre, high-quality studies. Potential future preventative and therapeutic options, such as modulation of conditioning, immunosuppression and engraftment, new antiviral and anti-inflammatory and less nephrotoxic agents need to be assessed.---------------------------Cite this article as:Vasdev N, Davidson A, Harkensee C, Slatter M, Gennery A, Willetts I, Thorpe A.Urological management (medical and surgical of BK

Free energy dissipation of the spontaneous gating of a single voltage-gated potassium channel.

Science.gov (United States)

Wang, Jia-Zeng; Wang, Rui-Zhen

2018-02-01

Potassium channels mainly contribute to the resting potential and re-polarizations, with the potassium electrochemical gradient being maintained by the pump Na + /K + -ATPase. In this paper, we construct a stochastic model mimicking the kinetics of a potassium channel, which integrates temporal evolving of the membrane voltage and the spontaneous gating of the channel. Its stationary probability density functions (PDFs) are found to be singular at the boundaries, which result from the fact that the evolving rates of voltage are greater than the gating rates of the channel. We apply PDFs to calculate the power dissipations of the potassium current, the leakage, and the gating currents. On a physical perspective, the essential role of the system is the K + -battery charging the leakage (L-)battery. A part of power will inevitably be dissipated among the process. So, the efficiency of energy transference is calculated.

Hypoosmotic cell swelling as a novel mechanism for modulation of cloned HCN2 channels

DEFF Research Database (Denmark)

Calloe, Kirstine; Elmedyb, Pernille; Olesen, Søren-Peter

2005-01-01

This work demonstrates cell swelling as a new regulatory mechanism for the cloned hyperpolarization-activated, cyclic nucleotide-gated channel 2 (HCN2). HCN2 channels were coexpressed with aquaporin1 in Xenopus laevis oocytes and currents were monitored using a two-electrode voltage-clamp. HCN2...... channels were activated by hyperpolarization to -100 mV and the currents were measured before and during hypoosmotic cell swelling. Cell swelling increased HCN2 currents by 30% without changing the kinetics of the currents. Injection of 50 nl intracellular solution resulted in a current increase of 20......%, indicating that an increase in cell volume also under isoosmotic conditions may lead to activation of HCN2. In the absence of aquaporin1 only negligible changes in oocyte cell volume occur during exposure to hypoosmotic media and no significant change in HCN2 channel activity was observed during perfusion...

Free energy dissipation of the spontaneous gating of a single voltage-gated potassium channel

Science.gov (United States)

Wang, Jia-Zeng; Wang, Rui-Zhen

2018-02-01

Potassium channels mainly contribute to the resting potential and re-polarizations, with the potassium electrochemical gradient being maintained by the pump Na+/K+-ATPase. In this paper, we construct a stochastic model mimicking the kinetics of a potassium channel, which integrates temporal evolving of the membrane voltage and the spontaneous gating of the channel. Its stationary probability density functions (PDFs) are found to be singular at the boundaries, which result from the fact that the evolving rates of voltage are greater than the gating rates of the channel. We apply PDFs to calculate the power dissipations of the potassium current, the leakage, and the gating currents. On a physical perspective, the essential role of the system is the K+-battery charging the leakage (L-)battery. A part of power will inevitably be dissipated among the process. So, the efficiency of energy transference is calculated.

Zebrafish CaV2.1 Calcium Channels Are Tailored for Fast Synchronous Neuromuscular Transmission

Science.gov (United States)

Naranjo, David; Wen, Hua; Brehm, Paul

2015-01-01

The CaV2.2 (N-type) and CaV2.1 (P/Q-type) voltage-dependent calcium channels are prevalent throughout the nervous system where they mediate synaptic transmission, but the basis for the selective presence at individual synapses still remains an open question. The CaV2.1 channels have been proposed to respond more effectively to brief action potentials (APs), an idea supported by computational modeling. However, the side-by-side comparison of CaV2.1 and CaV2.2 kinetics in intact neurons failed to reveal differences. As an alternative means for direct functional comparison we expressed zebrafish CaV2.1 and CaV2.2 α-subunits, along with their accessory subunits, in HEK293 cells. HEK cells lack calcium currents, thereby circumventing the need for pharmacological inhibition of mixed calcium channel isoforms present in neurons. HEK cells also have a simplified morphology compared to neurons, which improves voltage control. Our measurements revealed faster kinetics and shallower voltage-dependence of activation and deactivation for CaV2.1. Additionally, recordings of calcium current in response to a command waveform based on the motorneuron AP show, directly, more effective activation of CaV2.1. Analysis of calcium currents associated with the AP waveform indicate an approximately fourfold greater open probability (PO) for CaV2.1. The efficient activation of CaV2.1 channels during APs may contribute to the highly reliable transmission at zebrafish neuromuscular junctions. PMID:25650925

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

Science.gov (United States)

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

2013-08-01

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

CaV3.1 isoform of T-type calcium channels supports excitability of rat and mouse ventral tegmental area neurons.

Science.gov (United States)

Tracy, Matthew E; Tesic, Vesna; Stamenic, Tamara Timic; Joksimovic, Srdjan M; Busquet, Nicolas; Jevtovic-Todorovic, Vesna; Todorovic, Slobodan M

2018-03-23

Recent data have implicated voltage-gated calcium channels in the regulation of the excitability of neurons within the mesolimbic reward system. While the attention of most research has centered on high voltage L-type calcium channel activity, the presence and role of the low voltage-gated T-type calcium channel (T-channels) has not been well explored. Hence, we investigated T-channel properties in the neurons of the ventral tegmental area (VTA) utilizing wild-type (WT) rats and mice, Ca V 3.1 knock-out (KO) mice, and TH-eGFP knock-in (KI) rats in acute horizontal brain slices of adolescent animals. In voltage-clamp experiments, we first assessed T-channel activity in WT rats with characteristic properties of voltage-dependent activation and inactivation, as well as characteristic crisscrossing patterns of macroscopic current kinetics. T-current kinetics were similar in WT mice and WT rats but T-currents were abolished in Ca V 3.1 KO mice. In ensuing current-clamp experiments, we observed the presence of hyperpolarization-induced rebound burst firing in a subset of neurons in WT rats, as well as dopaminergic and non-dopaminergic neurons in TH-eGFP KI rats. Following the application of a pan-selective T-channel blocker TTA-P2, rebound bursting was significantly inhibited in all tested cells. In a behavioral assessment, the acute locomotor increase induced by a MK-801 (Dizocilpine) injection in WT mice was abolished in Ca V 3.1 KO mice, suggesting a tangible role for 3.1 T-type channels in drug response. We conclude that pharmacological targeting of Ca V 3.1 isoform of T-channels may be a novel approach for the treatment of disorders of mesolimbic reward system. Copyright © 2018. Published by Elsevier Ltd.

Path lumping: An efficient algorithm to identify metastable path channels for conformational dynamics of multi-body systems

Science.gov (United States)

Meng, Luming; Sheong, Fu Kit; Zeng, Xiangze; Zhu, Lizhe; Huang, Xuhui

2017-07-01

Constructing Markov state models from large-scale molecular dynamics simulation trajectories is a promising approach to dissect the kinetic mechanisms of complex chemical and biological processes. Combined with transition path theory, Markov state models can be applied to identify all pathways connecting any conformational states of interest. However, the identified pathways can be too complex to comprehend, especially for multi-body processes where numerous parallel pathways with comparable flux probability often coexist. Here, we have developed a path lumping method to group these parallel pathways into metastable path channels for analysis. We define the similarity between two pathways as the intercrossing flux between them and then apply the spectral clustering algorithm to lump these pathways into groups. We demonstrate the power of our method by applying it to two systems: a 2D-potential consisting of four metastable energy channels and the hydrophobic collapse process of two hydrophobic molecules. In both cases, our algorithm successfully reveals the metastable path channels. We expect this path lumping algorithm to be a promising tool for revealing unprecedented insights into the kinetic mechanisms of complex multi-body processes.

Balance of liquid-phase turbulence kinetic energy equation for bubble-train flow

International Nuclear Information System (INIS)

Ilic, Milica; Woerner, Martin; Cacuci, Dan Gabriel

2004-01-01

In this paper the investigation of bubble-induced turbulence using direct numerical simulation (DNS) of bubbly two-phase flow is reported. DNS computations are performed for a bubble-driven liquid motion induced by a regular train of ellipsoidal bubbles rising through an initially stagnant liquid within a plane vertical channel. DNS data are used to evaluate balance terms in the balance equation for the liquid phase turbulence kinetic energy. The evaluation comprises single-phase-like terms (diffusion, dissipation and production) as well as the interfacial term. Special emphasis is placed on the procedure for evaluation of interfacial quantities. Quantitative analysis of the balance equation for the liquid phase turbulence kinetic energy shows the importance of the interfacial term which is the only source term. The DNS results are further used to validate closure assumptions employed in modelling of the liquid phase turbulence kinetic energy transport in gas-liquid bubbly flows. In this context, the performance of respective closure relations in the transport equation for liquid turbulence kinetic energy within the two-phase k-ε and the two-phase k-l model is evaluated. (author)

The N-terminal domain of Slack determines the formation and trafficking of Slick/Slack heteromeric sodium-activated potassium channels.

Science.gov (United States)

Chen, Haijun; Kronengold, Jack; Yan, Yangyang; Gazula, Valeswara-Rao; Brown, Maile R; Ma, Liqun; Ferreira, Gonzalo; Yang, Youshan; Bhattacharjee, Arin; Sigworth, Fred J; Salkoff, Larry; Kaczmarek, Leonard K

2009-04-29

Potassium channels activated by intracellular Na(+) ions (K(Na)) play several distinct roles in regulating the firing patterns of neurons, and, at the single channel level, their properties are quite diverse. Two known genes, Slick and Slack, encode K(Na) channels. We have now found that Slick and Slack subunits coassemble to form heteromeric channels that differ from the homomers in their unitary conductance, kinetic behavior, subcellular localization, and response to activation of protein kinase C. Heteromer formation requires the N-terminal domain of Slack-B, one of the alternative splice variants of the Slack channel. This cytoplasmic N-terminal domain of Slack-B also facilitates the localization of heteromeric K(Na) channels to the plasma membrane. Immunocytochemical studies indicate that Slick and Slack-B subunits are coexpressed in many central neurons. Our findings provide a molecular explanation for some of the diversity in reported properties of neuronal K(Na) channels.

Non-kinetic capabilities: complementing the kinetic prevalence to targeting

OpenAIRE

Ducheine, P.

2014-01-01

Targeting is used in military doctrine to describe a military operational way, using (military) means to influence a target (or addressee) in order to achieve designated political and/or military goals. The four factors italicized are used to analyse non-kinetic targeting, complementing our knowledge and understanding of the kinetic prevalence. Paradoxically, non-kinetic targeting is not recognized as a separate concept: kinetic and non-kinetic are intertwined facets of targeting. Kinetic tar...

Channel Power in Multi-Channel Environments

NARCIS (Netherlands)

M.G. Dekimpe (Marnik); B. Skiera (Bernd)

2004-01-01

textabstractIn the literature, little attention has been paid to instances where companies add an Internet channel to their direct channel portfolio. However, actively managing multiple sales channels requires knowing the customers’ channel preferences and the resulting channel power. Two key

A three-dimensional model of PEM fuel cells with serpentine flow channels

International Nuclear Information System (INIS)

Nguyen, P.T.; Berning, T.; Bang, M.; Djilali, N.

2003-01-01

A three-dimensional computational model of PEM fuel cell with serpentine flow field channels is presented in this paper. This model presents a comprehensive account for all important transport phenomena in fuel cell such as heat transfer, mass transfer, electrode kinetics, and potential fields in the membrane and gas diffusion layers. A new approach of solving for the potential losses across the cell was also developed in this model. The dependency of local current density on oxygen concentration and activation overpotential is fully addressed in this model. The computational domain consists of serpentine gas flow channels, porous gas diffusion layers, catalyst layers, and a membrane. Results obtained from this model are in good agreement with experimental results. (author)

Propagation of an intense laser pulse in an under-dense plasma: channeling and stimulated Raman scattering

International Nuclear Information System (INIS)

Friou, A.

2012-01-01

This thesis is divided in two parts: i) the laser channeling in hundreds of microns long under-dense plasmas (0.1 nc ≤ n ≤ nc, nc being the critical density) of a laser pulse of intensity 10 18-20 W/cm 2 and duration 1-10 ps; ii) the saturation mechanisms of stimulated Raman back-scattering of a laser pulse of intensity 10 14 to 10 16 W/cm 2 and duration of about 1 ps. A parametric study was performed to study the channeling of a very intense laser pulse, using a 2D PIC (Particle In Cell) code. Various kinds of channels were obtained depending on the laser and plasma parameters, thereby reproducing and enlarging previous studies. Moreover, the channeling velocity was measured and scaling laws were established for homogeneous plasmas. They are then applied to inhomogeneous plasmas, similar to those encountered in inertial confinement fusion (ICF). It is then possible to estimate the energy necessary to channel to the critical density, an important step for the fast ignition scheme of ICF. Raman saturation was studied using numerical simulations, in order to determine if it is due to dephasing or to the growth of sidebands, using different approaches. The first is to study Raman simulations (electromagnetic) performed with kinetic PIC and Vlasov codes. The second, is to study the evolution of a plasma initialized with a distribution function after the adiabatic theory, using a Vlasov code (electrostatic). In this case, we observe the growth of a sideband, with dominant wave number and growth rate in good agreement with kinetic simulations. The saturation of the plasma wave can be caused by both saturation mechanisms. [fr

Flow separation on transversal ribs in an open channel

Czech Academy of Sciences Publication Activity Database

Příhoda, Jaromír; Šulc, J.; Sedlář, M.; Zubík, P.

2009-01-01

Roč. 13, - (2009), s. 218-220 ISSN 1335-2938. [Stretnutie katedier mechaniky tekutín a termomechaniky. Jasná, Demanovská dolina, 24.06.2009-26.06.2009] R&D Projects: GA ČR GA103/09/0977 Institutional research plan: CEZ:AV0Z20760514 Keywords : free-surface flow * supercritical flow over ribs * numerical and experimental modelling Subject RIV: BK - Fluid Dynamics

Numerical Study of Detonation Wave Propagation in the Variable Cross-Section Channel Using Unstructured Computational Grids

Directory of Open Access Journals (Sweden)

Alexander Lopato

2018-01-01

Full Text Available The work is dedicated to the numerical study of detonation wave initiation and propagation in the variable cross-section axisymmetric channel filled with the model hydrogen-air mixture. The channel models the large-scale device for the utilization of worn-out tires. Mathematical model is based on two-dimensional axisymmetric Euler equations supplemented by global chemical kinetics model. The finite volume computational algorithm of the second approximation order for the calculation of two-dimensional flows with detonation waves on fully unstructured grids with triangular cells is developed. Three geometrical configurations of the channel are investigated, each with its own degree of the divergence of the conical part of the channel from the point of view of the pressure from the detonation wave on the end wall of the channel. The problem in consideration relates to the problem of waste recycling in the devices based on the detonation combustion of the fuel.

A new kinetic biphasic approach applied to biodiesel process intensification

Energy Technology Data Exchange (ETDEWEB)

Russo, V.; Tesser, R.; Di Serio, M.; Santacesaria, E. [Naples Univ. (Italy). Dept. of Chemistry

2012-07-01

Many different papers have been published on the kinetics of the transesterification of vegetable oil with methanol, in the presence of alkaline catalysts to produce biodiesel. All the proposed approaches are based on the assumption of a pseudo-monophasic system. The consequence of these approaches is that some experimental aspects cannot be described. For the reaction performed in batch conditions, for example, the monophasic approach is not able to reproduce the different plateau obtained by using different amount of catalyst or the induction time observed at low stirring rates. Moreover, it has been observed by operating in continuous reactors that micromixing has a dramatic effect on the reaction rate. At this purpose, we have recently observed that is possible to obtain a complete conversion to biodiesel in less than 10 seconds of reaction time. This observation is confirmed also by other authors using different types of reactors like: static mixers, micro-reactors, oscillatory flow reactors, cavitational reactors, microwave reactors or centrifugal contactors. In this work we will show that a recently proposed biphasic kinetic approach is able to describe all the aspects before mentioned that cannot be described by the monophasic kinetic model. In particular, we will show that the biphasic kinetic model can describe both the induction time observed in the batch reactors, at low stirring rate, and the very high conversions obtainable in a micro-channel reactor. The adopted biphasic kinetic model is based on a reliable reaction mechanism that will be validated by the experimental evidences reported in this work. (orig.)

Molecular Evolution of Slow and Quick Anion Channels (SLACs and QUACs/ALMTs).

Science.gov (United States)

Dreyer, Ingo; Gomez-Porras, Judith Lucia; Riaño-Pachón, Diego Mauricio; Hedrich, Rainer; Geiger, Dietmar

2012-01-01

Electrophysiological analyses conducted about 25 years ago detected two types of anion channels in the plasma membrane of guard cells. One type of channel responds slowly to changes in membrane voltage while the other responds quickly. Consequently, they were named SLAC, for SLow Anion Channel, and QUAC, for QUick Anion Channel. Recently, genes SLAC1 and QUAC1/ALMT12, underlying the two different anion current components, could be identified in the model plant Arabidopsis thaliana. Expression of the gene products in Xenopus oocytes confirmed the quick and slow current kinetics. In this study we provide an overview on our current knowledge on slow and quick anion channels in plants and analyze the molecular evolution of ALMT/QUAC-like and SLAC-like channels. We discovered fingerprints that allow screening databases for these channel types and were able to identify 192 (177 non-redundant) SLAC-like and 422 (402 non-redundant) ALMT/QUAC-like proteins in the fully sequenced genomes of 32 plant species. Phylogenetic analyses provided new insights into the molecular evolution of these channel types. We also combined sequence alignment and clustering with predictions of protein features, leading to the identification of known conserved phosphorylation sites in SLAC1-like channels along with potential sites that have not been yet experimentally confirmed. Using a similar strategy to analyze the hydropathicity of ALMT/QUAC-like channels, we propose a modified topology with additional transmembrane regions that integrates structure and function of these membrane proteins. Our results suggest that cross-referencing phylogenetic analyses with position-specific protein properties and functional data could be a very powerful tool for genome research approaches in general.

Molecular evolution of slow and quick anion channels (SLACs and QUACs/ALMTs

Directory of Open Access Journals (Sweden)

Ingo eDreyer

2012-11-01

Full Text Available Electrophysiological analyses conducted about 25 years ago detected two types of anion channels in the plasma membrane of guard cells. One type of channel responds slowly to changes in membrane voltage while the other responds quickly. Consequently, they were named SLAC, for SLow Anion Channel, and QUAC, for QUick Anion Channel. Recently, genes SLAC1 and QUAC1/ALMT12, underlying the two different anion current components, could be identified in the model plant Arabidopsis thaliana. Expression of the gene products in Xenopus oocytes confirmed the quick and slow current kinetics. In this study we provide an overview on our current knowledge on slow and quick anion channels in plants and analyze the molecular evolution of ALMT/QUAC-like and SLAC-like channels. We discovered fingerprints that allow screening databases for these channel types and were able to identify 192 (177 non-redundant SLAC-like and 422 (402 non-redundant ALMT/QUAC-like proteins in the fully sequenced genomes of 32 plant species. Phylogenetic analyses provided new insights into the molecular evolution of these channel types. We also combined sequence alignment and clustering with predictions of protein features, leading to the identification of known conserved phosphorylation sites in SLAC1-like channels along with potential sites that have not been yet experimentally confirmed. Using a similar strategy to analyze the hydropathicity of ALMT/QUAC-like channels, we propose a modified topology with additional transmembrane regions that integrates structure and function of these membrane proteins. Our results suggest that cross-referencing phylogenetic analyses with position-specific protein properties and functional data could be a very powerful tool for genome research approaches in general.

"Slow" Voltage-Dependent Inactivation of CaV2.2 Calcium Channels Is Modulated by the PKC Activator Phorbol 12-Myristate 13-Acetate (PMA.

Directory of Open Access Journals (Sweden)

Lei Zhu

Full Text Available CaV2.2 (N-type voltage-gated calcium channels (Ca2+ channels play key roles in neurons and neuroendocrine cells including the control of cellular excitability, neurotransmitter / hormone secretion, and gene expression. Calcium entry is precisely controlled by channel gating properties including multiple forms of inactivation. "Fast" voltage-dependent inactivation is relatively well-characterized and occurs over the tens-to- hundreds of milliseconds timeframe. Superimposed on this is the molecularly distinct, but poorly understood process of "slow" voltage-dependent inactivation, which develops / recovers over seconds-to-minutes. Protein kinases can modulate "slow" inactivation of sodium channels, but little is known about if/how second messengers control "slow" inactivation of Ca2+ channels. We investigated this using recombinant CaV2.2 channels expressed in HEK293 cells and native CaV2 channels endogenously expressed in adrenal chromaffin cells. The PKC activator phorbol 12-myristate 13-acetate (PMA dramatically prolonged recovery from "slow" inactivation, but an inactive control (4α-PMA had no effect. This effect of PMA was prevented by calphostin C, which targets the C1-domain on PKC, but only partially reduced by inhibitors that target the catalytic domain of PKC. The subtype of the channel β-subunit altered the kinetics of inactivation but not the magnitude of slowing produced by PMA. Intracellular GDP-β-S reduced the effect of PMA suggesting a role for G proteins in modulating "slow" inactivation. We postulate that the kinetics of recovery from "slow" inactivation could provide a molecular memory of recent cellular activity and help control CaV2 channel availability, electrical excitability, and neurotransmission in the seconds-to-minutes timeframe.

Conductance of Ion Channels - Theory vs. Experiment

Science.gov (United States)

Pohorille, Andrew; Wilson, Michael; Mijajlovic, Milan

2013-01-01

Transmembrane ion channels mediate a number of essential physiological processes in a cell ranging from regulating osmotic pressure to transmission of neural signals. Kinetics and selectivity of ion transport is of critical importance to a cell and, not surprisingly, it is a subject of numerous experimental and theoretical studies. In this presentation we will analyze in detail computer simulations of two simple channels from fungi - antiamoebin and trichotoxin. Each of these channels is made of an alpha-helical bundle of small, nongenomically synthesized peptides containing a number of rare amino acids and exhibits strong antimicrobial activity. We will focus on calculating ionic conductance defined as the ratio of ionic current through the channel to applied voltage. From molecular dynamics simulations, conductance can be calculated in at least two ways, each involving different approximations. Specifically, the current, given as the number of charges transferred through the channel per unit of time, can be obtained from the number of events in which ions cross the channel during the simulation. This method works well for large currents (high conductance values and/or applied voltages). If the number of crossing events is small, reliable estimates of current are difficult to achieve. Alternatively, conductance can be estimated assuming that ion transport can be well approximated as diffusion in the external potential given by the free energy profile. Then, the current can be calculated by solving the one-dimensional diffusion equation in this external potential and applied voltage (the generalized Nernst-Planck equation). To do so three ingredients are needed: the free energy profile, the position-dependent diffusion coefficient and the diffusive flux of ions into the channel. All these quantities can be obtained from molecular dynamics simulations. An important advantage of this method is that it can be used equally well to estimating large and small currents

Effective channel approach to nuclear scattering at high energies

International Nuclear Information System (INIS)

Rule, D.W.

1975-01-01

The description of high energy nuclear reactions is considered within the framework of the effective channel approach. A variational procedure is used to obtain an expression for the Green's function in the effective channel, which includes the average fluctuation potential, average energy, and an additional term arising from the non-commutability of the kinetic energy operator and the effective target wave function. The resulting expression for the effective channel, containing one variational parameter, is used to obtain the coupling potential. The resulting formulation is applied to the elastic scattering of 1 GeV protons by 4 He nuclei. A simple Gaussian form is used for the spin--isospin averaged proton--nucleon interaction. The variational parameter in the effective channel wave function is fixed a posteriori via the total p-- 4 He cross section. The effect of the coupling to the effective channel is demonstrated, as well as the effect of each term in the coupled equation for this channel. The calculated elastic cross sections were compared to both the recent data from Saclay and the earlier Brookhaven data for the 1-GeV p-- 4 He elastic scattering cross section. Using proton--nucleus elastic scattering experiments to study the proton--nucleon elastic scattering amplitude is discussed. The main purpose of our study is to investigate the effects on the cross section of varying, within its estimated range of uncertainty, each parameter which enters into the coupled equations. The magnitude of these effects was found to be large enough to conclude that any effects due to dynamical correlations would be obscured by the uncertainties in the input parameters

Quantification of protein interaction kinetics in a micro droplet

Energy Technology Data Exchange (ETDEWEB)

Yin, L. L. [Center for Bioelectronics and Biosensors, Biodesign Institute, Arizona State University, Tempe, Arizona 85287 (United States); College of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400044 (China); Wang, S. P., E-mail: shaopeng.wang@asu.edu, E-mail: njtao@asu.edu; Shan, X. N.; Tao, N. J., E-mail: shaopeng.wang@asu.edu, E-mail: njtao@asu.edu [Center for Bioelectronics and Biosensors, Biodesign Institute, Arizona State University, Tempe, Arizona 85287 (United States); Zhang, S. T. [College of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400044 (China)

2015-11-15

Characterization of protein interactions is essential to the discovery of disease biomarkers, the development of diagnostic assays, and the screening for therapeutic drugs. Conventional flow-through kinetic measurements need relative large amount of sample that is not feasible for precious protein samples. We report a novel method to measure protein interaction kinetics in a single droplet with sub microliter or less volume. A droplet in a humidity-controlled environmental chamber is replacing the microfluidic channels as the reactor for the protein interaction. The binding process is monitored by a surface plasmon resonance imaging (SPRi) system. Association curves are obtained from the average SPR image intensity in the center area of the droplet. The washing step required by conventional flow-through SPR method is eliminated in the droplet method. The association and dissociation rate constants and binding affinity of an antigen-antibody interaction are obtained by global fitting of association curves at different concentrations. The result obtained by this method is accurate as validated by conventional flow-through SPR system. This droplet-based method not only allows kinetic studies for proteins with limited supply but also opens the door for high-throughput protein interaction study in a droplet-based microarray format that enables measurement of many to many interactions on a single chip.

Complete energetic description of hydrokinetic turbine impact on flow channel dynamics

Science.gov (United States)

Brasseale, E.; Kawase, M.

2016-02-01

Energy budget analysis on tidal channels quantifies and demarcates the impacts of marine renewables on environmental fluid dynamics. Energy budget analysis assumes the change in total kinetic energy within a volume of fluid can be described by the work done by each force acting on the flow. In a numerically simulated channel, the balance between energy change and work done has been validated up to 5% error.The forces doing work on the flow include pressure, turbulent dissipation, and stress from the estuary floor. If hydrokinetic turbines are installed in an estuarine channel to convert tidal energy into usable power, the dynamics of the channel change. Turbines provide additional pressure work against the flow of the channel which will slow the current and lessen turbulent dissipation and bottom stress. These losses may negatively impact estuarine circulation, seafloor scour, and stratification.The environmental effects of turbine deployment have been quantified using a three dimensional, Reynolds-averaged, Navier-Stokes model of an idealized flow channel situated between the ocean and a large estuarine basin. The channel is five kilometers wide, twenty kilometers long and fifty meters deep, and resolved to a grid size of 10 meters by 10 meters by 1 meter. Tidal currents are simulated by an initial difference in sea surface height across the channel of 160 centimeters from the channel entrance to the channel exit. This creates a pressure gradient which drives flow through the channel. Tidal power turbines are represented as disks that force the channel in proportion to the strength of the current. Three tidal turbines twenty meters in diameters have been included in the model to simulate the impacts of a pilot scale test deployment.This study is the first to appreciate the energetic impact of marine renewables in a three dimensional model through the energy equation's constituent terms. This study provides groundwork for understanding and predicting the

High Glucose Represses hERG K+ Channel Expression through Trafficking Inhibition

Directory of Open Access Journals (Sweden)

Yuan-Qi Shi

2015-08-01

Full Text Available Background/Aims: Abnormal QT prolongation is the most prominent cardiac electrical disturbance in patients with diabetes mellitus (DM. It is well known that the human ether-ago-go-related gene (hERG controls the rapid delayed rectifier K+ current (IKr in cardiac cells. The expression of the hERG channel is severely down-regulated in diabetic hearts, and this down-regulation is a critical contributor to the slowing of repolarization and QT prolongation. However, the intracellular mechanisms underlying the diabetes-induced hERG deficiency remain unknown. Methods: The expression of the hERG channel was assessed via western blot analysis, and the hERG current was detected with a patch-clamp technique. Results: The results of our study revealed that the expression of the hERG protein and the hERG current were substantially decreased in high-glucose-treated hERG-HEK cells. Moreover, we demonstrated that the high-glucose-mediated damage to the hERG channel depended on the down-regulation of protein levels but not the alteration of channel kinetics. These discoveries indicated that high glucose likely disrupted hERG channel trafficking. From the western blot and immunoprecipitation analyses, we found that high glucose induced trafficking inhibition through an effect on the expression of Hsp90 and its interaction with hERG. Furthermore, the high-glucose-induced inhibition of hERG channel trafficking could activate the unfolded protein response (UPR by up-regulating the expression levels of activating transcription factor-6 (ATF-6 and the ER chaperone protein calnexin. In addition, we demonstrated that 100 nM insulin up-regulated the expression of the hERG channel and rescued the hERG channel repression caused by high glucose. Conclusion: The results of our study provide the first evidence of a high-glucose-induced hERG channel deficiency resulting from the inhibition of channel trafficking. Furthermore, insulin promotes the expression of the hERG channel

Dynamics of ceramide channels detected using a microfluidic system.

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Chenren Shao

Full Text Available Ceramide, a proapoptotic sphingolipid, has been shown to form channels, in mitochondrial outer membranes, large enough to translocate proteins. In phospholipid membranes, electrophysiological studies and electron microscopic visualization both report that these channels form in a range of sizes with a modal value of 10 nm in diameter. A hydrogen bonded barrel-like structure consisting of hundreds of ceramide molecules has been proposed for the structure of the channel and this is supported by electrophysiological studies and molecular dynamic simulations. To our knowledge, the mechanical strength and deformability of such a large diameter but extremely thin cylindrical structure has never been reported. Here we present evidence for a reversible mechanical distortion of the cylinder following the addition of La(3+. A microfluidic system was used to repeatedly lower and then restore the conductance by alternatively perfusing La(3+ and EDTA. Although aspects of the kinetics of conductance drop and recovery are consistent with a disassembly/diffusion/reassembly model, others are inconsistent with the expected time scale of lateral diffusion of disassembled channel fragments in the membrane. The presence of a residual conductance following La(3+ treatment and the relationship between the residual conductance and the initial conductance were both indicative of a distortion/recovery process in analogy with a pressure-induced distortion of a flexible cylinder.

Mechanisms of the 40-70 Day Variability in the Yucatan Channel Volume Transport

Science.gov (United States)

van Westen, René M.; Dijkstra, Henk A.; Klees, Roland; Riva, Riccardo E. M.; Slobbe, D. Cornelis; van der Boog, Carine G.; Katsman, Caroline A.; Candy, Adam S.; Pietrzak, Julie D.; Zijlema, Marcel; James, Rebecca K.; Bouma, Tjeerd J.

2018-02-01

The Yucatan Channel connects the Caribbean Sea with the Gulf of Mexico and is the main outflow region of the Caribbean Sea. Moorings in the Yucatan Channel show high-frequent variability in kinetic energy (50-100 days) and transport (20-40 days), but the physical mechanisms controlling this variability are poorly understood. In this study, we show that the short-term variability in the Yucatan Channel transport has an upstream origin and arises from processes in the North Brazil Current. To establish this connection, we use data from altimetry and model output from several high resolution global models. A significant 40-70 day variability is found in the sea surface height in the North Brazil Current retroflection region with a propagation toward the Lesser Antilles. The frequency of variability is generated by intrinsic processes associated with the shedding of eddies, rather than by atmospheric forcing. This sea surface height variability is able to pass the Lesser Antilles, it propagates westward with the background ocean flow in the Caribbean Sea and finally affects the variability in the Yucatan Channel volume transport.

Identification of sodium channel isoforms that mediate action potential firing in lamina I/II spinal cord neurons

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Smith Paula L

2011-09-01

Full Text Available Abstract Background Voltage-gated sodium channels play key roles in acute and chronic pain processing. The molecular, biophysical, and pharmacological properties of sodium channel currents have been extensively studied for peripheral nociceptors while the properties of sodium channel currents in dorsal horn spinal cord neurons remain incompletely understood. Thus far, investigations into the roles of sodium channel function in nociceptive signaling have primarily focused on recombinant channels or peripheral nociceptors. Here, we utilize recordings from lamina I/II neurons withdrawn from the surface of spinal cord slices to systematically determine the functional properties of sodium channels expressed within the superficial dorsal horn. Results Sodium channel currents within lamina I/II neurons exhibited relatively hyperpolarized voltage-dependent properties and fast kinetics of both inactivation and recovery from inactivation, enabling small changes in neuronal membrane potentials to have large effects on intrinsic excitability. By combining biophysical and pharmacological channel properties with quantitative real-time PCR results, we demonstrate that functional sodium channel currents within lamina I/II neurons are predominantly composed of the NaV1.2 and NaV1.3 isoforms. Conclusions Overall, lamina I/II neurons express a unique combination of functional sodium channels that are highly divergent from the sodium channel isoforms found within peripheral nociceptors, creating potentially complementary or distinct ion channel targets for future pain therapeutics.

Controlling the position of a stabilized detonation wave in a supersonic gas mixture flow in a plane channel

Science.gov (United States)

Levin, V. A.; Zhuravskaya, T. A.

2017-03-01

Stabilization of a detonation wave in a stoichiometric hydrogen-air mixture flowing at a supersonic velocity into a plane symmetric channel with constriction has been studied in the framework of a detailed kinetic mechanism of the chemical interaction. Conditions ensuring the formation of a thrust-producing f low with a stabilized detonation wave in the channel are determined. The inf luence of the inf low Mach number, dustiness of the combustible gas mixture supplied to the channel, and output cross-section size on the position of a stabilized detonation wave in the f low has been analyzed with a view to increasing the efficiency of detonation combustion of the gas mixture. It is established that thrust-producing flow with a stabilized detonation wave can be formed in the channel without any energy consumption.

Characteristics of turbulent velocity and temperature in a wall channel of a heated rod bundle

Energy Technology Data Exchange (ETDEWEB)

Krauss, T.; Meyer, L. [Forschungszentrum Karlsruhe (Germany)

1995-09-01

Turbulent air flow in a wall sub-channel of a heated 37-rod bundle (P/D = 1.12, W/D = 1.06) was investigated. measurements were performed with hot-wire probe with X-wires and a temperature wire. The mean velocity, the mean fluid temperature, the wall shear stress and wall temperature, the turbulent quantities such as the turbulent kinetic energy, the Reynolds-stresses and the turbulent heat fluxes were measured and are discussed with respect to data from isothermal flow in a wall channel and heated flow in a central channel of the same rod bundle. Also, data on the power spectral densities of the velocity and temperature fluctuations are presented. These data show the existence of large scale periodic fluctuations are responsible for the high intersubchannel heat and momentum exchange.

MarkoLAB: A simulator to study ionic channel's stochastic behavior.

Science.gov (United States)

da Silva, Robson Rodrigues; Goroso, Daniel Gustavo; Bers, Donald M; Puglisi, José Luis

2017-08-01

Mathematical models of the cardiac cell have started to include markovian representations of the ionic channels instead of the traditional Hodgkin & Huxley formulations. There are many reasons for this: Markov models are not restricted to the idea of independent gates defining the channel, they allow more complex description with specific transitions between open, closed or inactivated states, and more importantly those states can be closely related to the underlying channel structure and conformational changes. We used the LabVIEW ® and MATLAB ® programs to implement the simulator MarkoLAB that allow a dynamical 3D representation of the markovian model of the channel. The Monte Carlo simulation was used to implement the stochastic transitions among states. The user can specify the voltage protocol by setting the holding potential, the step-to voltage and the duration of the stimuli. The most studied feature of a channel is the current flowing through it. This happens when the channel stays in the open state, but most of the time, as revealed by the low open probability values, the channel remains on the inactive or closed states. By focusing only when the channel enters or leaves the open state we are missing most of its activity. MarkoLAB proved to be quite useful to visualize the whole behavior of the channel and not only when the channel produces a current. Such dynamic representation provides more complete information about channel kinetics and will be a powerful tool to demonstrate the effect of gene mutations or drugs on the channel function. MarkoLAB provides an original way of visualizing the stochastic behavior of a channel. It clarifies concepts, such as recovery from inactivation, calcium- versus voltage-dependent inactivation, and tail currents. It is not restricted to ionic channels only but it can be extended to other transporters, such as exchangers and pumps. This program is intended as a didactical tool to illustrate the dynamical behavior of a

Modeling Hybridization Kinetics of Gene Probes in a DNA Biochip Using FEMLAB

Science.gov (United States)

Munir, Ahsan; Waseem, Hassan; Williams, Maggie R.; Stedtfeld, Robert D.; Gulari, Erdogan; Tiedje, James M.; Hashsham, Syed A.

2017-01-01

Microfluidic DNA biochips capable of detecting specific DNA sequences are useful in medical diagnostics, drug discovery, food safety monitoring and agriculture. They are used as miniaturized platforms for analysis of nucleic acids-based biomarkers. Binding kinetics between immobilized single stranded DNA on the surface and its complementary strand present in the sample are of interest. To achieve optimal sensitivity with minimum sample size and rapid hybridization, ability to predict the kinetics of hybridization based on the thermodynamic characteristics of the probe is crucial. In this study, a computer aided numerical model for the design and optimization of a flow-through biochip was developed using a finite element technique packaged software tool (FEMLAB; package included in COMSOL Multiphysics) to simulate the transport of DNA through a microfluidic chamber to the reaction surface. The model accounts for fluid flow, convection and diffusion in the channel and on the reaction surface. Concentration, association rate constant, dissociation rate constant, recirculation flow rate, and temperature were key parameters affecting the rate of hybridization. The model predicted the kinetic profile and signal intensities of eighteen 20-mer probes targeting vancomycin resistance genes (VRGs). Predicted signal intensities and hybridization kinetics strongly correlated with experimental data in the biochip (R2 = 0.8131). PMID:28555058

Modeling Hybridization Kinetics of Gene Probes in a DNA Biochip Using FEMLAB

Directory of Open Access Journals (Sweden)

Ahsan Munir

2017-05-01

Full Text Available Microfluidic DNA biochips capable of detecting specific DNA sequences are useful in medical diagnostics, drug discovery, food safety monitoring and agriculture. They are used as miniaturized platforms for analysis of nucleic acids-based biomarkers. Binding kinetics between immobilized single stranded DNA on the surface and its complementary strand present in the sample are of interest. To achieve optimal sensitivity with minimum sample size and rapid hybridization, ability to predict the kinetics of hybridization based on the thermodynamic characteristics of the probe is crucial. In this study, a computer aided numerical model for the design and optimization of a flow-through biochip was developed using a finite element technique packaged software tool (FEMLAB; package included in COMSOL Multiphysics to simulate the transport of DNA through a microfluidic chamber to the reaction surface. The model accounts for fluid flow, convection and diffusion in the channel and on the reaction surface. Concentration, association rate constant, dissociation rate constant, recirculation flow rate, and temperature were key parameters affecting the rate of hybridization. The model predicted the kinetic profile and signal intensities of eighteen 20-mer probes targeting vancomycin resistance genes (VRGs. Predicted signal intensities and hybridization kinetics strongly correlated with experimental data in the biochip (R2 = 0.8131.

Kinetics of current formation in molecular diode

International Nuclear Information System (INIS)

Petrov, Eh.G.; Leonov, V.A.; Shevchenko, E.V.

2012-01-01

Based on the kinetic theory of election transfer in low-dimensional molecular systems, the formation of transient and stationary currents in a system 'electrode l-molecule-electrode 2' (molecular diode) is studied for different regimes of charge transmission. In the framework of the HOMO-LUMO molecular model, a situation is considered where the current formation is initiated either by molecule photoexcitation or by change of interelectrode voltage bias. It is found that the distant (tunnel) inelastic electron transfer plays a crucial role in changing molecular electronic states and, as a result, in generating transmission channels for hopping (sequential) and distant (direct) current components. The effect of inelastic tunneling is especially pronounced in the condition of resonant electron transmission.

Structure-activity relationships for the action of 11 pyrethroid insecticides on rat Nav1.8 sodium channels expressed in Xenopus oocytes

International Nuclear Information System (INIS)

Choi, J.-S.; Soderlund, David M.

2006-01-01

Pyrethroid insecticides bind to voltage-sensitive sodium channels and modify their gating kinetics, thereby disrupting nerve function. This paper describes the action of 11 structurally diverse commercial pyrethroid insecticides on the rat Na v 1.8 sodium channel isoform, the principal carrier of the tetrodotoxin-resistant, pyrethroid-sensitive sodium current of sensory neurons, expressed in Xenopus laevis oocytes. All 11 compounds produced characteristic sodium tail currents following a depolarizing pulse that ranged from rapidly-decaying monoexponential currents (allethrin, cismethrin and permethrin) to persistent biexponential currents (cyfluthrin, cyhalothrin, cypermethrin and deltamethrin). Tail currents for the remaining compounds (bifenthrin, fenpropathrin, fenvalerate and tefluthrin) were monoexponential and decayed with kinetics intermediate between these extremes. Reconstruction of currents carried solely by the pyrethroid-modified subpopulation of channels revealed two types of pyrethroid-modified currents. The first type, found with cismethrin, allethrin, permethrin and tefluthrin, activated relatively rapidly and inactivated partially during a 40-ms depolarization. The second type, found with cypermethrin, cyfluthrin, cyhalothrin, deltamethrin, fenpropathrin and fenvalerate, activated more slowly and did not detectably inactivate during a 40-ms depolarization. Only bifenthrin did not produce modified currents that fit clearly into either of these categories. In all cases, the rate of activation of modified channels was strongly correlated with the rate of tail current decay following repolarization. Modification of Na v 1.8 sodium channels by cyfluthrin, cyhalothrin, cypermethrin and deltamethrin was enhanced 2.3- to 3.4-fold by repetitive stimulation; this effect appeared to result from the accumulation of persistently open channels rather than preferential binding to open channel states. Fenpropathrin was the most effective compound against Na v 1

The shaping of two distinct dendritic spikes by A-type voltage-gated K+ channels

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Sungchil eYang

2015-12-01

Full Text Available Dendritic ion channels have been a subject of intense research in neuroscience because active ion channels in dendrites shape input signals. Ca2+-permeable channels including NMDA receptors (NMDARs have been implicated in supralinear dendritic integration, and the IA conductance in sublinear integration. Despite their essential roles in dendritic integration, it has remained uncertain whether these conductances coordinate with, or counteract, each other in the process of dendritic integration. To address this question, experiments were designed in hippocampal CA1 neurons with a recent 3D digital holography system that has shown excellent performance for spatial photoactivation. The results demonstrated a role of IA as a key contributor to two distinct dendritic spikes, low- and high-threshold Ca2+ spikes, through a preferential action of IA on Ca2+-permeable channel-mediated currents, over fast AMPAR-mediated currents. It is likely that the rapid kinetics of IA provides feed-forward inhibition to counteract the delayed Ca2+ channel-mediated dendritic excitability. This research reveals one dynamic ionic mechanism of dendritic integration, and may contribute to a new understanding of neuronal hyperexcitability embedded in several neural diseases such as epilepsy, fragile X syndrome and Alzheimer's disease.

Kinetics and isotherm studies of methylene blue adsorption onto polyaniline nanotubes base/silica composite

Czech Academy of Sciences Publication Activity Database

Ayad, M. M.; Abu El-Nasr, A.; Stejskal, Jaroslav

2012-01-01

Roč. 18, č. 6 (2012), s. 1964-1969 ISSN 1226-086X R&D Projects: GA ČR GA202/09/1626 Institutional research plan: CEZ:AV0Z40500505 Keywords : polyaniline nanotubes * silica * composite Subject RIV: BK - Fluid Dynamics Impact factor: 2.145, year: 2012

Control of a channel-flow behind a backward-facing step by suction/blowing

Czech Academy of Sciences Publication Activity Database

Uruba, Václav; Jonáš, Pavel; Mazur, Oton

2007-01-01

Roč. 28, č. 4 (2007), s. 665-672 ISSN 0142-727X R&D Projects: GA AV ČR IAA2076403 Institutional research plan: CEZ:AV0Z20760514 Keywords : boundary layer separation * boundary layer reattachement * control Subject RIV: BK - Fluid Dynamics Impact factor: 1.283, year: 2007

Axial Couette-Poiseuille flow of power-law viscoplastic fluids in concentric annuli

Czech Academy of Sciences Publication Activity Database

Filip, Petr; David, Jiří

2003-01-01

Roč. 40, 3/4 (2003), s. 111-119 ISSN 0920-4105 R&D Projects: GA AV ČR IAA2060004 Institutional research plan: CEZ:AV0Z2060917 Keywords : boreholes * channel geometry * viscoplastic materials Subject RIV: BK - Fluid Dynamics Impact factor: 0.570, year: 2003

Propylparaben reduces the excitability of hippocampal neurons by blocking sodium channels.

Science.gov (United States)

Lara-Valderrábano, Leonardo; Rocha, Luisa; Galván, Emilio J

2016-12-01

Propylparaben (PPB) is an antimicrobial preservative widely used in food, cosmetics, and pharmaceutics. Virtual screening methodologies predicted anticonvulsant activity of PPB that was confirmed in vivo. Thus, we explored the effects of PPB on the excitability of hippocampal neurons by using standard patch clamp techniques. Bath perfusion of PPB reduced the fast-inactivating sodium current (I Na ) amplitude, causing a hyperpolarizing shift in the inactivation curve of the I Na, and markedly delayed the sodium channel recovery from the inactivation state. Also, PPB effectively suppressed the riluzole-sensitive, persistent sodium current (I NaP ). PPB perfusion also modified the action potential kinetics, and higher concentrations of PPB suppressed the spike activity. Nevertheless, the modulatory effects of PPB did not occur when PPB was internally applied by whole-cell dialysis. These results indicate that PPB reduces the excitability of CA1 pyramidal neurons by modulating voltage-dependent sodium channels. The mechanistic basis of this effect is a marked delay in the recovery from inactivation state of the voltage-sensitive sodium channels. Our results indicate that similar to local anesthetics and anticonvulsant drugs that act on sodium channels, PPB acts in a use-dependent manner. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of n-3 polyunsaturated fatty acids on cardiac ion channels

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Cristina eMoreno

2012-07-01

Full Text Available Dietary n-3 polyunsaturated fatty acids (PUFAs have been reported to exhibit antiarrhythmic properties, attributed to their capability to modulate ion channels. In the present review, we will focus on the effects of PUFAs on cardiac sodium channel (Nav1.5 and two potassium channels (Kv (Kv1.5 and Kv11.1. n-3 marine (docohexaenoic and eicohexapentaenoic acid and plant origin (alpha-linolenic acid PUFAs block Kv1.5 and Kv11.1 channels at physiological concentrations. Also, DHA and EPA decreased Nav1.5 and calcium channels. These effects on Na and Ca channels theoretically should shorten the cardiac APD, whereas the blocking actions of n-3 PUFAs of Kv channels should lengthen the cardiac action potential. Experiments performed in female rabbits fed with a diet rich in n-3 PUFAs show a longer cardiac action potential and effective refractory period. This study was performed to analyze if their antiarrhythmic effects are due to a reduction of triangulation, reverse use-dependence, instability and dispersion of the cardiac action potential (TRIaD as a measure of proarrhythmic effects. Dietary n-3 PUFAs supplementation markedly reduced dofetilide-induced TRIaD and abolished dofetilide-induced torsades de pointes (TdP. Ultrafast sodium channel block by DHA may account for the antiarrhythmic protection of dietary supplements of n-3 PUFAs against dofetilide induced proarrhythmia observed in this animal model. The cardiac effects of n-3 PUFAs resemble those of amiodarone: both block sodium, calcium and potassium channels, have anti-adrenergic properties, can prolong the cardiac action potential, reverse TRIaD and suppress TdP. The main difference is that sodium channel block by n-3 PUFAs has a much faster onset and offset kinetics. Therefore, the electrophysiological profile of n-3 PUFAs appears more desirable: the duration of reduced sodium current (facilitates re-entry is much shorter. The n-3 PUFAs appear as a safer alternative to other antiarrhythmic

Kinetic Typography

DEFF Research Database (Denmark)

van Leeuwen, Theo; Djonov, Emilia

2014-01-01

After discussing broad cultural drivers behind the development of kinetic typography, the chapter outlines an approach to analysing kinetic typography which is based on Halliday's theory of transitivity, as applied by Kress and Van Leeuwen to visual images.......After discussing broad cultural drivers behind the development of kinetic typography, the chapter outlines an approach to analysing kinetic typography which is based on Halliday's theory of transitivity, as applied by Kress and Van Leeuwen to visual images....

Properties of glutamate-gated ion channels in horizontal cells of the perch retina.

Science.gov (United States)

Schmidt, K F

1997-08-01

The effect of two different concentrations of L-glutamate and kainate on the gating kinetics of amino acid-sensitive non-NMDA channels were studied in cultured teleost retinal horizontal cells by single-channel recording and by noise analysis of whole-cell currents. When the glutamate agonist kainate was applied clearly parabolic mean-variance relations of whole-cell membrane currents (up to 3000 pA) indicated that this agonist was acting on one type of channels with a conductance of 5-10 pS. The cells were less sensitive when L-glutamate was used as the agonist and in most cases whole-cell currents amounted to less than 200 pA. The mean-variance relation of glutamate induced currents was complex, indicating that more than one type of channel opening could be involved. Power spectra of whole-cell currents were fitted with two Lorentzians with time constants of approx. 1 and 5-20 msec. Effects on amplitudes and time constants of agonist concentrations are demonstrated. Two categories of unitary events with mean open times of approx. 1 and 7 msec and conductances of approx. 7 and 12 pS, respectively, were obtained in single-channel recordings from cell-attached patches at different concentrations of glutamate in the pipette.

Kinetics of oxygen species in an electrically driven singlet oxygen generator

Science.gov (United States)

Azyazov, V. N.; Torbin, A. P.; Pershin, A. A.; Mikheyev, P. A.; Heaven, M. C.

2015-12-01

The kinetics of oxygen species in the gaseous medium of a discharge singlet oxygen generator has been revisited. Vibrationally excited ozone O3(υ) formed in O + O2 recombination is thought to be a significant agent in the deactivation of singlet oxygen O2(a1Δ), oxygen atom removal and ozone formation. It is shown that the process O3(υ ⩾ 2) + O2(a1Δ) → 2O2 + O is the main O2(a1Δ) deactivation channel in the post-discharge zone. If no measures are taken to decrease the oxygen atom concentration, the contribution of this process to the overall O2(a1Δ) removal is significant, even in the discharge zone. A simplified model for the kinetics of vibrationally excited ozone is proposed. Calculations based on this model yield results that are in good agreement with the experimental data.

Eleven new heaviest isotopes of elements Z=105 to Z=117 identified among the products of 249Bk+48Ca reactions

International Nuclear Information System (INIS)

Oganessian, Yu. Ts.; Abdullin, F. Sh.; Dmitriev, S. N.; Itkis, M. G.; Lobanov, Yu. V.; Mezentsev, A. N.; Polyakov, A. N.; Sagaidak, R. N.; Shirokovsky, I. V.; Subbotin, V. G.; Sukhov, A. M.; Tsyganov, Yu. S.; Utyonkov, V. K.; Voinov, A. A.; Vostokin, G. K.; Bailey, P. D.; Benker, D. E.; Ezold, J. G.; Porter, C. E.; Riley, F. D.

2011-01-01

The heaviest isotopes of elements Z=117 to Z=105, 294 117, 293 117, 290 115, 289 115, 286 113, 285 113, 282 Rg, 281 Rg, 278 Mt, 274 Bh, and 270 Db, were identified by means of the Dubna gas-filled recoil separator among the products of the 249 Bk + 48 Ca reaction. The details of the observed six decay chains, indicating the production and decay of isotopes 293 117 and 294 117, are presented and discussed. The decay energies and resulting half-lives of these new nuclei show a strong rise of stability with increasing neutron number, validating the concept of the island of enhanced stability for superheavy nuclei [Oganessian et al., Phys. Rev. Lett. 104, 142502 (2010)].

Intensification process of air-hydrogen mixture burning in the variable cross section channel by means of the air jet

Science.gov (United States)

Zamuraev, V. P.; Kalinina, A. P.

2018-03-01

The paper presents the results of numerical modeling of a transonic region formation in the flat channel. Hydrogen flows into the channel through the holes in the wall. The jet of compressed air is localized downstream the holes. The transonic region formation is formed by the burning of heterogeneous hydrogen-air mixture. It was considered in the framework of the simplified chemical kinetics. The interesting feature of the regime obtained is the following: the distribution of the Mach numbers is qualitatively similar to the case of pulse-periodic energy sources. This mode is a favorable prerequisite for the effective fuel combustion in the expanding part of the channel when injecting fuel into this part.

Clearance gap flow: Simulations by discontinuous Galerkin method and experiments

Czech Academy of Sciences Publication Activity Database

Hála, Jindřich; Luxa, Martin; Bublík, O.; Prausová, H.; Vimmr, J.

2016-01-01

Roč. 92, May (2016), 02073-02073 ISSN 2100-014X. [EFM14 – Experimental Fluid Mechanics 2014. Český Krumlov, 18.11.2014-21.11.2014] Institutional support: RVO:61388998 Keywords : compressible fluid flow * narrow channel flow * discontinuous Galerkin finite element method Subject RIV: BK - Fluid Dynamics

De Novo collapsing glomerulopathy in renal allograft in association with BK virus nephropathy in a child and stabilization of renal function by elimination of viremia

Directory of Open Access Journals (Sweden)

D N Gera

2017-01-01

Full Text Available Well-recognized association between HIV 1 infection and collapsing glomerulopathy (CG raises the possibility that intrarenal infection by other viruses may also contribute to the development of this lesion in native or post-transplant kidneys. There is evidence in literature about association of these lesions with cytomegalovirus, Epstein–Barr virus, hepatitis C virus, and parvovirus B19 infections. Here, we present a case report of post-transplant BK virus nephropathy in a male child who was found to have CG in subsequent biopsy 2 months later. His renal function and proteinuria were stabilized on elimination of viremia.

Contact activation: a revision.

Science.gov (United States)

Schmaier, A H

1997-07-01

In conclusion, a revised view of the contact system has been presented. This system has little to do with the initiation of hemostasis. Like lupus anticoagulants, deficiencies of contact proteins give prolonged APTTs but may be risk factors for thrombosis. BK from kininogens is a potent modulator of vascular biology inducing vasodilation, tissue plasminogen activator release, and prostacyclin liberation. Kininogens, themselves, are selective inhibitors of alpha-thrombin-induced platelet activation preventing alpha-thrombin from cleaving the cloned thrombin receptor after arginine41. Kininogens' alpha-thrombin inhibitory activity exists in intact kininogens, BK, and all of BK's breakdown products. HK also is the pivotal protein for contact protein assembly on endothelium. It is the receptor for prekallikrein which when bound to HK becomes activated to kallikrein by an endothelial cell enzyme system independent of activated forms of plasma factor XII. Prekallikrein activation on endothelial cells results in kinetically favorable single chain urokinase and plasminogen activation. Thus the "physiologic, negatively charged surface" for contact system activation is really the assembly of these proteins on cell membranes and activation by membrane-associated enzymes.

An upwind, kinetic flux-vector splitting method for flows in chemical and thermal non-equilibrium

Science.gov (United States)

Eppard, W. M.; Grossman, B.

1993-01-01

We have developed new upwind kinetic difference schemes for flows with non-equilibrium thermodynamics and chemistry. These schemes are derived from the Boltzmann equation with the resulting Euler schemes developed as moments of the discretized Boltzmann scheme with a locally Maxwellian velocity distribution. Splitting the velocity distribution at the Boltzmann level is seen to result in a flux-split Euler scheme and is called Kinetic Flux Vector Splitting (KFVS). Extensions to flows with finite-rate chemistry and vibrational relaxation is accomplished utilizing nonequilibrium kinetic theory. Computational examples are presented comparing KFVS with the schemes of Van Leer and Roe for a quasi-one-dimensional flow through a supersonic diffuser, inviscid flow through two-dimensional inlet, and viscous flow over a cone at zero angle-of-attack. Calculations are also shown for the transonic flow over a bump in a channel and the transonic flow over an NACA 0012 airfoil. The results show that even though the KFVS scheme is a Riemann solver at the kinetic level, its behavior at the Euler level is more similar to the existing flux-vector splitting algorithms than to the flux-difference splitting scheme of Roe.

Multi-channels coupling-induced pattern transition in a tri-layer neuronal network

Science.gov (United States)

Wu, Fuqiang; Wang, Ya; Ma, Jun; Jin, Wuyin; Hobiny, Aatef

2018-03-01

Neurons in nerve system show complex electrical behaviors due to complex connection types and diversity in excitability. A tri-layer network is constructed to investigate the signal propagation and pattern formation by selecting different coupling channels between layers. Each layer is set as different states, and the local kinetics is described by Hindmarsh-Rose neuron model. By changing the number of coupling channels between layers and the state of the first layer, the collective behaviors of each layer and synchronization pattern of network are investigated. A statistical factor of synchronization on each layer is calculated. It is found that quiescent state in the second layer can be excited and disordered state in the third layer is suppressed when the first layer is controlled by a pacemaker, and the developed state is dependent on the number of coupling channels. Furthermore, the collapse in the first layer can cause breakdown of other layers in the network, and the mechanism is that disordered state in the third layer is enhanced when sampled signals from the collapsed layer can impose continuous disturbance on the next layer.

Channels of energy redistribution in short-pulse laser interactions with metal targets

International Nuclear Information System (INIS)

Zhigilei, Leonid V.; Ivanov, Dmitriy S.

2005-01-01

The kinetics and channels of laser energy redistribution in a target irradiated by a short, 1 ps, laser pulse is investigated in computer simulations performed with a model that combines molecular dynamics (MD) simulations with a continuum description of the laser excitation and relaxation of the conduction band electrons, based on the two-temperature model (TTM). The energy transferred from the excited electrons to the lattice splits into several parts, namely the energy of the thermal motion of the atoms, the energy of collective atomic motions associated with the relaxation of laser-induced stresses, the energy carried away from the surface region of the target by a stress wave, the energy of quasi-static anisotropic stresses, and, at laser fluences above the melting threshold, the energy transferred to the latent heat of melting and then released upon recrystallization. The presence of the non-thermal channels of energy redistribution (stress wave and quasi-static stresses), not accounted for in the conventional TTM model, can have important implications for interpretation of experimental results on the kinetics of thermal and mechanical relaxation of a target irradiated by a short laser pulse as well as on the characteristics of laser-induced phase transformations. The fraction of the non-thermal energy in the total laser energy partitioning increases with increasing laser fluence

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

Science.gov (United States)

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

2017-08-01

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

Full-dimensional analytical potential energy surface describing the gas-phase Cl + C2H6 reaction and kinetics study of rate constants and kinetic isotope effects.

Science.gov (United States)

Rangel, Cipriano; Espinosa-Garcia, Joaquin

2018-02-07

Within the Born-Oppenheimer approximation a full-dimensional analytical potential energy surface, PES-2017, was developed for the gas-phase hydrogen abstraction reaction between the chlorine atom and ethane, which is a nine body system. This surface presents a valence-bond/molecular mechanics functional form dependent on 60 parameters and is fitted to high-level ab initio calculations. This reaction presents little exothermicity, -2.30 kcal mol -1 , with a low height barrier, 2.44 kcal mol -1 , and intermediate complexes in the entrance and exit channels. We found that the energetic description was strongly dependent on the ab initio level used and it presented a very flat topology in the entrance channel, which represents a theoretical challenge in the fitting process. In general, PES-2017 reproduces the ab initio information used as input, which is merely a test of self-consistency. As a first test of the quality of the PES-2017, a theoretical kinetics study was performed in the temperature range 200-1400 K using two approaches, i.e. the variational transition-state theory and quasi-classical trajectory calculations, with spin-orbit effects. The rate constants show reasonable agreement with experiments in the whole temperature range, with the largest differences at the lowest temperatures, and this behaviour agrees with previous theoretical studies, thus indicating the inherent difficulties in the theoretical simulation of the kinetics of the title reaction. Different sources of error were analysed, such as the limitations of the PES and theoretical methods, recrossing effects, and the tunnelling effect, which is negligible in this reaction, and the manner in which the spin-orbit effects were included in this non-relativistic study. We found that the variation of spin-orbit coupling along the reaction path, and the influence of the reactivity of the excited Cl( 2 P 1/2 ) state, have relative importance, but do not explain the whole discrepancy. Finally, the

How to resolve microsecond current fluctuations in single ion channels: The power of beta distributions

Science.gov (United States)

Schroeder, Indra

2015-01-01

Abstract A main ingredient for the understanding of structure/function correlates of ion channels is the quantitative description of single-channel gating and conductance. However, a wealth of information provided from fast current fluctuations beyond the temporal resolution of the recording system is often ignored, even though it is close to the time window accessible to molecular dynamics simulations. This kind of current fluctuations provide a special technical challenge, because individual opening/closing or blocking/unblocking events cannot be resolved, and the resulting averaging over undetected events decreases the single-channel current. Here, I briefly summarize the history of fast-current fluctuation analysis and focus on the so-called “beta distributions.” This tool exploits characteristics of current fluctuation-induced excess noise on the current amplitude histograms to reconstruct the true single-channel current and kinetic parameters. A guideline for the analysis and recent applications demonstrate that a construction of theoretical beta distributions by Markov Model simulations offers maximum flexibility as compared to analytical solutions. PMID:26368656

Exploring unimolecular dissociation kinetics of ethyl dibromide through electronic structure calculations

Science.gov (United States)

Gulvi, Nitin R.; Patel, Priyanka; Badani, Purav M.

2018-04-01

Pathway for dissociation of multihalogenated alkyls is observed to be competitive between molecular and atomic elimination products. Factors such as molecular structure, temperature and pressure are known to influence the same. Hence present work is focussed to explore mechanism and kinetics of atomic (Br) and molecular (HBr and Br2) elimination upon pyrolysis of 1,1- and 1,2-ethyl dibromide (EDB). For this purpose, electronic structure calculations were performed at DFT and CCSD(T) level of theory. In addition to concerted mechanism, an alternate energetically efficient isomerisation pathway has been exploited for molecular elimination. Energy calculations are further complimented by detailed kinetic investigation, over wide range of temperature and pressure, using suitable models like Canonical Transition State Theory, Statistical Adiabatic Channel Model and Troe's formalism. Our calculations suggest high branching ratio for dehydrohalogentation reaction, from both isomers of EDB. Fall off curve depicts good agreement between theoretically estimated and experimentally reported values.

Elucidating distinct ion channel populations on the surface of hippocampal neurons via single-particle tracking recurrence analysis

Science.gov (United States)

Sikora, Grzegorz; Wyłomańska, Agnieszka; Gajda, Janusz; Solé, Laura; Akin, Elizabeth J.; Tamkun, Michael M.; Krapf, Diego

2017-12-01

Protein and lipid nanodomains are prevalent on the surface of mammalian cells. In particular, it has been recently recognized that ion channels assemble into surface nanoclusters in the soma of cultured neurons. However, the interactions of these molecules with surface nanodomains display a considerable degree of heterogeneity. Here, we investigate this heterogeneity and develop statistical tools based on the recurrence of individual trajectories to identify subpopulations within ion channels in the neuronal surface. We specifically study the dynamics of the K+ channel Kv1.4 and the Na+ channel Nav1.6 on the surface of cultured hippocampal neurons at the single-molecule level. We find that both these molecules are expressed in two different forms with distinct kinetics with regards to surface interactions, emphasizing the complex proteomic landscape of the neuronal surface. Further, the tools presented in this work provide new methods for the analysis of membrane nanodomains, transient confinement, and identification of populations within single-particle trajectories.

Cesium removal and kinetics equilibrium: Precipitation kinetics

International Nuclear Information System (INIS)

Barnes, M.J.

1999-01-01

This task consisted of both non-radioactive and radioactive (tracer) tests examining the influence of potentially significant variables on cesium tetraphenylborate precipitation kinetics. The work investigated the time required to reach cesium decontamination and the conditions that affect the cesium precipitation kinetics

Information transmission and recovery in neural communications channels

International Nuclear Information System (INIS)

Eguia, M. C.; Rabinovich, M. I.; Abarbanel, H. D. I.

2000-01-01

Biological neural communications channels transport environmental information from sensors through chains of active dynamical neurons to neural centers for decisions and actions to achieve required functions. These kinds of communications channels are able to create information and to transfer information from one time scale to the other because of the intrinsic nonlinear dynamics of the component neurons. We discuss a very simple neural information channel composed of sensory input in the form of a spike train that arrives at a model neuron, then moves through a realistic synapse to a second neuron where the information in the initial sensory signal is read. Our model neurons are four-dimensional generalizations of the Hindmarsh-Rose neuron, and we use a model of chemical synapse derived from first-order kinetics. The four-dimensional model neuron has a rich variety of dynamical behaviors, including periodic bursting, chaotic bursting, continuous spiking, and multistability. We show that, for many of these regimes, the parameters of the chemical synapse can be tuned so that information about the stimulus that is unreadable at the first neuron in the channel can be recovered by the dynamical activity of the synapse and the second neuron. Information creation by nonlinear dynamical systems that allow chaotic oscillations is familiar in their autonomous oscillations. It is associated with the instabilities that lead to positive Lyapunov exponents in their dynamical behavior. Our results indicate how nonlinear neurons acting as input/output systems along a communications channel can recover information apparently ''lost'' in earlier junctions on the channel. Our measure of information transmission is the average mutual information between elements, and because the channel is active and nonlinear, the average mutual information between the sensory source and the final neuron may be greater than the average mutual information at an earlier neuron in the channel. This

HTP kinetics studies on isolated elementary combustion reactions over wide temperature ranges

Energy Technology Data Exchange (ETDEWEB)

Fontijn, A.; Adusei, G.Y.; Hranisavlevic, J.; Bajaj, P.N. [Rensselaer Polytechnic Institute, Troy, NY (United States)

1993-12-01

The goals of this project are to provide accurate data on the temperature dependence of the kinetics of elementary combustion reactions, (i) for use by combustion modelers, and (ii) to gain a better fundamental understanding of, and hence predictive ability for, the chemistry involved. Experimental measurements are made mainly by using the pseudo-static HTP (high-temperature photochemistry) technique. While continuing rate coefficient measurements, further aspects of kinetics research are being explored. Thus, starting from the data obtained, a method for predicting the temperature dependence of rate coefficients of oxygen-atom olefin experiment and confirms the underlying mechanistic assumptions. Mechanistic information of another sort, i.e. by product analysis, has recently become accessible with the inauguration of our heated flow tube mass spectrometer facility; early results are reported here. HTP experiments designed to lead to measurements of product channels by resonance fluorescence have started.

Channelling and electromagnetic radiation of channelling particles

International Nuclear Information System (INIS)

Kalashnikov, N.

1983-01-01

A brief description is presented of the channelling of charged particles between atoms in the crystal lattice. The specificities are discussed of the transverse motion of channelling particles as are the origin and properties of quasi-characteristic radiation of channelling particles which accompany transfers from one band of permissible energies of the transverse motion of channelling particles to the other. (B.S.)

Temperature and Voltage Coupling to Channel Opening in Transient Receptor Potential Melastatin 8 (TRPM8)*♦

Science.gov (United States)

Raddatz, Natalia; Castillo, Juan P.; Gonzalez, Carlos; Alvarez, Osvaldo; Latorre, Ramon

2014-01-01

Expressed in somatosensory neurons of the dorsal root and trigeminal ganglion, the transient receptor potential melastatin 8 (TRPM8) channel is a Ca2+-permeable cation channel activated by cold, voltage, phosphatidylinositol 4,5-bisphosphate, and menthol. Although TRPM8 channel gating has been characterized at the single channel and macroscopic current levels, there is currently no consensus regarding the extent to which temperature and voltage sensors couple to the conduction gate. In this study, we extended the range of voltages where TRPM8-induced ionic currents were measured and made careful measurements of the maximum open probability the channel can attain at different temperatures by means of fluctuation analysis. The first direct measurements of TRPM8 channel temperature-driven conformational rearrangements provided here suggest that temperature alone is able to open the channel and that the opening reaction is voltage-independent. Voltage is a partial activator of TRPM8 channels, because absolute open probability values measured with fully activated voltage sensors are less than 1, and they decrease as temperature rises. By unveiling the fast temperature-dependent deactivation process, we show that TRPM8 channel deactivation is well described by a double exponential time course. The fast and slow deactivation processes are temperature-dependent with enthalpy changes of 27.2 and 30.8 kcal mol−1. The overall Q10 for the closing reaction is about 33. A three-tiered allosteric model containing four voltage sensors and four temperature sensors can account for the complex deactivation kinetics and coupling between voltage and temperature sensor activation and channel opening. PMID:25352597

Primary photodissociation pathways of epichlorohydrin and analysis of the C-C bond fission channels from an O(3P)+allyl radical intermediate

International Nuclear Information System (INIS)

FitzPatrick, Benjamin L.; Alligood, Bridget W.; Butler, Laurie J.; Lee, Shih-Huang; Lin, Jim Jr-Min

2010-01-01

This study initially characterizes the primary photodissociation processes of epichlorohydrin, c-(H 2 COCH)CH 2 Cl. The three dominant photoproduct channels analyzed are c-(H 2 COCH)CH 2 +Cl, c-(H 2 COCH)+CH 2 Cl, and C 3 H 4 O+HCl. In the second channel, the c-(H 2 COCH) photofission product is a higher energy intermediate on C 2 H 3 O global potential energy surface and has a small isomerization barrier to vinoxy. The resulting highly vibrationally excited vinoxy radicals likely dissociate to give the observed signal at the mass corresponding to ketene, H 2 CCO. The final primary photodissociation pathway HCl+C 3 H 4 O evidences a recoil kinetic energy distribution similar to that of four-center HCl elimination in chlorinated alkenes, so is assigned to production of c-(H 2 COC)=CH 2 ; the epoxide product is formed with enough vibrational energy to isomerize to acrolein and dissociate. The paper then analyzes the dynamics of the C 3 H 5 O radical produced from C-Cl bond photofission. When the epoxide radical photoproduct undergoes facile ring opening, it is the radical intermediate formed in the O( 3 P)+allyl bimolecular reaction when the O atom adds to an end C atom. We focus on the HCO+C 2 H 4 and H 2 CO+C 2 H 3 product channels from this radical intermediate in this report. Analysis of the velocity distribution of the momentum-matched signals from the HCO+C 2 H 4 products at m/e=29 and 28 shows that the dissociation of the radical intermediate imparts a high relative kinetic energy, peaking near 20 kcal/mol, between the products. Similarly, the energy imparted to relative kinetic energy in the H 2 CO+C 2 H 3 product channel of the O( 3 P)+allyl radical intermediate also peaks at high-recoil kinetic energies, near 18 kcal/mol. The strongly forward-backward peaked angular distributions and the high kinetic energy release result from tangential recoil during the dissociation of highly rotationally excited nascent radicals formed photolytically in this experiment

Primary photodissociation pathways of epichlorohydrin and analysis of the C-C bond fission channels from an O(3P)+allyl radical intermediate

Science.gov (United States)

FitzPatrick, Benjamin L.; Alligood, Bridget W.; Butler, Laurie J.; Lee, Shih-Huang; Lin, Jim-Min, Jr.

2010-09-01

This study initially characterizes the primary photodissociation processes of epichlorohydrin, c-(H2COCH)CH2Cl. The three dominant photoproduct channels analyzed are c-(H2COCH)CH2+Cl, c-(H2COCH)+CH2Cl, and C3H4O+HCl. In the second channel, the c-(H2COCH) photofission product is a higher energy intermediate on C2H3O global potential energy surface and has a small isomerization barrier to vinoxy. The resulting highly vibrationally excited vinoxy radicals likely dissociate to give the observed signal at the mass corresponding to ketene, H2CCO. The final primary photodissociation pathway HCl+C3H4O evidences a recoil kinetic energy distribution similar to that of four-center HCl elimination in chlorinated alkenes, so is assigned to production of c-(H2COC)=CH2; the epoxide product is formed with enough vibrational energy to isomerize to acrolein and dissociate. The paper then analyzes the dynamics of the C3H5O radical produced from C-Cl bond photofission. When the epoxide radical photoproduct undergoes facile ring opening, it is the radical intermediate formed in the O(P3)+allyl bimolecular reaction when the O atom adds to an end C atom. We focus on the HCO+C2H4 and H2CO+C2H3 product channels from this radical intermediate in this report. Analysis of the velocity distribution of the momentum-matched signals from the HCO+C2H4 products at m/e=29 and 28 shows that the dissociation of the radical intermediate imparts a high relative kinetic energy, peaking near 20 kcal/mol, between the products. Similarly, the energy imparted to relative kinetic energy in the H2CO+C2H3 product channel of the O(P3)+allyl radical intermediate also peaks at high-recoil kinetic energies, near 18 kcal/mol. The strongly forward-backward peaked angular distributions and the high kinetic energy release result from tangential recoil during the dissociation of highly rotationally excited nascent radicals formed photolytically in this experiment. The data also reveal substantial branching to an HCCH+H3

Parametric study of the stability properties of a thermo hydraulic channel coupled to punctual kinetics; Estudio parametrico de las propiedades de estabilidad de un canal termohidraulico acoplado a cinetica puntual

Energy Technology Data Exchange (ETDEWEB)

Cecenas F, M.; Campos G, R.M. [Instituto de Investigaciones Electricas, Reforma 113, Col. Palmira, Temixco, Morelos (Mexico)]. e-mail: mcf@iie.org.mx

2005-07-01

The reason of decay is the indicator of stability usually used in the literature to evaluate stability of boiling water reactors, however, in the operation of this type of reactors is considered the length of boiling like an auxiliary parameter for the evaluation of stability. In this work its are studied the variation of these two indicators when modifying a given an operation parameter in a model of a thermo hydraulic channel coupled to punctual kinetics, maintaining all the other input constant variables. The parameters selected for study are the axial profile of power, the subcooling, the flow of coolant and the thermal power. The study is supplemented by means of real data of plant using the one Benchmark of Ringhals, and the results for the case of the ratio of decay its are compared with the decay reasons obtained by means of autoregression models of the local instrumentation of neutron flux. (Author)

Evaluation of the rod ejection accident in Westinghouse Pressurized Water Reactors using spatial kinetics methods

International Nuclear Information System (INIS)

Risher, D.H. Jr.

1975-01-01

The consequences of a rod ejection accident are investigated in relation to the latest, high power density Westinghouse reactors. Limiting criteria are presented, based on experimental evidence, and if not exceeded these criteria will ensure that there will be no interference with core cooling capability, and radiation releases, if any, will be within the guidelines of 10CFR100. A basis is presented for the conservative selection of plant parameters to be used in the analysis, such that the analysis is applicable to a wide range of past, present, and future reactors. The calculational method employs a one-dimensional spatial kinetics computer code and a transient fuel heat transfer computer code to determine the hot spot fuel temperature versus time following a rod ejection. Using these computer codes, the most limiting hot channel factor (which does not cause the fuel damage limit criteria to be exceeded) has been determined as a function of the ejected rod worth. By this means, the limit criteria have been translated into ejected rod worths and hot channel factors which can be used effectively by the nuclear designer and safety analyst. The calculational method is shown to be conservative, compared to the results of a three-dimensional spatial kinetics analysis

Flow around a horizontal cylinder and its effect on local scour in an open channel

Czech Academy of Sciences Publication Activity Database

Vlasák, Pavel; Chára, Zdeněk

1999-01-01

Roč. 363, - (1999), s. 51-60 ISSN 0867-7964. [Conference on "Safety and Durability of Hydrotechnic Structures" /2./. Kamien Slaski, 03.11.1999-05.11.1999] R&D Projects: GA AV ČR IAA2060701; GA ČR GA103/97/0860 Subject RIV: BK - Fluid Dynamics

Heparin kinetics

International Nuclear Information System (INIS)

Swart, C.A.M. de.

1983-01-01

The author has studied the kinetics of heparin and heparin fractions after intravenous administration in humans and in this thesis the results of this study are reported. Basic knowledge about the physico-chemical properties of heparin and its interactions with proteins resulting in anticoagulant and lipolytic effects are discussed in a review (chapter II), which also comprises some clinical aspects of heparin therapy. In chapter III the kinetics of the anticoagulant effect are described after intravenous administration of five commercial heparin preparations. A mathematical model is presented that fits best to these kinetics. The kinetics of the anticoagulant and lipolytic effects after intravenous injection of various 35 S-radiolabelled heparin fractions and their relationship with the disappearance of the radiolabel are described in chapter IV. Chapter V gives a description of the kinetics of two radiolabels after injection of in vitro formed complexes consisting of purified, 125 I-radiolabelled antithrombin III and various 35 S-radiolabelled heparin fractions. (Auth.)

SALLY - a computer programme for the calculation of the dynamical behaviour of a cooling channel

International Nuclear Information System (INIS)

Reiche, C.; Ziegenbein, D.

1978-12-01

This report describes the mathematical-physical fundamentals and provides a user's manual as well as some test examples for the programme SALLY. SALLY is suitable for the calculation of the dynamical behaviour of a cooling channel under following conditions: point-kinetics, heat transfer in the fuel in radial direction only, reactivity feedback, simple model of the first cooling cycle. Reactivity, coolant inlet temperature or coolant velocity can be disturbed. (author)

Limitations of the dual voltage clamp method in assaying conductance and kinetics of gap junction channels

NARCIS (Netherlands)

Wilders, R.; Jongsma, H. J.

1992-01-01

The electrical properties of gap junctions in cell pairs are usually studied by means of the dual voltage clamp method. The voltage across the junctional channels, however, cannot be controlled adequately due to an artificial resistance and a natural resistance, both connected in series with the gap

Calmodulin and calcium differentially regulate the neuronal Nav1.1 voltage-dependent sodium channel

Energy Technology Data Exchange (ETDEWEB)

Gaudioso, Christelle; Carlier, Edmond; Youssouf, Fahamoe [INSERM U641, Institut Jean Roche, Marseille F-13344 (France); Universite de la Mediterranee, Faculte de Medecine Secteur Nord, IFR 11, Marseille F-13344 (France); Clare, Jeffrey J. [Eaton Pharma Consulting, Eaton Socon, Cambridgeshire PE19 8EF (United Kingdom); Debanne, Dominique [INSERM U641, Institut Jean Roche, Marseille F-13344 (France); Universite de la Mediterranee, Faculte de Medecine Secteur Nord, IFR 11, Marseille F-13344 (France); Alcaraz, Gisele, E-mail: gisele.alcaraz@univmed.fr [INSERM U641, Institut Jean Roche, Marseille F-13344 (France); Universite de la Mediterranee, Faculte de Medecine Secteur Nord, IFR 11, Marseille F-13344 (France)

2011-07-29

Highlights: {yields} Both Ca{sup ++}-Calmodulin (CaM) and Ca{sup ++}-free CaM bind to the C-terminal region of Nav1.1. {yields} Ca{sup ++} and CaM have both opposite and convergent effects on I{sub Nav1.1}. {yields} Ca{sup ++}-CaM modulates I{sub Nav1.1} amplitude. {yields} CaM hyperpolarizes the voltage-dependence of activation, and increases the inactivation rate. {yields} Ca{sup ++} alone antagonizes CaM for both effects, and depolarizes the voltage-dependence of inactivation. -- Abstract: Mutations in the neuronal Nav1.1 voltage-gated sodium channel are responsible for mild to severe epileptic syndromes. The ubiquitous calcium sensor calmodulin (CaM) bound to rat brain Nav1.1 and to the human Nav1.1 channel expressed by a stably transfected HEK-293 cell line. The C-terminal region of the channel, as a fusion protein or in the yeast two-hybrid system, interacted with CaM via a consensus C-terminal motif, the IQ domain. Patch clamp experiments on HEK1.1 cells showed that CaM overexpression increased peak current in a calcium-dependent way. CaM had no effect on the voltage-dependence of fast inactivation, and accelerated the inactivation kinetics. Elevating Ca{sup ++} depolarized the voltage-dependence of fast inactivation and slowed down the fast inactivation kinetics, and for high concentrations this effect competed with the acceleration induced by CaM alone. Similarly, the depolarizing action of calcium antagonized the hyperpolarizing shift of the voltage-dependence of activation due to CaM overexpression. Fluorescence spectroscopy measurements suggested that Ca{sup ++} could bind the Nav1.1 C-terminal region with micromolar affinity.

On the flow around Glauert-Goldschmied body in the narrow channel and separation control strategy

Czech Academy of Sciences Publication Activity Database

Procházka, Pavel P.; Uruba, Václav

2016-01-01

Roč. 16, č. 1 (2016), s. 643-644 ISSN 1617-7061 R&D Projects: GA ČR(CZ) GP14-25354P Institutional support: RVO:61388998 Keywords : PIV * active flow control * Glauert-Goldschmied body Subject RIV: BK - Fluid Dynamics http://onlinelibrary.wiley.com/doi/10.1002/pamm.201610310/full

An Effective Channel Allocation Scheme to Reduce Co-Channel and Adjacent Channel Interference for WMN Backhaul

International Nuclear Information System (INIS)

Abbasi, S.; Ismaili, I.A.; Khuhawar, F.Y.

2016-01-01

Two folded work presents channel allocation scheme sustaining channel orthogonality and channel spacing to reduce CCI (Co-Channel Interference) and ACI (Adjacent Channel Interference) for inter flow of an intra-flow link. Proposed scheme as a part of radio resource allocation is applied on infrastructure based backhaul of wireless mesh network using directional antennas. The proposed approach is applied separately on 2.4 and 5GHz bands. Interference of connectivity graph is modelled by strongly connected directed graph and greedy algorithms are used for channel allocation. We have used OPNET Modeller suite to simulate network models for this research. The proposed arrangement reduces the channel interference and increases system throughput. In this research, the influence of channel is computed in terms of network throughput and delay. (author)

Kinetics of ion/molecule reactions in Xe++acteone system

International Nuclear Information System (INIS)

Vinogradov, P.S.; Misharin, A.S.

2002-01-01

A reaction of Xe+ ion with acetone and subsequent transformations of the product ions at a buffer gas pressure (He) of 1.1 Torr were studied by the flow reactor technique mass spectrometry. A kinetic scheme describing the evolution of the ionic composition has been determined. The rate constants of the key reactions involved in the scheme have been evaluated. A channel of the production of acetone cation in A state in a charge transfer reaction was observed. A production of slowly reacting isomer of the acetone cation in secondary reactions was detected. Its product in the reaction with acetone is the 'nonprotonated dimer'. The kinetics of the production of ternary ions - ( CH 3 CO + CH 3 COCH 3 )(m/e=101), CH 3 COCH 3 H + (m/e=59) as well as the production of ions of the fourth generation ( CH 3 CO + (CH 3 COCH 3 ) 2 ) (m/e=159) and (CH 3 COCH 3 ) 2 H + was observed. CH 3 CO + ion (m/e=43) was found as the main reaction product. The main pathways scheme of ionic transformations is shown. (nevyjel)

Comparison of superhydrophobic drag reduction between turbulent pipe and channel flows

Science.gov (United States)

Im, Hyung Jae; Lee, Jae Hwa

2017-09-01

It has been known over several decades that canonical wall-bounded internal flows of a pipe and channel share flow similarities, in particular, close to the wall due to the negligible curvature effect. In the present study, direct numerical simulations of fully developed turbulent pipe and channel flows are performed to investigate the influence of the superhydrophobic surfaces (SHSs) on the turbulence dynamics and the resultant drag reduction (DR) of the flows under similar conditions. SHSs at the wall are modeled in spanwise-alternating longitudinal regions with a boundary with no-slip and shear-free conditions, and the two parameters of the spanwise periodicity (P/δ) and SHS fraction (GF) within a pitch are considered. It is shown, in agreement with previous investigations in channels, that the turbulent drag for the pipe and channel flows over SHSs is continuously decreased with increases in P/δ and GF. However, the DR rate in the pipe flows is greater than that in the channel flows with an accompanying reduction of the Reynolds stress. The enhanced performance of the DR for the pipe flow is attributed to the increased streamwise slip and weakened Reynolds shear stress contributions. In addition, a mathematical analysis of the spanwise mean vorticity equation suggests that the presence of a strong secondary flow due to the increased spanwise slip of the pipe flows makes a greater negative contribution of advective vorticity transport than the channel flows, resulting in a higher DR value. Finally, an inspection of the origin of the mean secondary flow in turbulent flows over SHSs based on the spatial gradients of the turbulent kinetic energy demonstrates that the secondary flow is both driven and sustained by spatial gradients in the Reynolds stress components, i.e., Prandtl's secondary flow of the second kind.

C-terminus-mediated voltage gating of Arabidopsis guard cell anion channel QUAC1.

Science.gov (United States)

Mumm, Patrick; Imes, Dennis; Martinoia, Enrico; Al-Rasheid, Khaled A S; Geiger, Dietmar; Marten, Irene; Hedrich, Rainer

2013-09-01

Anion transporters in plants play a fundamental role in volume regulation and signaling. Currently, two plasma membrane-located anion channel families—SLAC/SLAH and ALMT—are known. Among the ALMT family, the root-expressed ALuminium-activated Malate Transporter 1 was identified by comparison of aluminum-tolerant and Al(3+)-sensitive wheat cultivars and was subsequently shown to mediate voltage-independent malate currents. In contrast, ALMT12/QUAC1 (QUickly activating Anion Channel1) is expressed in guard cells transporting malate in an Al(3+)-insensitive and highly voltage-dependent manner. So far, no information is available about the structure and mechanism of voltage-dependent gating with the QUAC1 channel protein. Here, we analyzed gating of QUAC1-type currents in the plasma membrane of guard cells and QUAC1-expressing oocytes revealing similar voltage dependencies and activation–deactivation kinetics. In the heterologous expression system, QUAC1 was electrophysiologically characterized at increasing extra- and intracellular malate concentrations. Thereby, malate additively stimulated the voltage-dependent QUAC1 activity. In search of structural determinants of the gating process, we could not identify transmembrane domains common for voltage-sensitive channels. However, site-directed mutations and deletions at the C-terminus of QUAC1 resulted in altered voltage-dependent channel activity. Interestingly, the replacement of a single glutamate residue, which is conserved in ALMT channels from different clades, by an alanine disrupted QUAC1 activity. Together with C- and N-terminal tagging, these results indicate that the cytosolic C-terminus is involved in the voltage-dependent gating mechanism of QUAC1.

Scaling of normalized mean energy and scalar dissipation rates in a turbulent channel flow

Science.gov (United States)

Abe, Hiroyuki; Antonia, Robert Anthony

2011-05-01

Non-dimensional parameters for the mean energy and scalar dissipation rates Cɛ and Cɛθ are examined using direct numerical simulation (DNS) data obtained in a fully developed turbulent channel flow with a passive scalar (Pr = 0.71) at several values of the Kármán (Reynolds) number h+. It is shown that Cɛ and Cɛθ are approximately equal in the near-equilibrium region (viz., y+ = 100 to y/h = 0.7) where the production and dissipation rates of either the turbulent kinetic energy or scalar variance are approximately equal and the magnitudes of the diffusion terms are negligibly small. The magnitudes of Cɛ and Cɛθ are about 2 and 1 in the logarithmic and outer regions, respectively, when h+ is sufficiently large. The former value is about the same for the channel, pipe, and turbulent boundary layer, reflecting the similarity between the mean velocity and temperature distributions among these three canonical flows. The latter value is, on the other hand, about twice as large as in homogeneous isotropic turbulence due to the existence of the large-scale u structures in the channel. The behaviour of Cɛ and Cɛθ impacts on turbulence modeling. In particular, the similarity between Cɛ and Cɛθ leads to a simple relation for the scalar variance to turbulent kinetic energy time-scale ratio, an important ingredient in the eddy diffusivity model. This similarity also yields a relation between the Taylor and Corrsin microscales and analogous relations, in terms of h+, for the Taylor microscale Reynolds number and Corrsin microscale Peclet number. This dependence is reasonably well supported by both the DNS data at small to moderate h+ and the experimental data of Comte-Bellot [Ph. D. thesis (University of Grenoble, 1963)] at larger h+. It does not however apply to a turbulent boundary layer where the mean energy dissipation rate, normalized on either wall or outer variables, is about 30% larger than for the channel flow.

EFFECTS OF SIMPLIFIED CHEMICAL KINETIC MODEL ON THE MICRO-FLAME STRUCTURE AND TEMPERATURE OF THE LEAN PREMIXED METHANE-AIR MIXTURES

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JUNJIE CHEN

2015-07-01

Full Text Available The effect of simplified chemical kinetic model on the micro-flame structure, central axis and wall temperatures were investigated with different one-step global chemical kinetic mechanisms following Mantel, Duterque and Fernández-Tarrazo models. Numerical investigations of the premixed methane-air flame in the micro-channel and lean conditions were carried out to compare and analyze the effect of the comprehensive chemical kinetic mechanisms. The results indicate that one-step global chemical kinetic mechanism affects both the micro-flame shape and the combustion temperature. Among three simulation models, Mantel model allows a stable micro-flame with a bamboo shoot form, which anchor at the inlet. Duterque model gives a stable elongated micro-flame with a considerable ignition delay, and a dead zone with fluid accumulation is observed at the entrance, which may explain the very high combustion temperature and the fast reaction rate obtained, despite the micro-flame development presents a very hot spot and causes a broadening of the combustion zone. Fernández-Tarrazo model results in a rapid extinction and doesn't seem to take all the kinetic behavior into account for the appropriate micro-combustion simulations.

The role of different linear and non-linear channels of relaxation in scintillator non-proportionality

Energy Technology Data Exchange (ETDEWEB)

Bizarri, G.; Moses, W.W. [Lawrence Berkeley Laboratory, Berkeley, CA 94720-8119 (United States); Singh, J. [Faculty of EHS, B-41, Charles Darwin University, Darwin NT 0909 (Australia); Vasil' ev, A.N., E-mail: anvasiliev@rambler.r [Institute of Nuclear Physics, Moscow State University, Moscow 119991 (Russian Federation); Williams, R.T. [Department of Physics, Wake Forest University, Winston-Salem, NC 27109 (United States)

2009-12-15

The non-proportional dependence of a scintillator's light yield on primary particle energy is believed to be influenced crucially by the interplay of non-linear kinetic terms in the radiative and non-radiative decay of excitations versus locally deposited excitation density. A calculation of energy deposition, -dE/dx, along the electron track for NaI is presented for an energy range from several electron-volt to 1 MeV. Such results can be used to specify an initial excitation distribution, if diffusion is neglected. An exactly solvable two-channel (exciton and hole(electron)) model containing 1st and 2nd order kinetic terms is constructed and used to illustrate important features seen in non-proportional light-yield curves, including a dependence on pulse shaping (detection gate width).

The role of different linear and non-linear channels of relaxation in scintillator non-proportionality

International Nuclear Information System (INIS)

Bizarri, G.; Moses, W.W.; Singh, J.; Vasil'ev, A.N.; Williams, R.T.

2009-01-01

The non-proportional dependence of a scintillator's light yield on primary particle energy is believed to be influenced crucially by the interplay of non-linear kinetic terms in the radiative and non-radiative decay of excitations versus locally deposited excitation density. A calculation of energy deposition, -dE/dx, along the electron track for NaI is presented for an energy range from several electron-volt to 1 MeV. Such results can be used to specify an initial excitation distribution, if diffusion is neglected. An exactly solvable two-channel (exciton and hole(electron)) model containing 1st and 2nd order kinetic terms is constructed and used to illustrate important features seen in non-proportional light-yield curves, including a dependence on pulse shaping (detection gate width).

Differential expression of hERG1 channel isoforms reproduces properties of native I(Kr) and modulates cardiac action potential characteristics

DEFF Research Database (Denmark)

Larsen, Anders Peter; Olesen, Søren-Peter

2010-01-01

The repolarizing cardiac rapid delayed rectifier current, I(Kr), is composed of ERG1 channels. It has been suggested that two isoforms of the ERG1 protein, ERG1a and ERG1b, both contribute to I(Kr). Marked heterogeneity in the kinetic properties of native I(Kr) has been described. We hypothesized...

A hand-held row-column addressed CMUT probe with integrated electronics for volumetric imaging

DEFF Research Database (Denmark)

Engholm, Mathias; Christiansen, Thomas Lehrmann; Beers, Christopher

2015-01-01

A 3 MHz, λ / 2-pitch 62+62 channel row-column addressed 2-D CMUT array designed to be mounted in a probe handle and connected to a commercial BK Medical scanner for real-time volumetric imaging is presented. It is mounted and wire-bonded on a flexible PCB, which is connected to two rigid PCBs...

Non-equilibrium plasma kinetics of reacting CO: an improved state to state approach

Science.gov (United States)

Pietanza, L. D.; Colonna, G.; Capitelli, M.

2017-12-01

Non-equilibrium plasma kinetics of reacting CO for conditions typically met in microwave discharges have been developed based on the coupling of excited state kinetics and the Boltzmann equation for the electron energy distribution function (EEDF). Particular attention is given to the insertion in the vibrational kinetics of a complete set of electron molecule resonant processes linking the whole vibrational ladder of the CO molecule, as well as to the role of Boudouard reaction, i.e. the process of forming CO2 by two vibrationally excited CO molecules, in shaping the vibrational distribution of CO and promoting reaction channels assisted by vibrational excitation (pure vibrational mechanisms, PVM). PVM mechanisms can become competitive with electron impact dissociation processes (DEM) in the activation of CO. A case study reproducing the conditions of a microwave discharge has been considered following the coupled kinetics also in the post discharge conditions. Results include the evolution of EEDF in discharge and post discharge conditions highlighting the role of superelastic vibrational and electronic collisions in shaping the EEDF. Moreover, PVM rate coefficients and DEM ones are studied as a function of gas temperature, showing a non-Arrhenius behavior, i.e. the rate coefficients increase with decreasing gas temperature as a result of a vibrational-vibrational (V-V) pumping up mechanism able to form plateaux in the vibrational distribution function. The accuracy of the results is discussed in particular in connection to the present knowledge of the activation energy of the Boudouard process.

A New Generation of FRET Sensors for Robust Measurement of Gαi1, Gαi2 and Gαi3 Activation Kinetics in Single Cells.

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Jakobus van Unen

Full Text Available G-protein coupled receptors (GPCRs can activate a heterotrimeric G-protein complex with subsecond kinetics. Genetically encoded biosensors based on Förster resonance energy transfer (FRET are ideally suited for the study of such fast signaling events in single living cells. Here we report on the construction and characterization of three FRET biosensors for the measurement of Gαi1, Gαi2 and Gαi3 activation. To enable quantitative long-term imaging of FRET biosensors with high dynamic range, fluorescent proteins with enhanced photophysical properties are required. Therefore, we use the currently brightest and most photostable CFP variant, mTurquoise2, as donor fused to Gαi subunit, and cp173Venus fused to the Gγ2 subunit as acceptor. The Gαi FRET biosensors constructs are expressed together with Gβ1 from a single plasmid, providing preferred relative expression levels with reduced variation in mammalian cells. The Gαi FRET sensors showed a robust response to activation of endogenous or over-expressed alpha-2A-adrenergic receptors, which was inhibited by pertussis toxin. Moreover, we observed activation of the Gαi FRET sensor in single cells upon stimulation of several GPCRs, including the LPA2, M3 and BK2 receptor. Furthermore, we show that the sensors are well suited to extract kinetic parameters from fast measurements in the millisecond time range. This new generation of FRET biosensors for Gαi1, Gαi2 and Gαi3 activation will be valuable for live-cell measurements that probe Gαi activation.

Citizens and service channels: channel choice and channel management implications

NARCIS (Netherlands)

Pieterson, Willem Jan

2010-01-01

The arrival of electronic channels in the 1990s has had a huge impact on governmental service delivery. The new channels have led to many new opportunities to improve public service delivery, not only in terms of citizen satisfaction, but also in cost reduction for governmental agencies. However,

Targeted deletion of Kcne2 impairs HCN channel function in mouse thalamocortical circuits.

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Shui-Wang Ying

Full Text Available Hyperpolarization-activated, cyclic nucleotide-gated (HCN channels generate the pacemaking current, I(h, which regulates neuronal excitability, burst firing activity, rhythmogenesis, and synaptic integration. The physiological consequence of HCN activation depends on regulation of channel gating by endogenous modulators and stabilization of the channel complex formed by principal and ancillary subunits. KCNE2 is a voltage-gated potassium channel ancillary subunit that also regulates heterologously expressed HCN channels; whether KCNE2 regulates neuronal HCN channel function is unknown.We investigated the effects of Kcne2 gene deletion on I(h properties and excitability in ventrobasal (VB and cortical layer 6 pyramidal neurons using brain slices prepared from Kcne2(+/+ and Kcne2(-/- mice. Kcne2 deletion shifted the voltage-dependence of I(h activation to more hyperpolarized potentials, slowed gating kinetics, and decreased I(h density. Kcne2 deletion was associated with a reduction in whole-brain expression of both HCN1 and HCN2 (but not HCN4, although co-immunoprecipitation from whole-brain lysates failed to detect interaction of KCNE2 with HCN1 or 2. Kcne2 deletion also increased input resistance and temporal summation of subthreshold voltage responses; this increased intrinsic excitability enhanced burst firing in response to 4-aminopyridine. Burst duration increased in corticothalamic, but not thalamocortical, neurons, suggesting enhanced cortical excitatory input to the thalamus; such augmented excitability did not result from changes in glutamate release machinery since miniature EPSC frequency was unaltered in Kcne2(-/- neurons.Loss of KCNE2 leads to downregulation of HCN channel function associated with increased excitability in neurons in the cortico-thalamo-cortical loop. Such findings further our understanding of the normal physiology of brain circuitry critically involved in cognition and have implications for our understanding of

Stochastic theory of interfacial enzyme kinetics: A kinetic Monte Carlo study

International Nuclear Information System (INIS)

Das, Biswajit; Gangopadhyay, Gautam

2012-01-01

Graphical abstract: Stochastic theory of interfacial enzyme kinetics is formulated. Numerical results of macroscopic phenomenon of lag-burst kinetics is obtained by using a kinetic Monte Carlo approach to single enzyme activity. Highlights: ► An enzyme is attached with the fluid state phospholipid molecules on the Langmuir monolayer. ► Through the diffusion, the enzyme molecule reaches the gel–fluid interface. ► After hydrolysing a phospholipid molecule it predominantly leaves the surface in the lag phase. ► The enzyme is strictly attached to the surface with scooting mode of motion and the burst phase appears. - Abstract: In the spirit of Gillespie’s stochastic approach we have formulated a theory to explore the advancement of the interfacial enzyme kinetics at the single enzyme level which is ultimately utilized to obtain the ensemble average macroscopic feature, lag-burst kinetics. We have provided a theory of the transition from the lag phase to the burst phase kinetics by considering the gradual development of electrostatic interaction among the positively charged enzyme and negatively charged product molecules deposited on the phospholipid surface. It is shown that the different diffusion time scales of the enzyme over the fluid and product regions are responsible for the memory effect in the correlation of successive turnover events of the hopping mode in the single trajectory analysis which again is reflected on the non-Gaussian distribution of turnover times on the macroscopic kinetics in the lag phase unlike the burst phase kinetics.

BK virus encephalopathy and sclerosing vasculopathy in a patient with hypohidrotic ectodermal dysplasia and immunodeficiency.

Science.gov (United States)

Darbinyan, Armine; Major, Eugene O; Morgello, Susan; Holland, Steven; Ryschkewitsch, Caroline; Monaco, Maria Chiara; Naidich, Thomas P; Bederson, Joshua; Malaczynska, Joanna; Ye, Fei; Gordon, Ronald; Cunningham-Rundles, Charlotte; Fowkes, Mary; Tsankova, Nadejda M

2016-07-13

Human BK polyomavirus (BKV) is reactivated under conditions of immunosuppression leading most commonly to nephropathy or cystitis; its tropism for the brain is rare and poorly understood. We present a unique case of BKV-associated encephalopathy in a man with hypohidrotic ectodermal dysplasia and immunodeficiency (HED-ID) due to IKK-gamma (NEMO) mutation, who developed progressive neurological symptoms. Brain biopsy demonstrated polyomavirus infection of gray and white matter, with predominant involvement of cortex and distinct neuronal tropism, in addition to limited demyelination and oligodendroglial inclusions. Immunohistochemistry demonstrated polyoma T-antigen in neurons and glia, but expression of VP1 capsid protein only in glia. PCR analysis on both brain biopsy tissue and cerebrospinal fluid detected high levels of BKV DNA. Sequencing studies further identified novel BKV variant and disclosed unique rearrangements in the noncoding control region of the viral DNA (BKVN NCCR). Neuropathological analysis also demonstrated an unusual form of obliterative fibrosing vasculopathy in the subcortical white matter with abnormal lysosomal accumulations, possibly related to the patient's underlying ectodermal dysplasia. Our report provides the first neuropathological description of HED-ID due to NEMO mutation, and expands the diversity of neurological presentations of BKV infection in brain, underscoring the importance of its consideration in immunodeficient patients with unexplained encephalopathy. We also document novel BKVN NCCR rearrangements that may be associated with the unique neuronal tropism in this patient.

UV protection filters by dielectric multilayer thin films on Glass BK-7 and Infrasil 301

International Nuclear Information System (INIS)

Abdel-Aziz, M.M.; Azim, Osama A.; Abdel-Wahab, L.A.; Seddik, Mohamed M.

2006-01-01

The increasing use of Ultraviolet (UV) light in medicine, industrial environments, for cosmetic use, and even in consumer products necessitates that greater attention be paid to the potential hazards of this type of electromagnetic radiation. To avoid any adverse effects of exposure to this type of radiation, four suitable protection filters were produced to block three UV bands (UVA, UVB, and UVC). The design structure of the required dielectric multilayer filters was done by optical thin film technology using the absorbing property of UV radiation for the substrates and dielectric materials. The computer analyses of the multilayer filter formulas were prepared using Macleod Software for the production processes. The deposition technique was achieved on optical substrates (Glass BK-7 and Infrasil 301) by dielectric material combinations including Titanium dioxide (Ti 2 O 3 ), Hafnium dioxide (HfO 2 ), and Lima (mixture of oxides SiO 2 /Al 2 O 3 ); deposition being achieved using an electron beam gun. The output results of the theoretical and experimental transmittance values for spectral band from 200 nm to 800 nm were discussed in four processes. To analyze the suitability for use in 'real world' applications, the test pieces were subjected to the durability tests (adhesion, abrasion resistance, and humidity) according to Military Standard MIL-C-675C and MIL-C-48497A

UV protection filters by dielectric multilayer thin films on Glass BK-7 and Infrasil 301

Science.gov (United States)

Abdel-Aziz, M. M.; Azim, Osama A.; Abdel-Wahab, L. A.; Seddik, Mohamed M.

2006-10-01

The increasing use of Ultraviolet (UV) light in medicine, industrial environments, for cosmetic use, and even in consumer products necessitates that greater attention be paid to the potential hazards of this type of electromagnetic radiation. To avoid any adverse effects of exposure to this type of radiation, four suitable protection filters were produced to block three UV bands (UVA, UVB, and UVC). The design structure of the required dielectric multilayer filters was done by optical thin film technology using the absorbing property of UV radiation for the substrates and dielectric materials. The computer analyses of the multilayer filter formulas were prepared using Macleod Software for the production processes. The deposition technique was achieved on optical substrates (Glass BK-7 and Infrasil 301) by dielectric material combinations including Titanium dioxide (Ti 2O 3), Hafnium dioxide (HfO 2), and Lima (mixture of oxides SiO 2/Al 2O 3); deposition being achieved using an electron beam gun. The output results of the theoretical and experimental transmittance values for spectral band from 200 nm to 800 nm were discussed in four processes. To analyze the suitability for use in 'real world' applications, the test pieces were subjected to the durability tests (adhesion, abrasion resistance, and humidity) according to Military Standard MIL-C-675C and MIL-C-48497A.

Transfer of tritium released into the marine environment by French nuclear facilities bordering the English Channel.

Science.gov (United States)

Fiévet, Bruno; Pommier, Julien; Voiseux, Claire; Bailly du Bois, Pascal; Laguionie, Philippe; Cossonnet, Catherine; Solier, Luc

2013-06-18

Controlled amounts of liquid tritium are discharged as tritiated water (HTO) by the nuclear industry into the English Channel. Because the isotopic discrimination between 3H and H is small, organically bound tritium (OBT) and HTO should show the same T/H ratio under steady-state conditions. We report data collected from the environment in the English Channel. Tritium concentrations measured in seawater HTO, as well as in biota HTO and OBT, confirm that tritium transfers from HTO to OBT result in conservation of the T/H ratio (ca. 1 × 10(-16)). The kinetics of the turnover of tritium between seawater HTO, biota HTO, and OBT was investigated. HTO in two algae and a mollusk is shown to exchange rapidly with seawater HTO. However, the overall tritium turnover between HTO and the whole-organism OBT is a slow process with a tritium biological half-life on the order of months. Nonsteady-state conditions exist where there are sharp changes in seawater HTO. As a consequence, for kinetic reasons, the T/H ratio in OBT may deviate transiently from that observed in HTO of samples from the marine ecosystem. Dynamic modeling is thus more realistic for predicting tritium transfers to biota OBT under nonsteady-state conditions.

Biphasic character of ribosomal translocation and non-Michaelis-Menten kinetics of translation

Science.gov (United States)

Xie, Ping

2014-12-01

We study theoretically the kinetics of mRNA translocation in the wild-type (WT) Escherichia coli ribosome, which is composed of a small 30 S and large 50 S subunit, and the ribosomes with mutations to some intersubunit bridges such as B1a, B4, B7a, and B8. The theoretical results reproduce well the available in vitro experimental data on the biphasic kinetics of the forward mRNA translocation catalyzed by elongation factor G (EF-G) hydrolyzing GTP, which can be best fit by the sum of two exponentials, and the monophasic kinetics of the spontaneous reverse mRNA translocation in the absence of the elongation factor, which can be best fit by a single-exponential function, in both the WT and mutant ribosomes. We show that both the mutation-induced increase in the maximal rate of the slow phase for the forward mRNA translocation and that in the rate of the spontaneous reverse mRNA translocation result from a reduction in the intrinsic energy barrier to resist the rotational movements between the two subunits, giving the same degree of increase in the two rates. The mutation-induced increase in the maximal rate of the fast phase for the forward mRNA translocation results mainly from the increase in the rate of the ribosomal unlocking, a conformational change in the ribosome that widens the mRNA channel for the mRNA translocation to take place, which could be partly due to the effect of the mutation on the intrasubunit 30S head rotation. Moreover, we study the translation rate of the WT and mutant ribosomes. It is shown that the translation rate versus the concentration of EF-G-GTP does not follow the Michaelis-Menten (MM) kinetics, which is in sharp contrast to the general property of other enzymes that the rate of the enzymatic reaction versus the concentration of a substrate follows the MM kinetics. The physical origin of this non-MM kinetics for the ribosome is revealed.

Endothelium-dependent vasorelaxant effect of procyanidin B2 on human internal mammary artery.

Science.gov (United States)

Novakovic, Aleksandra; Marinko, Marija; Jankovic, Goran; Stojanovic, Ivan; Milojevic, Predrag; Nenezic, Dragoslav; Kanjuh, Vladimir; Yang, Qin; He, Guo-Wei

2017-07-15

The aim of the present study was to investigate and characterize vasorelaxant effect of procyanidin B2 on human internal mammary artery (HIMA) as one of the mechanisms of its protective effect against vascular risk. Procyanidin B2 induced strong concentration-dependent relaxation of HIMA rings pre-contracted by phenylephrine. Pretreatment with L-NAME, a NO synthase inhibitor, hydroxocobalamin, a NO scavenger, and ODQ, an inhibitor of soluble guanylate cyclase, significantly inhibited procyanidin B2-induced relaxation of HIMA, while indomethacin, a cyclooxygenase inhibitor, considerably reduced effects of low concentrations. Among K + channel blockers, iberiotoxin, a selective blocker of large conductance Ca 2+ -activated K + channels (BK Ca ), abolished procyanidin B2-induced relaxation, glibenclamide, a selective ATP-sensitive K + (K ATP ) channels blocker, induced partial inhibition, while 4-aminopyridine, a blocker of voltage-gated K + (K V ) channels, and TRAM-34, an inhibitor of intermediate-conductance Ca 2+ -activated K + (IK Ca ) channels, slightly reduced maximal relaxation of HIMA. Further, procyanidin B2 relaxed contraction induced by phenylephrine in Ca 2+ -free Krebs solution, but had no effect on contraction induced by caffeine. Finally, thapsigargin, a sarcoplasmic reticulum Ca 2+ -ATPase inhibitor, significantly reduced relaxation of HIMA produced by procyanidin B2. These results demonstrate that procyanidin B2 produces endothelium-dependent relaxation of HIMA pre-contracted by phenylephrine. This effect is primarily the result of an increased NO synthesis and secretion by endothelial cells and partially of prostacyclin, although it involves activation of BK Ca and K ATP , as well as K V and IK Ca channels in high concentrations of procyanidin B2. Copyright © 2017 Elsevier B.V. All rights reserved.

Physical kinetics