Differential Regulation of Action Potential Shape and Burst-Frequency Firing by BK and Kv2 Channels in Substantia Nigra Dopaminergic Neurons.

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Kimm, Tilia; Khaliq, Zayd M; Bean, Bruce P

2015-12-16

Little is known about the voltage-dependent potassium currents underlying spike repolarization in midbrain dopaminergic neurons. Studying mouse substantia nigra pars compacta dopaminergic neurons both in brain slice and after acute dissociation, we found that BK calcium-activated potassium channels and Kv2 channels both make major contributions to the depolarization-activated potassium current. Inhibiting Kv2 or BK channels had very different effects on spike shape and evoked firing. Inhibiting Kv2 channels increased spike width and decreased the afterhyperpolarization, as expected for loss of an action potential-activated potassium conductance. BK inhibition also increased spike width but paradoxically increased the afterhyperpolarization. Kv2 channel inhibition steeply increased the slope of the frequency-current (f-I) relationship, whereas BK channel inhibition had little effect on the f-I slope or decreased it, sometimes resulting in slowed firing. Action potential clamp experiments showed that both BK and Kv2 current flow during spike repolarization but with very different kinetics, with Kv2 current activating later and deactivating more slowly. Further experiments revealed that inhibiting either BK or Kv2 alone leads to recruitment of additional current through the other channel type during the action potential as a consequence of changes in spike shape. Enhancement of slowly deactivating Kv2 current can account for the increased afterhyperpolarization produced by BK inhibition and likely underlies the very different effects on the f-I relationship. The cross-regulation of BK and Kv2 activation illustrates that the functional role of a channel cannot be defined in isolation but depends critically on the context of the other conductances in the cell. This work shows that BK calcium-activated potassium channels and Kv2 voltage-activated potassium channels both regulate action potentials in dopamine neurons of the substantia nigra pars compacta. Although both

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.

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

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.

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.

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...

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

DEFF Research Database (Denmark)

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...

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 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

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

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

Science.gov (United States)

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

Science.gov (United States)

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.

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...

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

Science.gov (United States)

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 ?

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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

Science.gov (United States)

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

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.

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

Science.gov (United States)

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...

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.

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...

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

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.

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.

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...

Pharmacological investigation of the role of ion channels in salivary secretion

DEFF Research Database (Denmark)

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...

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.

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.

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)

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.

Science.gov (United States)

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.

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

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.

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.

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.

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.

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.

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

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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.

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

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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

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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

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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...

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

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...

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

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.

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.

Iron status of channel catfish Ictalurus punctatus affected by channel catfish anemia and response to parenteral iron

Science.gov (United States)

Originally reported in 1983, channel catfish anemia (CCA), also ‘white lip’ or ‘no blood,’ is a major idiopathic disease affecting commercial production in the Mississippi Delta region of the USA. Affected individuals are characterized by lethargy, anorexia, extreme pallor, and packed cell volumes o...

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.

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

Fine sediment in pools: An index of how sediment is affecting a stream channel

Science.gov (United States)

Tom Lisle; Sue Hilton

1991-01-01

One of the basic issues facing managers of fisheries watersheds is how inputs of sediment affect stream channels. In some cases we can measure and even roughly predict effects of land use on erosion and delivery of sediment from hillslopes to streams. But we are at a loss about how a given increase in sediment load will affect channel morphology, flow conditions, and...

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

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

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.

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

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

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.

A Novel KCNJ2 Mutation Identified in an Autistic Proband Affects the Single Channel Properties of Kir2.1

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Anna Binda

2018-03-01

Full Text Available Inwardly rectifying potassium channels (Kir have been historically associated to several cardiovascular disorders. In particular, loss-of-function mutations in the Kir2.1 channel have been reported in cases affected by Andersen-Tawil syndrome while gain-of-function mutations in the same channel cause the short QT3 syndrome. Recently, a missense mutation in Kir2.1, as well as mutations in the Kir4.1, were reported to be involved in autism spectrum disorders (ASDs suggesting a role of potassium channels in these diseases and introducing the idea of the existence of K+ channel ASDs. Here, we report the identification in an Italian affected family of a novel missense mutation (p.Phe58Ser in the KCNJ2 gene detected in heterozygosity in a proband affected by autism and borderline for short QT syndrome type 3. The mutation is located in the N-terminal region of the gene coding for the Kir2.1 channel and in particular in a very conserved domain. In vitro assays demonstrated that this mutation results in an increase of the channel conductance and in its open probability. This gain-of-function of the protein is consistent with the autistic phenotype, which is normally associated to an altered neuronal excitability.

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.

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...

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.

Science communication on YouTube: Factors that affect channel and video popularity.

Science.gov (United States)

Welbourne, Dustin J; Grant, Will J

2016-08-01

YouTube has become one of the largest websites on the Internet. Among its many genres, both professional and amateur science communicators compete for audience attention. This article provides the first overview of science communication on YouTube and examines content factors that affect the popularity of science communication videos on the site. A content analysis of 390 videos from 39 YouTube channels was conducted. Although professionally generated content is superior in number, user-generated content was significantly more popular. Furthermore, videos that had consistent science communicators were more popular than those without a regular communicator. This study represents an important first step to understand content factors, which increases the channel and video popularity of science communication on YouTube. © The Author(s) 2015.

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

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

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.

[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.

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

Selection of Inhibitor-Resistant Viral Potassium Channels Identifies a Selectivity Filter Site that Affects Barium and Amantadine Block

Science.gov (United States)

Fujiwara, Yuichiro; Arrigoni, Cristina; Domigan, Courtney; Ferrara, Giuseppina; Pantoja, Carlos; Thiel, Gerhard; Moroni, Anna; Minor, Daniel L.

2009-01-01

Background Understanding the interactions between ion channels and blockers remains an important goal that has implications for delineating the basic mechanisms of ion channel function and for the discovery and development of ion channel directed drugs. Methodology/Principal Findings We used genetic selection methods to probe the interaction of two ion channel blockers, barium and amantadine, with the miniature viral potassium channel Kcv. Selection for Kcv mutants that were resistant to either blocker identified a mutant bearing multiple changes that was resistant to both. Implementation of a PCR shuffling and backcrossing procedure uncovered that the blocker resistance could be attributed to a single change, T63S, at a position that is likely to form the binding site for the inner ion in the selectivity filter (site 4). A combination of electrophysiological and biochemical assays revealed a distinct difference in the ability of the mutant channel to interact with the blockers. Studies of the analogous mutation in the mammalian inward rectifier Kir2.1 show that the T→S mutation affects barium block as well as the stability of the conductive state. Comparison of the effects of similar barium resistant mutations in Kcv and Kir2.1 shows that neighboring amino acids in the Kcv selectivity filter affect blocker binding. Conclusions/Significance The data support the idea that permeant ions have an integral role in stabilizing potassium channel structure, suggest that both barium and amantadine act at a similar site, and demonstrate how genetic selections can be used to map blocker binding sites and reveal mechanistic features. PMID:19834614

Brittle stalk 2 encodes a putative glycosylphosphatidylinositol-anchored protein that affects mechanical strength of maize tissues by altering the composition and structure of secondary cell walls.

Science.gov (United States)

Ching, Ada; Dhugga, Kanwarpal S; Appenzeller, Laura; Meeley, Robert; Bourett, Timothy M; Howard, Richard J; Rafalski, Antoni

2006-10-01

A spontaneous maize mutant, brittle stalk-2 (bk2-ref), exhibits dramatically reduced tissue mechanical strength. Reduction in mechanical strength in the stalk tissue was highly correlated with a reduction in the amount of cellulose and an uneven deposition of secondary cell wall material in the subepidermal and perivascular sclerenchyma fibers. Cell wall accounted for two-thirds of the observed reduction in dry matter content per unit length of the mutant stalk in comparison to the wildtype stalk. Although the cell wall composition was significantly altered in the mutant in comparison to the wildtype stalks, no compensation by lignin and cell wall matrix for reduced cellulose amount was observed. We demonstrate that Bk2 encodes a Cobra-like protein that is homologous to the rice Bc1 protein. In the bk2-ref gene, a 1 kb transposon-like element is inserted in the beginning of the second exon, disrupting the open reading frame. The Bk2 gene was expressed in the stalk, husk, root, and leaf tissues, but not in the embryo, endosperm, pollen, silk, or other tissues with comparatively few or no secondary cell wall containing cells. The highest expression was in the isolated vascular bundles. In agreement with its role in secondary wall formation, the expression pattern of the Bk2 gene was very similar to that of the ZmCesA10, ZmCesA11, and ZmCesA12 genes, which are known to be involved in secondary wall formation. We have isolated an independent Mutator-tagged allele of bk2, referred to as bk2-Mu7, the phenotype of which is similar to that of the spontaneous mutant. Our results demonstrate that mutations in the Bk2 gene affect stalk strength in maize by interfering with the deposition of cellulose in the secondary cell wall in fiber cells.

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

Profil Siswa Agresif dan Peranan Guru BK

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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.

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

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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.

Vehicle type affects filling of fractional laser-ablated channels imaged by optical coherence tomography

DEFF Research Database (Denmark)

Olesen, Uffe Høgh; Mogensen, Mette; Haedersdal, Merete

2017-01-01

Ablative fractional laser (AFXL) is an emerging method that enhances topical drug delivery. Penetrating the skin in microscopic, vertical channels, termed microscopic treatment zones (MTZs), the fractional technique circumvents the skin barrier and allows increased uptake of topically applied dru...... was overall greater for more superficial MTZs. In conclusion, vehicle type affects filling of MTZs, which may be of importance for AFXL-assisted drug delivery....

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

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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

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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

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.

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

Science.gov (United States)

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.

Science.gov (United States)

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.

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.

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

Science.gov (United States)

Carvalho-de-Souza, Joao L; Bezanilla, Francisco

2018-02-05

Voltage sensitivity in ion channels is a function of highly conserved arginine residues in their voltage-sensing domains (VSDs), but this conservation does not explain the diversity in voltage dependence among different K + channels. Here we study the non-voltage-sensing residues 353 to 361 in Shaker K + channels and find that residues 358 and 361 strongly modulate the voltage dependence of the channel. We mutate these two residues into all possible remaining amino acids (AAs) and obtain Q-V and G-V curves. We introduced the nonconducting W434F mutation to record sensing currents in all mutants except L361R, which requires K + depletion because it is affected by W434F. By fitting Q-Vs with a sequential three-state model for two voltage dependence-related parameters ( V 0 , the voltage-dependent transition from the resting to intermediate state and V 1 , from the latter to the active state) and G-Vs with a two-state model for the voltage dependence of the pore domain parameter ( V 1/2 ), Spearman's coefficients denoting variable relationships with hydrophobicity, available area, length, width, and volume of the AAs in 358 and 361 positions could be calculated. We find that mutations in residue 358 shift Q-Vs and G-Vs along the voltage axis by affecting V 0 , V 1 , and V 1/2 according to the hydrophobicity of the AA. Mutations in residue 361 also shift both curves, but V 0 is affected by the hydrophobicity of the AA in position 361, whereas V 1 and V 1/2 are affected by size-related AA indices. Small-to-tiny AAs have opposite effects on V 1 and V 1/2 in position 358 compared with 361. We hypothesize possible coordination points in the protein that residues 358 and 361 would temporarily and differently interact with in an intermediate state of VSD activation. Our data contribute to the accumulating knowledge of voltage-dependent ion channel activation by adding functional information about the effects of so-called non-voltage-sensing residues on VSD dynamics. © 2018

An Investigation of How the Channel of Input and Access to Test Questions Affect L2 Listening Test Performance

Science.gov (United States)

Wagner, Elvis

2013-01-01

The use of video technology has become widespread in the teaching and testing of second-language (L2) listening, yet research into how this technology affects the learning and testing process has lagged. The current study investigated how the channel of input (audiovisual vs. audio-only) used on an L2 listening test affected test-taker…

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.

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.

Channel-Island Connectivity Affects Water Exposure Time Distributions in a Coastal River Delta

Science.gov (United States)

Hiatt, Matthew; Castañeda-Moya, Edward; Twilley, Robert; Hodges, Ben R.; Passalacqua, Paola

2018-03-01

The exposure time is a water transport time scale defined as the cumulative amount of time a water parcel spends in the domain of interest regardless of the number of excursions from the domain. Transport time scales are often used to characterize the nutrient removal potential of aquatic systems, but exposure time distribution estimates are scarce for deltaic systems. Here we analyze the controls on exposure time distributions using a hydrodynamic model in two domains: the Wax Lake delta in Louisiana, USA, and an idealized channel-island complex. In particular, we study the effects of river discharge, vegetation, network geometry, and tides and use a simple model for the fractional removal of nitrate. In both domains, we find that channel-island hydrological connectivity significantly affects exposure time distributions and nitrate removal. The relative contributions of the island and channel portions of the delta to the overall exposure time distribution are controlled by island vegetation roughness and network geometry. Tides have a limited effect on the system's exposure time distribution but can introduce significant spatial variability in local exposure times. The median exposure time for the WLD model is 10 h under the conditions tested and water transport within the islands contributes to 37-50% of the network-scale exposure time distribution and 52-73% of the modeled nitrate removal, indicating that islands may account for the majority of nitrate removal in river deltas.

Effects of dislocations on electron channeling

International Nuclear Information System (INIS)

George, Juby; Pathak, A P

2009-01-01

The phenomenon of electron channeling in a crystal affected by dislocations is considered. Earlier we had considered the quantum aspects of the positron channeling in a crystal bent by dislocations where the effects of longitudinal motion of the particle were also considered along with the transverse motion. In this paper, the effective potential for the electron case is found for the two regions of dislocation-affected channel. There is considerable shift in the potential minima due to dislocations. The frequency and the corresponding spectrum of the channeling radiation due to electrons channeling through the perfect channel and the two regions of dislocation-affected channels are calculated. The spectral distribution of radiation intensity changes with the parameters of dislocation. The continuity of wavefunctions and their derivatives is used at the three boundaries and the reflection and transmission coefficients are found using these boundary conditions in the same way as in the positron case.

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.

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.

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

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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.

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....

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...

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.

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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.

The acrylamide (S)-1 differentially affects Kv7 (KCNQ) potassium channels

DEFF Research Database (Denmark)

Bentzen, Bo Hjorth; Schmitt, Nicole; Calloe, Kirstine

2006-01-01

The family of Kv7 (KCNQ) potassium channels consists of five members. Kv7.2 and 3 are the primary molecular correlates of the M-current, but also Kv7.4 and Kv7.5 display M-current characteristics. M-channel modulators include blockers (e.g., linopirdine) for cognition enhancement and openers (e.g...

MONETARY TRANSMISSION CHANNELS IN ROMANIA – THE CREDIT CHANNEL

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Magdalena RĂDULESCU

2009-12-01

Full Text Available The theoretical – intuitive analysis applied to the segment of monetary transmission evidences the fact that forming the traditional monetary impulses transmission channels are in a starting phase due to the long financial non – intermediary process which Romanian economy had known. In these conditions, the exchange rate channel, and also NBR currency purchases was, for a long time, an important way through which monetary authorities actions influenced macro economical behaviors. But starting with 2000, it is observed a credit channel reactivation and, especially, interest rate channel. Anyhow, the credit channel continues to be undermined by the existence of liquidity surplus within the system, by the phenomena of substitution of national currency credit with currency credits, and also moral hazardous displays. Albeit some of these phenomena also affect the interest rate channel, its role in sending monetary policy impulses is in a continuous progress. Apparently, it acts by way of nominal interest rates, their real level seeming less relevant. Once with remaking the two traditional channels, the companies and households balance is configured and consolidated, which shall potentate in the future the efficiency of the monetary policy. This paper analyses the credit channel in Romania, through an unrestricted VAR analysis.. It shows the responses of exchange rate, inflation rate, GDP, interest rate, imports and exports to a shock on non-governmental credit

Toxins That Affect Voltage-Gated Sodium Channels.

Science.gov (United States)

Ji, Yonghua

2017-10-26

Voltage-gated sodium channels (VGSCs) are critical in generation and conduction of electrical signals in multiple excitable tissues. Natural toxins, produced by animal, plant, and microorganisms, target VGSCs through diverse strategies developed over millions of years of evolutions. Studying of the diverse interaction between VGSC and VGSC-targeting toxins has been contributing to the increasing understanding of molecular structure and function, pharmacology, and drug development potential of VGSCs. This chapter aims to summarize some of the current views on the VGSC-toxin interaction based on the established receptor sites of VGSC for natural toxins.

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

Channel perceptions and usage: beyond media richness factors

NARCIS (Netherlands)

Pieterson, Willem Jan; Teerling, Marije; Ebbers, Wolfgang E.; Wimmer, Maria A.; Scholl, Hans J.; Ferro, Enrico

2008-01-01

In this paper, we asses how service channel perceptions affect channel choice and channel usage. Building on communication theories, such as the Media Richness Theory, we explore how different channel characteristics are perceived by citizens in a Dutch governmental service chain. The results of our

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

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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

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

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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.

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

Discovery and characterization of cnidarian peptide toxins that affect neuronal potassium ion channels.

Science.gov (United States)

Castañeda, Olga; Harvey, Alan L

2009-12-15

Peptides have been isolated from several species of sea anemones and shown to block currents through various potassium ion channels, particularly in excitable cells. The toxins can be grouped into four structural classes: type 1 with 35-37 amino acid residues and three disulphide bridges; type 2 with 58-59 residues and three disulphide bridges; type 3 with 41-42 residues and three disulphide bridges; and type 4 with 28 residues and two disulphide bridges. Examples from the first class are BgK from Bunodosoma granulifera, ShK from Stichodactyla helianthus and AsKS (or kaliseptine) from Anemonia sulcata (now A. viridis). These interfere with binding of radiolabelled dendrotoxin to synaptosomal membranes and block currents through channels with various Kv1 subunits and also intermediate conductance K(Ca) channels. Toxins in the second class are homologous to Kunitz-type inhibitors of serine proteases; these toxins include kalicludines (AsKC 1-3) from A. sulcata and SHTXIII from S. haddoni; they block Kv1.2 channels. The third structural group includes BDS-I, BDS-II (from A. sulcata) and APETx 1 (from Anthropleura elegantissima). Their pharmacological specificity differs: BDS-I and -II block currents involving Kv3 subunits, while APETx1 blocks ERG channels. The fourth group comprises the more recently discovered SHTX I and II from S. haddoni. Their channel blocking specificity is not yet known but they displace dendrotoxin binding from synaptosomal membranes. Sea anemones can be predicted to be a continued source of new toxins that will serve as molecular probes of various K(+) channels.

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.

Comparing Effects of BK Virus Agnoprotein and Herpes Simplex-1 ICP47 on MHC-I and MHC-II Expression

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Michela Cioni

2013-01-01

Full Text Available Background. Among human polyomaviruses, only BK virus (BKV and JC virus (JCV encode an agnoprotein upstream of VP1 on the viral late transcript. BKV agnoprotein is abundantly expressed late in the viral life cycle, but specific cellular and humoral immune responses are low or absent. We hypothesized that agnoprotein might contribute to BKV immune evasion by downregulating HLA expression, similar to Herpes simplex virus-1 ICP47. Methods UTA-6 or primary human renal proximal tubular epithelial cells (RPTEC were co-transfected with plasmids constitutively expressing agnoprotein, or ICP47, and enhanced green-fluorescent protein (EGFP. EGFP-gated cells were analyzed for HLA-ABC and HLA-DR expression by flow cytometry. HLA-ABC and HLA-DR expression was also analyzed on UTA-6 bearing tetracycline-regulated agnoprotein or ICP47. Effects of agnoprotein on viral peptide-dependent T-cell killing were investigated using 51Cr release. Results. ICP47 downregulated HLA-ABC without affecting HLA-DR, whereas agnoprotein did not affect HLA-ABC or HLA-DR expression. Interferon-γ treatment increased HLA-ABC in a dose-dependent manner, which was antagonized by ICP47, but not by agnoprotein. In UTA-6 cells, agnoprotein expression did neither impair HLA-ABC or -DR expression nor peptide-specific killing impaired by HLA-matched T-cells. Conclusion. Unlike the HSV-1 ICP47, BKV agnoprotein does not contribute to viral immune evasion by down-regulating HLA-ABC, or interfere with HLA-DR expression or peptide-dependent T-cell cytotoxicity.

[Channels: a new way to revisit pathology].

Science.gov (United States)

Fournier, Emmanuel

2014-02-01

Many "essential" diseases that manifest themselves in the form of crises or fits (epilepsies, episodic ataxia, periodic paralyses, myotonia, heart rhythm disorders, etc.) are due to ionic channel dysfunction and are thus referred to as "channelopathies". Some of these disorders are congenital, due to mutations of genes encoding channel subunits, while others result from toxic, immune or hormonal disturbances affecting channelfunction. Channelopathies take on a wide variety of clinical forms, depending on the type of channel (sodium, potassium, calcium, chloride...) and the type of dysfunction (loss or gain of function). Some apparently unrelated diseases affecting distinct organs are due to a similar dysfunction of the same channel, revealing unsuspected relationships between organs and between medical specialties. In addition, a given syndrome can be caused by distinct channel dysfunctions. This provides new opportunities for diferential diagnosis and specific correction of the causal defects, although some treatments find applications across multiple medical specialties.

Automatic pickup of arrival time of channel wave based on multi-channel constraints

Science.gov (United States)

Wang, Bao-Li

2018-03-01

Accurately detecting the arrival time of a channel wave in a coal seam is very important for in-seam seismic data processing. The arrival time greatly affects the accuracy of the channel wave inversion and the computed tomography (CT) result. However, because the signal-to-noise ratio of in-seam seismic data is reduced by the long wavelength and strong frequency dispersion, accurately timing the arrival of channel waves is extremely difficult. For this purpose, we propose a method that automatically picks up the arrival time of channel waves based on multi-channel constraints. We first estimate the Jaccard similarity coefficient of two ray paths, then apply it as a weight coefficient for stacking the multichannel dispersion spectra. The reasonableness and effectiveness of the proposed method is verified in an actual data application. Most importantly, the method increases the degree of automation and the pickup precision of the channel-wave arrival time.

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.

Ethanol affects network activity in cultured rat hippocampus: mediation by potassium channels.

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Eduard Korkotian

Full Text Available The effects of ethanol on neuronal network activity were studied in dissociated cultures of rat hippocampus. Exposure to low (0.25-0.5% ethanol concentrations caused an increase in synchronized network spikes, and a decrease in the duration of individual spikes. Ethanol also caused an increase in rate of miniature spontaneous excitatory postsynaptic currents. Higher concentrations of ethanol eliminated network spikes. These effects were reversible upon wash. The effects of the high, but not the low ethanol were blocked by the GABA antagonist bicuculline. The enhancing action of low ethanol was blocked by apamin, an SK potassium channel antagonist, and mimicked by 1-EBIO, an SK channel opener. It is proposed that in cultured hippocampal networks low concentration of ethanol is associated with SK channel activity, rather than the GABAergic receptor.

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.

THE DAIRY VALUE CHAIN AND FACTORS AFFECTING CHOICE OF MILK CHANNELS IN HARAR AND DIRE DAWA AREAS, EASTERN ETHIOPIA

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Mengistu KETEMA

2016-11-01

Full Text Available The study was aimed at mapping the dairy value chain, assessing constraints and opportunities in the sector, and identifying factors affecting channel choices of producers in Harar and Dire Dawa milkshed areas. Data were collected from 93 producers, six collectors, seven wholesalers, seven retailers, and ten consumers. Both descriptive and econometric analysis were employed. The study revealed that the channel choices available to producers include selling to collectors, wholesalers, retailers, and directly to consumers. The multinomial model output indicated that being in rural areas, breed type, separate milking place, and supply of hay negatively determined the choice to sell to wholesalers, retailers, and consumers. In contrast, education status and milk storage duration positively determined producers’ choice not to sell to collectors. The major recommendations include provision of training, disseminating dairy technologies, encouraging value chain actors to add values; and enhancing collective actions of producers.

Skeletal Muscle Na+ Channel Disorders

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Dina eSimkin

2011-10-01

Full Text Available Five inherited human disorders affecting skeletal muscle contraction have been traced to mutations in the gene encoding the voltage-gated sodium channel Nav1.4. The main symptoms of these disorders are myotonia or periodic paralysis caused by changes in skeletal muscle fiber excitability. Symptoms of these disorders vary from mild or latent disease to incapacitating or even death in severe cases. As new human sodium channel mutations corresponding to disease states become discovered, the importance of understanding the role of the sodium channel in skeletal muscle function and disease state grows.

How Equalization Techniques Affect the TCP Performance of MC-CDMA Systems in Correlated Fading Channels

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Giacomo Leonardi

2007-12-01

Full Text Available This paper investigates the impact of several equalization techniques for multicarrier code division multiple access systems on the performance at both lower and upper layers (i.e., physical and TCP layers. Classical techniques such as maximal ratio combining, equal gain combining, orthogonality restoring combining, minimum mean square error, as well as a partial equalization (PE are investigated in time- and frequency-correlated fading channels with various numbers of interferers. Their impact on the performance at upper level is then studied. The results are obtained through an integrated simulation platform carefully reproducing all main aspects affecting the quality of service perceived by the final user, allowing an investigation of the real gain produced by signal processing techniques at TCP level.

Post-Translational Modifications of TRP Channels

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Olaf Voolstra

2014-04-01

Full Text Available Transient receptor potential (TRP channels constitute an ancient family of cation channels that have been found in many eukaryotic organisms from yeast to human. TRP channels exert a multitude of physiological functions ranging from Ca2+ homeostasis in the kidney to pain reception and vision. These channels are activated by a wide range of stimuli and undergo covalent post-translational modifications that affect and modulate their subcellular targeting, their biophysical properties, or channel gating. These modifications include N-linked glycosylation, protein phosphorylation, and covalent attachment of chemicals that reversibly bind to specific cysteine residues. The latter modification represents an unusual activation mechanism of ligand-gated ion channels that is in contrast to the lock-and-key paradigm of receptor activation by its agonists. In this review, we summarize the post-translational modifications identified on TRP channels and, when available, explain their physiological role.

Novel CLCNKB mutations causing Bartter syndrome affect channel surface expression.

Science.gov (United States)

Keck, Mathilde; Andrini, Olga; Lahuna, Olivier; Burgos, Johanna; Cid, L Pablo; Sepúlveda, Francisco V; L'hoste, Sébastien; Blanchard, Anne; Vargas-Poussou, Rosa; Lourdel, Stéphane; Teulon, Jacques

2013-09-01

Mutations in the CLCNKB gene encoding the ClC-Kb Cl(-) channel cause Bartter syndrome, which is a salt-losing renal tubulopathy. Here, we investigate the functional consequences of seven mutations. When expressed in Xenopus laevis oocytes, four mutants carried no current (c.736G>C, p.Gly246Arg; c.1271G>A, p.Gly424Glu; c.1313G>A, p.Arg438His; c.1316T>C, p.Leu439Pro), whereas others displayed a 30%-60% reduction in conductance as compared with wild-type ClC-Kb (c.242T>C, p.Leu81Pro; c.274C>T, p.Arg92Trp; c.1052G>C, p.Arg351Pro). Anion selectivity and sensitivity to external Ca(2+) and H(+), typical of the ClC-Kb channel, were not modified in the partially active mutants. In oocytes, we found that all the mutations reduced surface expression with a profile similar to that observed for currents. In HEK293 cells, the currents in the mutants had similar profiles to those obtained in oocytes, except for p.Leu81Pro, which produced no current. Furthermore, p.Arg92Trp and p.Arg351Pro mutations did not modify the unit-conductance of closely related ClC-K1. Western blot analysis in HEK293 cells showed that ClC-Kb protein abundance was lower for the nonconducting mutants but similar to wild-type for other mutants. Overall, two classes of mutants can be distinguished: nonconducting mutants associated with low total protein expression, and partially conducting mutants with unaltered channel properties and ClC-Kb protein abundance. © 2013 WILEY PERIODICALS, INC.

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

2007-05-01

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.

Recent advances in Multi-Channel Algebraic Scattering

International Nuclear Information System (INIS)

Karataglidis, S.; Fraser, P. R.; Amos, K.; Canton, L.; Pisent, G.; Svenne, J. P.; Knijff, D. van der

2011-01-01

For coupled-channel descriptions of low-energy nucleon-induced interactions involving nuclei with particle-unstable exited states, it is necessary to include the widths of the target states. How those widths may affect the elastic scattering cross sections is examined within the framework of the Multi-Channel Algebraic Scattering (MCAS) method.

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.

Physiology and pathophysiology of ClC-K/barttin channels.

Science.gov (United States)

Fahlke, Christoph; Fischer, Martin

2010-01-01

ClC-K channels form a subgroup of anion channels within the ClC family of anion transport proteins. They are expressed predominantly in the kidney and in the inner ear, and are necessary for NaCl resorption in the loop of Henle and for K+ secretion by the stria vascularis. Subcellular distribution as well as the function of these channels are tightly regulated by an accessory subunit, barttin. Barttin improves the stability of ClC-K channel protein, stimulates the exit from the endoplasmic reticulum and insertion into the plasma membrane and changes its function by modifying voltage-dependent gating processes. The importance of ClC-K/barttin channels is highlighted by several genetic diseases. Dysfunctions of ClC-K channels result in Bartter syndrome, an inherited human condition characterized by impaired urinary concentration. Mutations in the gene encoding barttin, BSND, affect the urinary concentration as well as the sensory function of the inner ear. Surprisingly, there is one BSND mutation that causes deafness without affecting renal function, indicating that kidney function tolerates a reduction of anion channel activity that is not sufficient to support normal signal transduction in inner hair cells. This review summarizes recent work on molecular mechanisms, physiology, and pathophysiology of ClC-K/barttin channels.

Physiology and pathophysiology of ClC-K/barttin channels

Directory of Open Access Journals (Sweden)

Christoph eFahlke

2010-11-01

Full Text Available ClC-K channels form a subgroup of anion channels within the ClC family of anion transport proteins. They are expressed predominantly in the kidney and in the inner ear, and are necessary for NaCl resorption in the loop of Henle and for K+ secretion by the stria vascularis. Subcellular distribution as well as the function of these channels are tightly regulated by an accessory subunit, barttin. Barttin improves the stability of ClC-K channel protein, stimulates the exit from the endoplasmic reticulum and insertion into the plasma membrane and changes its function by modifying voltage-dependent gating processes. The importance of ClC-K/barttin channels is highlighted by several genetic diseases. Dysfunctions of ClC-K channels result in Bartter syndrome, an inherited human condition characterized by impaired urinary concentration. Mutations in the gene encoding barttin, BSND, affect the urinary concentration as well as the sensory function of the inner ear. Surprisingly, there is one BSND mutation that causes deafness without affecting renal function, indicating that kidney function tolerates a reduction of anion channel activity that is not sufficient to support normal signal transduction in inner hair cells. This review summarizes recent work on molecular mechanisms, physiology and pathophysiology of ClC-K/barttin channels.

Use of navigation channels by Lake Sturgeon: Does channelization increase vulnerability of fish to ship strikes?

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Darryl W Hondorp

Full Text Available Channelization for navigation and flood control has altered the hydrology and bathymetry of many large rivers with unknown consequences for fish species that undergo riverine migrations. In this study, we investigated whether altered flow distributions and bathymetry associated with channelization attracted migrating Lake Sturgeon (Acipenser fulvescens into commercial navigation channels, potentially increasing their exposure to ship strikes. To address this question, we quantified and compared Lake Sturgeon selection for navigation channels vs. alternative pathways in two multi-channel rivers differentially affected by channelization, but free of barriers to sturgeon movement. Acoustic telemetry was used to quantify Lake Sturgeon movements. Under the assumption that Lake Sturgeon navigate by following primary flow paths, acoustic-tagged Lake Sturgeon in the more-channelized lower Detroit River were expected to choose navigation channels over alternative pathways and to exhibit greater selection for navigation channels than conspecifics in the less-channelized lower St. Clair River. Consistent with these predictions, acoustic-tagged Lake Sturgeon in the more-channelized lower Detroit River selected the higher-flow and deeper navigation channels over alternative migration pathways, whereas in the less-channelized lower St. Clair River, individuals primarily used pathways alternative to navigation channels. Lake Sturgeon selection for navigation channels as migratory pathways also was significantly higher in the more-channelized lower Detroit River than in the less-channelized lower St. Clair River. We speculated that use of navigation channels over alternative pathways would increase the spatial overlap of commercial vessels and migrating Lake Sturgeon, potentially enhancing their vulnerability to ship strikes. Results of our study thus demonstrated an association between channelization and the path use of migrating Lake Sturgeon that could prove

Roughness coefficients for stream channels in Arizona

Science.gov (United States)

Aldridge, B.N.; Garrett, J.M.

1973-01-01

When water flows in an open channel, energy is lost through friction along the banks and bed of the channel and through turbulence within the channel. The amount of energy lost is governed by channel roughness, which is expressed in terms of a roughness coefficient. An evaluation of the roughness coefficient is necessary in many hydraulic computations that involve flow in an open channel. Owing to the lack of satisfactory quantitative procedure, the ability of evaluate roughness coefficients can be developed only through experience; however, a basic knowledge of the methods used to assign the coefficients and the factors affecting them will be a great help. One of the most commonly used equations in open-channel hydraulics is that of Manning. The Manning equation is       1.486

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...

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?

Directory of Open Access Journals (Sweden)

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.

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.

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

Directory of Open Access Journals (Sweden)

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

Consumers Attitudes towards Internet and Brick and Mortar Store Channels Switching Behavior

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Abdolrazagh MADAHI

2014-12-01

Full Text Available he purpose of this study is to examine the role of consumers’ behavioral attitude and intention toward channel switching behavior in regards to Internet and brick and mortar store channels in Malaysia. The survey instrument administered to the Malaysian consumers from regions of Klang Valley and Penang. A total of 497 completed surveys were obtained. Partial least squares (PLS based structural equation modeling (SEM technique was used to analyze data. A total of 497 completed surveys were obtained. Findings showed that compatibility and complexity were significant in predicting attitude in regard to switching channel from Internet to brick and mortar store. Relative advantage and compatibility were relevant in predicting attitude in brick and mortar store channel. Attitude also significantly affected channel switching intention regarding to both channels. Our findings reveal that gender and intention significantly affect channel switching behavior.

Study of flow instabilities in double-channel natural circulation boiling systems

International Nuclear Information System (INIS)

Durga Prasad, Gonella V.; Pandey, Manmohan; Pradhan, Santosh K.; Gupta, Satish K.

2008-01-01

Natural circulation boiling systems consisting of parallel channels can undergo different types of oscillations (in-phase or out-of-phase) depending on the geometric parameters and operating conditions. Disturbances in one channel affect the flow in other channels, which triggers thermal-hydraulic oscillations. In the present work, the modes of oscillation under different operating conditions and channel-to-channel interaction during power fluctuations and on-power refueling in a double-channel natural circulation boiling system are investigated. The system is modeled using a lumped parameter mathematical model and RELAP5/MOD3.4. Parametric studies are carried out for an equal-power double-channel system, at different operating conditions, with both the models, and the results are compared. Instabilities, non-linear oscillations, and effects of recirculation loop dynamics and geometric parameters on the mode of oscillations, are studied using the lumped model. The two channels oscillate out-of-phase in Type-I region, but in Type-II region, both the modes of oscillation are observed under different conditions. Channel-to-channel interaction and on-power refueling studies are carried out using the RELAP model. At high powers, disturbances in one channel significantly affect the stability of the other channel. During on-power refueling, a near-stagnation condition or low-velocity reverse flow can occur, the possibility of reverse flow being higher at lower pressures

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.

The Relative Importance of the Channels of Monetary Policy ...

African Journals Online (AJOL)

importance channels of monetary policy which are working in Zambia. It answers the ... several ways through which monetary policy affect the balance sheets of economic agents and hence ... economies, especially those with flexible exchange rate regimes. ..... transmission channels work endogenously or exogenously.

CFD analyses of coolant channel flowfields

Science.gov (United States)

Yagley, Jennifer A.; Feng, Jinzhang; Merkle, Charles L.

1993-01-01

The flowfield characteristics in rocket engine coolant channels are analyzed by means of a numerical model. The channels are characterized by large length to diameter ratios, high Reynolds numbers, and asymmetrical heating. At representative flow conditions, the channel length is approximately twice the hydraulic entrance length so that fully developed conditions would be reached for a constant property fluid. For the supercritical hydrogen that is used as the coolant, the strong property variations create significant secondary flows in the cross-plane which have a major influence on the flow and the resulting heat transfer. Comparison of constant and variable property solutions show substantial differences. In addition, the property variations prevent fully developed flow. The density variation accelerates the fluid in the channels increasing the pressure drop without an accompanying increase in heat flux. Analyses of the inlet configuration suggest that side entry from a manifold can affect the development of the velocity profile because of vortices generated as the flow enters the channel. Current work is focused on studying the effects of channel bifurcation on the flow field and the heat transfer characteristics.

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.

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

Inflation Dynamics and the Cost Channel of Monetary Transmission

NARCIS (Netherlands)

Chowdhury, I.; Hoffmann, M.; Schabert, A.

2006-01-01

Evidence from vector autoregressions indicates that the impact of interest rate shocks on macroeconomic aggregates can substantially be affected by the so-called cost channel of monetary transmission. In this paper, we apply a structural approach to examine the relevance of the cost channel for

Differential Effects of TRPA and TRPV Channels on Behaviors of

Directory of Open Access Journals (Sweden)

Jennifer Thies

2016-01-01

Full Text Available TRPA and TRPV ion channels are members of the transient receptor potential (TRP cation channel superfamily, which mediates various sensory transductions. In Caenorhabditis elegans , the TRPV channels are known to affect chemosensation, while the TRPA-1 channel is associated with thermosensation and mechanosensation. We examined thermosensation, chemosensation, and osmosensation in strains lacking TRPA-1 or TRPV channels. We found that TRPV channel knockout worms exhibited similar behavioral deficits associated with thermotaxis as the TRPA-1 channel knockout, suggesting a dual role for TRPV channels. In contrast, chemosensation responses, assessed by both avoidance reversal behavior and NaCl osmosensation, were dependent on TRPV channels but seemed independent of TRPA-1 channel. Our findings suggest that, in addition to TRPA-1 channel, TRPV channels are necessary for thermotaxis and may activate, or modulate, the function of TRPA-1 channels. In contrast, TRPA-1 channels do not have a dual responsibility, as they have no functional role in odorant avoidance or osmosensation.

Developmental regulation of voltage-sensitive sodium channels in rat skeletal muscle

International Nuclear Information System (INIS)

Sherman, S.J.

1985-01-01

The developmental regulation of the voltage-sensitive Na + channel in rat skeletal muscle was studied in vivo and in vitro. In triceps surae muscle developing in vivo the development of TTX-sensitive Na + channel occurred primarily during the first three postnatal weeks as determined by the specific binding of [ 3 H]saxitoxin. This development proceeded in two separate phases. The first phase occurs independently of continuing motor neuron innervation and accounts for 60% of the adult density of TTX-sensitive Na + channels. The second phase, which begins about day 11, requires innervation. Muscle cells in primary culture were found to have both TTX-sensitive and insensitive Na + channels. The development of the TTX-sensitive channel, in vitro, paralleled the initial innervation-independent phase of development observed in vivo. The density of TTX-sensitive Na + channels in cultured muscle cells was regulated by electrical activity and cytosolic Ca ++ levels. Pharmacological blockade of the spontaneous electrical activity present in these cells lead to a nearly 2-fold increase in the surface density of TTX-sensitive channels. The turnover time of the TTX-sensitive Na + channel was measured by blocking the incorporation of newly synthesized channels with tunicamycin, an inhibitor of N-linked protein glycosylation. The regulation of channel density by electrical activity, cytosolic Ca ++ levels, and agents affecting cyclic neucleotide levels had no effect on the turnover time of the TTX-sensitive Na + channel, indicating that these regulatory agents instead affect the synthesis of the channel

Long-range forces affecting equilibrium inertial focusing behavior in straight high aspect ratio microfluidic channels

Energy Technology Data Exchange (ETDEWEB)

Reece, Amy E.; Oakey, John, E-mail: joakey@uwyo.edu [Department of Chemical Engineering, University of Wyoming, Laramie, Wyoming 82071 (United States)

2016-04-15

The controlled and directed focusing of particles within flowing fluids is a problem of fundamental and technological significance. Microfluidic inertial focusing provides passive and precise lateral and longitudinal alignment of small particles without the need for external actuation or sheath fluid. The benefits of inertial focusing have quickly enabled the development of miniaturized flow cytometers, size-selective sorting devices, and other high-throughput particle screening tools. Straight channel inertial focusing device design requires knowledge of fluid properties and particle-channel size ratio. Equilibrium behavior of inertially focused particles has been extensively characterized and the constitutive phenomena described by scaling relationships for straight channels of square and rectangular cross section. In concentrated particle suspensions, however, long-range hydrodynamic repulsions give rise to complex particle ordering that, while interesting and potentially useful, can also dramatically diminish the technique’s effectiveness for high-throughput particle handling applications. We have empirically investigated particle focusing behavior within channels of increasing aspect ratio and have identified three scaling regimes that produce varying degrees of geometrical ordering between focused particles. To explore the limits of inertial particle focusing and identify the origins of these long-range interparticle forces, we have explored equilibrium focusing behavior as a function of channel geometry and particle concentration. Experimental results for highly concentrated particle solutions identify equilibrium thresholds for focusing that scale weakly with concentration and strongly with channel geometry. Balancing geometry mediated inertial forces with estimates for interparticle repulsive forces now provide a complete picture of pattern formation among concentrated inertially focused particles and enhance our understanding of the fundamental limits

Results of the examination of channel H12/1

International Nuclear Information System (INIS)

Bauer, E.

1983-01-01

Channel H12/1 is one part of the channel unit of the High-Flux Reactor that has been affected by corrosion attack. It was disassembled after the appearance of a heavy water leak and examined in a hot cell. Results of the examination are presented

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.

Adaptive estimation and discrimination of Holevo-Werner channels

Directory of Open Access Journals (Sweden)

Cope Thomas P. W.

2017-12-01

Full Text Available The class of quantum states known as Werner states have several interesting properties, which often serve to illuminate unusual properties of quantum information. Closely related to these states are the Holevo- Werner channels whose Choi matrices are Werner states. Exploiting the fact that these channels are teleportation covariant, and therefore simulable by teleportation, we compute the ultimate precision in the adaptive estimation of their channel-defining parameter. Similarly, we bound the minimum error probability affecting the adaptive discrimination of any two of these channels. In this case, we prove an analytical formula for the quantum Chernoff bound which also has a direct counterpart for the class of depolarizing channels. Our work exploits previous methods established in [Pirandola and Lupo, PRL 118, 100502 (2017] to set the metrological limits associated with this interesting class of quantum channels at any finite dimension.

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

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

Probability distribution functions of turbulence in seepage-affected alluvial channel

Energy Technology Data Exchange (ETDEWEB)

Sharma, Anurag; Kumar, Bimlesh, E-mail: anurag.sharma@iitg.ac.in, E-mail: bimk@iitg.ac.in [Department of Civil Engineering, Indian Institute of Technology Guwahati, 781039 (India)

2017-02-15

The present experimental study is carried out on the probability distribution functions (PDFs) of turbulent flow characteristics within near-bed-surface and away-from-bed surfaces for both no seepage and seepage flow. Laboratory experiments were conducted in the plane sand bed for no seepage (NS), 10% seepage (10%S) and 15% seepage (15%) cases. The experimental calculation of the PDFs of turbulent parameters such as Reynolds shear stress, velocity fluctuations, and bursting events is compared with theoretical expression obtained by Gram–Charlier (GC)-based exponential distribution. Experimental observations follow the computed PDF distributions for both no seepage and seepage cases. Jensen-Shannon divergence (JSD) method is used to measure the similarity between theoretical and experimental PDFs. The value of JSD for PDFs of velocity fluctuation lies between 0.0005 to 0.003 while the JSD value for PDFs of Reynolds shear stress varies between 0.001 to 0.006. Even with the application of seepage, the PDF distribution of bursting events, sweeps and ejections are well characterized by the exponential distribution of the GC series, except that a slight deflection of inward and outward interactions is observed which may be due to weaker events. The value of JSD for outward and inward interactions ranges from 0.0013 to 0.032, while the JSD value for sweep and ejection events varies between 0.0001 to 0.0025. The theoretical expression for the PDF of turbulent intensity is developed in the present study, which agrees well with the experimental observations and JSD lies between 0.007 and 0.015. The work presented is potentially applicable to the probability distribution of mobile-bed sediments in seepage-affected alluvial channels typically characterized by the various turbulent parameters. The purpose of PDF estimation from experimental data is that it provides a complete numerical description in the areas of turbulent flow either at a single or finite number of points

A touch of affect: mediated social touch and affect

NARCIS (Netherlands)

Huisman, Gijs

2012-01-01

This position paper outlines the first stages in an ongoing PhD project on mediated social touch, and the effects mediated touch can have on someone's affective state. It is argued that touch is a profound communication channel for humans, and that communication through touch can, to some extent,

The role of transient receptor potential channels in joint diseases.

Science.gov (United States)

Krupkova, O; Zvick, J; Wuertz-Kozak, K

2017-10-10

Transient receptor potential channels (TRP channels) are cation selective transmembrane receptors with diverse structures, activation mechanisms and physiological functions. TRP channels act as cellular sensors for a plethora of stimuli, including temperature, membrane voltage, oxidative stress, mechanical stimuli, pH and endogenous, as well as, exogenous ligands, thereby illustrating their versatility. As such, TRP channels regulate various functions in both excitable and non-excitable cells, mainly by mediating Ca2+ homeostasis. Dysregulation of TRP channels is implicated in many pathologies, including cardiovascular diseases, muscular dystrophies and hyperalgesia. However, the importance of TRP channel expression, physiological function and regulation in chondrocytes and intervertebral disc (IVD) cells is largely unexplored. Osteoarthritis (OA) and degenerative disc disease (DDD) are chronic age-related disorders that significantly affect the quality of life by causing pain, activity limitation and disability. Furthermore, currently available therapies cannot effectively slow-down or stop progression of these diseases. Both OA and DDD are characterised by reduced tissue cellularity, enhanced inflammatory responses and molecular, structural and mechanical alterations of the extracellular matrix, hence affecting load distribution and reducing joint flexibility. However, knowledge on how chondrocytes and IVD cells sense their microenvironment and respond to its changes is still limited. In this review, we introduced six families of mammalian TRP channels, their mechanisms of activation, as well as, activation-driven cellular consequences. We summarised the current knowledge on TRP channel expression and activity in chondrocytes and IVD cells, as well as, the significance of TRP channels as therapeutic targets for the treatment of OA and DDD.

The role of transient receptor potential channels in joint diseases

Directory of Open Access Journals (Sweden)

O Krupkova

2017-10-01

Full Text Available ransient receptor potential channels (TRP channels are cation selective transmembrane receptors with diverse structures, activation mechanisms and physiological functions. TRP channels act as cellular sensors for a plethora of stimuli, including temperature, membrane voltage, oxidative stress, mechanical stimuli, pH and endogenous, as well as, exogenous ligands, thereby illustrating their versatility. As such, TRP channels regulate various functions in both excitable and non-excitable cells, mainly by mediating Ca2+ homeostasis. Dysregulation of TRP channels is implicated in many pathologies, including cardiovascular diseases, muscular dystrophies and hyperalgesia. However, the importance of TRP channel expression, physiological function and regulation in chondrocytes and intervertebral disc (IVD cells is largely unexplored. Osteoarthritis (OA and degenerative disc disease (DDD are chronic age-related disorders that significantly affect the quality of life by causing pain, activity limitation and disability. Furthermore, currently available therapies cannot effectively slow-down or stop progression of these diseases. Both OA and DDD are characterised by reduced tissue cellularity, enhanced inflammatory responses and molecular, structural and mechanical alterations of the extracellular matrix, hence affecting load distribution and reducing joint flexibility. However, knowledge on how chondrocytes and IVD cells sense their microenvironment and respond to its changes is still limited. In this review, we introduced six families of mammalian TRP channels, their mechanisms of activation, as well as, activation-driven cellular consequences. We summarised the current knowledge on TRP channel expression and activity in chondrocytes and IVD cells, as well as, the significance of TRP channels as therapeutic targets for the treatment of OA and DDD.

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

D-Arg0-Bradykinin-Arg-Arg, a Latent Vasoactive Bradykinin B2 Receptor Agonist Metabolically Activated by Carboxypeptidases

Directory of Open Access Journals (Sweden)

Hélène Bachelard

2018-03-01

Full Text Available We previously reported hypotensive and vasodilator effects from C-terminally extended bradykinin (BK sequences that behave as B2 receptor (B2R agonists activated by vascular or plasma peptidases. D-Arg0-BK-Arg-Arg (r-BK-RR is a novel prodrug peptide hypothetically activated by two catalytic cycles of Arg-carboxypeptidases (CPs to release the direct agonist D-Arg0-BK. N-terminally extending the BK sequence with D-Arg0 in the latter peptide was meant to block the second kinin inactivation pathway in importance, aminopeptidase P. The affinity of r-BK and r-BK-RR for recombinant B2R was assessed using a [3H]BK binding displacement assay. Their pharmacology was evaluated in human isolated umbilical vein, a contractile bioassay for the B2R, in a morphological assay involving the endocytosis of B2R-green fusion protein (GFP and in anesthetized rats instrumented to record hemodynamic responses to bolus intravenous injection of both peptides. r-BK exhibited an affinity equal to that of BK for the rat B2R, while r-BK-RR was 61-fold less potent. In the vein and the B2R-GFP internalization assay, r-BK was a direct agonist unaffected by the blockade of angiotensin converting enzyme (ACE with enalaprilat, or Arg-CPs with Plummer’s inhibitor. However, the in vitro effects of r-BK-RR were reduced by these inhibitors, more so by enalaprilat. In anesthetized rats, r-BK and r-BK-RR were equipotent hypotensive agents and their effects were inhibited by icatibant (a B2R antagonist. The hypotensive effects of r-BK were potentiated by enalaprilat, but not influenced by the Arg-CPs inhibitor, which is consistent with a minor role of Arg-CPs in the metabolism of r-BK. However, in rats pretreated with both enalaprilat and Plummer’s inhibitor, the hypotensive responses and the duration of the hypotensive episode to r-BK were significantly potentiated. The hypotensive responses to r-BK-RR were not affected by enalaprilat, but were reduced by pre-treatment with the Arg

Understanding carbon nanotube channel formation in the lipid membrane

Science.gov (United States)

Choi, Moon-ki; Kim, Hyunki; Lee, Byung Ho; Kim, Teayeop; Rho, Junsuk; Kim, Moon Ki; Kim, Kyunghoon

2018-03-01

Carbon nanotubes (CNTs) have been considered a prominent nano-channel in cell membranes because of their prominent ion-conductance and ion-selectivity, offering agents for a biomimetic channel platform. Using a coarse-grained molecular dynamics simulation, we clarify a construction mechanism of vertical CNT nano-channels in a lipid membrane for a long period, which has been difficult to observe in previous CNT-lipid interaction simulations. The result shows that both the lipid coating density and length of CNT affect the suitable fabrication condition for a vertical and stable CNT channel. Also, simulation elucidated that a lipid coating on the surface of the CNT prevents the CNT from burrowing into the lipid membrane and the vertical channel is stabilized by the repulsion force between the lipids in the coating and membrane. Our study provides an essential understanding of how CNTs can form stable and vertical channels in the membrane, which is important for designing new types of artificial channels as biosensors for bio-fluidic studies.

The genetic background affects the vascular response in T-type calcium channels 3.2 deficient mice

DEFF Research Database (Denmark)

Svenningsen, Per; Hansen, Pernille B L

2016-01-01

-type channels are the dominant Ca(2+) entry pathway in vascular smooth muscle cells, however, T-type calcium channels are also expressed in the cardiovascular system where they play a functional role in the regulation of both contraction and vasodilation in (Chen et al. 2003; Hansen et al. 2001). This article...... is protected by copyright. All rights reserved....

Multi-Channel Capacitive Sensor Arrays

Directory of Open Access Journals (Sweden)

Bingnan Wang

2016-01-01

Full Text Available In this paper, multi-channel capacitive sensor arrays based on microstrip band-stop filters are studied. The sensor arrays can be used to detect the proximity of objects at different positions and directions. Each capacitive sensing structure in the array is connected to an inductive element to form resonance at different frequencies. The resonances are designed to be isolated in the frequency spectrum, such that the change in one channel does not affect resonances at other channels. The inductive element associated with each capacitive sensor can be surface-mounted inductors, integrated microstrip inductors or metamaterial-inspired structures. We show that by using metamaterial split-ring structures coupled to a microstrip line, the quality factor of each resonance can be greatly improved compared to conventional surface-mounted or microstrip meander inductors. With such a microstrip-coupled split-ring design, more sensing elements can be integrated in the same frequency spectrum, and the sensitivity can be greatly improved.

47 CFR 74.1205 - Protection of channel 6 TV broadcast stations.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Protection of channel 6 TV broadcast stations... 6 TV broadcast stations. The provisions of this section apply to all applications for construction... applicant and each affected TV Channel 6 broadcast station licensee or permittee concurring with the...

Energy tunneling through narrow waveguide channel and design of small antennas

Directory of Open Access Journals (Sweden)

Mitrović Miranda

2011-01-01

Full Text Available In this paper we investigate the conditions for energy tunneling through narrow channel obtained by reducing the height of rectangular waveguide. Tunneling of the energy occurs at the frequency for which the effective dielectric permittivity of the channel becomes equal to zero, so it can be treated as an ENZ (epsilon-near-zero metamaterial. We investigated how geometry of the channel and dielectric permittivity affect the transmission coefficient and field density in the channel. Adding slots in the channel, which are placed orthogonally to the wave propagation, we designed a small antenna with directivity of 5.44 dBi at the frequency of 3 GHz.

Critical heat flux correlation for thin rectangular channels

International Nuclear Information System (INIS)

Tanaka, Futoshi; Mishima, Kaichiro; Hibiki, Takashi

2007-01-01

The effect of heated length on Critical heat flux (CHF) in thin rectangular channels was studied based on CHF data obtained under atmospheric pressure. CHF in small channels has been widely studied in the past decades but most of the studies are related to CHF in round tubes. Although basic mechanisms of burnout in thin rectangular channels are similar to tubes, applicability of CHF correlations for tubes to rectangular channels are questionable since CHF in rectangular channels are affected by the existence of non-heated walls and the non-circular geometry of channel circumference. Several studies of CHF in thin rectangular channels have been reported in relation to thermal hydraulic design of research reactors and neutron source targets and CHF correlations have been proposed, but the studies mostly focus on CHFs under geometrical conditions of the application of interest. In his study, existing CHF data obtained in thin rectangular channels were collected and the effect of heated length on CHF was examined. Existing CHF correlations were verified with positive quality flow CHF data but none of the correlations successfully reproduced the CHF for a wide range of heated length. A new CHF correlation for qualify region applicable to a wide range of heated length was developed based on the collected data. (author)

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

Fatty acid analogue N-arachidonoyl taurine restores function of IKs channels with diverse long QT mutations

DEFF Research Database (Denmark)

Liin, Sara I; Larsson, Johan E; Barro-Soria, Rene

2016-01-01

. Finally, we find that the fatty acid analogue N-arachidonoyl taurine restores channel gating of many different mutant channels, even though the mutations are in different domains of the IKs channel and affect the channel by different molecular mechanisms. N-arachidonoyl taurine is therefore an interesting...

Study on effective MOSFET channel length extracted from gate capacitance

Science.gov (United States)

Tsuji, Katsuhiro; Terada, Kazuo; Fujisaka, Hisato

2018-01-01

The effective channel length (L GCM) of metal-oxide-semiconductor field-effect transistors (MOSFETs) is extracted from the gate capacitances of actual-size MOSFETs, which are measured by charge-injection-induced-error-free charge-based capacitance measurement (CIEF CBCM). To accurately evaluate the capacitances between the gate and the channel of test MOSFETs, the parasitic capacitances are removed by using test MOSFETs having various channel sizes and a source/drain reference device. A strong linear relationship between the gate-channel capacitance and the design channel length is obtained, from which L GCM is extracted. It is found that L GCM is slightly less than the effective channel length (L CRM) extracted from the measured MOSFET drain current. The reason for this is discussed, and it is found that the capacitance between the gate electrode and the source and drain regions affects this extraction.

An equipment for the dimensional characterization of irradiated fuel channels

International Nuclear Information System (INIS)

Cederquist, H.

1985-01-01

The reuse of irradiated fuel channels in BWRs is highly beneficial. However, one prerequisite for reuse of a fuel channel is the detailed knowledge of its dimensions, which are affected by irradiation and pressure drop during operation. Therefore an equipment for fast and accurate dimensional measurement of irradiated fuel channels has been developed. The measurements are carried out when the fuel assembly is supported in the same manner as in the reactor core. The equipment utilizes stationary ultrasonic transducers that measure the fuel channel at a number of predetermined axial levels. Measurement data are fed into a computer which calculates the requested dimensional characteristics such as transversal flatness, bow, twist, side perpendicularity etc. Data are automatically printed for subsequent evaluation. Measurements can be performed both when the fuel channel is placed on a fuel bundle and on an empty fuel channel

Voltage-gated calcium channels of Paramecium cilia.

Science.gov (United States)

Lodh, Sukanya; Yano, Junji; Valentine, Megan S; Van Houten, Judith L

2016-10-01

Paramecium cells swim by beating their cilia, and make turns by transiently reversing their power stroke. Reversal is caused by Ca 2+ entering the cilium through voltage-gated Ca 2+ (Ca V ) channels that are found exclusively in the cilia. As ciliary Ca 2+ levels return to normal, the cell pivots and swims forward in a new direction. Thus, the activation of the Ca V channels causes cells to make a turn in their swimming paths. For 45 years, the physiological characteristics of the Paramecium ciliary Ca V channels have been known, but the proteins were not identified until recently, when the P. tetraurelia ciliary membrane proteome was determined. Three Ca V α1 subunits that were identified among the proteins were cloned and confirmed to be expressed in the cilia. We demonstrate using RNA interference that these channels function as the ciliary Ca V channels that are responsible for the reversal of ciliary beating. Furthermore, we show that Pawn (pw) mutants of Paramecium that cannot swim backward for lack of Ca V channel activity do not express any of the three Ca V 1 channels in their ciliary membrane, until they are rescued from the mutant phenotype by expression of the wild-type PW gene. These results reinforce the correlation of the three Ca V channels with backward swimming through ciliary reversal. The PwB protein, found in endoplasmic reticulum fractions, co-immunoprecipitates with the Ca V 1c channel and perhaps functions in trafficking. The PwA protein does not appear to have an interaction with the channel proteins but affects their appearance in the cilia. © 2016. Published by The Company of Biologists Ltd.

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

Science.gov (United States)

Held, Katharina; Gruss, Fabian; Aloi, Vincenzo Davide; Janssens, Annelies; Ulens, Chris; Voets, Thomas; Vriens, Joris

2018-03-31

Mutagenesis at positively charged amino acids (arginines and lysines) (R1-R4) in the voltage-sensor domain (transmembrane segment (S) 4) of voltage-gated Na + , K + and Ca 2+ channels can lead to an alternative ion permeation pathway distinct from the central pore. Recently, a non-canonical ion permeation pathway was described in TRPM3, a member of the transient receptor potential (TRP) superfamily. The non-canonical pore exists in the native TRPM3 channel and can be activated by co-stimulation of the endogenous agonist pregnenolone sulphate and the antifungal drug clotrimazole or by stimulation of the synthetic agonist CIM0216. Alignment of the voltage sensor of Shaker K + channels with the entire TRPM3 sequence revealed the highest degree of similarity in the putative S4 region of TRPM3, and suggested that only one single gating charge arginine (R2) in the putative S4 region is conserved. Mutagenesis studies in the voltage-sensing domain of TRPM3 revealed several residues in the voltage sensor (S4) as well as in S1 and S3 that are crucial for the occurrence of the non-canonical inward currents. In conclusion, this study provides evidence for the involvement of the voltage-sensing domain of TRPM3 in the formation of an alternative ion permeation pathway. Transient receptor potential (TRP) channels are cationic channels involved in a broad array of functions, including homeostasis, motility and sensory functions. TRP channel subunits consist of six transmembrane segments (S1-S6), and form tetrameric channels with a central pore formed by the region encompassing S5 and S6. Recently, evidence was provided for the existence of an alternative ion permeation pathway in TRPM3, which allows large inward currents upon hyperpolarization independently of the central pore. However, very little knowledge is available concerning the localization of this alternative pathway in the native TRPM3 channel protein. Guided by sequence homology with Shaker K + channels, in which

Analysis of D2D Communications over Gamma/Nakagami Fading Channels

Directory of Open Access Journals (Sweden)

Z. Hussain

2018-04-01

Full Text Available In this paper, we investigate the outage probability, channel capacity and symbol error rate (SER performance of device-to-device (D2D communication systems. The D2D communication system is affected by several co-channel interferers. Gamma fading channel is considered for the D2D communication system. The channel for the co-channel interference is assumed to be Nakagami faded. An expression for the probability density function (PDF of the signal-to-interference ratio (SIR is presented. The PDF is a function of distances between various devices in the D2D system, path-loss, channel fading conditions and signal powers. Based on the PDF expression, we present the expressions for the outage, channel capacity and SER. With the help of numerical results the performance of D2D communication system is discussed under various conditions of interference, path-loss and channel fading.

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)].

Long-pore Electrostatics in Inward-rectifier Potassium Channels

Science.gov (United States)

Robertson, Janice L.; Palmer, Lawrence G.; Roux, Benoît

2008-01-01

Inward-rectifier potassium (Kir) channels differ from the canonical K+ channel structure in that they possess a long extended pore (∼85 Å) for ion conduction that reaches deeply into the cytoplasm. This unique structural feature is presumably involved in regulating functional properties specific to Kir channels, such as conductance, rectification block, and ligand-dependent gating. To elucidate the underpinnings of these functional roles, we examine the electrostatics of an ion along this extended pore. Homology models are constructed based on the open-state model of KirBac1.1 for four mammalian Kir channels: Kir1.1/ROMK, Kir2.1/IRK, Kir3.1/GIRK, and Kir6.2/KATP. By solving the Poisson-Boltzmann equation, the electrostatic free energy of a K+ ion is determined along each pore, revealing that mammalian Kir channels provide a favorable environment for cations and suggesting the existence of high-density regions in the cytoplasmic domain and cavity. The contribution from the reaction field (the self-energy arising from the dielectric polarization induced by the ion's charge in the complex geometry of the pore) is unfavorable inside the long pore. However, this is well compensated by the electrostatic interaction with the static field arising from the protein charges and shielded by the dielectric surrounding. Decomposition of the static field provides a list of residues that display remarkable correspondence with existing mutagenesis data identifying amino acids that affect conduction and rectification. Many of these residues demonstrate interactions with the ion over long distances, up to 40 Å, suggesting that mutations potentially affect ion or blocker energetics over the entire pore. These results provide a foundation for understanding ion interactions in Kir channels and extend to the study of ion permeation, block, and gating in long, cation-specific pores. PMID:19001143

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

A numerical model for meltwater channel evolution in glaciers

Directory of Open Access Journals (Sweden)

A. H. Jarosch

2012-04-01

Full Text Available Meltwater channels form an integral part of the hydrological system of a glacier. Better understanding of how meltwater channels develop and evolve is required to fully comprehend supraglacial and englacial meltwater drainage. Incision of supraglacial stream channels and subsequent roof closure by ice deformation has been proposed in recent literature as a possible englacial conduit formation process. Field evidence for supraglacial stream incision has been found in Svalbard and Nepal. In Iceland, where volcanic activity provides meltwater with temperatures above 0 °C, rapid enlargement of supraglacial channels has been observed. Supraglacial channels provide meltwater through englacial passages to the subglacial hydrological systems of big ice sheets, which in turn affects ice sheet motion and their contribution to eustatic sea level change. By coupling, for the first time, a numerical ice dynamic model to a hydraulic model which includes heat transfer, we investigate the evolution of meltwater channels and their incision behaviour. We present results for different, constant meltwater fluxes, different channel slopes, different meltwater temperatures, different melt rate distributions in the channel as well as temporal variations in meltwater flux. The key parameters governing incision rate and depth are channel slope, meltwater temperature loss to the ice and meltwater flux. Channel width and geometry are controlled by melt rate distribution along the channel wall. Calculated Nusselt numbers suggest that turbulent mixing is the main heat transfer mechanism in the meltwater channels studied.

Voltage-gated sodium channels as targets for pyrethroid insecticides.

Science.gov (United States)

Field, Linda M; Emyr Davies, T G; O'Reilly, Andrias O; Williamson, Martin S; Wallace, B A

2017-10-01

The pyrethroid insecticides are a very successful group of compounds that have been used extensively for the control of arthropod pests of agricultural crops and vectors of animal and human disease. Unfortunately, this has led to the development of resistance to the compounds in many species. The mode of action of pyrethroids is known to be via interactions with the voltage-gated sodium channel. Understanding how binding to the channel is affected by amino acid substitutions that give rise to resistance has helped to elucidate the mode of action of the compounds and the molecular basis of their selectivity for insects vs mammals and between insects and other arthropods. Modelling of the channel/pyrethroid interactions, coupled with the ability to express mutant channels in oocytes and study function, has led to knowledge of both how the channels function and potentially how to design novel insecticides with greater species selectivity.

Membrane oscillations in the channel of a stationary plasma motor

International Nuclear Information System (INIS)

Bugrova, A.I.; Lipatov, A.S.; Morozov, A.I.; Kharchevnikov, V.K.

1999-01-01

Results of measuring the ion flux density in the channel of the stationary plasma drive are presented. Two plane easters move both along and transverse to the plasma flux. During the experiment, the strong low-frequency oscillations (∼ 35 kHz) are observed in the channel of the stationary plasma drive. It is found that membrane oscillations are accompanied by oscillations of the electron temperature. These membrane oscillations affect the divergence of the output plasma jet and the erosion of the output part of the channel of the stationary plasma drive [ru

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.

Critical voltage effects in electron channeling patterns

International Nuclear Information System (INIS)

Farrow, R.C.

1984-01-01

Electron channeling patterns were used to study critical voltage effects in the metals molybdenum and tungsten. The purpose was to characterize both theoretically and experimentally how a critical voltage will affect the channeling pattern line shapes. The study focused on the second order critical voltage that results from the degeneracy between the Bloch wave states of the (110) and (220) reflections. Theoretical (110) series electron channeling pattern line profiles were calculated using the dynamical theory of Hirsch and Humphreys (1970). A 10 beam dynamical electron diffraction calculation was performed (using complex Fourier lattice potentials) to generate Bloch wave coefficients, excitation amplitudes, and absorption coefficients needed for determining backscattering coefficients and subsequent backscattered electron intensities. The theoretical model is applicable to electron diffraction at all energies since no high energy approximation or perturbation method was used

Structural determinants of PIP(2) regulation of inward rectifier K(ATP) channels.

Science.gov (United States)

Shyng, S L; Cukras, C A; Harwood, J; Nichols, C G

2000-11-01

Phosphatidylinositol 4,5-bisphosphate (PIP(2)) activates K(ATP) and other inward rectifier (Kir) channels. To determine residues important for PIP(2) regulation, we have systematically mutated each positive charge in the COOH terminus of Kir6.2 to alanine. The effects of these mutations on channel function were examined using (86)Rb efflux assays on intact cells and inside-out patch-clamp methods. Both methods identify essentially the same basic residues in two narrow regions (176-222 and 301-314) in the COOH terminus that are important for the maintenance of channel function and interaction with PIP(2). Only one residue (R201A) simultaneously affected ATP and PIP(2) sensitivity, which is consistent with the notion that these ligands, while functionally competitive, are unlikely to bind to identical sites. Strikingly, none of 13 basic residues in the terminal portion (residues 315-390) of the COOH terminus affected channel function when neutralized. The data help to define the structural requirements for PIP(2) sensitivity of K(ATP) channels. Moreover, the regions and residues defined in this study parallel those uncovered in recent studies of PIP(2) sensitivity in other inward rectifier channels, indicating a common structural basis for PIP(2) regulation.

The development and application of a sub-channel code in ocean environment

International Nuclear Information System (INIS)

Wu, Pan; Shan, Jianqiang; Xiang, Xiong; Zhang, Bo; Gou, Junli; Zhang, Bin

2016-01-01

Highlights: • A sub-channel code named ATHAS/OE is developed for nuclear reactors in ocean environment. • ATHAS/OE is verified by another modified sub-channel code based on COBRA-IV. • ATHAS/OE is used to analyze thermal hydraulic of a typical SMR in heaving and rolling motion. • Calculation results show that ocean condition affect the thermal hydraulic of a reactor significantly. - Abstract: An upgraded version of ATHAS sub-channel code ATHAS/OE is developed for the investigation of the thermal hydraulic behavior of nuclear reactor core in ocean environment with consideration of heaving and rolling motion effect. The code is verified by another modified sub-channel code based on COBRA-IV and used to analyze the thermal hydraulic characteristics of a typical SMR under heaving and rolling motion condition. The calculation results show that the heaving and rolling motion affect the thermal hydraulic behavior of a reactor significantly.

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.

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

Science.gov (United States)

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

2016-02-25

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

Do TRPC channels support working memory? Comparing modulations of TRPC channels and working memory through G-protein coupled receptors and neuromodulators.

Science.gov (United States)

Reboreda, Antonio; Theissen, Frederik M; Valero-Aracama, Maria J; Arboit, Alberto; Corbu, Mihaela A; Yoshida, Motoharu

2018-03-01

Working memory is a crucial ability we use in daily life. However, the cellular mechanisms supporting working memory still remain largely unclear. A key component of working memory is persistent neural firing which is believed to serve short-term (hundreds of milliseconds up to tens of seconds) maintenance of necessary information. In this review, we will focus on the role of transient receptor potential canonical (TRPC) channels as a mechanism underlying persistent firing. Many years of in vitro work have been suggesting a crucial role of TRPC channels in working memory and temporal association tasks. If TRPC channels are indeed a central mechanism for working memory, manipulations which impair or facilitate working memory should have a similar effect on TRPC channel modulation. However, modulations of working memory and TRPC channels were never systematically compared, and it remains unanswered whether TRPC channels indeed contribute to working memory in vivo or not. In this article, we review the effects of G-protein coupled receptors (GPCR) and neuromodulators, including acetylcholine, noradrenalin, serotonin and dopamine, on working memory and TRPC channels. Based on comparisons, we argue that GPCR and downstream signaling pathways that activate TRPC, generally support working memory, while those that suppress TRPC channels impair it. However, depending on the channel types, areas, and systems tested, this is not the case in all studies. Further work to clarify involvement of specific TRPC channels in working memory tasks and how they are affected by neuromodulators is still necessary in the future. Copyright © 2018 Elsevier B.V. All rights reserved.

Decision making by superimposing information from parallel cognitive channels

Science.gov (United States)

Aityan, Sergey K.

1993-08-01

A theory of decision making with perception through parallel information channels is presented. Decision making is considered a parallel competitive process. Every channel can provide confirmation or rejection of a decision concept. Different channels provide different impact on the specific concepts caused by the goals and individual cognitive features. All concepts are divided into semantic clusters due to the goals and the system defaults. The clusters can be alternative or complimentary. The 'winner-take-all' concept nodes firing takes place within the alternative cluster. Concepts can be independently activated in the complimentary cluster. A cognitive channel affects a decision concept by sending an activating or inhibitory signal. The complimentary clusters serve for building up complex concepts by superimposing activation received from various channels. The decision making is provided by the alternative clusters. Every active concept in the alternative cluster tends to suppress the competitive concepts in the cluster by sending inhibitory signals to the other nodes of the cluster. The model accounts for a time delay in signal transmission between the nodes and explains decreasing of the reaction time if information is confirmed by different channels and increasing of the reaction time if deceiving information received from the channels.

Chloride channels as tools for developing selective insecticides.

Science.gov (United States)

Bloomquist, Jeffrey R

2003-12-01

Ligand-gated chloride channels underlie inhibition in excitable membranes and are proven target sites for insecticides. The gamma-aminobutyric acid (GABA(1)) receptor/chloride ionophore complex is the primary site of action for a number of currently used insecticides, such as lindane, endosulfan, and fipronil. These compounds act as antagonists by stabilizing nonconducting conformations of the chloride channel. Blockage of the GABA-gated chloride channel reduces neuronal inhibition, which leads to hyperexcitation of the central nervous system, convulsions, and death. We recently investigated the mode of action of the silphinenes, plant-derived natural compounds that structurally resemble picrotoxinin. These materials antagonize the action of GABA on insect neurons and block GABA-mediated chloride uptake into mouse brain synaptoneurosomes in a noncompetitive manner. In mammals, avermectins have a blocking action on the GABA-gated chloride channel consistent with a coarse tremor, whereas at longer times and higher concentrations, activation of the channel suppresses neuronal activity. Invertebrates display ataxia, paralysis, and death as the predominant signs of poisoning, with a glutamate-gated chloride channel playing a major role. Additional target sites for the avermectins or other chloride channel-directed compounds might include receptors gated by histamine, serotonin, or acetylcholine.The voltage-sensitive chloride channels form another large gene family of chloride channels. Voltage-dependent chloride channels are involved in a number of physiological processes including: maintenance of electrical excitability, chloride ion secretion and resorption, intravesicular acidification, and cell volume regulation. A subset of these channels is affected by convulsants and insecticides in mammals, although the role they play in acute lethality in insects is unclear. Given the wide range of functions that they mediate, these channels are also potential targets for

Paramecium BBS genes are key to presence of channels in Cilia

Directory of Open Access Journals (Sweden)

Valentine Megan

2012-09-01

Full Text Available Abstract Background Changes in genes coding for ciliary proteins contribute to complex human syndromes called ciliopathies, such as Bardet-Biedl Syndrome (BBS. We used the model organism Paramecium to focus on ciliary ion channels that affect the beat form and sensory function of motile cilia and evaluate the effects of perturbing BBS proteins on these channels. Methods We used immunoprecipitations and mass spectrometry to explore whether Paramecium proteins interact as in mammalian cells. We used RNA interference (RNAi and swimming behavior assays to examine the effects of BBS depletion on ciliary ion channels that control ciliary beating. Combining RNA interference and epitope tagging, we examined the effects of BBS depletion of BBS 7, 8 and 9 on the location of three channels and a chemoreceptor in cilia. Results We found 10 orthologs of 8 BBS genes in P. tetraurelia. BBS1, 2, 4, 5, 7, 8 and 9 co-immunoprecipitate. While RNAi reduction of BBS 7 and 9 gene products caused loss and shortening of cilia, RNAi for all BBS genes except BBS2 affected patterns of ciliary motility that are governed by ciliary ion channels. Swimming behavior assays pointed to loss of ciliary K+ channel function. Combining RNAi and epitope tagged ciliary proteins we demonstrated that a calcium activated K+ channel was no longer located in the cilia upon depletion of BBS 7, 8 or 9, consistent with the cells’ swimming behavior. The TRPP channel PKD2 was also lost from the cilia. In contrast, the ciliary voltage gated calcium channel was unaffected by BBS depletion, consistent with behavioral assays. The ciliary location of a chemoreceptor for folate was similarly unperturbed by the depletion of BBS 7, 8 or 9. Conclusions The co-immunoprecipitation of BBS 1,2,4,5,7,8, and 9 suggests a complex of BBS proteins. RNAi for BBS 7, 8 or 9 gene products causes the selective loss of K+ and PKD2 channels from the cilia while the critical voltage gated calcium channel and a

Typology and Financial Performance of Champagne Makers According to Distribution Channel

OpenAIRE

Declerck, Francis

2005-01-01

A typology of strategies related to the distribution channels used by Champagne makers is established. Champagne makers' operating profit depends on their distribution network, which affects selling prices. Based on a sample of 20 Champagne makers ("Maisons de Champagne"), economic and financial performance indicators for Champagne makers are analyzed with reference to the type of distribution channel.

Pricing Model for Dual Sales Channel with Promotion Effect Consideration

Directory of Open Access Journals (Sweden)

Chuiri Zhou

2016-01-01

Full Text Available We focus on the pricing strategy of a dual sales channel member when his/her online retailer faces an upcoming overloaded express delivery service due to the sales peak of online shopping, especially referring to the occurring affairs in China. We characterize the pricing problem of the dual selling channel system as a two-period game. When the price discount is only provided by the online seller, we find that the prices of the traditional channel and the online channel in the two periods are higher while the overloaded degree of express delivery is lower and the overloaded delivery services can decrease the profits of both channels. When the price discounts are provided by both traditional and online sellers, we find that the derived Nash price equilibrium of both channels includes five possible combinations of prices. Both traditional and online sellers will choose their price strategies, respectively, according to their cost advantages which are affected by the overloaded degree of express delivery.

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.)

Chloride channels in myotonia congenita assessed by velocity recovery cycles.

Science.gov (United States)

Tan, S Veronica; Z'Graggen, Werner J; Boërio, Delphine; Rayan, Dipa Raja; Norwood, Fiona; Ruddy, Deborah; Howard, R; Hanna, Michael G; Bostock, Hugh

2014-06-01

Myotonia congenita (MC) is caused by congenital defects in the muscle chloride channel CLC-1. This study used muscle velocity recovery cycles (MVRCs) to investigate how membrane function is affected. MVRCs and responses to repetitive stimulation were compared between 18 patients with genetically confirmed MC (13 recessive, 7 dominant) and 30 age-matched, normal controls. MC patients exhibited increased early supernormality, but this was prevented by treatment with sodium channel blockers. After multiple conditioning stimuli, late supernormality was enhanced in all MC patients, indicating delayed repolarization. These abnormalities were similar between the MC subtypes, but recessive patients showed a greater drop in amplitude during repetitive stimulation. MVRCs indicate that chloride conductance only becomes important when muscle fibers are depolarized. The differential responses to repetitive stimulation suggest that, in dominant MC, the affected chloride channels are activated by strong depolarization, consistent with a positive shift of the CLC-1 activation curve. Copyright © 2013 Wiley Periodicals, Inc.

No apparent role for T-type Ca2+ channels in renal autoregulation

DEFF Research Database (Denmark)

Frandsen, Rasmus Hassing; Salomonsson, Max; Hansen, Pernille B. Lærkegaard

2016-01-01

-type and CaV3.1 knockout mice were assessed. Autoregulation of renal blood flow was examined during acute increases in RPP in normo- and hypertensive rats under pharmacological blockade of T- and L-type calcium channels using mibefradil (0.1 μM) and nifedipine (1 μM). In contrast to the results from previous......Renal autoregulation protects glomerular capillaries against increases in renal perfusion pressure (RPP). In the mesentery, both L- and T-type calcium channels are involved in autoregulation. L-type calcium channels participate in renal autoregulation, but the role of T-type channels is not fully...... pharmacological studies, genetic deletion of T-type channels CaV3.1 did not affect renal autoregulation. Pharmacological blockade of T-type channels using concentrations of mibefradil which specifically blocks T-type channels also had no effect in wild-type or knockout mice. Blockade of L-type channels...

A Simulator of Periodically Switching Channels for Power Line Communications

Science.gov (United States)

Hayasaki, Taro; Umehara, Daisuke; Denno, Satoshi; Morikura, Masahiro

An indoor power line is one of the most attractive media for in-home networks. However, there are many technical problems for achieving in-home power line communication (PLC) with high rate and high reliability. One of such problem is the degradation in the performance of the in-home PLC caused by periodically time-varying channel responses, particularly when connecting the switching power supply equipment. We present a measurement method for power line channel responses and reveal the switching of the channel responses synchronized with power-frequency voltage when connecting switching power supply equipment in sending or receiving outlets. In this paper, we term them periodically switching channel responses. The performance of PLC adapters is seriously affected by the periodically switching channel responses. Therefore, we provide a modeling of the periodically switching channel responses by using finite impulse response (FIR) filters with a shared channel memory and construct a simulator for in-home power line channels including the periodically switching channel responses in order to evaluate the various communication systems through the power line. We present the validity of the proposed simulator through the performance evaluation of OFDM/64QAM over periodically switching channels with additive white Gaussian noise. Furthermore, we evaluate the influence of the periodically switching channel responses on the communication quality of a time-invariant modulation scheme by using the proposed simulator.

2D IR spectroscopy reveals the role of water in the binding of channel-blocking drugs to the influenza M2 channel

International Nuclear Information System (INIS)

Ghosh, Ayanjeet; Gai, Feng; Hochstrasser, Robin M.; Wang, Jun; DeGrado, William F.; Moroz, Yurii S.; Korendovych, Ivan V.; Zanni, Martin

2014-01-01

Water is an integral part of the homotetrameric M2 proton channel of the influenza A virus, which not only assists proton conduction but could also play an important role in stabilizing channel-blocking drugs. Herein, we employ two dimensional infrared (2D IR) spectroscopy and site-specific IR probes, i.e., the amide I bands arising from isotopically labeled Ala30 and Gly34 residues, to probe how binding of either rimantadine or 7,7-spiran amine affects the water dynamics inside the M2 channel. Our results show, at neutral pH where the channel is non-conducting, that drug binding leads to a significant increase in the mobility of the channel water. A similar trend is also observed at pH 5.0 although the difference becomes smaller. Taken together, these results indicate that the channel water facilitates drug binding by increasing its entropy. Furthermore, the 2D IR spectral signatures obtained for both probes under different conditions collectively support a binding mechanism whereby amantadine-like drugs dock in the channel with their ammonium moiety pointing toward the histidine residues and interacting with a nearby water cluster, as predicted by molecular dynamics simulations. We believe these findings have important implications for designing new anti-influenza drugs

2D IR spectroscopy reveals the role of water in the binding of channel-blocking drugs to the influenza M2 channel

Energy Technology Data Exchange (ETDEWEB)

Ghosh, Ayanjeet, E-mail: ayanjeet@sas.upenn.edu, E-mail: gai@sas.upenn.edu; Gai, Feng, E-mail: ayanjeet@sas.upenn.edu, E-mail: gai@sas.upenn.edu; Hochstrasser, Robin M. [Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 (United States); Wang, Jun; DeGrado, William F. [Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California 94143 (United States); Moroz, Yurii S.; Korendovych, Ivan V. [Department of Chemistry, Syracuse University, Syracuse, New York 13244 (United States); Zanni, Martin [Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706 (United States)

2014-06-21

Water is an integral part of the homotetrameric M2 proton channel of the influenza A virus, which not only assists proton conduction but could also play an important role in stabilizing channel-blocking drugs. Herein, we employ two dimensional infrared (2D IR) spectroscopy and site-specific IR probes, i.e., the amide I bands arising from isotopically labeled Ala30 and Gly34 residues, to probe how binding of either rimantadine or 7,7-spiran amine affects the water dynamics inside the M2 channel. Our results show, at neutral pH where the channel is non-conducting, that drug binding leads to a significant increase in the mobility of the channel water. A similar trend is also observed at pH 5.0 although the difference becomes smaller. Taken together, these results indicate that the channel water facilitates drug binding by increasing its entropy. Furthermore, the 2D IR spectral signatures obtained for both probes under different conditions collectively support a binding mechanism whereby amantadine-like drugs dock in the channel with their ammonium moiety pointing toward the histidine residues and interacting with a nearby water cluster, as predicted by molecular dynamics simulations. We believe these findings have important implications for designing new anti-influenza drugs.

Speaker Recognition Using Real vs Synthetic Parallel Data for DNN Channel Compensation

Science.gov (United States)

2016-09-08

Analysis of factors affecting system performance in the aspire chal- lenge,” in Proc. of IEEE ASRU, 2015. [22] M. Jeub, M. Schafer, and P. Vary, “A binaurl...Introduction Recently there has been a great deal of interest in using deep neural networks (DNNs) for channel compensation under re- verberant or noisy...time align the data from each mi- crophone channels to the telephone channel. Audio files were rejected if the alignment process failed. At the end of

Turbulent shear layers in confining channels

Science.gov (United States)

Benham, Graham P.; Castrejon-Pita, Alfonso A.; Hewitt, Ian J.; Please, Colin P.; Style, Rob W.; Bird, Paul A. D.

2018-06-01

We present a simple model for the development of shear layers between parallel flows in confining channels. Such flows are important across a wide range of topics from diffusers, nozzles and ducts to urban air flow and geophysical fluid dynamics. The model approximates the flow in the shear layer as a linear profile separating uniform-velocity streams. Both the channel geometry and wall drag affect the development of the flow. The model shows good agreement with both particle image velocimetry experiments and computational turbulence modelling. The simplicity and low computational cost of the model allows it to be used for benchmark predictions and design purposes, which we demonstrate by investigating optimal pressure recovery in diffusers with non-uniform inflow.

Sequential grouping constraints on across-channel auditory processing

DEFF Research Database (Denmark)

Oxenham, Andrew J.; Dau, Torsten

2005-01-01

Søren Buus was one of the pioneers in the study of across-channel auditory processing. His influential 1985 paper showed that introducing slow fluctuations to a low-frequency masker could reduce the detection thresholds of a high-frequency signal by as much as 25 dB [S. Buus, J. Acoust. Soc. Am. 78......, 1958–1965 (1985)]. Søren explained this surprising result in terms of the spread of masker excitation and across-channel processing of envelope fluctuations. A later study [S. Buus and C. Pan, J. Acoust. Soc. Am. 96, 1445–1457 (1994)] pioneered the use of the same stimuli in tasks where across......-channel processing could either help or hinder performance. In the present set of studies we also use paradigms in which across-channel processing can lead to either improvement or deterioration in performance. We show that sequential grouping constraints can affect both types of paradigm. In particular...

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.

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

Disruption of the IS6-AID linker affects voltage-gated calcium channel inactivation and facilitation.

Science.gov (United States)

Findeisen, Felix; Minor, Daniel L

2009-03-01

Two processes dominate voltage-gated calcium channel (Ca(V)) inactivation: voltage-dependent inactivation (VDI) and calcium-dependent inactivation (CDI). The Ca(V)beta/Ca(V)alpha(1)-I-II loop and Ca(2+)/calmodulin (CaM)/Ca(V)alpha(1)-C-terminal tail complexes have been shown to modulate each, respectively. Nevertheless, how each complex couples to the pore and whether each affects inactivation independently have remained unresolved. Here, we demonstrate that the IS6-alpha-interaction domain (AID) linker provides a rigid connection between the pore and Ca(V)beta/I-II loop complex by showing that IS6-AID linker polyglycine mutations accelerate Ca(V)1.2 (L-type) and Ca(V)2.1 (P/Q-type) VDI. Remarkably, mutations that either break the rigid IS6-AID linker connection or disrupt Ca(V)beta/I-II association sharply decelerate CDI and reduce a second Ca(2+)/CaM/Ca(V)alpha(1)-C-terminal-mediated process known as calcium-dependent facilitation. Collectively, the data strongly suggest that components traditionally associated solely with VDI, Ca(V)beta and the IS6-AID linker, are essential for calcium-dependent modulation, and that both Ca(V)beta-dependent and CaM-dependent components couple to the pore by a common mechanism requiring Ca(V)beta and an intact IS6-AID linker.

Morphodynamic assessment of side channel systems using a simple one-dimensional bifurcation model and a comparison with aerial images

NARCIS (Netherlands)

van Denderen, R. Pepijn; Schielen, Ralph M.J.; Blom, Astrid; Hulscher, Suzanne J.M.H.; Kleinhans, Maarten G.

2017-01-01

Side channel construction is a common intervention applied to increase a river's conveyance capacity and to increase its ecological value. Past modelling efforts suggest two mechanisms affecting the morphodynamic change of a side channel: (1) a difference in channel slope between the side channel

Morphodynamic assessment of side channel systems using a simple one-dimensional bifurcation model and a comparison with aerial images

NARCIS (Netherlands)

van Denderen, R. Pepijn; Schielen, Ralph M.J.; Blom, A.; Hulscher, Suzanne J.M.H.; Kleinhans, Maarten G.

2017-01-01

Side channel construction is a common intervention applied to increase a river's conveyance capacity and to increase its ecological value. Past modelling efforts suggest two mechanisms affecting the morphodynamic change of a side channel: (1) a difference in channel slope between the side channel

Morphodynamic assessment of side channel systems using a simple one-dimensional bifurcation model and a comparison with aerial images

NARCIS (Netherlands)

Van Denderen, R. Pepijn; Schielen, Ralph Mathias Johannes; Blom, Astrid; Hulscher, Suzanne J.M.H.; Kleinhans, Maarten G.

2018-01-01

Side channel construction is a common intervention applied to increase the river's conveyance capacity and to increase its ecological value. Past modelling efforts suggest two mechanisms affecting the morphodynamic change of a side channel: 1) a difference in channel slope between the side channel

Channel Coordination in Logistics Service Supply Chain considering Fairness

Directory of Open Access Journals (Sweden)

Ningning Wang

2016-01-01

Full Text Available Logistics service supply chain (LSSC is a new type of service supply chain. This paper investigates the channel coordination issue in a two-echelon LSSC composed of one logistics service integrator (LSI and one functional logistics service provider (FLSP under fairness concerns. The models for a reservation price-only contract under disadvantageous inequality and advantageous inequality are established, respectively, in which the procurement cost, the potential shortage cost, and the operation cost are considered under stochastic market demand. Based on this model, the LSI’s optimal reservation quantity can be determined. Furthermore, we analyze the impact of fairness concerns and the related costs on channel performance and channel coordination. The results are presented in four aspects: (1 channel coordination of the LSSC can be achieved under certain conditions when the LSI experiences advantageous inequality; (2 the spiteful behavior of the LSI leads to the reduction of the channel profit, and channel coordination cannot be achieved when the LSI suffers from disadvantageous inequality; (3 the LSI’s reservation quantity and the channel profit are affected by the LSI’s fairness concerns; (4 motivated by the concerns of fairness, the LSI’s reservation quantity is related not only to his procurement cost and shortage cost but also to the FLSP’s operation cost.

Modeling of dislocation channel width evolution in irradiated metals

Science.gov (United States)

Doyle, Peter J.; Benensky, Kelsa M.; Zinkle, Steven J.

2018-02-01

without affecting channel dependence on the given parameters.

A negative charge in transmembrane segment 1 of domain II of the cockroach sodium channel is critical for channel gating and action of pyrethroid insecticides

International Nuclear Information System (INIS)

Du Yuzhe; Song Weizhong; Groome, James R.; Nomura, Yoshiko; Luo Ningguang; Dong Ke

2010-01-01

Voltage-gated sodium channels are the primary target of pyrethroids, an important class of synthetic insecticides. Pyrethroids bind to a distinct receptor site on sodium channels and prolong the open state by inhibiting channel deactivation and inactivation. Recent studies have begun to reveal sodium channel residues important for pyrethroid binding. However, how pyrethroid binding leads to inhibition of sodium channel deactivation and inactivation remains elusive. In this study, we show that a negatively charged aspartic acid residue at position 802 (D802) located in the extracellular end of transmembrane segment 1 of domain II (IIS1) is critical for both the action of pyrethroids and the voltage dependence of channel activation. Charge-reversing or -neutralizing substitutions (K, G, or A) of D802 shifted the voltage dependence of activation in the depolarizing direction and reduced channel sensitivity to deltamethrin, a pyrethroid insecticide. The charge-reversing mutation D802K also accelerated open-state deactivation, which may have counteracted the inhibition of sodium channel deactivation by deltamethrin. In contrast, the D802G substitution slowed open-state deactivation, suggesting an additional mechanism for neutralizing the action of deltamethrin. Importantly, Schild analysis showed that D802 is not involved in pyrethroid binding. Thus, we have identified a sodium channel residue that is critical for regulating the action of pyrethroids on the sodium channel without affecting the receptor site of pyrethroids.

Coupling of laser energy into plasma channels

International Nuclear Information System (INIS)

Dimitrov, D. A.; Giacone, R. E.; Bruhwiler, D. L.; Busby, R.; Cary, J. R.; Geddes, C. G. R.; Esarey, E.; Leemans, W. P.

2007-01-01

Diffractive spreading of a laser pulse imposes severe limitations on the acceleration length and maximum electron energy in the laser wake field accelerator (LWFA). Optical guiding of a laser pulse via plasma channels can extend the laser-plasma interaction distance over many Rayleigh lengths. Energy efficient coupling of laser pulses into and through plasma channels is very important for optimal LWFA performance. Results from simulation parameter studies on channel guiding using the particle-in-cell (PIC) code VORPAL [C. Nieter and J. R. Cary, J. Comput. Phys. 196, 448 (2004)] are presented and discussed. The effects that density ramp length and the position of the laser pulse focus have on coupling into channels are considered. Moreover, the effect of laser energy leakage out of the channel domain and the effects of tunneling ionization of a neutral gas on the guided laser pulse are also investigated. Power spectral diagnostics were developed and used to separate pump depletion from energy leakage. The results of these simulations show that increasing the density ramp length decreases the efficiency of coupling a laser pulse to a channel and increases the energy loss when the pulse is vacuum focused at the channel entrance. Then, large spot size oscillations result in increased energy leakage. To further analyze the coupling, a differential equation is derived for the laser spot size evolution in the plasma density ramp and channel profiles are simulated. From the numerical solution of this equation, the optimal spot size and location for coupling into a plasma channel with a density ramp are determined. This result is confirmed by the PIC simulations. They show that specifying a vacuum focus location of the pulse in front of the top of the density ramp leads to an actual focus at the top of the ramp due to plasma focusing, resulting in reduced spot size oscillations. In this case, the leakage is significantly reduced and is negligibly affected by ramp length

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

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

Science.gov (United States)

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

2010-01-01

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

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

Directory of Open Access Journals (Sweden)

Francesco eMiceli

2011-02-01

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

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)

Computer Simulation Studies of Ion Channels at High Temperatures

Science.gov (United States)

Song, Hyun Deok

The gramicidin channel is the smallest known biological ion channel, and it exhibits cation selectivity. Recently, Dr. John Cuppoletti's group at the University of Cincinnati showed that the gramicidin channel can function at high temperatures (360 ˜ 380K) with significant currents. This finding may have significant implications for fuel cell technology. In this thesis, we have examined the gramicidin channel at 300K, 330K, and 360K by computer simulation. We have investigated how the temperature affects the current and differences in magnitude of free energy between the two gramicidin forms, the helical dimer (HD) and the double helix (DH). A slight decrease of the free energy barrier inside the gramicidin channel and increased diffusion at high temperatures result in an increase of current. An applied external field of 0.2V/nm along the membrane normal results in directly observable ion transport across the channels at high temperatures for both HD and DH forms. We found that higher temperatures also affect the probability distribution of hydrogen bonds, the bending angle, the distance between dimers, and the size of the pore radius for the helical dimer structure. These findings may be related to the gating of the gramicidin channel. Methanococcus jannaschii (MJ) is a methane-producing thermophile, which was discovered at a depth of 2600m in a Pacific Ocean vent in 1983. It has the ability to thrive at high temperatures and high pressures, which are unfavorable for most life forms. There have been some experiments to study its stability under extreme conditions, but still the origin of the stability of MJ is not exactly known. MJ0305 is the chloride channel protein from the thermophile MJ. After generating a structure of MJ0305 by homology modeling based on the Ecoli ClC templates, we examined the thermal stability, and the network stability from the change of network entropy calculated from the adjacency matrices of the protein. High temperatures increase the

Effects of channel noise on firing coherence of small-world Hodgkin-Huxley neuronal networks

Science.gov (United States)

Sun, X. J.; Lei, J. Z.; Perc, M.; Lu, Q. S.; Lv, S. J.

2011-01-01

We investigate the effects of channel noise on firing coherence of Watts-Strogatz small-world networks consisting of biophysically realistic HH neurons having a fraction of blocked voltage-gated sodium and potassium ion channels embedded in their neuronal membranes. The intensity of channel noise is determined by the number of non-blocked ion channels, which depends on the fraction of working ion channels and the membrane patch size with the assumption of homogeneous ion channel density. We find that firing coherence of the neuronal network can be either enhanced or reduced depending on the source of channel noise. As shown in this paper, sodium channel noise reduces firing coherence of neuronal networks; in contrast, potassium channel noise enhances it. Furthermore, compared with potassium channel noise, sodium channel noise plays a dominant role in affecting firing coherence of the neuronal network. Moreover, we declare that the observed phenomena are independent of the rewiring probability.

BAD and KATP channels regulate neuron excitability and epileptiform activity.

Science.gov (United States)

Martínez-François, Juan Ramón; Fernández-Agüera, María Carmen; Nathwani, Nidhi; Lahmann, Carolina; Burnham, Veronica L; Danial, Nika N; Yellen, Gary

2018-01-25

Brain metabolism can profoundly influence neuronal excitability. Mice with genetic deletion or alteration of Bad ( B CL-2 a gonist of cell d eath) exhibit altered brain-cell fuel metabolism, accompanied by resistance to acutely induced epileptic seizures; this seizure protection is mediated by ATP-sensitive potassium (K ATP ) channels. Here we investigated the effect of BAD manipulation on K ATP channel activity and excitability in acute brain slices. We found that BAD's influence on neuronal K ATP channels was cell-autonomous and directly affected dentate granule neuron (DGN) excitability. To investigate the role of neuronal K ATP channels in the anticonvulsant effects of BAD, we imaged calcium during picrotoxin-induced epileptiform activity in entorhinal-hippocampal slices. BAD knockout reduced epileptiform activity, and this effect was lost upon knockout or pharmacological inhibition of K ATP channels. Targeted BAD knockout in DGNs alone was sufficient for the antiseizure effect in slices, consistent with a 'dentate gate' function that is reinforced by increased K ATP channel activity. © 2018, Martínez-François et al.

KV7 Channels Regulate Firing during Synaptic Integration in GABAergic Striatal Neurons

Directory of Open Access Journals (Sweden)

M. Belén Pérez-Ramírez

2015-01-01

Full Text Available Striatal projection neurons (SPNs process motor and cognitive information. Their activity is affected by Parkinson’s disease, in which dopamine concentration is decreased and acetylcholine concentration is increased. Acetylcholine activates muscarinic receptors in SPNs. Its main source is the cholinergic interneuron that responds with a briefer latency than SPNs during a cortical command. Therefore, an important question is whether muscarinic G-protein coupled receptors and their signaling cascades are fast enough to intervene during synaptic responses to regulate synaptic integration and firing. One of the most known voltage dependent channels regulated by muscarinic receptors is the KV7/KCNQ channel. It is not known whether these channels regulate the integration of suprathreshold corticostriatal responses. Here, we study the impact of cholinergic muscarinic modulation on the synaptic response of SPNs by regulating KV7 channels. We found that KV7 channels regulate corticostriatal synaptic integration and that this modulation occurs in the dendritic/spines compartment. In contrast, it is negligible in the somatic compartment. This modulation occurs on sub- and suprathreshold responses and lasts during the whole duration of the responses, hundreds of milliseconds, greatly altering SPNs firing properties. This modulation affected the behavior of the striatal microcircuit.

Segmentized Clear Channel Assessment for IEEE 802.15.4 Networks.

Science.gov (United States)

Son, Kyou Jung; Hong, Sung Hyeuck; Moon, Seong-Pil; Chang, Tae Gyu; Cho, Hanjin

2016-06-03

This paper proposed segmentized clear channel assessment (CCA) which increases the performance of IEEE 802.15.4 networks by improving carrier sense multiple access with collision avoidance (CSMA/CA). Improving CSMA/CA is important because the low-power consumption feature and throughput performance of IEEE 802.15.4 are greatly affected by CSMA/CA behavior. To improve the performance of CSMA/CA, this paper focused on increasing the chance to transmit a packet by assessing precise channel status. The previous method used in CCA, which is employed by CSMA/CA, assesses the channel by measuring the energy level of the channel. However, this method shows limited channel assessing behavior, which comes from simple threshold dependent channel busy evaluation. The proposed method solves this limited channel decision problem by dividing CCA into two groups. Two groups of CCA compare their energy levels to get precise channel status. To evaluate the performance of the segmentized CCA method, a Markov chain model has been developed. The validation of analytic results is confirmed by comparing them with simulation results. Additionally, simulation results show the proposed method is improving a maximum 8.76% of throughput and decreasing a maximum 3.9% of the average number of CCAs per packet transmission than the IEEE 802.15.4 CCA method.

Role of aquaporin and sodium channel in pleural water movement.

Science.gov (United States)

Jiang, Jinjun; Hu, Jie; Bai, Chunxue

2003-12-16

The role of the ENaC sodium channel and aquaporin-1 (AQP1) water channel on pleural fluid dynamics in mice was investigated. 0.25 ml of hypertonic or isosmolar fluid was infused into the pleural space in anesthetized wildtype and AQP1 null mice. Pleural fluid was sampled at specified times to quantify the osmolality and volume. The sodium channel activator terbutaline increased isosmolar fluid clearance by 90% while the sodium channel inhibitor amiloride decreased it by 15%, but had no effect on osmotically driven water transport. AQP1 deletion significantly decreased osmotic water transport in pleural space by twofold, but it had no effect on isosmolar fluid clearance. Pretreatment with dexamethasone increased pleural osmotic fluid entry by 25%, while intravenous injection of HgCl2 decreased osmotic pleural water movement by 43%. These results provided evidence for a role of a sodium channel in pleural fluid absorption; AQP1 plays a major role in osmotic liquid transport but it does not affect isosmolar fluid clearance.

Escitalopram block of hERG potassium channels.

Science.gov (United States)

Chae, Yun Ju; Jeon, Ji Hyun; Lee, Hong Joon; Kim, In-Beom; Choi, Jin-Sung; Sung, Ki-Wug; Hahn, Sang June

2014-01-01

Escitalopram, a selective serotonin reuptake inhibitor, is the pharmacologically active S-enantiomer of the racemic mixture of RS-citalopram and is widely used in the treatment of depression. The effects of escitalopram and citalopram on the human ether-a-go-go-related gene (hERG) channels expressed in human embryonic kidney cells were investigated using voltage-clamp and Western blot analyses. Both drugs blocked hERG currents in a concentration-dependent manner with an IC50 value of 2.6 μM for escitalopram and an IC50 value of 3.2 μM for citalopram. The blocking of hERG by escitalopram was voltage-dependent, with a steep increase across the voltage range of channel activation. However, voltage independence was observed over the full range of activation. The blocking by escitalopram was frequency dependent. A rapid application of escitalopram induced a rapid and reversible blocking of the tail current of hERG. The extent of the blocking by escitalopram during the depolarizing pulse was less than that during the repolarizing pulse, suggesting that escitalopram has a high affinity for the open state of the hERG channel, with a relatively lower affinity for the inactivated state. Both escitalopram and citalopram produced a reduction of hERG channel protein trafficking to the plasma membrane but did not affect the short-term internalization of the hERG channel. These results suggest that escitalopram blocked hERG currents at a supratherapeutic concentration and that it did so by preferentially binding to both the open and the inactivated states of the channels and by inhibiting the trafficking of hERG channel protein to the plasma membrane.

CANDU-PHW fuel channel replacement experience

International Nuclear Information System (INIS)

Dunn, J.T.; Kakaria, B.K.

1982-09-01

One of the main characteristics of the CANDU pressurized heavy water reactor is the use of pressure tubes rather than one large pressure vessel to contain the fuel and coolant. This provides an inherent design capability to permit their replacement in an expeditious manner, without seriously affecting the high capacity factors of the reactor units. Of th eight Ontario Hydro commercial nuclear generating units, the lifetime performance places seven of them (including two that have had some of their fuel channels replaced), in the top ten positions in the world's large nuclear-electric unit performance ranking. Pressure tube cracks in the rolled joint region have resulted in 70 fuel channels being replaced in three reactor units, the latest being at the Bruce Nuclear Generating Station 'A', Unit 2 in February 1982. The rolled joint design and rolling procedures have been modified to eliminate this problem on CANDU units subsequent to Bruce 'A'. This paper describes the CANDU pressure tube performance history and expectations, and the tooling and procedures used to carry out the fuel channel replacement

Study on density wave oscillation in parallel channel by section form

International Nuclear Information System (INIS)

Huang Jun; Huang Yanping; Wang Yanlin

2013-01-01

Based on 170 density wave oscillation experimental data from parallel round tube and narrow rectangular channel, the experiment method, identification method of oscillation and analysis method of experimental data have be uniformed, and the oscillation boundary of round tube and narrow rectangular channel have be analyzed. The investigation results show that the oscillation boundary is not affected by the channel section forms with identical equivalent diameter with pressure l.0∼19.2 MPa, mass flux 101.9∼1200.0 kg·m-2·s -1 and inlet sub cooling 18.0∼85.2℃. (authors)

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

Science.gov (United States)

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

2011-01-01

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

Investigation of the potential barrier lowering for quasi-ballistic transport in short channel MOSFETs

International Nuclear Information System (INIS)

Lee, Jaehong; Kwon, Yongmin; Ji, Junghwan; Shin, Hyungcheol

2011-01-01

In this paper, the quasi-ballistic carrier transport in short channel MOSFETs is investigated from the point of potential barrier lowering. To investigate the ballistic characteristic of transistors, we extracted the channel backscattering coefficient and the ballistic ratio from experimental data obtained by RF C-V and DC I-V measurements. Two factors that modulate the potential barrier height, besides the gate bias, are considered in this work: the drain bias (V DS ) and the channel doping concentration (N A ). We extract the critical length by calculating the potential drop in the channel region and conclude that the drain bias and the channel doping concentration affect the quasi-ballistic carrier transport.

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...

Sediment Dynamics Affecting the Threatened Santa Ana Sucker in the Highly-modified Santa Ana River and Inset Channel, Southern California, USA

Science.gov (United States)

Minear, J. T.; Wright, S. A.

2015-12-01

In this study, we investigate the sediment dynamics of the low-flow channel of the Santa Ana River that is formed by wastewater discharges and contains some of the last remaining habitat of the Santa Ana Sucker (Catostomus santaanae). The Santa Ana River is a highly-modified river draining the San Bernardino Mountains and Inland Empire metropolitan area east of Los Angeles. Home to over 4 million people, the watershed provides habitat for the federally-threatened Santa Ana Sucker, which presently reside within the mainstem Santa Ana River in a reach supported by year-round constant discharges from water treatment plants. The nearly constant low-flow wastewater discharges and infrequent runoff events create a small, approximately 8 m wide, inset channel within the approximately 300 m wide mainstem channel that is typically dry except for large flood flows. The sediment dynamics within the inset channel are characterized by constantly evolving bed substrate and sediment transport rates, and occasional channel avulsions. The sediment dynamics have large influence on the Sucker, which rely on coarse-substrate (gravel and cobble) for their food production. In WY 2013 through the present, we investigated the sediment dynamics of the inset channel using repeat bathymetric and substrate surveys, bedload sampling, and discharge measurements. We found two distinct phases of the inset channel behavior: 1. 'Reset' flows, where sediment-laden mainstem discharges from upstream runoff events result in sand deposition in the inset channel or avulse the inset channel onto previously dry riverbed; and 2. 'Winnowing' flows, whereby the sand within the inset channel is removed by clear-water low flows from the wastewater treatment plant discharges. Thus, in contrast to many regulated rivers where high flows are required to flush fine sediments from the bed (for example, downstream from dams), in the Santa Ana River the low flows from wastewater treatment plants serve as the flushing

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,

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.

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.

Do cysteine residues regulate transient receptor potential canonical type 6 (TRPC6) channel protein expression?

DEFF Research Database (Denmark)

Thilo, Florian; Liu, Ying; Krueger, Katharina

2012-01-01

The regulation of calcium influx through transient receptor potential canonical type 6 channel is mandatory for the activity of human monocytes. We submit the first evidence that cysteine residues of homocysteine or acetylcysteine affect TRPC6 expression in human monocytes. We observed that patie......The regulation of calcium influx through transient receptor potential canonical type 6 channel is mandatory for the activity of human monocytes. We submit the first evidence that cysteine residues of homocysteine or acetylcysteine affect TRPC6 expression in human monocytes. We observed...... that patients with chronic renal failure had significantly elevated homocysteine levels and TRPC6 mRNA expression levels in monocytes compared to control subjects. We further observed that administration of homocysteine or acetylcysteine significantly increased TRPC6 channel protein expression compared...... to control conditions. We therefore hypothesize that cysteine residues increase TRPC6 channel protein expression in humans....

Substituted N-(biphenyl-4'-yl)methyl (R)-2-acetamido-3-methoxypropionamides: potent anticonvulsants that affect frequency (use) dependence and slow inactivation of sodium channels.

Science.gov (United States)

Lee, Hyosung; Park, Ki Duk; Torregrosa, Robert; Yang, Xiao-Fang; Dustrude, Erik T; Wang, Yuying; Wilson, Sarah M; Barbosa, Cindy; Xiao, Yucheng; Cummins, Theodore R; Khanna, Rajesh; Kohn, Harold

2014-07-24

We prepared 13 derivatives of N-(biphenyl-4'-yl)methyl (R)-2-acetamido-3-methoxypropionamide that differed in type and placement of a R-substituent in the terminal aryl unit. We demonstrated that the R-substituent impacted the compound's whole animal and cellular pharmacological activities. In rodents, select compounds exhibited excellent anticonvulsant activities and protective indices (PI=TD50/ED50) that compared favorably with clinical antiseizure drugs. Compounds with a polar, aprotic R-substituent potently promoted Na+ channel slow inactivation and displayed frequency (use) inhibition of Na+ currents at low micromolar concentrations. The possible advantage of affecting these two pathways to decrease neurological hyperexcitability is discussed.

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.

Endolysosomal Cation Channels and Cancer—A Link with Great Potential

Science.gov (United States)

Grimm, Christian; Bartel, Karin; Vollmar, Angelika M.; Biel, Martin

2018-01-01

The endolysosomal system (ES) consists of lysosomes; early, late, and recycling endosomes; and autophagosomes. It is a key regulator not only of macromolecule degradation and recycling, plasma membrane repair, homeostasis, and lipid storage, but also of antigen presentation, immune defense, cell motility, cell death signaling, tumor growth, and cancer progression. In addition, it plays a critical role in autophagy, and the autophagy-lysosome pathway is intimately associated with the hallmarks of cancer, such as escaping cell death pathways, evading immune surveillance, and deregulating metabolism. The function of endolysosomes is critically dependent on both soluble and endolysosomal membrane proteins such as ion channels and transporters. Cation channels found in the ES include members of the TRP (transient receptor potential) channel superfamily, namely TRPML channels (mucolipins) as well as two-pore channels (TPCs). In recent studies, these channels have been found to play crucial roles in endolysosomal trafficking, lysosomal exocytosis, and autophagy. Mutation or loss of these channel proteins can impact multiple endolysosomal trafficking pathways. A role for TPCs in cancer cell migration and metastasis, linked to distinct defects in endolysosomal trafficking such as integrin trafficking, has been recently established. In this review, we give an overview on the function of lysosomes in cancer with a particular focus on the roles which TPCs and TRPML channels play in the ES and how this can affect cancer cells. PMID:29303993

Endolysosomal Cation Channels and Cancer-A Link with Great Potential.

Science.gov (United States)

Grimm, Christian; Bartel, Karin; Vollmar, Angelika M; Biel, Martin

2018-01-05

The endolysosomal system (ES) consists of lysosomes; early, late, and recycling endosomes; and autophagosomes. It is a key regulator not only of macromolecule degradation and recycling, plasma membrane repair, homeostasis, and lipid storage, but also of antigen presentation, immune defense, cell motility, cell death signaling, tumor growth, and cancer progression. In addition, it plays a critical role in autophagy, and the autophagy-lysosome pathway is intimately associated with the hallmarks of cancer, such as escaping cell death pathways, evading immune surveillance, and deregulating metabolism. The function of endolysosomes is critically dependent on both soluble and endolysosomal membrane proteins such as ion channels and transporters. Cation channels found in the ES include members of the TRP (transient receptor potential) channel superfamily, namely TRPML channels (mucolipins) as well as two-pore channels (TPCs). In recent studies, these channels have been found to play crucial roles in endolysosomal trafficking, lysosomal exocytosis, and autophagy. Mutation or loss of these channel proteins can impact multiple endolysosomal trafficking pathways. A role for TPCs in cancer cell migration and metastasis, linked to distinct defects in endolysosomal trafficking such as integrin trafficking, has been recently established. In this review, we give an overview on the function of lysosomes in cancer with a particular focus on the roles which TPCs and TRPML channels play in the ES and how this can affect cancer cells.

Improving Channel Coordination Through Franchising

OpenAIRE

Rajiv Lal

1990-01-01

In this paper, we explore the role of franchising arrangements in improving coordination between channel members. In particular we focus on two elements of the franchising contract, namely, the royalty structure and the monitoring technology. We begin with a simple analysis where a manufacturer distributes its product through a retailer and the retail demand is affected by the retail price and the service provided by the retailer. In this context we show that neither royalty payments nor moni...

Potential ocean–atmosphere preconditioning of late autumn Barents-Kara sea ice concentration anomaly

Directory of Open Access Journals (Sweden)

Martin P. King

2016-02-01

Full Text Available Many recent studies have revealed the importance of the climatic state in November on the seasonal climate of the subsequent winter. In particular, it has been shown that interannual variability of sea ice concentration (SIC over the Barents-Kara (BK seas in November is linked to winter atmospheric circulation anomaly that projects on the North Atlantic Oscillation. Understanding the lead–lag processes involving the different components of the climate system from autumn to winter is therefore important. This note presents dynamical interpretation for the ice-ocean–atmosphere relationships that can affect the BK SIC anomaly in late autumn. It is found that cyclonic (anticyclonic wind anomaly over the Arctic in October, by Ekman drift, can be responsible for positive (negative SIC in the BK seas in November. The results also suggest that ocean heat transport via the Barents Sea Opening in September and October can contribute to BK SIC anomaly in November.

Physical origin of selectivity in ionic channels of biological membranes.

Science.gov (United States)

Laio, A; Torre, V

1999-01-01

This paper shows that the selectivity properties of monovalent cation channels found in biological membranes can originate simply from geometrical properties of the inner core of the channel without any critical contribution from electrostatic interactions between the permeating ions and charged or polar groups. By using well-known techniques of statistical mechanics, such as the Langevin equations and Kramer theory of reaction rates, a theoretical equation is provided relating the permeability ratio PB/PA between ions A and B to simple physical properties, such as channel geometry, thermodynamics of ion hydration, and electrostatic interactions between the ion and charged (or polar) groups. Diffusive corrections and recrossing rates are also considered and evaluated. It is shown that the selectivity found in usual K+, gramicidin, Na+, cyclic nucleotide gated, and end plate channels can be explained also in the absence of any charged or polar group. If these groups are present, they significantly change the permeability ratio only if the ion at the selectivity filter is in van der Waals contact with them, otherwise these groups simply affect the channel conductance, lowering the free energy barrier of the same amount for the two ions, thus explaining why single channel conductance, as it is experimentally observed, can be very different in channels sharing the same selectivity sequence. The proposed theory also provides an estimate of channel minimum radius for K+, gramicidin, Na+, and cyclic nucleotide gated channels.

β1 subunit stabilises sodium channel Nav1.7 against mechanical stress.

Science.gov (United States)

Körner, Jannis; Meents, Jannis; Machtens, Jan-Philipp; Lampert, Angelika

2018-06-01

The voltage-gated sodium channel Nav1.7 is a key player in neuronal excitability and pain signalling. In addition to voltage sensing, the channel is also modulated by mechanical stress. Using whole-cell patch-clamp experiments, we discovered that the sodium channel subunit β1 is able to prevent the impact of mechanical stress on Nav1.7. An intramolecular disulfide bond of β1 was identified to be essential for stabilisation of inactivation, but not activation, against mechanical stress using molecular dynamics simulations, homology modelling and site-directed mutagenesis. Our results highlight the role of segment 6 of domain IV in fast inactivation. We present a candidate mechanism for sodium channel stabilisation against mechanical stress, ensuring reliable channel functionality in living systems. Voltage-gated sodium channels are key players in neuronal excitability and pain signalling. Precise gating of these channels is crucial as even small functional alterations can lead to pathological phenotypes such as pain or heart failure. Mechanical stress has been shown to affect sodium channel activation and inactivation. This suggests that stabilising components are necessary to ensure precise channel gating in living organisms. Here, we show that mechanical shear stress affects voltage dependence of activation and fast inactivation of the Nav1.7 channel. Co-expression of the β1 subunit, however, protects both gating modes of Nav1.7 against mechanical shear stress. Using molecular dynamics simulation, homology modelling and site-directed mutagenesis, we identify an intramolecular disulfide bond of β1 (Cys21-Cys43) which is partially involved in this process: the β1-C43A mutant prevents mechanical modulation of voltage dependence of activation, but not of fast inactivation. Our data emphasise the unique role of segment 6 of domain IV for sodium channel fast inactivation and confirm previous reports that the intracellular process of fast inactivation can be

Channel estimation in few mode fiber mode division multiplexing transmission system

Science.gov (United States)

Hei, Yongqiang; Li, Li; Li, Wentao; Li, Xiaohui; Shi, Guangming

2018-03-01

It is abundantly clear that obtaining the channel state information (CSI) is of great importance for the equalization and detection in coherence receivers. However, to the best of the authors' knowledge, in most of the existing literatures, CSI is assumed to be perfectly known at the receiver. So far, few literature discusses the effects of imperfect CSI on MDM system performance caused by channel estimation. Motivated by that, in this paper, the channel estimation in few mode fiber (FMF) mode division multiplexing (MDM) system is investigated, in which two classical channel estimation methods, i.e., least square (LS) method and minimum mean square error (MMSE) method, are discussed with the assumption of the spatially white noise lumped at the receiver side of MDM system. Both the capacity and BER performance of MDM system affected by mode-dependent gain or loss (MDL) with different channel estimation errors have been studied. Simulation results show that the capacity and BER performance can be further deteriorated in MDM system by the channel estimation, and an 1e-3 variance of channel estimation error is acceptable in MDM system with 0-6 dB MDL values.

Quantum-state transfer through long-range correlated disordered channels

Science.gov (United States)

Almeida, Guilherme M. A.; de Moura, Francisco A. B. F.; Lyra, Marcelo L.

2018-05-01

We study quantum-state transfer in XX spin-1/2 chains where both communicating spins are weakly coupled to a channel featuring disordered on-site magnetic fields. Fluctuations are modeled by long-range correlated sequences with self-similar profile obeying a power-law spectrum. We show that the channel is able to perform almost perfect quantum-state transmissions even in the presence of significant amounts of disorder provided the degree of those correlations is strong enough, with the cost of having long transfer times and unavoidable timing errors. Still, we show that the lack of mirror symmetry in the channel does not affect much the likelihood of having high-quality outcomes. Our results suggest that coexistence between localized and delocalized states can diminish effects of static perturbations in solid-state devices for quantum communication.

Competition between abstraction and exchange channels in H + HCN reaction: Full-dimensional quantum dynamics

Energy Technology Data Exchange (ETDEWEB)

Jiang, Bin; Guo, Hua, E-mail: hguo@unm.edu [Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, New Mexico 87131 (United States)

2013-12-14

Dynamics of the title reaction is investigated on an ab initio based potential energy surface using a full-dimensional quantum wave packet method within the centrifugal sudden approximation. It is shown that the reaction between H and HCN leads to both the hydrogen exchange and hydrogen abstraction channels. The exchange channel has a lower threshold and larger cross section than the abstraction channel. It also has more oscillations due apparently to quantum resonances. Both channels are affected by long-lived resonances supported by potential wells. Comparison with experimental cross sections indicates underestimation of the abstraction barrier height.

Polyunsaturated fatty acid analogs act antiarrhythmically on the cardiac I_Ks channel

DEFF Research Database (Denmark)

Liin, Sara I.; Silverå Ejneby, Malin; Barro-Soria, Rene

2015-01-01

Polyunsaturated fatty acids (PUFAs) affect cardiac excitability. Kv7.1 and the β-subunit KCNE1 form the cardiac IKs channel that is central for cardiac repolarization. In this study, we explore the prospects of PUFAs as IKs channel modulators. We report that PUFAs open Kv7.1 via an electrostatic...... charge at neutral pH, restore the sensitivity to open IKs channels. PUFA analogs with a positively charged head group inhibit IKs channels. These different PUFA analogs could be developed into drugs to treat cardiac arrhythmias. In support of this possibility, we show that PUFA analogs act...

[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.

Channel box

International Nuclear Information System (INIS)

Tanabe, Akira.

1993-01-01

In a channel box of a BWR type reactor, protruding pads are disposed in axial position on the lateral side of a channel box opposing to a control rod and facing the outer side portion of the control rod in a reactor core loaded state. In the initial loading stage of fuel assemblies, channel fasteners and spacer pads are abutted against each other in the upper portion between the channel boxes sandwiching the control rod therebetween. Further, in the lower portion, a gap as a channel for the movement of the control rod is ensured by the support of fuel support metals. If the channel box is bent toward the control rod along with reactor operation, the pads are abutted against each other to always ensure the gap through which the control rod can move easily. Further, when the pads are brought into contact with each other, the bending deformation of the channel box is corrected by urging to each other. Thus, the control rod can always be moved smoothly to attain reactor safety operation. (N.H.)

Prevalence of Polyoma BK Virus (BKPyV), Epstein-Barr Virus (EBV) and Human Papilloma Virus (HPV) in Oropharyngeal Cancer.

Science.gov (United States)

Polz-Gruszka, Dorota; Morshed, Kamal; Jarzyński, Adrian; Polz-Dacewicz, Małgorzata

2015-01-01

The aim of this study was to analyze the prevalence of BK virus, Human Papillomavirus and Epstein-Barr virus in oropharyngeal cancer, and to test our hypothesis that BKV/HPV/EBV co-infection plays a role in oropharyngeal squamous cell carcinoma. The correlation between viral infection, OSCC, anatomic location, pre-treatment staging, evidence of metastases to lymph nodes, and grading was also investigated. The examination samples were collected from 62 patients from paraffin tissue blocks. Males (90.3%) with, smoking (83.9%) and alcohol abuse (67.7%) problems prevailed in the studied group. G2 histological type was recognized in 80.6% cases. T4 (77.4%) and N2 (56.5%) traits occurred in the majority of patients. No cases of metastasis were observed (M0 100%). HPV - 24.2%, EBV - 27.4% and BKV 17.7% were detected in the studied samples. We observed co-infection EBV/BKV in 8% of cases, HPV/BKV in 4.8%, and HPV/EBV in 9% cases. Only in two cases co-infection of all three viruses was found.

Assessment of long-term channel changes in the Mekong River using remote sensing and a channel-evolution model

Science.gov (United States)

Miyazawa, N.

2011-12-01

River-channel changes are a key factor affecting physical, ecological and management issues in the fluvial environment. In this study, long-term channel changes in the Mekong River were assessed using remote sensing and a channel-evolution model. A channel-evolution model for calculating long-term channel changes of a measndering river was developed using a previous fluid-dynamic model [Zolezzi and Seminara, 2001], and was applied in order to quantify channel changes of two meandering reaches in the Mekong River. Quite few attempts have been made so far to combine remote sensing observation of meandering planform change with the application of channel evolution models within relatively small-scale gravel-bed systems in humid temperate regions. The novel point of the present work is to link state-of-art meandering planform evolution model with observed morphological changes within large-scale sand-bed rivers with higher bank height in tropical monsoonal climate regions, which are the highly dynamic system, and assess the performance. Unstable extents of the reaches could be historically identified using remote-sensing technique. The instability caused i) bank erosion and accretion of meander bends and ii) movement or development of bars and changes in the flow around the bars. The remote sensing measurements indicate that maximum erosion occurred downstream of the maximum curvature of the river-center line in both reaches. The model simulations indicates that under the mean annual peak discharge the maximum of excess longitudinal velocity near the banks occurs downstream of the maximum curvature in both reaches. The channel migration coefficients of the reaches were calibrated by comparing remote-sensing measurements and model simulations. The diffrence in the migration coefficients between both reaches depends on the diffrence in bank height rather than the geotechnical properties of floodplain sediments. Possible eroded floodplain areas and accreted floodplain

The Breakdown: Hillslope Sources of Channel Blocks in Bedrock Landscapes

Science.gov (United States)

Selander, B.; Anderson, S. P.; Rossi, M.

2017-12-01

Block delivery from hillslopes is a poorly understood process that influences bedrock channel incision rates and shapes steep terrain. Previous studies demonstrate that hillslope sediment delivery rate and grain size increases with channel downcutting rate or fracture density (Attal et al., 2015, ESurf). However, blocks that exceed the competence of the channel can inhibit incision. In Boulder Creek, a bedrock channel in the Colorado Front Range, large boulders (>1 m diameter) are most numerous in the steepest channel reaches; their distribution seems to reflect autogenic channel-hillslope feedback between incision rate and block delivery (Shobe et al., 2016, GRL). It is clear that the processes, rates of production, and delivery of large blocks from hillslopes into channels are critical to our understanding of steep terrain evolution. Fundamental questions are 1) whether block production or block delivery is rate limiting, 2) what mechanisms release blocks, and 3) how block production and transport affect slope morphology. As a first step, we map rock outcrops on the granodiorite hillslopes lining Boulder Creek within Boulder Canyon using a high resolution DEM. Our algorithm uses high ranges of curvature values in conjunction with slopes steeper than the angle of repose to quickly identify rock outcrops. We field verified mapped outcrop and sediment-mantled locations on hillslopes above and below the channel knickzone. We find a greater abundance of exposed rock outcrops on steeper hillslopes in Boulder Canyon. Additionally, we find that channel reaches with large in-channel blocks are located at the base of hillslopes with large areas of exposed bedrock, while reaches lacking large in-channel blocks tend to be at the base of predominately soil mantled and forested hillslopes. These observations support the model of block delivery and channel incision of Shobe et al. (2016, GRL). Moreover, these results highlight the conundrum of how rapid channel incision is

Ion channeling

International Nuclear Information System (INIS)

Erramli, H.; Blondiaux, G.

1994-01-01

Channeling phenomenon was predicted, many years ago, by stark. The first channeling experiments were performed in 1963 by Davies and his coworkers. Parallely Robinson and Oen have investigated this process by simulating trajectories of ions in monocrystals. This technique has been combined with many methods like Rutherford Backscattering Spectrometry (R.B.S.), Particles Induced X-rays Emission (P.I.X.E) and online Nuclear Reaction (N.R.A.) to localize trace elements in the crystal or to determine crystalline quality. To use channeling for material characterization we need data about the stopping power of the incident particle in the channeled direction. The ratios of channeled to random stopping powers of silicon for irradiation in the direction have been investigated and compared to the available theoretical results. We describe few applications of ion channeling in the field of materials characterization. Special attention is given to ion channeling combined with Charged Particle Activation Analysis (C.P.A.A.) for studying the behaviour of oxygen atoms in Czochralski silicon lattices under the influence of internal gettering and in different gaseous atmospheres. Association between ion channeling and C.P.A.A was also utilised for studying the influence of the growing conditions on concentration and position of carbon atoms at trace levels in the MOVPE Ga sub (1-x) Al sub x lattice. 6 figs., 1 tab., 32 refs. (author)

The donut and dynamic polarization effects in proton channeling through carbon nanotubes

DEFF Research Database (Denmark)

Borka, D.; Mowbray, Duncan; Miskovic, Z.L.

2010-01-01

We investigate the angular and spatial distributions of protons with an energy of 0.223 MeV after channeling them through an (11, 9) single-wall carbon nanotube of 0.2 mu m length. The proton incident angle is varied between 0 and 10 mrad, being close to the critical angle for channeling. We show...... that, as the proton incident angle increases and approaches the critical angle for channeling, a ring-like structure is developed in the angular distribution-the donut effect. We demonstrate that it is the rainbow effect. If the proton incident angle is between zero and half of the critical angle...... for channeling, the image force affects considerably the number and positions of the maxima of the angular and spatial distributions. However, if the proton incident angle is close to the critical angle for channeling, its influence on the angular and spatial distributions is considerably decreased. We...

Channel characteristics and coordination in three-echelon dual-channel supply chain

Science.gov (United States)

Saha, Subrata

2016-02-01

We explore the impact of channel structure on the manufacturer, the distributer, the retailer and the entire supply chain by considering three different channel structures in radiance of with and without coordination. These structures include a traditional retail channel and two manufacturer direct channels with and without consistent pricing. By comparing the performance of the manufacturer, the distributer and the retailer, and the entire supply chain in three different supply chain structures, it is established analytically that, under some conditions, a dual channel can outperform a single retail channel; as a consequence, a coordination mechanism is developed that not only coordinates the dual channel but also outperforms the non-cooperative single retail channel. All the analytical results are further analysed through numerical examples.

Analysis of real-time mixture cytotoxicity data following repeated exposure using BK/TD models.

Science.gov (United States)

Teng, S; Tebby, C; Barcellini-Couget, S; De Sousa, G; Brochot, C; Rahmani, R; Pery, A R R

2016-08-15

Cosmetic products generally consist of multiple ingredients. Thus, cosmetic risk assessment has to deal with mixture toxicity on a long-term scale which means it has to be assessed in the context of repeated exposure. Given that animal testing has been banned for cosmetics risk assessment, in vitro assays allowing long-term repeated exposure and adapted for in vitro - in vivo extrapolation need to be developed. However, most in vitro tests only assess short-term effects and consider static endpoints which hinder extrapolation to realistic human exposure scenarios where concentration in target organs is varies over time. Thanks to impedance metrics, real-time cell viability monitoring for repeated exposure has become possible. We recently constructed biokinetic/toxicodynamic models (BK/TD) to analyze such data (Teng et al., 2015) for three hepatotoxic cosmetic ingredients: coumarin, isoeugenol and benzophenone-2. In the present study, we aim to apply these models to analyze the dynamics of mixture impedance data using the concepts of concentration addition and independent action. Metabolic interactions between the mixture components were investigated, characterized and implemented in the models, as they impacted the actual cellular exposure. Indeed, cellular metabolism following mixture exposure induced a quick disappearance of the compounds from the exposure system. We showed that isoeugenol substantially decreased the metabolism of benzophenone-2, reducing the disappearance of this compound and enhancing its in vitro toxicity. Apart from this metabolic interaction, no mixtures showed any interaction, and all binary mixtures were successfully modeled by at least one model based on exposure to the individual compounds. Copyright © 2016 Elsevier Inc. All rights reserved.

Computer simulations of channel meandering and the formation of point bars: Linking channel dynamics to the preserved stratigraphy

Science.gov (United States)

Sun, T.; Covault, J. A.; Pyrcz, M.; Sullivan, M.

2012-12-01

a,b) is used to investigate the formation and preservation of point bars with meandering rivers. Rather than consisting of a single set of concentric scroll bar like feature as one would expect from the pattern of meandering channels, observations of point bar deposits in map view reveal the previously mentioned complexity in their internal organization. A preserved point bar deposit is often found to be composed of multiple sets of remnant scroll bar like features, each with different orientations. Each set is bounded by the unconformity resulting from one set of the scroll bar like feature truncated by the other set. This study links the channel dynamics to the preserved point bar architectures, and delineates the key controls that affect the point bar internal organization.

Modeling of Doppler frequency shift in multipath radio channels

Directory of Open Access Journals (Sweden)

Penzin M.S.

2016-06-01

Full Text Available We discuss the modeling of propagation of a quasi-monochromatic radio signal, represented by a coherent pulse sequence, in a non-stationary multipath radio channel. In such a channel, signal propagation results in the observed frequency shift for each ray (Doppler effect. The modeling is based on the assumption that during propagation of a single pulse a channel can be considered stationary. A phase variation in the channel transfer function is shown to cause the observed frequency shift in the received signal. Thus, instead of measuring the Doppler frequency shift, we can measure the rate of variation in the mean phase of one pulse relative to another. The modeling is carried out within the framework of the method of normal waves. The method enables us to model the dynamics of the electromagnetic field at a given point with the required accuracy. The modeling reveals that a local change in ionospheric conditions more severely affects the rays whose reflection region is in the area where the changes occur.

Sculpting ion channel functional expression with engineered ubiquitin ligases

Science.gov (United States)

Kanner, Scott A; Morgenstern, Travis

2017-01-01

The functional repertoire of surface ion channels is sustained by dynamic processes of trafficking, sorting, and degradation. Dysregulation of these processes underlies diverse ion channelopathies including cardiac arrhythmias and cystic fibrosis. Ubiquitination powerfully regulates multiple steps in the channel lifecycle, yet basic mechanistic understanding is confounded by promiscuity among E3 ligase/substrate interactions and ubiquitin code complexity. Here we targeted the catalytic domain of E3 ligase, CHIP, to YFP-tagged KCNQ1 ± KCNE1 subunits with a GFP-nanobody to selectively manipulate this channel complex in heterologous cells and adult rat cardiomyocytes. Engineered CHIP enhanced KCNQ1 ubiquitination, eliminated KCNQ1 surface-density, and abolished reconstituted K+ currents without affecting protein expression. A chemo-genetic variation enabling chemical control of ubiquitination revealed KCNQ1 surface-density declined with a ~ 3.5 hr t1/2 by impaired forward trafficking. The results illustrate utility of engineered E3 ligases to elucidate mechanisms underlying ubiquitin regulation of membrane proteins, and to achieve effective post-translational functional knockdown of ion channels. PMID:29256394

Channeling in helium ion microscopy: Mapping of crystal orientation

Directory of Open Access Journals (Sweden)

Vasilisa Veligura

2012-07-01

Full Text Available Background: The unique surface sensitivity and the high resolution that can be achieved with helium ion microscopy make it a competitive technique for modern materials characterization. As in other techniques that make use of a charged particle beam, channeling through the crystal structure of the bulk of the material can occur.Results: Here, we demonstrate how this bulk phenomenon affects secondary electron images that predominantly contain surface information. In addition, we will show how it can be used to obtain crystallographic information. We will discuss the origin of channeling contrast in secondary electron images, illustrate this with experiments, and develop a simple geometric model to predict channeling maxima.Conclusion: Channeling plays an important role in helium ion microscopy and has to be taken into account when trying to achieve maximum image quality in backscattered helium images as well as secondary electron images. Secondary electron images can be used to extract crystallographic information from bulk samples as well as from thin surface layers, in a straightforward manner.

Inhibition of HERG potassium channels by celecoxib and its mechanism.

Directory of Open Access Journals (Sweden)

Roman V Frolov

Full Text Available Celecoxib (Celebrex, a widely prescribed selective inhibitor of cyclooxygenase-2, can modulate ion channels independently of cyclooxygenase inhibition. Clinically relevant concentrations of celecoxib can affect ionic currents and alter functioning of neurons and myocytes. In particular, inhibition of Kv2.1 channels by celecoxib leads to arrhythmic beating of Drosophila heart and of rat heart cells in culture. However, the spectrum of ion channels involved in human cardiac excitability differs from that in animal models, including mammalian models, making it difficult to evaluate the relevance of these observations to humans. Our aim was to examine the effects of celecoxib on hERG and other human channels critically involved in regulating human cardiac rhythm, and to explore the mechanisms of any observed effect on the hERG channels.Celecoxib inhibited the hERG, SCN5A, KCNQ1 and KCNQ1/MinK channels expressed in HEK-293 cells with IC(50s of 6.0 µM, 7.5 µM, 3.5 µM and 3.7 µM respectively, and the KCND3/KChiP2 channels expressed in CHO cells with an IC(50 of 10.6 µM. Analysis of celecoxib's effects on hERG channels suggested gating modification as the mechanism of drug action.The above channels play a significant role in drug-induced long QT syndrome (LQTS and short QT syndrome (SQTS. Regulatory guidelines require that all new drugs under development be tested for effects on the hERG channel prior to first administration in humans. Our observations raise the question of celecoxib's potential to induce cardiac arrhythmias or other channel related adverse effects, and make a case for examining such possibilities.

Effect of channel size on sweet potato storage root enlargement in the Tuskegee University hydroponic nutrient film system

Science.gov (United States)

Morris, Carlton E.; Martinez, Edwin; Bonsi, C. K.; Mortley, Desmond G.; Hill, Walter A.; Ogbuehi, Cyriacus R.; Loretan, Phil A.

1989-01-01

The potential of the sweet potato as a food source for future long term manned space missions is being evaluated for NASA's Controlled Ecological Life Support Systems (CELSS) program. Sweet potatoes have been successfully grown in a specially designed Tuskegee University nutrient film technique (TU NFT) system. This hydroponic system yielded storage roots as high as 1790 g/plant fresh weight. In order to determine the effect of channel size on the yield of sweet potatoes, the width and depth of the growing channels were varied in two separate experiments. Widths were studied using the rectangular TU NFT channels with widths of 15 cm (6 in), 30 cm (12 in) and 45 cm (18 in). Channel depths of 5 cm (2 in), 10 cm (4 in), and 15 cm (6 in) were studied using a standard NASA fan shaped Biomass Production Chamber (BPC) channel. A comparison of preliminary results indicated that, except for storage root number, the growth and yield of sweet potatoes were not affected by channel width. Storage root yield was affected by channel depth although storage root number and foliage growth were not. Both experiments are being repeated.

Analysing Gas-Liquid Flow in PEM Electrolyser Micro-Channels (Poster)

DEFF Research Database (Denmark)

Lafmejani, Saeed Sadeghi; Olesen, Anders Christian; Kær, Søren Knudsen

One means of increasing the hydrogen yield to cost ratio of a PEM water electrolyser, is to increase the operating current density. However, at high current densities (higher than 1 A/cm2), management of heat and mass transfer in the anode current collector and channel becomes crucial and can lead...... to hot spots. Management of heat and fluid flow through the micro-channels play a great role in the capability of PEM water electrolysis when working at high current densities. Despite, many studies have been done on gas-liquid flows; still there is a lack of research on gas-liquid flows in micro......-sized channels (hydraulic diameter of 1 mm) of PEM water electrolysis. Precisely controlling all the parameters that affect the gas-liquid flow in a PEM water electrolysis cell is quite challenging, hence a simplified setup is constructed consisting of only a transparent channel with a sheet of titanium felt...

Analytical characterization of three cathinone derivatives, 4-MPD, 4F-PHP and bk-EPDP, purchased as bulk powder from online vendors.

Science.gov (United States)

Apirakkan, Orapan; Frinculescu, Anca; Shine, Trevor; Parkin, Mark C; Cilibrizzi, Agostino; Frascione, Nunzianda; Abbate, Vincenzo

2018-02-01

Novel emerging drugs of abuse, also referred as new psychoactive substances, constitute an ever-changing mixture of chemical compounds designed to circumvent legislative controls by means of chemical modifications of previously banned recreational drugs. One such class, synthetic cathinones, namely β-keto derivatives of amphetamines, has been largely abused over the past decade. A number of new synthetic cathinones are detected each year, either in bulk powders/crystals or in biological matrices. It is therefore important to continuously monitor the supply of new synthetic derivatives and promptly report them. By using complementary analytical techniques (i.e. one- and two-dimensional NMR, FT-IR, GC-MS, HRMS and HPLC-UV), this study investigates the detection, identification and full characterization of 1-(4-methylphenyl)-2-(methylamino)pentanone (4-methylpentedrone, 4-MPD), 1-(4-fluorophenyl)-2-(pyrrolidin-1-yl)hexanone (4F-PHP) and 1-(1,3-benzodioxol-5-yl)-2-(ethylamino)-1-pentanone (bk-EPDP), three emerging cathinone derivatives. Copyright © 2017 John Wiley & Sons, Ltd.

‘Sleepy’ inward rectifier channels in guinea-pig cardiomyocytes are activated only during strong hyperpolarization

Science.gov (United States)

Liu, Gong Xin; Daut, Jürgen

2002-01-01

K+ channels of isolated guinea-pig cardiomyocytes were studied using the patch-clamp technique. At transmembrane potentials between −120 and −220 mV we observed inward currents through an apparently novel channel. The novel channel was strongly rectifying, no outward currents could be recorded. Between −200 and −160 mV it had a slope conductance of 42.8 ± 3.0 pS (s.d.; n = 96). The open probability (Po) showed a sigmoid voltage dependence and reached a maximum of 0.93 at −200 mV, half-maximal activation was approximately −150 mV. The voltage dependence of Po was not affected by application of 50 μm isoproterenol. The open-time distribution could be described by a single exponential function, the mean open time ranged between 73.5 ms at −220 mV and 1.4 ms at −160 mV. At least two exponential components were required to fit the closed time distribution. Experiments with different external Na+, K+ and Cl− concentrations suggested that the novel channel is K+ selective. Extracellular Ba2+ ions gave rise to a voltage-dependent reduction in Po by inducing long closed states; Cs+ markedly reduced mean open time at −200 mV. In cell-attached recordings the novel channel frequently converted to a classical inward rectifier channel, and vice versa. This conversion was not voltage dependent. After excision of the patch, the novel channel always converted to a classical inward rectifier channel within 0–3 min. This conversion was not affected by intracellular Mg2+, phosphatidylinositol (4,5)-bisphosphate or spermine. Taken together, our findings suggest that the novel K+ channel represents a different ‘mode’ of the classical inward rectifier channel in which opening occurs only at very negative potentials. PMID:11897847

ZnO-channel thin-film transistors: Channel mobility

International Nuclear Information System (INIS)

Hoffman, R.L.

2004-01-01

ZnO-channel thin-film transistor (TFT) test structures are fabricated using a bottom-gate structure on thermally oxidized Si; ZnO is deposited via RF sputtering from an oxide target, with an unheated substrate. Electrical characteristics are evaluated, with particular attention given to the extraction and interpretation of transistor channel mobility. ZnO-channel TFT mobility exhibits severe deviation from that assumed by ideal TFT models; mobility extraction methodology must accordingly be recast so as to provide useful insight into device operation. Two mobility metrics, μ avg and μ inc , are developed and proposed as relevant tools in the characterization of nonideal TFTs. These mobility metrics are employed to characterize the ZnO-channel TFTs reported herein; values for μ inc as high as 25 cm2/V s are measured, comprising a substantial increase in ZnO-channel TFT mobility as compared to previously reported performance for such devices

Disguising quantum channels by mixing and channel distance trade-off

International Nuclear Information System (INIS)

Fung, Chi-Hang Fred; Chau, H F

2014-01-01

We consider the reverse problem of the distinguishability of two quantum channels, which we call the disguising problem. Given two quantum channels, the goal here is to make the two channels identical by mixing with some other channels with minimal mixing probabilities. This quantifies how much one channel can disguise as the other. In addition, the possibility to trade-off between the two mixing probabilities allows one channel to be more preserved (less mixed) at the expense of the other. We derive lower- and upper-bounds of the trade-off curve and apply them to a few example channels. Optimal trade-off is obtained in one example. We relate the disguising problem and the distinguishability problem by showing that the former can lower and upper bound the diamond norm. We also show that the disguising problem gives an upper-bound on the key generation rate in quantum cryptography. (paper)

Computational study of hippocampal-septal theta rhythm changes due to β-amyloid-altered ionic channels.

Directory of Open Access Journals (Sweden)

Xin Zou

Full Text Available Electroencephagraphy (EEG of many dementia patients has been characterized by an increase in low frequency field potential oscillations. One of the characteristics of early stage Alzheimer's disease (AD is an increase in theta band power (4-7 Hz. However, the mechanism(s underlying the changes in theta oscillations are still unclear. To address this issue, we investigate the theta band power changes associated with β-Amyloid (Aβ peptide (one of the main markers of AD using a computational model, and by mediating the toxicity of hippocampal pyramidal neurons. We use an established biophysical hippocampal CA1-medial septum network model to evaluate four ionic channels in pyramidal neurons, which were demonstrated to be affected by Aβ. They are the L-type Ca²⁺ channel, delayed rectifying K⁺ channel, A-type fast-inactivating K⁺ channel and large-conductance Ca²⁺-activated K⁺ channel. Our simulation results demonstrate that only the Aβ inhibited A-type fast-inactivating K⁺ channel can induce an increase in hippocampo-septal theta band power, while the other channels do not affect theta rhythm. We further deduce that this increased theta band power is due to enhanced synchrony of the pyramidal neurons. Our research may elucidate potential biomarkers and therapeutics for AD. Further investigation will be helpful for better understanding of AD-induced theta rhythm abnormalities and associated cognitive deficits.

Spatial Diversity in Composition and Structure of Nekton in Ngenep Spring and its Channels, Karangploso - Malang

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Lia Hapsari

2014-04-01

Full Text Available Water springs and its channel degradation due to anthropogenic pollution may alter the community structure of aquatic organisms. Water spring degradation tehrefore affect the quality of water as tourism resources. This study aims to investigate the changes in community structure of nekton  and determine the relationships between water quality characteristics to the diversity of nekton.  The field survey was set up in Ngenep spring and its channels. Results showed that nekton species found in Ngenep spring and its channels consists of 4 classes, 4 orders, 6 families, and 7 species with total 627 nekton samples. It is comprises of fishes, shrimp, frogs and waterstriders. Nekton diversity index (H’ in the spring and irrigation channel were in moderate level (1channel was low (0,67. Evenness values of nekton ranged 0,24 – 0,53, whereas dominancy index of nekton ranged 0,41 – 0,74. Evenness value in settlement channel was very low (0, 24 with high dominancy index (0, 74; it indicates that nekton species were spread not evenly in the channel, it dominated by fish Rasbora sp. (highest IVI, 184,95. There were spatial variations of  physico-chemical water qualitiy parameters in Ngenep springs and its channels (temperature, stream velocity, turbidity, conductivity, pH, DO, BOD and TOM which affected to nekton diversity and community structure. Clustering analyses and PCA result shows correlation pattern between nekton distribution with physico-chemical water quality parameters. However, physico-chemical water quality parameters in Ngenep springs and its channel were still optimum as nekton habitat (PP No. 82/ 2001. Keywords: Community structure, Nekton, Spatial diversity, Spring, Water channel

A Study on the Inter-Channel Communication Independence for SMART I and C System

International Nuclear Information System (INIS)

Jeong, Kwang Il; Keum, Jong Yong; Park, Je Yun

2009-01-01

In nuclear power plants (NPP) the greatest concern is to ensure the safety goal, so it is designed with a protection conception using diversity and redundancy methods. Usually the I and C (Instrumentation and Control) system of NPP is composed of four channels to enhance the performance of the safety functions and performs the monitoring and control functions. In these redundant structures, the most important thing is that a malfunction in one channel cannot affect the safety functions of the redundant channels. The communication network of the digital I and C system is playing a role in intra-channel communication and inter-channel communication in four-channel I and C structure. Recent licensee experience indicates that companies planning to use the interchannel communication must perform a detailed analysis of all credible failure modes. In this paper, we propose some evaluation criteria to evaluate the inter-channel communication independence of SMART I and C system and preliminary design for mitigating methodologies of each credible failure

Rendimento da alface e atributos químicos de um Latossolo em função da aplicação de biofertilizantes de rochas com fósforo e potássio Lettuce yield and chemical attributes of an Oxisol by application of biofertilizers from phosphate and potash rocks

Directory of Open Access Journals (Sweden)

Rita de Cássia Matias de Lima

2007-06-01

crops the biofertilizers BP, BK, and chemical fertilizers SFS and KCl were effective on lettuce yield. In the first crop the best results were obtained with the treatments SFS700 BK90, SFS700 BK60, and in the consecutive crop applying the treatments BP700 BK90, SFS700 BK60 and SFS700 BK90. In the two crops the positive response of the PK biofertilizers and PK mineral fertilizers was evident. Residual effect was observed when the treatment BP1050 BK90 was applied. Soil pH was not affected by application of PK biofertilizers plus worm-compound, increasing available P and K, especially for available P in the consecutive crop. The PK rock biofertilizers, plus worm-compound, may be applied as an alternative to PK mineral soluble fertilizers.

Compound Wiretap Channels

Directory of Open Access Journals (Sweden)

Kramer Gerhard

2009-01-01

Full Text Available Abstract This paper considers the compound wiretap channel, which generalizes Wyner's wiretap model to allow the channels to the (legitimate receiver and to the eavesdropper to take a number of possible states. No matter which states occur, the transmitter guarantees that the receiver decodes its message and that the eavesdropper is kept in full ignorance about the message. The compound wiretap channel can also be viewed as a multicast channel with multiple eavesdroppers, in which the transmitter sends information to all receivers and keeps the information secret from all eavesdroppers. For the discrete memoryless channel, lower and upper bounds on the secrecy capacity are derived. The secrecy capacity is established for the degraded channel and the semideterministic channel with one receiver. The parallel Gaussian channel is further studied. The secrecy capacity and the secrecy degree of freedom ( are derived for the degraded case with one receiver. Schemes to achieve the for the case with two receivers and two eavesdroppers are constructed to demonstrate the necessity of a prefix channel in encoder design. Finally, the multi-antenna (i.e., MIMO compound wiretap channel is studied. The secrecy capacity is established for the degraded case and an achievable is given for the general case.

ATP Release Channels

Directory of Open Access Journals (Sweden)

Akiyuki Taruno

2018-03-01

Full Text Available Adenosine triphosphate (ATP has been well established as an important extracellular ligand of autocrine signaling, intercellular communication, and neurotransmission with numerous physiological and pathophysiological roles. In addition to the classical exocytosis, non-vesicular mechanisms of cellular ATP release have been demonstrated in many cell types. Although large and negatively charged ATP molecules cannot diffuse across the lipid bilayer of the plasma membrane, conductive ATP release from the cytosol into the extracellular space is possible through ATP-permeable channels. Such channels must possess two minimum qualifications for ATP permeation: anion permeability and a large ion-conducting pore. Currently, five groups of channels are acknowledged as ATP-release channels: connexin hemichannels, pannexin 1, calcium homeostasis modulator 1 (CALHM1, volume-regulated anion channels (VRACs, also known as volume-sensitive outwardly rectifying (VSOR anion channels, and maxi-anion channels (MACs. Recently, major breakthroughs have been made in the field by molecular identification of CALHM1 as the action potential-dependent ATP-release channel in taste bud cells, LRRC8s as components of VRACs, and SLCO2A1 as a core subunit of MACs. Here, the function and physiological roles of these five groups of ATP-release channels are summarized, along with a discussion on the future implications of understanding these channels.

Milrinone relaxes pulmonary veins in guinea pigs and humans.

Directory of Open Access Journals (Sweden)

Annette D Rieg

Full Text Available INTRODUCTION: The phosphodiesterase-III inhibitor milrinone improves ventricular contractility, relaxes pulmonary arteries and reduces right ventricular afterload. Thus, it is used to treat heart failure and pulmonary hypertension (PH. However, its action on pulmonary veins (PVs is not defined, although particularly PH due to left heart disease primarily affects the pulmonary venous bed. We examined milrinone-induced relaxation in PVs from guinea pigs (GPs and humans. MATERIAL AND METHODS: Precision-cut lung slices (PCLS were prepared from GPs or from patients undergoing lobectomy. Milrinone-induced relaxation was studied by videomicroscopy in naïve PVs and in PVs pre-constricted with the ETA-receptor agonist BP0104. Baseline luminal area was defined as 100%. Intracellular cAMP was measured by ELISA and milrinone-induced changes of segmental vascular resistances were studied in the GP isolated perfused lung (IPL. RESULTS: In the IPL (GP, milrinone (10 µM lowered the postcapillary resistance of pre-constricted vessels. In PCLS (GP, milrinone relaxed naïve and pre-constricted PVs (120% and this relaxation was attenuated by inhibition of protein kinase G (KT 5823, adenyl cyclase (SQ 22536 and protein kinase A (KT 5720, but not by inhibition of NO-synthesis (L-NAME. In addition, milrinone-induced relaxation was dependent on the activation of K ATP-, BK Ca (2+- and Kv-channels. Human PVs also relaxed to milrinone (121%, however only if pre-constricted. DISCUSSION: Milrinone relaxes PVs from GPs and humans. In GPs, milrinone-induced relaxation is based on K ATP-, BK Ca (2+- and Kv-channel-activation and on cAMP/PKA/PKG. The relaxant properties of milrinone on PVs lead to reduced postcapillary resistance and hydrostatic pressures. Hence they alleviate pulmonary edema and suggest beneficial effects of milrinone in PH due to left heart disease.

Milrinone relaxes pulmonary veins in guinea pigs and humans.

Science.gov (United States)

Rieg, Annette D; Suleiman, Said; Perez-Bouza, Alberto; Braunschweig, Till; Spillner, Jan W; Schröder, Thomas; Verjans, Eva; Schälte, Gereon; Rossaint, Rolf; Uhlig, Stefan; Martin, Christian

2014-01-01

The phosphodiesterase-III inhibitor milrinone improves ventricular contractility, relaxes pulmonary arteries and reduces right ventricular afterload. Thus, it is used to treat heart failure and pulmonary hypertension (PH). However, its action on pulmonary veins (PVs) is not defined, although particularly PH due to left heart disease primarily affects the pulmonary venous bed. We examined milrinone-induced relaxation in PVs from guinea pigs (GPs) and humans. Precision-cut lung slices (PCLS) were prepared from GPs or from patients undergoing lobectomy. Milrinone-induced relaxation was studied by videomicroscopy in naïve PVs and in PVs pre-constricted with the ETA-receptor agonist BP0104. Baseline luminal area was defined as 100%. Intracellular cAMP was measured by ELISA and milrinone-induced changes of segmental vascular resistances were studied in the GP isolated perfused lung (IPL). In the IPL (GP), milrinone (10 µM) lowered the postcapillary resistance of pre-constricted vessels. In PCLS (GP), milrinone relaxed naïve and pre-constricted PVs (120%) and this relaxation was attenuated by inhibition of protein kinase G (KT 5823), adenyl cyclase (SQ 22536) and protein kinase A (KT 5720), but not by inhibition of NO-synthesis (L-NAME). In addition, milrinone-induced relaxation was dependent on the activation of K ATP-, BK Ca (2+)- and Kv-channels. Human PVs also relaxed to milrinone (121%), however only if pre-constricted. Milrinone relaxes PVs from GPs and humans. In GPs, milrinone-induced relaxation is based on K ATP-, BK Ca (2+)- and Kv-channel-activation and on cAMP/PKA/PKG. The relaxant properties of milrinone on PVs lead to reduced postcapillary resistance and hydrostatic pressures. Hence they alleviate pulmonary edema and suggest beneficial effects of milrinone in PH due to left heart disease.

The Effect of Extending the Length of the Coupling Coils in a Muon Ionization Cooling Channel

International Nuclear Information System (INIS)

Green, Michael A.

2007-01-01

RF cavities are used to re-accelerate muons that have been cooled by absorbers that are in low beta regions of a muon ionization cooling channel. A superconducting coupling magnet (or magnets) are around or among the RF cavities of a muon ionization-cooling channel. The field from the magnet guides the muons so that they are kept within the iris of the RF cavities that are used to accelerate the muons. This report compares the use of a single short coupling magnet with an extended coupling magnet that has one or more superconducting coils as part of a muon-cooling channel of the same design as the muon ionization cooling experiment (MICE). Whether the superconducting magnet is short and thick or long and this affects the magnet stored energy and the peak field in the winding. The magnetic field distribution also affects is the muon beam optics in the cooling cell of a muon cooling channel

Spark Channels

Energy Technology Data Exchange (ETDEWEB)

Haydon, S. C. [Department of Physics, University of New England, Armidale, NSW (Australia)

1968-04-15

A brief summary is given of the principal methods used for initiating spark channels and the various highly time-resolved techniques developed recently for studies with nanosecond resolution. The importance of the percentage overvoltage in determining the early history and subsequent development of the various phases of the growth of the spark channel is discussed. An account is then given of the recent photographic, oscillographic and spectroscopic investigations of spark channels initiated by co-axial cable discharges of spark gaps at low [{approx} 1%] overvoltages. The phenomena observed in the development of the immediate post-breakdown phase, the diffuse glow structure, the growth of the luminous filament and the final formation of the spark channel in hydrogen are described. A brief account is also given of the salient features emerging from corresponding studies of highly overvolted spark gaps in which the spark channel develops from single avalanche conditions. The essential differences between the two types of channel formation are summarized and possible explanations of the general features are indicated. (author)

Dual-Recycling Channel Decision in a Closed-Loop Supply Chain with Cost Disruptions

Directory of Open Access Journals (Sweden)

Yanting Huang

2017-11-01

Full Text Available This paper investigates cost disruptions of new and remanufactured products in a closed-loop supply chain where a manufacturer and a third-party collector recycle used products through online-recycling and offline-recycling channels, respectively. We use a Stackelberg game to acquire the equilibrium decisions of dual-recycling and single-recycling channels and analyze how cost disruptions affect the manufacturer’ production and collection strategies. We show that, cost disruption of new products produces a positive impact whilst the remanufacturing cost disruption has a negative impact on collection quantity of used products and negative cost disruptions of both new and remanufactured products could be profitable to the manufacturer. As for the manufacturer’s channel choice, the dual-recycling channel dominates single-recycling channels when new product cost faces positive disruption, because the manufacturer acts as both a buyer and a competitor to the collector and can determine an appropriate acquisition price and transfer price to coordinate the online-offline recycling channel. While if cost disruption of new products is negative, the manufacturer prefers the dual-recycling channel instead of single-recycling channels only if the remanufacturing cost faces large size of negative disruption.

Boundary vapor contentsin an annular channel

International Nuclear Information System (INIS)

Remizov, O.V.; Shurkin, N.G.; Podgornyj, K.K.; Gal'chenko, Eh.F.; Bukhteev, I.S.

1978-01-01

The work is aimed at the experimental investigation of the worsening of the heat transfer in an annular channel. The experiments have been carried out on the annular channel 32x28x3000 mm with the even distribution of the heat flux along the length at pressures of 6.9-19.6 MPa, flow rate of 350-1000 kg/m 2 s, and specific heat fluxes from 0.18 up to 0.6 MW/m 2 . Heating is external, oneside. Water monodistillate of the following composition has been used as a coolant: pH 9; dry residue - 0.8-1.2 mg/kg, oxygen -10-15 mg/kg. It is found out that the change character of the temperature field of the heating surface of the annular channel at the regime with the worsen of heat emission depends on the ratio of regime parameters. At pressures of 6.9-13.7 MPa and flow rate of 350-500 kg/m 2 s the channel wall temperature rises monotoneously, never reaching its maximum. With pressure rise > 13.7 MPa and mass velocity > 500 kg/m 2 s the temperature of the heat emitting surface reaches its maximum, and then slowly falls. At pressures of 6.9-11.8 MPa the boundary vapor content value within the whole range of mass velocities does not depend on the specific heat flux q. At pressures higher than 13.7 MPa and mass velocities of 350-1000 kg/m 2 s the boundary vapor content depends on q. The heating of the external or internal surface of the annular channel affects the value of the boundary vapor content within the whole range of regime parameters' change under investigation

Do we need to know more about the effects of hormones on lower urinary tract dysfunction? ICI-RS 2014.

Science.gov (United States)

Hanna-Mitchell, Ann T; Robinson, Dudley; Cardozo, Linda; Everaert, Karel; Petkov, Georgi V

2016-02-01

This review article reflects the presentations and subsequent discussions during a think tank at the 5th International Consultation on Incontinence Research Society's annual meeting, held in Bristol, UK (September 22-24, 2014). It reviews the current state of knowledge on the role of hormones in lower urinary tract dysfunction (LUTD) and overactive bladder (OAB) and in particular: highlights some specific basic research findings from discussion participants; reviews future research topics; and discusses potential new therapeutic opportunities for LUTD and OAB. The role of the large conductance voltage- and Ca(2+) -activated K(+) (BK) channels, as novel therapeutic targets for OAB was discussed, in particular as recent studies on human detrusor smooth muscle suggest that estradiol exerts a direct non-genomic activation of the BK channels. Recent developments on the roles of sex hormones on diuresis, as well as the roles of melatonin and vitamin D on LUTD were also discussed. It was concluded that further basic science and translational studies are needed to better understand hormonal regulatory mechanisms of the lower urinary tract and the implications for novel treatment options for LUTD and OAB. © 2016 Wiley Periodicals, Inc.

Spectroelectrochemical sensing: planar waveguides

Energy Technology Data Exchange (ETDEWEB)

Ross, Susan E.; Shi Yining; Seliskar, Carl J.; Heineman, William R

2003-09-30

The spectroelectrochemical sensor combines in a single device electrochemistry, spectroscopy, and selective partitioning into a film, giving improved selectivity for applications that involve complex samples. Sensing is based on the change in optical signal that accompanies electrochemical modulation of analyte that has partitioned into the film. Two classes of optical quality chemically-selective films based on two different host materials, namely, sol-gel processed silica and cross-linked poly(vinyl alcohol) have been developed. Films are typically 400-700 nm thick. Three types of sensor platforms are discussed: a multiple internal reflection (MIR) optic consisting of a bilayer of an indium tin oxide (ITO) optically transparent electrode deposited on a 1-mm thick glass substrate, a planar waveguide in which a potassium ion-exchanged BK7 glass waveguide (5-9 {mu}m thick) was over-coated with a thin film of ITO, and a planar waveguide in which a potassium ion-exchanged BK7 glass waveguide channel was formed and a pair of electrodes deposited along side the channel. These sensors were evaluated with ferrocyanide and a selective film of PDMDAAC-SiO{sub 2}, where PDMDAAC=poly(dimethyl diallylammonium chloride)

Spectroelectrochemical sensing: planar waveguides

International Nuclear Information System (INIS)

Ross, Susan E.; Shi Yining; Seliskar, Carl J.; Heineman, William R.

2003-01-01

The spectroelectrochemical sensor combines in a single device electrochemistry, spectroscopy, and selective partitioning into a film, giving improved selectivity for applications that involve complex samples. Sensing is based on the change in optical signal that accompanies electrochemical modulation of analyte that has partitioned into the film. Two classes of optical quality chemically-selective films based on two different host materials, namely, sol-gel processed silica and cross-linked poly(vinyl alcohol) have been developed. Films are typically 400-700 nm thick. Three types of sensor platforms are discussed: a multiple internal reflection (MIR) optic consisting of a bilayer of an indium tin oxide (ITO) optically transparent electrode deposited on a 1-mm thick glass substrate, a planar waveguide in which a potassium ion-exchanged BK7 glass waveguide (5-9 μm thick) was over-coated with a thin film of ITO, and a planar waveguide in which a potassium ion-exchanged BK7 glass waveguide channel was formed and a pair of electrodes deposited along side the channel. These sensors were evaluated with ferrocyanide and a selective film of PDMDAAC-SiO 2 , where PDMDAAC=poly(dimethyl diallylammonium chloride)

Joint source/channel coding of scalable video over noisy channels

Energy Technology Data Exchange (ETDEWEB)

Cheung, G.; Zakhor, A. [Department of Electrical Engineering and Computer Sciences University of California Berkeley, California94720 (United States)

1997-01-01

We propose an optimal bit allocation strategy for a joint source/channel video codec over noisy channel when the channel state is assumed to be known. Our approach is to partition source and channel coding bits in such a way that the expected distortion is minimized. The particular source coding algorithm we use is rate scalable and is based on 3D subband coding with multi-rate quantization. We show that using this strategy, transmission of video over very noisy channels still renders acceptable visual quality, and outperforms schemes that use equal error protection only. The flexibility of the algorithm also permits the bit allocation to be selected optimally when the channel state is in the form of a probability distribution instead of a deterministic state. {copyright} {ital 1997 American Institute of Physics.}

Compound Wiretap Channels

Directory of Open Access Journals (Sweden)

Shlomo Shamai (Shitz

2009-01-01

Full Text Available This paper considers the compound wiretap channel, which generalizes Wyner's wiretap model to allow the channels to the (legitimate receiver and to the eavesdropper to take a number of possible states. No matter which states occur, the transmitter guarantees that the receiver decodes its message and that the eavesdropper is kept in full ignorance about the message. The compound wiretap channel can also be viewed as a multicast channel with multiple eavesdroppers, in which the transmitter sends information to all receivers and keeps the information secret from all eavesdroppers. For the discrete memoryless channel, lower and upper bounds on the secrecy capacity are derived. The secrecy capacity is established for the degraded channel and the semideterministic channel with one receiver. The parallel Gaussian channel is further studied. The secrecy capacity and the secrecy degree of freedom (s.d.o.f. are derived for the degraded case with one receiver. Schemes to achieve the s.d.o.f. for the case with two receivers and two eavesdroppers are constructed to demonstrate the necessity of a prefix channel in encoder design. Finally, the multi-antenna (i.e., MIMO compound wiretap channel is studied. The secrecy capacity is established for the degraded case and an achievable s.d.o.f. is given for the general case.

Quantification of shear stress in a meandering native topographic channel using a physical hydraulic model

Science.gov (United States)

Michael E. Ursic; Christopher I. Thornton; Amanda L. Cox; Steven R. Abt

2012-01-01

Fluvial systems respond to changes in boundary conditions in order to sustain the flow and sediment supplied to the system. Local channel responses are typically difficult to predict due to possible affects from upstream, downstream, or local boundary conditions that cause changes in channel or planform geometry. Changes to the system can threaten riverside...

Arachnoid granulation affected by subarachnoid hemorrhage

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R.P. Chopard

1993-11-01

Full Text Available The purpose of this study was to investigate using light microscopy the fibro-cellular components of arachnoid granulations affected by mild and severe subarachnoid hemorrage. The erythrocytes were in the channels delimitated by collagenous and elastic bundles and arachnoid cells, showing their tortuous and intercommunicating row from the pedicle to the fibrous capsule. The core portion of the pedicle and the center represented a principal route to the bulk outflow of cerebrospinal fluid and erythrocytes. In the severe hemorrhage, the fibrocellular components are desorganized, increasing the extracellular channels. We could see arachnoid granulations without erythrocytes, which cells showed big round nucleous suggesting their transformation into phagocytic cells.

Analysis of flow distribution instability in parallel thin rectangular multi-channel system

Energy Technology Data Exchange (ETDEWEB)

Xia, G.L. [School of Nuclear Science and Technology, Xi’an Jiaotong University, Xi’an City 710049 (China); Fundamental Science on Nuclear Safety and Simulation Technology Laboratory, Harbin Engineering University, Harbin City 150001 (China); Su, G.H., E-mail: ghsu@mail.xjtu.edu.cn [School of Nuclear Science and Technology, Xi’an Jiaotong University, Xi’an City 710049 (China); Peng, M.J. [Fundamental Science on Nuclear Safety and Simulation Technology Laboratory, Harbin Engineering University, Harbin City 150001 (China)

2016-08-15

Highlights: • Flow distribution instability in parallel thin rectangular multi-channel system is studied using RELAP5 codes. • Flow excursion may bring parallel heating channel into the density wave oscillations region. • Flow distribution instability is more likely to happen at low power/flow ratio conditions. • The increase of channel number will not affect the flow distribution instability boundary. • Asymmetry inlet throttling and heating will make system more unstable. - Abstract: The flow distribution instability in parallel thin rectangular multi-channel system has been researched in the present study. The research model of parallel channel system is established by using RELAP5/MOD3.4 codes. The transient process of flow distribution instability is studied at imposed inlet mass flow rate and imposed pressure drop conditions. The influence of heating power, mass flow rate, system pressure and channel number on flow distribution instability are analyzed. Furthermore, the flow distribution instability of parallel two-channel system under asymmetric inlet throttling and heating power is studied. The results show that, if multi-channel system operates at the negative slope region of channel ΔP–G curve, small disturbance in pressure drop will lead to flow redistribution between parallel channels. Flow excursion may bring the operating point of heating channel into the density-wave oscillations region, this will result in out-phase or in-phase flow oscillations. Flow distribution instability is more likely to happen at low power/flow ratio conditions, the stability of parallel channel system increases with system pressure, the channel number has a little effect on system stability, but the asymmetry inlet throttling or heating power will make the system more unstable.

Channel systems and lobe construction in the Mississippi Fan

Science.gov (United States)

Garrison, L. E.; Kenyon, Neil H.; Bouma, A.H.

1982-01-01

Morphological features on the Mississippi Fan in the eastern Gulf of Mexico were mapped using GLORIA II, a long-range side-scan sonar system. Prominent is a sinuous channel flanked by well-developed levees and occasional crevasse splays. The channel follows the axis and thickest part of the youngest fan lobe; seismic-reflection profiles offer evidence that its course has remained essentially constant throughout lobe development. Local modification and possible erosion of levees by currents indicates a present state of inactivity. Superficial sliding has affected part of the fan lobe, but does not appear to have been a factor in lobe construction. ?? 1982 A. M. Dowden, Inc.

AdE-1, a new inotropic Na(+) channel toxin from Aiptasia diaphana, is similar to, yet distinct from, known anemone Na(+) channel toxins.

Science.gov (United States)

Nesher, Nir; Shapira, Eli; Sher, Daniel; Moran, Yehu; Tsveyer, Liora; Turchetti-Maia, Ana Luiza; Horowitz, Michal; Hochner, Binyamin; Zlotkin, Eliahu

2013-04-01

Heart failure is one of the most prevalent causes of death in the western world. Sea anemone contains a myriad of short peptide neurotoxins affecting many pharmacological targets, several of which possess cardiotonic activity. In the present study we describe the isolation and characterization of AdE-1 (ion channel modifier), a novel cardiotonic peptide from the sea anemone Aiptasia diaphana, which differs from other cnidarian toxins. Although AdE-1 has the same cysteine residue arrangement as sea anemone type 1 and 2 Na(+) channel toxins, its sequence contains many substitutions in conserved and essential sites and its overall homology to other toxins identified to date is low (Anemonia viridis toxin II), AdE-1 markedly inhibits Na(+) current inactivation with no significant effect on current activation, suggesting a similar mechanism of action. However, its effects on twitch relaxation velocity, action potential amplitude and on the time to peak suggest that this novel toxin affects cardiomyocyte function via a more complex mechanism. Additionally, Av2's characteristic delayed and early after-depolarizations were not observed. Despite its structural differences, AdE-1 physiologic effectiveness is comparable with Av2 with a similar ED(50) value to blowfly larvae. This finding raises questions regarding the extent of the universality of structure-function in sea anemone Na(+) channel toxins.

3D numerical model of the spherical particle saltation in a channel with a rough fixed bed

Czech Academy of Sciences Publication Activity Database

Lukerchenko, Nikolay; Piatsevich, Siarhei; Chára, Zdeněk; Vlasák, Pavel

2009-01-01

Roč. 57, č. 2 (2009), s. 100-112 ISSN 0042-790X R&D Projects: GA ČR GA103/06/1487 Institutional research plan: CEZ:AV0Z20600510 Keywords : 3D Saltation Model * Bed-Load Transport * Particle-Bed Collision * Particle Rotation * Particle Lateral Dispersion Subject RIV: BK - Fluid Dynamics Impact factor: 1.000, year: 2009

KANDUNGAN ASAM AMINO, TAURIN, MINERAL MAKRO-MIKRO, DAN VITAMIN B12 UBUR-UBUR (Aurelia aurita SEGAR DAN KERING

Directory of Open Access Journals (Sweden)

- - Nurjanah

2014-06-01

Full Text Available Tujuan penelitian adalah menentukan komposisi gizi, asam amino, taurin, mineral makro dan mikro,dan vitamin B12 pada ubur-ubur (Aurelia aurita segar dan kering. Asam amino esensial pada ubur-uburyaitu arginina, leusina, valina, treonina, lisina, isoleusina, fenilalanina, metionina, dan histidina, sedangkanasam amino non esensial yaitu asam glutamat, glisina, asam aspartat, serina, alanina, dan tirosina. Asamamino esensial tertinggi segar dan kering adalah arginina sebesar 1,72% (bk dan 1,44% (bk dan terendahhistidina yaitu sebesar 0,19% (bk dan 0,13% (bk. Asam amino non esensial segar dan kering tertinggiadalah asam glutamat dan glisina yaitu sebesar 3,26% (bk dan 2,62% (bk dan terkecil tirosina sebesar0,38% (bk dan 0,41% (bk. Taurin segar sebesar 2,68% (bk dan kering sebesar 0,67% (bk. Mineral makrotertinggi segar dan kering adalah natrium yaitu 180.092,1 ppm (bk dan 111.209,4 ppm (bk, terkecil adalahkalsium yaitu 5.750,2 ppm (bk dan 11,1 ppm (bk. Mineral mikro tertinggi segar dan kering adalah iodium yaitu8.291,5 ppm (bk dan 1.800 ppm (bk dan yang terkecil adalah tembaga yaitu 1,1 ppm (bk dan 0,6 ppm (bk.Vitamin B12 segar adalah 396,6 μm/100 g (bk dan kering 63,5 μm/100 g (bk.Kata kunci: asam amino, mineral, taurin, ubur-ubur (Aurelia aurita, vitamin B12

Threshold and channel interaction in cochlear implant users: evaluation of the tripolar electrode configuration.

Science.gov (United States)

Bierer, Julie Arenberg

2007-03-01

The efficacy of cochlear implants is limited by spatial and temporal interactions among channels. This study explores the spatially restricted tripolar electrode configuration and compares it to bipolar and monopolar stimulation. Measures of threshold and channel interaction were obtained from nine subjects implanted with the Clarion HiFocus-I electrode array. Stimuli were biphasic pulses delivered at 1020 pulses/s. Threshold increased from monopolar to bipolar to tripolar stimulation and was most variable across channels with the tripolar configuration. Channel interaction, quantified by the shift in threshold between single- and two-channel stimulation, occurred for all three configurations but was largest for the monopolar and simultaneous conditions. The threshold shifts with simultaneous tripolar stimulation were slightly smaller than with bipolar and were not as strongly affected by the timing of the two channel stimulation as was monopolar. The subjects' performances on clinical speech tests were correlated with channel-to-channel variability in tripolar threshold, such that greater variability was related to poorer performance. The data suggest that tripolar channels with high thresholds may reveal cochlear regions of low neuron survival or poor electrode placement.

An Extension of the Burridge-Knopoff Model for Friction

Directory of Open Access Journals (Sweden)

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.

Flow rate-pressure drop relation for deformable shallow microfluidic channels

Science.gov (United States)

Christov, Ivan C.; Cognet, Vincent; Shidhore, Tanmay C.; Stone, Howard A.

2018-04-01

Laminar flow in devices fabricated from soft materials causes deformation of the passage geometry, which affects the flow rate--pressure drop relation. For a given pressure drop, in channels with narrow rectangular cross-section, the flow rate varies as the cube of the channel height, so deformation can produce significant quantitative effects, including nonlinear dependence on the pressure drop [{Gervais, T., El-Ali, J., G\\"unther, A. \\& Jensen, K.\\ F.}\\ 2006 Flow-induced deformation of shallow microfluidic channels.\\ \\textit{Lab Chip} \\textbf{6}, 500--507]. Gervais et. al. proposed a successful model of the deformation-induced change in the flow rate by heuristically coupling a Hookean elastic response with the lubrication approximation for Stokes flow. However, their model contains a fitting parameter that must be found for each channel shape by performing an experiment. We present a perturbation approach for the flow rate--pressure drop relation in a shallow deformable microchannel using the theory of isotropic quasi-static plate bending and the Stokes equations under a lubrication approximation (specifically, the ratio of the channel's height to its width and of the channel's height to its length are both assumed small). Our result contains no free parameters and confirms Gervais et. al.'s observation that the flow rate is a quartic polynomial of the pressure drop. The derived flow rate--pressure drop relation compares favorably with experimental measurements.

Dopamine negatively modulates the NCA ion channels in C. elegans.

Science.gov (United States)

Topalidou, Irini; Cooper, Kirsten; Pereira, Laura; Ailion, Michael

2017-10-01

The NALCN/NCA ion channel is a cation channel related to voltage-gated sodium and calcium channels. NALCN has been reported to be a sodium leak channel with a conserved role in establishing neuronal resting membrane potential, but its precise cellular role and regulation are unclear. The Caenorhabditis elegans orthologs of NALCN, NCA-1 and NCA-2, act in premotor interneurons to regulate motor circuit activity that sustains locomotion. Recently we found that NCA-1 and NCA-2 are activated by a signal transduction pathway acting downstream of the heterotrimeric G protein Gq and the small GTPase Rho. Through a forward genetic screen, here we identify the GPCR kinase GRK-2 as a new player affecting signaling through the Gq-Rho-NCA pathway. Using structure-function analysis, we find that the GPCR phosphorylation and membrane association domains of GRK-2 are required for its function. Genetic epistasis experiments suggest that GRK-2 acts on the D2-like dopamine receptor DOP-3 to inhibit Go signaling and positively modulate NCA-1 and NCA-2 activity. Through cell-specific rescuing experiments, we find that GRK-2 and DOP-3 act in premotor interneurons to modulate NCA channel function. Finally, we demonstrate that dopamine, through DOP-3, negatively regulates NCA activity. Thus, this study identifies a pathway by which dopamine modulates the activity of the NCA channels.

48Ca+249Bk fusion reaction leading to element Z = 117: long-lived α-decaying 270Db and discovery of 266Lr.

Science.gov (United States)

Khuyagbaatar, J; Yakushev, A; Düllmann, Ch E; Ackermann, D; Andersson, L-L; Asai, M; Block, M; Boll, R A; Brand, H; Cox, D M; Dasgupta, M; Derkx, X; Di Nitto, A; Eberhardt, K; Even, J; Evers, M; Fahlander, C; Forsberg, U; Gates, J M; Gharibyan, N; Golubev, P; Gregorich, K E; Hamilton, J H; Hartmann, W; Herzberg, R-D; Heßberger, F P; Hinde, D J; Hoffmann, J; Hollinger, R; Hübner, A; Jäger, E; Kindler, B; Kratz, J V; Krier, J; Kurz, N; Laatiaoui, M; Lahiri, S; Lang, R; Lommel, B; Maiti, M; Miernik, K; Minami, S; Mistry, A; Mokry, C; Nitsche, H; Omtvedt, J P; Pang, G K; Papadakis, P; Renisch, D; Roberto, J; Rudolph, D; Runke, J; Rykaczewski, K P; Sarmiento, L G; Schädel, M; Schausten, B; Semchenkov, A; Shaughnessy, D A; Steinegger, P; Steiner, J; Tereshatov, E E; Thörle-Pospiech, P; Tinschert, K; Torres De Heidenreich, T; Trautmann, N; Türler, A; Uusitalo, J; Ward, D E; Wegrzecki, M; Wiehl, N; Van Cleve, S M; Yakusheva, V

2014-05-02

The superheavy element with atomic number Z=117 was produced as an evaporation residue in the (48)Ca+(249)Bk fusion reaction at the gas-filled recoil separator TASCA at GSI Darmstadt, Germany. The radioactive decay of evaporation residues and their α-decay products was studied using a detection setup that allowed measuring decays of single atomic nuclei with half-lives between sub-μs and a few days. Two decay chains comprising seven α decays and a spontaneous fission each were identified and are assigned to the isotope (294)117 and its decay products. A hitherto unknown α-decay branch in (270)Db (Z = 105) was observed, which populated the new isotope (266)Lr (Z = 103). The identification of the long-lived (T(1/2) = 1.0(-0.4)(+1.9) h) α-emitter (270)Db marks an important step towards the observation of even more long-lived nuclei of superheavy elements located on an "island of stability."

Quantum Channels With Memory

International Nuclear Information System (INIS)

Rybar, T.

2012-01-01

Quantum memory channels represent a very general, yet simple and comprehensible model for causal processes. As such they have attracted considerable research interest, mostly aimed on their transfer capabilities and structure properties. Most notably it was shown that memory channels can be implemented via physically naturally motivated collision models. We also define the concept of repeatable channels and show that only unital channels can be implemented repeat ably with pure memory channels. In the special case of qubit channels we also show that every unital qubit channel has a repeatable implementation. We also briefly explore the possibilities of stroboscopical simulation of channels and show that all random unitary channels can be stroboscopically simulated. Particularly in qubit case, all indivisible qubit channels are also random unitary, hence for qubit all indivisible channels can be stroboscopically simulated. Memory channels also naturally capture the framework of correlated experiments. We develop methods to gather and interpret data obtained in such setting and in detail examine the two qubit case. We also show that for control unitary interactions the measured data will never contradict a simple unitary evolution. Thus no memory effects can be spotted then. (author)

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.

Mimicking multi-channel scattering with single-channel approaches

OpenAIRE

Grishkevich, Sergey; Schneider, Philipp-Immanuel; Vanne, Yulian V.; Saenz, Alejandro

2009-01-01

The collision of two atoms is an intrinsic multi-channel (MC) problem as becomes especially obvious in the presence of Feshbach resonances. Due to its complexity, however, single-channel (SC) approximations, which reproduce the long-range behavior of the open channel, are often applied in calculations. In this work the complete MC problem is solved numerically for the magnetic Feshbach resonances (MFRs) in collisions between generic ultracold 6Li and 87Rb atoms in the ground state and in the ...

Fine Channel Networks

Science.gov (United States)

1997-01-01

A color image of fine channel networks on Mars; north toward top. The scene shows heavily cratered highlands dissected by dendritic open channel networks that dissect steep slopes of impact crater walls. This image is a composite of Viking high-resolution images in black and white and low-resolution images in color. The image extends from latitude 9 degrees S. to 5 degrees S. and from longitude 312 degrees to 320 degrees; Mercator projection. The dendritic pattern of the fine channels and their location on steep slopes leads to the interpretation that these are runoff channels. The restriction of these types of channels to ancient highland rocks suggests that these channels are old and date from a time on Mars when conditions existed for precipitation to actively erode rocks. After the channels reach a low plain, they appear to end. Termination may have resulted from burial by younger deposits or perhaps the flows percolated into the surface materials and continued underground.

Inhibition of parathyroid hormone release by maitotoxin, a calcium channel activator

International Nuclear Information System (INIS)

Fitzpatrick, L.A.; Yasumoto, T.; Aurbach, G.D.

1989-01-01

Maitotoxin, a toxin derived from a marine dinoflagellate, is a potent activator of voltage-sensitive calcium channels. To further test the hypothesis that inhibition of PTH secretion by calcium is mediated via a calcium channel we studied the effect of maitotoxin on dispersed bovine parathyroid cells. Maitotoxin inhibited PTH release in a dose-dependent fashion, and inhibition was maximal at 1 ng/ml. Chelation of extracellular calcium by EGTA blocked the inhibition of PTH by maitotoxin. Maitotoxin enhanced the effects of the dihydropyridine calcium channel agonist (+)202-791 and increased the rate of radiocalcium uptake in parathyroid cells. Pertussis toxin, which ADP-ribosylates and inactivates a guanine nucleotide regulatory protein that interacts with calcium channels in the parathyroid cell, did not affect the inhibition of PTH secretion by maitotoxin. Maitotoxin, by its action on calcium channels allows entry of extracellular calcium and inhibits PTH release. Our results suggest that calcium channels are involved in the release of PTH. Inhibition of PTH release by maitotoxin is not sensitive to pertussis toxin, suggesting that maitotoxin may act distal to the site interacting with a guanine nucleotide regulatory protein, or maitotoxin could interact with other ions or second messengers to inhibit PTH release

Heteromeric Slick/Slack K+ channels show graded sensitivity to cell volume changes.

Science.gov (United States)

Tejada, Maria A; Hashem, Nadia; Calloe, Kirstine; Klaerke, Dan A

2017-01-01

Slick and Slack high-conductance K+ channels are found in the CNS, kidneys, pancreas, among other organs, where they play an important role in cell excitability as well as in ion transport processes. They are both activated by Na+ and Cl- but show a differential regulation by cell volume changes. Slick has been shown to be regulated by cell volume changes, whereas Slack is insensitive. α-subunits of these channels form homomeric as well as heteromeric channels. It is the aim of this work to explore whether the subunit composition of the Slick/Slack heteromeric channel affects the response to osmotic challenges. In order to provide with the adequate water permeability to the cell membrane of Xenopus laevis oocytes, mRNA of aquaporin 1 was co-expressed with homomeric or heteromeric Slick and Slack α-subunits. Oocytes were superfused with hypotonic or hypertonic buffers and changes in currents were measured by two-electrode voltage clamp. This work presents the first heteromeric K+ channel with a characteristic graded sensitivity to small and fast changes in cell volume. Our results show that the cell volume sensitivity of Slick/Slack heteromeric channels is dependent on the number of volume sensitive Slick α-subunits in the tetrameric channels, giving rise to graded cell volume sensitivity. Regulation of the subunit composition of a channel may constitute a novel mechanism to determine volume sensitivity of cells.

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

Science.gov (United States)

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

1993-06-01

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

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.

Volume Regulated Channels

DEFF Research Database (Denmark)

Klausen, Thomas Kjær

of volume perturbations evolution have developed system of channels and transporters to tightly control volume homeostasis. In the past decades evidence has been mounting, that the importance of these volume regulated channels and transporters are not restricted to the defense of cellular volume...... but are also essential for a number of physiological processes such as proliferation, controlled cell death, migration and endocrinology. The thesis have been focusing on two Channels, namely the swelling activated Cl- channel (ICl, swell) and the transient receptor potential Vanilloid (TRPV4) channel. I: Cl......- serves a multitude of functions in the mammalian cell, regulating the membrane potential (Em), cell volume, protein activity and the driving force for facilitated transporters giving Cl- and Cl- channels a major potential of regulating cellular function. These functions include control of the cell cycle...

Visualization experimental investigation on long stripe coherent structure in small-scale rectangular channel

International Nuclear Information System (INIS)

Su Jiqiang; Sun Zhongning; Fan Guangming; Wang Shiming

2013-01-01

The long stripe coherent structure of the turbulent boundary layer in a small- scale vertical rectangular channel was observed by using hydrogen bubble flow trace visualization technique. The statistical properties of the long stripe in the experimental channel boundary layer were compared with that in the smooth flat plate boundary layer. The pitch characteristics were explained by the formation mechanism of the long stripe. It was analyzed that how the change of y + affected the distribution of the long stripe. In addition, the frequency characteristics of the long stripe were also investigated, and the correlation of the long stripe frequency in such a flow channel was obtained. (authors)

Heat and mass transfer caused by a laminar channel flow equipped with a synthetic jet array

Czech Academy of Sciences Publication Activity Database

Trávníček, Zdeněk; Dančová, Petra; Kordík, Jozef; Vít, Tomáš; Pavelka, Miroslav

2011-01-01

Roč. 2, č. 4 (2011), 041006-041006 ISSN 1948-5085 R&D Projects: GA AV ČR(CZ) IAA200760801; GA ČR(CZ) GA101/09/1959 Institutional research plan: CEZ:AV0Z20760514 Keywords : synthetic jet * flow control * naphthalene sublimation Subject RIV: BK - Fluid Dynamics http://scitation.aip.org/getabs/servlet/GetabsServlet?prog=normal&id=JTSEBV000002000004041006000001&idtype=cvips&gifs=yes

Phylogenetic reconstruction and polymorphism analysis of BK virus VP2 gene isolated from renal transplant recipients in China.

Science.gov (United States)

Wang, Zhang-Yang; Hong, Wei-Long; Zhu, Zhe-Hui; Chen, Yun-Hao; Ye, Wen-LE; Chu, Guang-Yu; Li, Jia-Lin; Chen, Bi-Cheng; Xia, Peng

2015-11-01

BK polyomavirus (BKV) is important pathogen for kidney transplant recipients, as it is frequently re-activated, leading to nephropathy. The aim of this study was to investigate the phylogenetic reconstruction and polymorphism of the VP2 gene in BKV isolated from Chinese kidney transplant recipients. Phylogenetic analysis was carried out in the VP2 region from 135 BKV-positive samples and 28 reference strains retrieved from GenBank. The unweighted pair-group method with arithmetic mean (UPGMA) grouped all strains into subtypes, but failed to subdivide strains into subgroups. Among the plasma and urine samples, all plasma (23/23) and 82 urine samples (82/95) were identified to contain subtype I; the other 10 urine samples contained subtype IV. A 86-bp fragment was identified as a highly conserved sequence. Following alignment with 36 published BKV sequences from China, 92 sites of polymorphism were identified, including 11 single nucleotide polymorphisms (SNPs) prevalent in Chinese individuals and 30 SNPs that were specific to the two predominant subtypes I and IV. The limitations of the VP2 gene segment in subgrouping were confirmed by phylogenetic analysis. The conserved sequence and polymorphism identified in this study may be helpful in the detection and genotyping of BKV.

Recent advances in blood flow vector velocity imaging

DEFF Research Database (Denmark)

Jensen, Jørgen Arendt; Nikolov, Svetoslav; Udesen, Jesper

2011-01-01

tracking. The key advantages of these techniques are very fast imaging that can attain an order of magnitude higher precision than conventional methods. SA flow imaging was implemented on the experimental scanner RASMUS using an 8-emission spherical emission sequence and reception of 64 channels on a BK...... investigated using both simulations, flow rig measurements, and in-vivo validation against MR scans. The TO method obtains a relative accuracy of 10% for a fully transverse flow in both simulations and flow rig experiments. In-vivo studies performed on 11 healthy volunteers comparing the TO method...... been acquired using a commercial implementation of the method (BK Medical ProFocus Ultraview scanner). A range of other methods are also presented. This includes synthetic aperture imaging using either spherical or plane waves with velocity estimation performed with directional beamforming or speckle...

A new pH-sensitive rectifying potassium channel in mitochondria from the embryonic rat hippocampus.

Science.gov (United States)

Kajma, Anna; Szewczyk, Adam

2012-10-01

Patch-clamp single-channel studies on mitochondria isolated from embryonic rat hippocampus revealed the presence of two different potassium ion channels: a large-conductance (288±4pS) calcium-activated potassium channel and second potassium channel with outwardly rectifying activity under symmetric conditions (150/150mM KCl). At positive voltages, this channel displayed a conductance of 67.84pS and a strong voltage dependence at holding potentials from -80mV to +80mV. The open probability was higher at positive than at negative voltages. Patch-clamp studies at the mitoplast-attached mode showed that the channel was not sensitive to activators and inhibitors of mitochondrial potassium channels but was regulated by pH. Moreover, we demonstrated that the channel activity was not affected by the application of lidocaine, an inhibitor of two-pore domain potassium channels, or by tertiapin, an inhibitor of inwardly rectifying potassium channels. In summary, based on the single-channel recordings, we characterised for the first time mitochondrial pH-sensitive ion channel that is selective for cations, permeable to potassium ions, displays voltage sensitivity and does not correspond to any previously described potassium ion channels in the inner mitochondrial membrane. This article is part of a Special Issue entitled: 17th European Bioenergetics Conference (EBEC 2012). Copyright © 2012 Elsevier B.V. All rights reserved.

Heteromeric Slick/Slack K+ channels show graded sensitivity to cell volume changes

DEFF Research Database (Denmark)

Tejada, Maria A; Hashem, Nadia; Callø, Kirstine

2017-01-01

Slick and Slack high-conductance K+ channels are found in the CNS, kidneys, pancreas, among other organs, where they play an important role in cell excitability as well as in ion transport processes. They are both activated by Na+ and Cl- but show a differential regulation by cell volume changes....... Slick has been shown to be regulated by cell volume changes, whereas Slack is insensitive. α-subunits of these channels form homomeric as well as heteromeric channels. It is the aim of this work to explore whether the subunit composition of the Slick/Slack heteromeric channel affects the response...... to osmotic challenges. In order to provide with the adequate water permeability to the cell membrane of Xenopus laevis oocytes, mRNA of aquaporin 1 was co-expressed with homomeric or heteromeric Slick and Slack α-subunits. Oocytes were superfused with hypotonic or hypertonic buffers and changes in currents...

Surface deformation and friction characteristic of nano scratch at ductile-removal regime for optical glass BK7.

Science.gov (United States)

Li, Chen; Zhang, Feihu; Ding, Ye; Liu, Lifei

2016-08-20

Nano scratch for optical glass BK7 based on the ductile-removal regime was carried out, and the influence rule of scratch parameters on surface deformation and friction characteristic was analyzed. Experimental results showed that, with increase of normal force, the deformation of burrs in the edge of the scratch was more obvious, and with increase of the scratch velocity, the deformation of micro-fracture and burrs in the edge of the scratch was more obvious similarly. The residual depth of the scratch was measured by atomic force microscope. The experimental results also showed that, with increase of normal force, the residual depth of the scratch increased linearly while the elastic recovery rate decreased. Furthermore, with increase of scratch velocity, the residual depth of the scratch decreased while the elastic recovery rate increased. The scratch process of the Berkovich indenter was divided into the cutting process of many large negative rake faces based on the improved cutting model, and the friction characteristic of the Berkovich indenter and the workpiece was analyzed. The analysis showed that the coefficient of friction increased and then tended to be stable with the increase of normal force. Meanwhile, the coefficient of friction decreased with the increase of scratch velocity, and the coefficients, k ln(v) and μ0, were introduced to improve the original formula of friction coefficient.

Effects of channel blocking on information transmission and energy efficiency in squid giant axons.

Science.gov (United States)

Liu, Yujiang; Yue, Yuan; Yu, Yuguo; Liu, Liwei; Yu, Lianchun

2018-04-01

Action potentials are the information carriers of neural systems. The generation of action potentials involves the cooperative opening and closing of sodium and potassium channels. This process is metabolically expensive because the ions flowing through open channels need to be restored to maintain concentration gradients of these ions. Toxins like tetraethylammonium can block working ion channels, thus affecting the function and energy cost of neurons. In this paper, by computer simulation of the Hodgkin-Huxley neuron model, we studied the effects of channel blocking with toxins on the information transmission and energy efficiency in squid giant axons. We found that gradually blocking sodium channels will sequentially maximize the information transmission and energy efficiency of the axons, whereas moderate blocking of potassium channels will have little impact on the information transmission and will decrease the energy efficiency. Heavy blocking of potassium channels will cause self-sustained oscillation of membrane potentials. Simultaneously blocking sodium and potassium channels with the same ratio increases both information transmission and energy efficiency. Our results are in line with previous studies suggesting that information processing capacity and energy efficiency can be maximized by regulating the number of active ion channels, and this indicates a viable avenue for future experimentation.

Bed shear stress distribution in straight channels with arbitrary cross section

DEFF Research Database (Denmark)

Christensen, Henrik Bo; Fredsøe, Jørgen

1998-01-01

The bed shear stress distribution in straight open channels is affected by mechanisms as bed curvature of the cross section profile, shear diffusion, and secondary currents. This paper compares some analytical and numerical methods to estimate the bed shear stress distribution. The methods...

Groundwater controls on river channel pattern

Science.gov (United States)

Bätz, Nico; Colombini, Pauline; Cherubini, Paolo; Lane, Stuart N.

2017-04-01

Braided rivers are characterized by high rates of morphological change. However, despite the potential for frequent disturbance, vegetated patches may develop within this system and influence long-term channel dynamics and channel patterns through the "engineering effects" of vegetation. The stabilizing effect of developing vegetation on morphological change has been widely shown by flume experiments and (historic) aerial pictures analysis. Thus, there is a balance between disturbance and stabilization, mediated through vegetation, that may determine the long-term geomorphic and biogeomorphic evolution of the river. It follows that with a change in disturbance frequency relative to the rate of vegetation establishment, a systematic geomorphological shift could occur. Research has addressed how changes in disturbance frequency affect river channel pattern, but has rarely addressed the way in which the stabilizing effects of biogeomorphic succession interact with disturbance frequency to maintain a river in a more dynamic or a less dynamic state. Here, we quantify how the interplay between groundwater access, disturbance frequency and vegetation succession, drive changes in channel pattern. We studied this complex interplay on a transitional gravel-bed river system (braided, wandering, meandering) close to Geneva (Switzerland) - the Allondon River. Dendroecological analysis demonstrate that vegetation growth is driven by groundwater access. Groundwater access conditions the rate of vegetation stabilization at the sub-reach scale and, due to a reduction in flood-related disturbance frequency over the last 50 years, drives a change in channel pattern. Where groundwater is shallower, vegetation encroachment rates were high and as flood-related disturbance decreased, the river has shifted towards a meandering state. Where groundwater was deeper, vegetation growth was limited by water-access and thus vegetation encroachment rates were low. Even though there was a

A channel profile analyser

International Nuclear Information System (INIS)

Gobbur, S.G.

1983-01-01

It is well understood that due to the wide band noise present in a nuclear analog-to-digital converter, events at the boundaries of adjacent channels are shared. It is a difficult and laborious process to exactly find out the shape of the channels at the boundaries. A simple scheme has been developed for the direct display of channel shape of any type of ADC on a cathode ray oscilliscope display. This has been accomplished by sequentially incrementing the reference voltage of a precision pulse generator by a fraction of a channel and storing ADC data in alternative memory locations of a multichannel pulse height analyser. Alternative channels are needed due to the sharing at the boundaries of channels. In the flat region of the profile alternate memory locations are channels with zero counts and channels with the full scale counts. At the boundaries all memory locations will have counts. The shape of this is a direct display of the channel boundaries. (orig.)

Transmembrane helical interactions in the CFTR channel pore.

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Jhuma Das

2017-06-01

Full Text Available Mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR gene affect CFTR protein biogenesis or its function as a chloride channel, resulting in dysregulation of epithelial fluid transport in the lung, pancreas and other organs in cystic fibrosis (CF. Development of pharmaceutical strategies to treat CF requires understanding of the mechanisms underlying channel function. However, incomplete 3D structural information on the unique ABC ion channel, CFTR, hinders elucidation of its functional mechanism and correction of cystic fibrosis causing mutants. Several CFTR homology models have been developed using bacterial ABC transporters as templates but these have low sequence similarity to CFTR and are not ion channels. Here, we refine an earlier model in an outward (OWF and develop an inward (IWF facing model employing an integrated experimental-molecular dynamics simulation (200 ns approach. Our IWF structure agrees well with a recently solved cryo-EM structure of a CFTR IWF state. We utilize cysteine cross-linking to verify positions and orientations of residues within trans-membrane helices (TMHs of the OWF conformation and to reconstruct a physiologically relevant pore structure. Comparison of pore profiles of the two conformations reveal a radius sufficient to permit passage of hydrated Cl- ions in the OWF but not the IWF model. To identify structural determinants that distinguish the two conformations and possible rearrangements of TMHs within them responsible for channel gating, we perform cross-linking by bifunctional reagents of multiple predicted pairs of cysteines in TMH 6 and 12 and 6 and 9. To determine whether the effects of cross-linking on gating observed are the result of switching of the channel from open to close state, we also treat the same residue pairs with monofunctional reagents in separate experiments. Both types of reagents prevent ion currents indicating that pore blockage is primarily responsible.

Choline Modulation of the Aβ P1-40 Channel Reconstituted into a Model Lipid Membrane

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Daniela Meleleo

2010-01-01

Full Text Available Nicotinic acetylcholine receptors (AChRs, implicated in memory and learning, in subjects affected by Alzheimer's disease result altered. Stimulation of α7-nAChRs inhibits amyloid plaques and increases ACh release. β-amyloid peptide (AβP forms ion channels in the cell and model phospholipid membranes that are retained responsible in Alzheimer disease. We tested if choline, precursor of ACh, could affect the AβP1-40 channels in oxidized cholesterol (OxCh and in palmitoyl-oleoyl-phosphatidylcholine (POPC:Ch lipid bilayers. Choline concentrations of 5 × 10−11 M–1.5 × 10−8 M added to the cis- or trans-side of membrane quickly increased AβP1-40 ion channel frequency (events/min and ion conductance in OxCh membranes, but not in POPC:Ch membranes. Circular Dichroism (CD spectroscopy shows that after 24 and 48 hours of incubation with AβP1-40, choline stabilizes the random coil conformation of the peptide, making it less prone to fibrillate. These actions seem to be specific in that ACh is ineffective either in solution or on AβP1-40 channel incorporated into PLMs.

Heterologous Expression of Tulip Petal Plasma Membrane Aquaporins in Pichia pastoris for Water Channel Analysis▿

Science.gov (United States)

Azad, Abul Kalam; Sawa, Yoshihiro; Ishikawa, Takahiro; Shibata, Hitoshi

2009-01-01

Water channels formed by aquaporins (AQPs) play an important role in the control of water homeostasis in individual cells and in multicellular organisms. Plasma membrane intrinsic proteins (PIPs) constitute a subclass of plant AQPs. TgPIP2;1 and TgPIP2;2 from tulip petals are members of the PIP family. In this study, we overexpressed TgPIP2;1 and TgPIP2;2 in Pichia pastoris and monitored their water channel activity (WCA) either by an in vivo spheroplast-bursting assay performed after hypo-osmotic shock or by growth assay. Osmolarity, pH, and inhibitors of AQPs, protein kinases (PKs), and protein phosphatases (PPs) affect the WCA of heterologous AQPs in this expression system. The WCA of TgPIP2;2-expressing spheroplasts was affected by inhibitors of PKs and PPs, which indicates that the water channel of this homologue is regulated by phosphorylation in P. pastoris. From the results reported herein, we suggest that P. pastoris can be employed as a heterologous expression system to assay the WCA of PIPs and to monitor the AQP-mediated channel gating mechanism, and it can be developed to screen inhibitors/effectors of PIPs. PMID:19251885

Heterologous expression of tulip petal plasma membrane aquaporins in Pichia pastoris for water channel analysis.

Science.gov (United States)

Azad, Abul Kalam; Sawa, Yoshihiro; Ishikawa, Takahiro; Shibata, Hitoshi

2009-05-01

Water channels formed by aquaporins (AQPs) play an important role in the control of water homeostasis in individual cells and in multicellular organisms. Plasma membrane intrinsic proteins (PIPs) constitute a subclass of plant AQPs. TgPIP2;1 and TgPIP2;2 from tulip petals are members of the PIP family. In this study, we overexpressed TgPIP2;1 and TgPIP2;2 in Pichia pastoris and monitored their water channel activity (WCA) either by an in vivo spheroplast-bursting assay performed after hypo-osmotic shock or by growth assay. Osmolarity, pH, and inhibitors of AQPs, protein kinases (PKs), and protein phosphatases (PPs) affect the WCA of heterologous AQPs in this expression system. The WCA of TgPIP2;2-expressing spheroplasts was affected by inhibitors of PKs and PPs, which indicates that the water channel of this homologue is regulated by phosphorylation in P. pastoris. From the results reported herein, we suggest that P. pastoris can be employed as a heterologous expression system to assay the WCA of PIPs and to monitor the AQP-mediated channel gating mechanism, and it can be developed to screen inhibitors/effectors of PIPs.

Nakama : A companion for non-verbal affective communication

NARCIS (Netherlands)

Willemse, C.J.A.M.; Munters, G.M.; Erp, J.B.F. van; Heylen, D.K.J.

2015-01-01

We present "Nakama": A communication device that supports affective communication between a child and its - geographically separated - parent. Nakama consists of a control unit at the parent's end and an actuated teddy bear for the child. The bear contains several communication channels, including

Nakama: a companion for non-verbal affective communication

NARCIS (Netherlands)

Willemse, Christian Jacob Arendt Maria; Munters, Gerald M.; van Erp, Johannes Bernardus Fransiscus; Heylen, Dirk K.J.

2015-01-01

We present "Nakama": A communication device that supports affective communication between a child and its - geographically separated - parent. Nakama consists of a control unit at the parent's end and an actuated teddy bear for the child. The bear contains several communication channels, including

Study on parallel-channel asymmetry in supercritical flow instability experiment

International Nuclear Information System (INIS)

Xiong Ting; Yu Junchong; Yan Xiao; Huang Yanping; Xiao Zejun; Huang Shanfang

2013-01-01

Due to the urgent need for experimental study on supercritical water flow instability, the parallel-channel asymmetry which determines the feasibility of such experiments was studied with the experimental and numerical results in parallel dual channel. The evolution of flow rates in the experiments was analyzed, and the steady-state characteristics as well as transient characteristics of the system were obtained by self-developed numerical code. The results show that the asymmetry of the parallel dual channel would reduce the feasibility of experiments. The asymmetry of flow rates is aroused by geometrical asymmetry. Due to the property variation characteristics of supercritical water, the flow rate asymmetry is enlarged while rising beyond the pseudo critical point. The extent of flow rate asymmetry is affected by the bulk temperature and total flow rate; therefore the experimental feasibility can be enhanced by reducing the total flow rate. (authors)

Source Material and Concentration of Wildfire-Produced Pyrogenic Carbon Influence Post-Fire Soil Nutrient Dynamics

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Lucas A. Michelotti

2015-04-01

Full Text Available Pyrogenic carbon (PyC is produced by the thermal decomposition of organic matter in the absence of oxygen (O. PyC affects nutrient availability, may enhance post-fire nitrogen (N mineralization rates, and can be a significant carbon (C pool in fire-prone ecosystems. Our objectives were to characterize PyC produced by wildfires and examine the influence that contrasting types of PyC have on C and N mineralization rates. We determined C, N, O, and hydrogen (H concentrations and atomic ratios of charred bark (BK, charred pine cones (PC, and charred woody debris (WD using elemental analysis. We also incubated soil amended with BK, PC, and WD at two concentrations for 60 days to measure C and N mineralization rates. PC had greater H/C and O/C ratios than BK and WD, suggesting that PC may have a lesser aromatic component than BK and WD. C and N mineralization rates decreased with increasing PyC concentrations, and control samples produced more CO2 than soils amended with PyC. Soils with PC produced greater CO2 and had lower N mineralization rates than soils with BK or WD. These results demonstrate that PyC type and concentration have potential to impact nutrient dynamics and C flux to the atmosphere in post-fire forest soils.

Ion channels in plants.

Science.gov (United States)

Hedrich, Rainer

2012-10-01

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

A cyclic nucleotide-gated channel mutation associated with canine daylight blindness provides insight into a role for the S2 segment tri-Asp motif in channel biogenesis.

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Naoto Tanaka

Full Text Available Cone cyclic nucleotide-gated channels are tetramers formed by CNGA3 and CNGB3 subunits; CNGA3 subunits function as homotetrameric channels but CNGB3 exhibits channel function only when co-expressed with CNGA3. An aspartatic acid (Asp to asparagine (Asn missense mutation at position 262 in the canine CNGB3 (D262N subunit results in loss of cone function (daylight blindness, suggesting an important role for this aspartic acid residue in channel biogenesis and/or function. Asp 262 is located in a conserved region of the second transmembrane segment containing three Asp residues designated the Tri-Asp motif. This motif is conserved in all CNG channels. Here we examine mutations in canine CNGA3 homomeric channels using a combination of experimental and computational approaches. Mutations of these conserved Asp residues result in the absence of nucleotide-activated currents in heterologous expression. A fluorescent tag on CNGA3 shows mislocalization of mutant channels. Co-expressing CNGB3 Tri-Asp mutants with wild type CNGA3 results in some functional channels, however, their electrophysiological characterization matches the properties of homomeric CNGA3 channels. This failure to record heteromeric currents suggests that Asp/Asn mutations affect heteromeric subunit assembly. A homology model of S1-S6 of the CNGA3 channel was generated and relaxed in a membrane using molecular dynamics simulations. The model predicts that the Tri-Asp motif is involved in non-specific salt bridge pairings with positive residues of S3/S4. We propose that the D262N mutation in dogs with CNGB3-day blindness results in the loss of these inter-helical interactions altering the electrostatic equilibrium within in the S1-S4 bundle. Because residues analogous to Tri-Asp in the voltage-gated Shaker potassium channel family were implicated in monomer folding, we hypothesize that destabilizing these electrostatic interactions impairs the monomer folding state in D262N mutant CNG

Down-regulation of voltage-dependent sodium channels initiated by sodium influx in developing neurons

International Nuclear Information System (INIS)

Dargent, B.; Couraud, F.

1990-01-01

To address the issue of whether regulatory feedback exists between the electrical activity of a neuron and ion-channel density, the authors investigated the effect of Na + -channel activators (scorpion α toxin, batrachotoxin, and veratridine) on the density of Na + channels in fetal rat brain neurons in vitro. A partial but rapid (t 1/2 , 15 min) disappearance of surface Na + channels was observed as measured by a decrease in the specific binding of [ 3 H]saxitoxin and 125 I-labeled scorpion β toxin and a decrease in specific 22 Na + uptake. Moreover, the increase in the number of Na + channels that normally occurs during neuronal maturation in vitro was inhibited by chronic channel activator treatment. The induced disappearance of Na + channels was abolished by tetrodotoxin, was found to be dependent on the external Na + concentration, and was prevented when either choline (a nonpermeant ion) or Li + (a permeant ion) was substituted for Na + . Amphotericin B, a Na + ionophore, and monensin were able to mimick the effect of Na + -channel activators, while a KCl depolarization failed to do this. This feedback regulation seems to be a neuronal property since Na + -channel density in cultured astrocytes was not affected by channel activator treatment or by amphotericin B. The present evidence suggests that an increase in intracellular Na + concentration, whether elicited by Na + -channel activators or mediated by a Na + ionophore, can induce a decrease in surface Na + channels and therefore is involved in down-regulation of Na + -channel density in fetal rat brain neurons in vitro

Anti-calmodulins and tricyclic adjuvants in pain therapy block the TRPV1 channel.

Directory of Open Access Journals (Sweden)

Zoltán Oláh

2007-06-01

Full Text Available Ca(2+-loaded calmodulin normally inhibits multiple Ca(2+-channels upon dangerous elevation of intracellular Ca(2+ and protects cells from Ca(2+-cytotoxicity, so blocking of calmodulin should theoretically lead to uncontrolled elevation of intracellular Ca(2+. Paradoxically, classical anti-psychotic, anti-calmodulin drugs were noted here to inhibit Ca(2+-uptake via the vanilloid inducible Ca(2+-channel/inflamatory pain receptor 1 (TRPV1, which suggests that calmodulin inhibitors may block pore formation and Ca(2+ entry. Functional assays on TRPV1 expressing cells support direct, dose-dependent inhibition of vanilloid-induced (45Ca(2+-uptake at microM concentrations: calmidazolium (broad range > or = trifluoperazine (narrow range chlorpromazine/amitriptyline>fluphenazine>>W-7 and W-13 (only partially. Most likely a short acidic domain at the pore loop of the channel orifice functions as binding site either for Ca(2+ or anti-calmodulin drugs. Camstatin, a selective peptide blocker of calmodulin, inhibits vanilloid-induced Ca(2+-uptake in intact TRPV1(+ cells, and suggests an extracellular site of inhibition. TRPV1(+, inflammatory pain-conferring nociceptive neurons from sensory ganglia, were blocked by various anti-psychotic and anti-calmodulin drugs. Among them, calmidazolium, the most effective calmodulin agonist, blocked Ca(2+-entry by a non-competitive kinetics, affecting the TRPV1 at a different site than the vanilloid binding pocket. Data suggest that various calmodulin antagonists dock to an extracellular site, not found in other Ca(2+-channels. Calmodulin antagonist-evoked inhibition of TRPV1 and NMDA receptors/Ca(2+-channels was validated by microiontophoresis of calmidazolium to laminectomised rat monitored with extracellular single unit recordings in vivo. These unexpected findings may explain empirically noted efficacy of clinical pain adjuvant therapy that justify efforts to develop hits into painkillers, selective to sensory Ca(2

The Importance of Providing Multiple-Channel Sections in Dredging Activities to Improve Fish Habitat Environments

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Hung-Pin Chiu

2016-01-01

Full Text Available After Typhoon Morakot, dredging engineering was conducted while taking the safety of humans and structures into consideration, but partial stream reaches were formed in the multiple-channel sections in Cishan Stream because of anthropogenic and natural influences. This study mainly explores the distribution of each fish species in both the multiple- and single-channel sections in the Cishan Stream. Parts of the environments did not exhibit significant differences according to a one-way ANOVA comparing the multiple- and single-channel sections, but certain areas of the multiple-channel sections had more diverse habitats. Each fish species was widely distributed by non-metric multidimensional scaling in the multiple-channel sections as compared to those in the single-channel sections. In addition, according to the principal component analysis, each fish species has a preferred environment, and all of them have a wide choice of habitat environments in the multiple-channel sections. Finally, the existence of multiple-channel sections could significantly affect the existence of the fish species under consideration in this study. However, no environmental factors were found to have an influence on fish species in the single-channel sections, with the exception of Rhinogobius nantaiensis. The results show that providing multiple-channel sections in dredging activities could improve fish habitat environments.

Channel and Timeslot Co-Scheduling with Minimal Channel Switching for Data Aggregation in MWSNs

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Sanggil Yeoum

2017-05-01

Full Text Available Collision-free transmission and efficient data transfer between nodes can be achieved through a set of channels in multichannel wireless sensor networks (MWSNs. While using multiple channels, we have to carefully consider channel interference, channel and time slot (resources optimization, channel switching delay, and energy consumption. Since sensor nodes operate on low battery power, the energy consumed in channel switching becomes an important challenge. In this paper, we propose channel and time slot scheduling for minimal channel switching in MWSNs, while achieving efficient and collision-free transmission between nodes. The proposed scheme constructs a duty-cycled tree while reducing the amount of channel switching. As a next step, collision-free time slots are assigned to every node based on the minimal data collection delay. The experimental results demonstrate that the validity of our scheme reduces the amount of channel switching by 17.5%, reduces energy consumption for channel switching by 28%, and reduces the schedule length by 46%, as compared to the existing schemes.

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.)

Calcium channel modulation as a target in chronic pain control.

Science.gov (United States)

Patel, Ryan; Montagut-Bordas, Carlota; Dickenson, Anthony H

2018-06-01

Neuropathic pain remains poorly treated for large numbers of patients, and little progress has been made in developing novel classes of analgesics. To redress this issue, ziconotide (Prialt™) was developed and approved as a first-in-class synthetic version of ω-conotoxin MVIIA, a peptide blocker of Ca v 2.2 channels. Unfortunately, the impracticalities of intrathecal delivery, low therapeutic index and severe neurological side effects associated with ziconotide have restricted its use to exceptional circumstances. Ziconotide exhibits no state or use-dependent block of Ca v 2.2 channels; activation state-dependent blockers were hypothesized to circumvent the side effects of state-independent blockers by selectively targeting high-frequency firing of nociceptive neurones in chronic pain states, thus alleviating aberrant pain but not affecting normal sensory transduction. Unfortunately, numerous drugs, including state-dependent calcium channel blockers, have displayed efficacy in preclinical models but have subsequently been disappointing in clinical trials. In recent years, it has become more widely acknowledged that trans-aetiological sensory profiles exist amongst chronic pain patients and may indicate similar underlying mechanisms and drug sensitivities. Heterogeneity amongst patients, a reliance on stimulus-evoked endpoints in preclinical studies and a failure to utilize translatable endpoints, all are likely to have contributed to negative clinical trial results. We provide an overview of how electrophysiological and operant-based assays provide insight into sensory and affective aspects of pain in animal models and how these may relate to chronic pain patients in order to improve the bench-to-bedside translation of calcium channel modulators. This article is part of a themed section on Recent Advances in Targeting Ion Channels to Treat Chronic Pain. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175

The human role in changing river channels