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Sample records for bk channel localization

  1. BK channel modulators: a comprehensive overview

    DEFF Research Database (Denmark)

    Nardi, Antonio; Olesen, Søren-Peter

    2008-01-01

    The large Ca(2+)-activated K(+) channel (BK channel) reflects per excellence the dilemma of the molecular target driven drug discovery process. Significant experimental evidence suggests that the BK channels play a pivotal and specific role in many pathophysiological conditions supporting...... the notion that the channel represents an innovative and promising drug target. However, after more than ten years of intense research effort both in academia and industry, scientists have yet to witness the approval of a single BK channel modulator for clinical use. On the contrary, three BK openers...... and blockers 4) Marketed and/or investigational drugs with BK-modulating side properties and structural analogues 5) Naturally-occurring BK channel openers and structural analogues 6) Synthetic BK channel openers. This review is intended to provide readers with current opinion on the BK channel as a drug...

  2. BK channel modulators: a comprehensive overview

    DEFF Research Database (Denmark)

    Nardi, Antonio; Olesen, Søren-Peter

    2008-01-01

    channels as a potentially attractive target, the design and synthesis of potent and selective BK modulators continue based on novel chemical ideas. A comprehensive overview of BK channel modulators is therefore timely and important to the current medicinal chemist for review, summary, and classification......The large Ca(2+)-activated K(+) channel (BK channel) reflects per excellence the dilemma of the molecular target driven drug discovery process. Significant experimental evidence suggests that the BK channels play a pivotal and specific role in many pathophysiological conditions supporting...... the notion that the channel represents an innovative and promising drug target. However, after more than ten years of intense research effort both in academia and industry, scientists have yet to witness the approval of a single BK channel modulator for clinical use. On the contrary, three BK openers...

  3. BK channel activators and their therapeutic perspectives

    DEFF Research Database (Denmark)

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

    2014-01-01

    The large conductance calcium- and voltage-activated K(+) channel (KCa1.1, BK, MaxiK) is ubiquitously expressed in the body, and holds the ability to integrate changes in intracellular calcium and membrane potential. This makes the BK channel an important negative feedback system linking increases...... 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...... a short introduction to the structure, function and regulation of BK channels, we review the small organic molecules activating BK channels and how these tool compounds have helped delineate the roles of BK channels in health and disease....

  4. Regulation of BK channels by auxiliary γ subunits

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    Jiyuan eZhang

    2014-10-01

    Full Text Available The large-conductance, calcium- and voltage-activated potassium (BK channel has the largest single-channel conductance among potassium channels and can be activated by both membrane depolarization and increases in intracellular calcium concentration. BK channels consist of pore-forming, voltage- and calcium-sensing α subunits, either alone or in association with regulatory subunits. BK channels are widely expressed in various tissues and cells including both excitable and non-excitable cells and display diverse biophysical and pharmacological characteristics. This diversity can be explained in part by posttranslational modifications and alternative splicing of the α subunit, which is encoded by a single gene, KCNMA1, as well as by tissue-specific β subunit modulation. Recently, a leucine-rich repeat-containing membrane protein, LRRC26, was found to interact with BK channels and cause an unprecedented large negative shift (~-140 mV in the voltage dependence of the BK channel activation. LRRC26 allows BK channels to open even at near-physiological calcium concentration and membrane voltage in non-excitable cells. Three LRRC26-related proteins, LRRC52, LRRC55, and LRRC38, were subsequently identified as BK channel modulators. These LRRC proteins are structurally and functionally distinct from the BK channel β subunits and were designated as γ subunits. The discovery of the γ subunits adds a new dimension to BK channel regulation and improves our understanding of the physiological functions of BK channels in various tissues and cell types. Unlike BK channel β subunits, which have been intensively investigated both mechanistically and physiologically, our understanding of the γ subunits is very limited at this stage. This article reviews the structure, modulatory mechanisms, physiological relevance, and potential therapeutic implications of γ subunits as they are currently understood.

  5. Intrinsic disorder in the BK channel and its interactome.

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    Zhenling Peng

    Full Text Available The large-conductance Ca2+-activated K+ (BK channel is broadly expressed in various mammalian cells and tissues such as neurons, skeletal and smooth muscles, exocrine cells, and sensory cells of the inner ear. Previous studies suggest that BK channels are promiscuous binders involved in a multitude of protein-protein interactions. To gain a better understanding of the potential mechanisms underlying BK interactions, we analyzed the abundance, distribution, and potential mechanisms of intrinsic disorder in 27 BK channel variants from mouse cochlea, 104 previously reported BK-associated proteins (BKAPS from cytoplasmic and membrane/cytoskeletal regions, plus BK β- and γ-subunits. Disorder was evaluated using the MFDp algorithm, which is a consensus-based predictor that provides a strong and competitive predictive quality and PONDR, which can determine long intrinsically disordered regions (IDRs. Disorder-based binding sites or molecular recognition features (MoRFs were found using MoRFpred and ANCHOR. BKAP functions were categorized based on Gene Ontology (GO terms. The analyses revealed that the BK variants contain a number of IDRs. Intrinsic disorder is also common in BKAPs, of which ∼ 5% are completely disordered. However, intrinsic disorder is very differently distributed within BK and its partners. Approximately 65% of the disordered segments in BK channels are long (IDRs (>50 residues, whereas >60% of the disordered segments in BKAPs are short IDRs that range in length from 4 to 30 residues. Both α and γ subunits showed various amounts of disorder as did hub proteins of the BK interactome. Our analyses suggest that intrinsic disorder is important for the function of BK and its BKAPs. Long IDRs in BK are engaged in protein-protein and protein-ligand interactions, contain multiple post-translational modification sites, and are subjected to alternative splicing. The disordered structure of BK and its BKAPs suggests one of the underlying

  6. Single-channel kinetics of BK (Slo1 channels

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    Yanyan eGeng

    2015-01-01

    Full Text Available Single-channel kinetics has proven a powerful tool to reveal information about the gating mechanisms that control the opening and closing of ion channels. This introductory review focuses on the gating of large conductance Ca2+- and voltage-activated K+ (BK or Slo1 channels at the single-channel level. It starts with single-channel current records and progresses to presentation and analysis of single-channel data and the development of gating mechanisms in terms of discrete state Markov (DSM models. The DSM models are formulated in terms of the tetrameric modular structure of BK channels, consisting of a central transmembrane pore-gate domain (PGD attached to four surrounding transmembrane voltage sensing domains (VSD and a large intracellular cytosolic domain (CTD, also referred to as the gating ring. The modular structure and data analysis shows that the Ca2+ and voltage dependent gating considered separately can each be approximated by 10-state two-tiered models with 5 closed states on the upper tier and 5 open states on the lower tier. The modular structure and joint Ca2+ and voltage dependent gating are consistent with a 50 state two-tiered model with 25 closed states on the upper tier and 25 open states on the lower tier. Adding an additional tier of brief closed (flicker states to the 10-state or 50-state models improved the description of the gating. For fixed experimental conditions a channel would gate in only a subset of the potential number of states. The detected number of states and the correlations between adjacent interval durations are consistent with the tiered models. The examined models can account for the single-channel kinetics and the bursting behavior of gating. Ca2+ and voltage activate BK channels by predominantly increasing the effective opening rate of the channel with a smaller decrease in the effective closing rate. Ca2+ and depolarization thus activate by mainly destabilizing the closed states.

  7. Relationship between Pore Occupancy and Gating in BK Potassium Channels

    OpenAIRE

    Piskorowski, Rebecca A.; Aldrich, Richard W.

    2006-01-01

    Permeant ions can have significant effects on ion channel conformational changes. To further understand the relationship between ion occupancy and gating conformational changes, we have studied macroscopic and single-channel gating of BK potassium channels with different permeant monovalent cations. While the slopes of the conductance?voltage curve were reduced with respect to potassium for all permeant ions, BK channels required stronger depolarization to open only when thallium was the perm...

  8. The brain-specific Beta4 subunit downregulates BK channel cell surface expression.

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    Sonal Shruti

    Full Text Available The large-conductance K(+ channel (BK channel can control neural excitability, and enhanced channel currents facilitate high firing rates in cortical neurons. The brain-specific auxiliary subunit β4 alters channel Ca(++- and voltage-sensitivity, and β4 knock-out animals exhibit spontaneous seizures. Here we investigate β4's effect on BK channel trafficking to the plasma membrane. Using a novel genetic tag to track the cellular location of the pore-forming BKα subunit in living cells, we find that β4 expression profoundly reduces surface localization of BK channels via a C-terminal ER retention sequence. In hippocampal CA3 neurons from C57BL/6 mice with endogenously high β4 expression, whole-cell BK channel currents display none of the characteristic properties of BKα+β4 channels observed in heterologous cells. Finally, β4 knock-out animals exhibit a 2.5-fold increase in whole-cell BK channel current, indicating that β4 also regulates current magnitude in vivo. Thus, we propose that a major function of the brain-specific β4 subunit in CA3 neurons is control of surface trafficking.

  9. 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......-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...... and localization of both mRNA and protein expression of the BK(Ca) channel in the smooth muscle cell layer in rat basilar, middle cerebral, and middle meningeal arteries....

  10. BK channel activation by NS11021 decreases excitability and contractility of urinary bladder smooth muscle

    DEFF Research Database (Denmark)

    Layne, Jeffrey J; Nausch, Bernhard; Olesen, Søren-Peter

    2009-01-01

    reduction was blocked by pretreatment with the BK channel blocker iberiotoxin. NS11021 (3 microM) had no effect on contractions evoked by nerve stimulation. These findings indicate that activating BK channels reduces the force of UBSM spontaneous phasic contractions, principally through decreasing......Large-conductance Ca(2+)-activated potassium (BK) channels play an important role in regulating the function and activity of urinary bladder smooth muscle (UBSM), and the loss of BK channel function has been shown to increase UBSM excitability and contractility. However, it is not known whether...... activation of BK channels has the converse effect of reducing UBSM excitability and contractility. Here, we have sought to investigate this possibility by using the novel BK channel opener NS11021. NS11021 (3 microM) caused an approximately threefold increase in both single BK channel open probability (P...

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    that BK mediates the beneficial effects of IP. These findings suggest that cardiac BK channels are important for proper oxidative energy supply of cardiomyocytes at normoxia and upon re-oxygenation after prolonged anoxia and that IP might indeed favor survival of the myocardium upon I/R injury in a BK...

  12. BK channels regulate spontaneous action potential rhythmicity in the suprachiasmatic nucleus.

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    Jack Kent

    Full Text Available BACKGROUND: Circadian ( approximately 24 hr rhythms are generated by the central pacemaker localized to the suprachiasmatic nucleus (SCN of the hypothalamus. Although the basis for intrinsic rhythmicity is generally understood to rely on transcription factors encoded by "clock genes", less is known about the daily regulation of SCN neuronal activity patterns that communicate a circadian time signal to downstream behaviors and physiological systems. Action potentials in the SCN are necessary for the circadian timing of behavior, and individual SCN neurons modulate their spontaneous firing rate (SFR over the daily cycle, suggesting that the circadian patterning of neuronal activity is necessary for normal behavioral rhythm expression. The BK K(+ channel plays an important role in suppressing spontaneous firing at night in SCN neurons. Deletion of the Kcnma1 gene, encoding the BK channel, causes degradation of circadian behavioral and physiological rhythms. METHODOLOGY/PRINCIPAL FINDINGS: To test the hypothesis that loss of robust behavioral rhythmicity in Kcnma1(-/- mice is due to the disruption of SFR rhythms in the SCN, we used multi-electrode arrays to record extracellular action potentials from acute wild-type (WT and Kcnma1(-/- slices. Patterns of activity in the SCN were tracked simultaneously for up to 3 days, and the phase, period, and synchronization of SFR rhythms were examined. Loss of BK channels increased arrhythmicity but also altered the amplitude and period of rhythmic activity. Unexpectedly, Kcnma1(-/- SCNs showed increased variability in the timing of the daily SFR peak. CONCLUSIONS/SIGNIFICANCE: These results suggest that BK channels regulate multiple aspects of the circadian patterning of neuronal activity in the SCN. In addition, these data illustrate the characteristics of a disrupted SCN rhythm downstream of clock gene-mediated timekeeping and its relationship to behavioral rhythms.

  13. Cholesterol influences voltage-gated calcium channels and BK-type potassium channels in auditory hair cells.

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    Erin K Purcell

    Full Text Available The influence of membrane cholesterol content on a variety of ion channel conductances in numerous cell models has been shown, but studies exploring its role in auditory hair cell physiology are scarce. Recent evidence shows that cholesterol depletion affects outer hair cell electromotility and the voltage-gated potassium currents underlying tall hair cell development, but the effects of cholesterol on the major ionic currents governing auditory hair cell excitability are unknown. We investigated the effects of a cholesterol-depleting agent (methyl beta cyclodextrin, MβCD on ion channels necessary for the early stages of sound processing. Large-conductance BK-type potassium channels underlie temporal processing and open in a voltage- and calcium-dependent manner. Voltage-gated calcium channels (VGCCs are responsible for calcium-dependent exocytosis and synaptic transmission to the auditory nerve. Our results demonstrate that cholesterol depletion reduced peak steady-state calcium-sensitive (BK-type potassium current by 50% in chick cochlear hair cells. In contrast, MβCD treatment increased peak inward calcium current (~30%, ruling out loss of calcium channel expression or function as a cause of reduced calcium-sensitive outward current. Changes in maximal conductance indicated a direct impact of cholesterol on channel number or unitary conductance. Immunoblotting following sucrose-gradient ultracentrifugation revealed BK expression in cholesterol-enriched microdomains. Both direct impacts of cholesterol on channel biophysics, as well as channel localization in the membrane, may contribute to the influence of cholesterol on hair cell physiology. Our results reveal a new role for cholesterol in the regulation of auditory calcium and calcium-activated potassium channels and add to the growing evidence that cholesterol is a key determinant in auditory physiology.

  14. Nitroblue tetrazolium blocks BK channels in cerebrovascular smooth muscle cell membranes

    OpenAIRE

    Ye, D; Pospisilik, J A; Mathers, D A

    2000-01-01

    The effects of p-nitroblue tetrazolium (NBT) on large conductance, calcium-activated potassium channels (BK channels) in enzymatically dispersed rat cerebrovascular smooth muscle cells (CVSMCs) were examined.Patch clamp methods were employed to record single BK channel currents from inside-out patches of CVMC membrane maintained at 21–23°C.When applied to the cytoplasmic face of inside-out membrane patches (internally applied NBT), micromolar concentrations of NBT reversible reduced the mean ...

  15. Pharmacological consequences of the coexpression of BK channel α and auxiliary β subunits

    Science.gov (United States)

    Torres, Yolima P.; Granados, Sara T.; Latorre, Ramón

    2014-01-01

    Coded by a single gene (Slo1, KCM) and activated by depolarizing potentials and by a rise in intracellular Ca2+ concentration, the large conductance voltage- and Ca2+-activated K+ channel (BK) is unique among the superfamily of K+ channels. BK channels are tetramers characterized by a pore-forming α subunit containing seven transmembrane segments (instead of the six found in voltage-dependent K+ channels) and a large C terminus composed of two regulators of K+ conductance domains (RCK domains), where the Ca2+-binding sites reside. BK channels can be associated with accessory β subunits and, although different BK modulatory mechanisms have been described, greater interest has recently been placed on the role that the β subunits may play in the modulation of BK channel gating due to its physiological importance. Four β subunits have currently been identified (i.e., β1, β2, β3, and β4) and despite the fact that they all share the same topology, it has been shown that every β subunit has a specific tissue distribution and that they modify channel kinetics as well as their pharmacological properties and the apparent Ca2+ sensitivity of the α subunit in different ways. Additionally, different studies have shown that natural, endogenous, and synthetic compounds can modulate BK channels through β subunits. Considering the importance of these channels in different pathological conditions, such as hypertension and neurological disorders, this review focuses on the mechanisms by which these compounds modulate the biophysical properties of BK channels through the regulation of β subunits, as well as their potential therapeutic uses for diseases such as those mentioned above. PMID:25346693

  16. 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

    secretory K(+) channel in the apical membrane of the murine distal colon. The BK channel is responsible for both resting and Ca(2+)-activated colonic K(+) secretion and is up-regulated by aldosterone. Agonists (e.g. adrenaline) that elevate cAMP are potent activators of distal colonic K(+) secretion....... 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...... by anion secretion and a smaller electrically opposing K(+) secretion. Using tissue from (i) BK wildtype (BK(+/+)) and knockout (BK(/)) and (ii) cystic fibrosis transmembrane regulator (CFTR) wildtype (CFTR(+/+)) and knockout (CFTR(/)) mice we were able to isolate the adrenaline-induced K(+) secretion. We...

  17. Molecular Mechanisms Underlying Renin-Angiotensin-Aldosterone System Mediated Regulation of BK Channels

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    Zhen-Ye Zhang

    2017-09-01

    Full Text Available Large-conductance calcium-activated potassium channels (BK channels belong to a family of Ca2+-sensitive voltage-dependent potassium channels and play a vital role in various physiological activities in the human body. The renin-angiotensin-aldosterone system is acknowledged as being vital in the body's hormone system and plays a fundamental role in the maintenance of water and electrolyte balance and blood pressure regulation. There is growing evidence that the renin-angiotensin-aldosterone system has profound influences on the expression and bioactivity of BK channels. In this review, we focus on the molecular mechanisms underlying the regulation of BK channels mediated by the renin-angiotensin-aldosterone system and its potential as a target for clinical drugs.

  18. Role of BK channels in the apoptotic volume decrease in native eel intestinal cells

    DEFF Research Database (Denmark)

    Lionetto, Maria Giulia; Giordano, Maria Elena; Calisi, Antonio

    2010-01-01

    of these channels in the Apoptotic Volume Decrease (AVD) of isolated eel enterocytes, and the possible interaction between BK channels and the progression of apoptosis. The detection of apoptosis was performed by confocal microscopy and annexin V and propidium iodide labelling; cell volume changes were monitored...

  19. Functional regulation of BK potassium channels by γ1 auxiliary subunits.

    Science.gov (United States)

    Gonzalez-Perez, Vivian; Xia, Xiao-Ming; Lingle, Christopher J

    2014-04-01

    Many K(+) channels are oligomeric complexes with intrinsic structural symmetry arising from the homo-tetrameric core of their pore-forming subunits. Allosteric regulation of tetramerically symmetric proteins, whether by intrinsic sensing domains or associated auxiliary subunits, often mirrors the fourfold structural symmetry. Here, through patch-clamp recordings of channel population ensembles and also single channels, we examine regulation of the Ca(2+)- and voltage-activated large conductance Ca(2+)-activated K(+) (BK) channel by associated γ1-subunits. Through expression of differing ratios of γ1:α-subunits, the results reveal an all-or-none functional regulation of BK channels by γ-subunits: channels either exhibit a full gating shift or no shift at all. Furthermore, the γ1-induced shift exhibits a state-dependent labile behavior that recapitulates the fully shifted or unshifted behavior. The γ1-induced shift contrasts markedly to the incremental shifts in BK gating produced by 1-4 β-subunits and adds a new layer of complexity to the mechanisms by which BK channel functional diversity is generated.

  20. Cholesterol Down-Regulates BK Channels Stably Expressed in HEK 293 Cells

    Science.gov (United States)

    Deng, Xiu-Ling; Sun, Hai-Ying; Li, Gui-Rong

    2013-01-01

    Cholesterol is one of the major lipid components of the plasma membrane in mammalian cells and is involved in the regulation of a number of ion channels. The present study investigates how large conductance Ca2+-activated K+ (BK) channels are regulated by membrane cholesterol in BK-HEK 293 cells expressing both the α-subunit hKCa1.1 and the auxiliary β1-subunit or in hKCa1.1-HEK 293 cells expressing only the α-subunit hKCa1.1 using approaches of electrophysiology, molecular biology, and immunocytochemistry. Membrane cholesterol was depleted in these cells with methyl-β-cyclodextrin (MβCD), and enriched with cholesterol-saturated MβCD (MβCD-cholesterol) or low-density lipoprotein (LDL). We found that BK current density was decreased by cholesterol enrichment in BK-HEK 293 cells, with a reduced expression of KCa1.1 protein, but not the β1-subunit protein. This effect was fully countered by the proteasome inhibitor lactacystin or the lysosome function inhibitor bafilomycin A1. Interestingly, in hKCa1.1-HEK 293 cells, the current density was not affected by cholesterol enrichment, but directly decreased by MβCD, suggesting that the down-regulation of BK channels by cholesterol depends on the auxiliary β1-subunit. The reduced KCa1.1 channel protein expression was also observed in cultured human coronary artery smooth muscle cells with cholesterol enrichment using MβCD-cholesterol or LDL. These results demonstrate the novel information that cholesterol down-regulates BK channels by reducing KCa1.1 protein expression via increasing the channel protein degradation, and the effect is dependent on the auxiliary β1-subunit. PMID:24260325

  1. The temperature dependence of the BK channel activity - kinetics, thermodynamics, and long-range correlations.

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    Wawrzkiewicz-Jałowiecka, Agata; Dworakowska, Beata; Grzywna, Zbigniew J

    2017-10-01

    Large-conductance, voltage dependent, Ca 2+ -activated potassium channels (BK) are transmembrane proteins that regulate many biological processes by controlling potassium flow across cell membranes. Here, we investigate to what extent temperature (in the range of 17-37°C with ΔT=5°C step) is a regulating parameter of kinetic properties of the channel gating and memory effect in the series of dwell-time series of subsequent channel's states, at membrane depolarization and hyperpolarization. The obtained results indicate that temperature affects strongly the BK channels' gating, but, counterintuitively, it exerts no effect on the long-range correlations, as measured by the Hurst coefficient. Quantitative differences between dependencies of appropriate channel's characteristics on temperature are evident for different regimes of voltage. Examining the characteristics of BK channel activity as a function of temperature allows to estimate the net activation energy (E act ) and changes of thermodynamic parameters (ΔH, ΔS, ΔG) by channel opening. Larger E act corresponds to the channel activity at membrane hyperpolarization. The analysis of entropy and enthalpy changes of closed to open channel's transition suggest the entropy-driven nature of the increase of open state probability during voltage activation and supports the hypothesis about the voltage-dependent geometry of the channel vestibule. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Molecular Mechanisms Underlying Renin-Angiotensin-Aldosterone System Mediated Regulation of BK Channels

    OpenAIRE

    Zhang, Zhen-Ye; Qian, Ling-Ling; Wang, Ru-Xing

    2017-01-01

    Large-conductance calcium-activated potassium channels (BK channels) belong to a family of Ca2+-sensitive voltage-dependent potassium channels and play a vital role in various physiological activities in the human body. The renin-angiotensin-aldosterone system is acknowledged as being vital in the body's hormone system and plays a fundamental role in the maintenance of water and electrolyte balance and blood pressure regulation. There is growing evidence that the renin-angiotensin-aldosterone...

  3. Molecular investigations of BK(Ca) channels and the modulatory beta-subunits in porcine basilar and middle cerebral arteries

    DEFF Research Database (Denmark)

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

    2009-01-01

    arteries using reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time PCR. Western blotting was used to detect immunoreactivity for the porcine BK(Ca) channel alpha-subunit and beta-subunit proteins. The BK(Ca) channel alpha-subunit RNA and protein distribution patterns were......Large conductance calcium-activated potassium (BK(Ca)) channels are fundamental in the regulation of cerebral vascular basal tone. We investigated the expression of the mRNA transcripts for the BK(Ca) channel and its modulatory beta-subunits (beta1-beta4) in porcine basilar and middle cerebral...... visualized using in situ hybridization and immunofluorescence studies, respectively. The study verified that the BK(Ca) channel alpha-subunit is located to smooth muscle cells of porcine basilar and middle cerebral arteries. The mRNA transcript for beta1-, beta2- and beta4-subunit were shown by RT...

  4. A non-cardiomyocyte autonomous mechanism of cardioprotection involving the SLO1 BK channel

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    Andrew P. Wojtovich

    2013-03-01

    Full Text Available Opening of BK-type Ca2+ activated K+ channels protects the heart against ischemia-reperfusion (IR injury. However, the location of BK channels responsible for cardioprotection is debated. Herein we confirmed that openers of the SLO1 BK channel, NS1619 and NS11021, were protective in a mouse perfused heart model of IR injury. As anticipated, deletion of the Slo1 gene blocked this protection. However, in an isolated cardiomyocyte model of IR injury, protection by NS1619 and NS11021 was insensitive to Slo1 deletion. These data suggest that protection in intact hearts occurs by a non-cardiomyocyte autonomous, SLO1-dependent, mechanism. In this regard, an in-situ assay of intrinsic cardiac neuronal function (tachycardic response to nicotine revealed that NS1619 preserved cardiac neurons following IR injury. Furthermore, blockade of synaptic transmission by hexamethonium suppressed cardioprotection by NS1619 in intact hearts. These results suggest that opening SLO1 protects the heart during IR injury, via a mechanism that involves intrinsic cardiac neurons. Cardiac neuronal ion channels may be useful therapeutic targets for eliciting cardioprotection.

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

    Science.gov (United States)

    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.

  6. The activation of mitochondrial BK potassium channels contributes to the protective effects of naringenin against myocardial ischemia/reperfusion injury.

    Science.gov (United States)

    Testai, L; Martelli, A; Marino, A; D'Antongiovanni, V; Ciregia, F; Giusti, L; Lucacchini, A; Chericoni, S; Breschi, M C; Calderone, V

    2013-06-01

    Naringenin (NAR), flavonoid abundant in the genus Citrus, has been reported to interact with the large-conductance calcium-activated potassium channels (BK). Since activators of BK channels expressed in cardiac mitochondria trigger protective effects in several models of myocardial ischemia/reperfusion (I/R), this work aimed to evaluate the potential cardioprotective effects of NAR and the involvement of mitochondrial BK channels. In an in vivo model of acute infarct in rats, NAR (100mg/kg i.p.) significantly reduced the heart injury induced by I/R. This effect was antagonized by the selective BK-blocker paxilline (PAX). The cardioprotective dose of NAR did not cause significant effects on the blood pressure. In Largendorff-perfused rat hearts submitted to ischemia/reperfusion, NAR improved the post-ischemic functional parameters (left ventricle developed pressure and dP/dt) with lower extension of myocardial injury. On isolated rat cardiac mitochondria, NAR caused a concentration-dependent depolarization of mitochondrial membrane and caused a trans-membrane flow of thallium (potassium-mimetic cation). Both these effects were antagonized by selective blockers of BK channels. Furthermore, NAR half-reduced the calcium accumulation into the matrix of cardiac mitochondria exposed to high calcium concentrations. In conclusion, NAR exerts anti-ischemic effects through a "pharmacological preconditioning" that it is likely to be mediated, at least in part, by the activation of mitochondrial BK channels. Copyright © 2013. Published by Elsevier Inc.

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

    Science.gov (United States)

    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

  8. Recombinant Expression and Functional Characterization of Martentoxin: A Selective Inhibitor for BK Channel (α + β4

    Directory of Open Access Journals (Sweden)

    Jie Tao

    2014-04-01

    Full Text Available Martentoxin (MarTX, a 37-residue peptide purified from the venom of East-Asian scorpion (Buthus martensi Karsch, was capable of blocking large-conductance Ca2+-activated K+ (BK channels. Here, we report an effective expression and purification approach for this toxin. The cDNA encoding martentoxin was expressed by the prokaryotic expression system pGEX-4T-3 which was added an enterokinase cleavage site by PCR. The fusion protein (GST-rMarTX was digested by enterokinase to release hetero-expressed toxin and further purified via reverse-phase HPLC. The molecular weight of the hetero-expressed rMarTX was 4059.06 Da, which is identical to that of the natural peptide isolated from scorpion venom. Functional characterization through whole-cell patch clamp showed that rMarTX selectively and potently inhibited the currents of neuronal BK channels (α + β4 (IC50 = 186 nM, partly inhibited mKv1.3, but hardly having any significant effect on hKv4.2 and hKv3.1a even at 10 μM. Successful expression of martentoxin lays basis for further studies of structure-function relationship underlying martentoxin or other potassium-channel specific blockers.

  9. Activation of big conductance Ca(2+)-activated K (+) channels (BK) protects the heart against ischemia-reperfusion injury

    DEFF Research Database (Denmark)

    Bentzen, Bo Hjorth; Osadchii, Oleg; Jespersen, Thomas

    2009-01-01

    Activation of the large-conductance Ca(2+)-activated K(+) channel (BK) in the cardiac inner mitochondrial membrane has been suggested to protect the heart against ischemic injury. However, these findings are limited by the low selectivity profile and potency of the BK channel activator (NS1619...... complexes, while producing no effect on cardiac K(ATP) channels. The cardioprotective effects of NS11021-induced BK channel activation were studied in isolated, perfused rat hearts subjected to 35 min of global ischemia followed by 120 min of reperfusion. 3 microM NS11021 applied prior to ischemia...... or at the onset of reperfusion significantly reduced the infarct size [control: 44.6 +/- 2.0%; NS11021: 11.4 +/- 2.0%; NS11021 at reperfusion: 19.8 +/- 3.3% (p

  10. Location of the β4 transmembrane helices in the BK potassium channel

    Science.gov (United States)

    Wu, Roland S.; Chudasama, Neelesh; Zakharov, Sergey I.; Doshi, Darshan; Motoike, Howard; Liu, Guoxia; Yao, Yongneng; Niu, Xiaowei; Deng, Shi-Xian; Landry, Donald W.; Karlin, Arthur; Marx, Steven O.

    2009-01-01

    Large-conductance, voltage- and Ca2+-gated potassium (BK) channels control excitability in a number of cell types. BK channels are composed of α subunits, which contain the voltage-sensor domains and the Ca2+- sensor domains, and form the pore, and often one of four types of β subunits, which modulate the channel in a cell-specific manner. β4 is expressed in neurons throughout the brain. Deletion of β4 in mice causes temporal lobe epilepsy. Compared to channels composed of α alone, channels composed of α and β4 activate and deactivate more slowly. We inferred the locations of the two β4 transmembrane (TM) helices, TM1 and TM2, relative to the seven αTM helices, S0-S6, from the extent of disulfide bond formation between cysteines substituted in the extracellular flanks of these TM helices. We found that β4 TM2 is close to α S0 and that β4 TM1 is close to both α S1 and S2. At least at their extracellular ends, TM1 and TM2 are not close to S3 through S6. In six of eight of the most highly crosslinked cysteine pairs, four crosslinks from TM2 to S0 and one each from TM1 to S1 and S2 had small effects on the V50 and on the rates of activation and deactivation. That disulfide crosslinking caused only small functional perturbations is consistent with the proximity of the extracellular ends of TM2 to S0 and of TM1 to S1 and to S2, in both the open and closed states. PMID:19571123

  11. Ethanol modulation of mammalian BK channels in excitable tissues: molecular targets and their possible contribution to alcohol-induced altered behavior

    Directory of Open Access Journals (Sweden)

    Alex M. Dopico

    2014-12-01

    Full Text Available In most tissues, the function of calcium- and voltage-gated potassium (BK channels is modified in response to ethanol concentrations reached in human blood during alcohol intoxication. In general, modification of BK current from ethanol-naïve preparations in response to brief ethanol exposure results from changes in channel open probability without modification of unitary conductance or change in BK protein levels in the membrane. Protracted and/or repeated ethanol exposure, however, may evoke changes in BK expression. The final ethanol effect on BK open probability leading to either BK current potentiation or BK current reduction is determined by an orchestration of molecular factors, including levels of activating ligand (cytosolic calcium, BK subunit composition and posttranslational modifications, and the channel’s lipid microenvironment. These factors seem to allosterically regulate a direct interaction between ethanol and a recognition pocket of discrete dimensions recently mapped to the channel-forming (slo1 subunit. Type of ethanol exposure also plays a role in the final BK response to the drug: in several central nervous system regions (e.g., striatum, primary sensory neurons, and supraoptic nucleus, acute exposure to ethanol reduces neuronal excitability by enhancing BK activity. In contrast, protracted or repetitive ethanol administration may alter BK subunit composition and membrane expression, rendering the BK complex insensitive to further ethanol exposure. In neurohypophysial axon terminals, ethanol potentiation of BK channel activity leads to a reduction in neuropeptide release. In vascular smooth muscle, however, ethanol inhibition of BK current leads to cell contraction and vascular constriction.

  12. Testosterone decreases urinary bladder smooth muscle excitability via novel signaling mechanism involving direct activation of the BK channels

    Science.gov (United States)

    Hristov, Kiril L.; Parajuli, Shankar P.; Provence, Aaron

    2016-01-01

    In addition to improving sexual function, testosterone has been reported to have beneficial effects in ameliorating lower urinary tract symptoms by increasing bladder capacity and compliance, while decreasing bladder pressure. However, the cellular mechanisms by which testosterone regulates detrusor smooth muscle (DSM) excitability have not been elucidated. Here, we used amphotericin-B perforated whole cell patch-clamp and single channel recordings on inside-out excised membrane patches to investigate the regulatory role of testosterone in guinea pig DSM excitability. Testosterone (100 nM) significantly increased the depolarization-induced whole cell outward currents in DSM cells. The selective pharmacological inhibition of the large-conductance voltage- and Ca2+-activated K+ (BK) channels with paxilline (1 μM) completely abolished this stimulatory effect of testosterone, suggesting a mechanism involving BK channels. At a holding potential of −20 mV, DSM cells exhibited transient BK currents (TBKCs). Testosterone (100 nM) significantly increased TBKC activity in DSM cells. In current-clamp mode, testosterone (100 nM) significantly hyperpolarized the DSM cell resting membrane potential and increased spontaneous transient hyperpolarizations. Testosterone (100 nM) rapidly increased the single BK channel open probability in inside-out excised membrane patches from DSM cells, clearly suggesting a direct BK channel activation via a nongenomic mechanism. Live-cell Ca2+ imaging showed that testosterone (100 nM) caused a decrease in global intracellular Ca2+ concentration, consistent with testosterone-induced membrane hyperpolarization. In conclusion, the data provide compelling mechanistic evidence that under physiological conditions, testosterone at nanomolar concentrations directly activates BK channels in DSM cells, independent from genomic testosterone receptors, and thus regulates DSM excitability. PMID:27605581

  13. Activation of BK(Ca channels in zoledronic acid-induced apoptosis of MDA-MB-231 breast cancer cells.

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    Yu-Guang Ma

    Full Text Available BACKGROUND: Zoledronic acid, one of the most potent nitrogen-containing biphosphonates, has been demonstrated to have direct anti-tumor and anti-metastatic properties in breast cancer in vitro and in vivo. In particular, tumor-cell apoptosis has been recognized to play an important role in the treatment of metastatic breast cancer with zoledronic acid. However, the precise mechanisms remain less clear. In the present study, we investigated the specific role of large conductance Ca(2+-activated potassium (BK(Ca channel in zoledronic acid-induced apoptosis of estrogen receptor (ER-negative MDA-MB-231 breast cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: The action of zoledronic acid on BK(Ca channel was investigated by whole-cell and cell-attached patch clamp techniques. Cell apoptosis was assessed with immunocytochemistry, analysis of fragmented DNA by agarose gel electrophoresis, and flow cytometry assays. Cell proliferation was investigated by MTT test and immunocytochemistry. In addition, such findings were further confirmed with human embryonic kidney 293 (HEK293 cells which were transfected with functional BK(Ca α-subunit (hSloα. Our results clearly indicated that zoledronic acid directly increased the activities of BK(Ca channels, and then activation of BK(Ca channel by zoledronic acid contributed to induce apoptosis in MDA-MB-231 cells. The possible mechanisms were associated with the elevated level of intracellular Ca(2+ and a concomitant depolarization of mitochondrial membrane potential (Δψm in MDA-MB-231 cells. CONCLUSIONS: Activation of BK(Ca channel was here shown to be a novel molecular pathway involved in zoledronic acid-induced apoptosis of MDA-MB-231 cells in vitro.

  14. Coupling and cooperativity in voltage activation of a limited-state BK channel gating in saturating Ca2+.

    Science.gov (United States)

    Shelley, Christopher; Niu, Xiaowei; Geng, Yanyan; Magleby, Karl L

    2010-05-01

    Voltage-dependent gating mechanisms of large conductance Ca(2+) and voltage-activated (BK) channels were investigated using two-dimensional maximum likelihood analysis of single-channel open and closed intervals. To obtain sufficient data at negative as well as positive voltages, single-channel currents were recorded at saturating Ca(2+) from BK channels mutated to remove the RCK1 Ca(2+) and Mg(2+) sensors. The saturating Ca(2+) acting on the Ca(2+) bowl sensors of the resulting BK(B) channels increased channel activity while driving the gating into a reduced number of states, simplifying the model. Five highly constrained idealized gating mechanisms based on extensions of the Monod-Wyman-Changeux model for allosteric proteins were examined. A 10-state model without coupling between the voltage sensors and the opening/closing transitions partially described the voltage dependence of Po but not the single-channel kinetics. With allowed coupling, the model gave improved descriptions of Po and approximated the single-channel kinetics; each activated voltage sensor increased the opening rate approximately an additional 23-fold while having little effect on the closing rate. Allowing cooperativity among voltage sensors further improved the description of the data: each activated voltage sensor increased the activation rate of the remaining voltage sensors approximately fourfold, with little effect on the deactivation rate. The coupling factor was decreased in models with cooperativity from approximately 23 to approximately 18. Whether the apparent cooperativity among voltage sensors arises from imposing highly idealized models or from actual cooperativity will require additional studies to resolve. For both cooperative and noncooperative models, allowing transitions to five additional brief (flicker) closed states further improved the description of the data. These observations show that the voltage-dependent single-channel kinetics of BK(B) channels can be approximated

  15. [Co-location of ACh-sensitive BK channels and L-type calcium channels in type II vestibular hair cells of guinea pig].

    Science.gov (United States)

    Guo, Chang-Kai; Li, Guan-Qiao; Kong, Wei-Jia; Zhang, Song; Wu, Ting-Ting; Li, Jia-Li; Li, Qing-Tian

    2008-03-01

    To explore the mechanisms of the influx of calcium ions during the activation of ACh-sensitive BK channel (big conductance, calcium-dependent potassium channel) in type II vestibular hair cells of guinea pigs. Type II vestibular hair cells were isolated by collagenase type IA. Under the whole-cell patch mode, the sensitivity of ACh-sensitive BK current to the calcium channels blockers was investigated, the pharmacological property of L-type calcium channel activator-sensitive current and ACh-sensitive BK current was compared. Following application of ACh, type II vestibular hair cells displayed a sustained outward potassium current, with a reversal potential of (-70.5 +/- 10.6) mV (x +/- s, n = 10). At the holding potential of -50 mV, the current amplitude of ACh-sensitive potassium current activated by 100 micromol/L ACh was (267 +/- 106) pA (n = 11). ACh-sensitive potassium current was potently sensitive to the BK current blocker, IBTX (iberiotoxin, 200 nmol/L). Apamin, the well-known small conductance, calcium-dependent potassium current blocker, failed to inhibit the amplitude of ACh-sensitive potassium current at a dose of 1 micromol/L. ACh-sensitive BK current was sensitive to NiCl2 and potently inhibited by CdCl2. NiCl2 and CdCl2 showed a dose-dependent blocking effect with a half inhibition-maximal response of (135.5 +/- 18.5) micromol/L (n = 7) and (23.4 +/- 2.6) micromol/L (n = 7). The L-type calcium channel activator, (-) -Bay-K 8644 (10 micromol /L), mimicked the role of ACh and activated the IBTX-sensitive outward current. ACh-sensitive BK and L-type calcium channels are co-located in type II vestibular hair cells of guinea pigs.

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

    DEFF Research Database (Denmark)

    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 expressed...... (RT-PCR) in nervous tissue only where also the SS4(+81) variant was dominating with little expression of the short form SS4(0). SS4(+81) was present in some cerebral vessels too. The SS2(+174) variant (STREX) was found in both blood vessels and in nervous tissue. In situ hybridization data supported...... the finding of SS4(+81) and SS2(+174) in vascular smooth muscle and trigeminal ganglion. beta-subunits beta2 and beta4 showed high expression in brain and trigeminal ganglion and some in cerebral vessels while beta1 showed highest expression in blood vessels. beta3 was found only in testis and possibly brain...

  17. Mice with deficient BK channel function show impaired prepulse inhibition and spatial learning, but normal working and spatial reference memory.

    Science.gov (United States)

    Typlt, Marei; Mirkowski, Magdalena; Azzopardi, Erin; Ruettiger, Lukas; Ruth, Peter; Schmid, Susanne

    2013-01-01

    Genetic variations in the large-conductance, voltage- and calcium activated potassium channels (BK channels) have been recently implicated in mental retardation, autism and schizophrenia which all come along with severe cognitive impairments. In the present study we investigate the effects of functional BK channel deletion on cognition using a genetic mouse model with a knock-out of the gene for the pore forming α-subunit of the channel. We tested the F1 generation of a hybrid SV129/C57BL6 mouse line in which the slo1 gene was deleted in both parent strains. We first evaluated hearing and motor function to establish the suitability of this model for cognitive testing. Auditory brain stem responses to click stimuli showed no threshold differences between knockout mice and their wild-type littermates. Despite of muscular tremor, reduced grip force, and impaired gait, knockout mice exhibited normal locomotion. These findings allowed for testing of sensorimotor gating using the acoustic startle reflex, as well as of working memory, spatial learning and memory in the Y-maze and the Morris water maze, respectively. Prepulse inhibition on the first day of testing was normal, but the knockout mice did not improve over the days of testing as their wild-type littermates did. Spontaneous alternation in the y-maze was normal as well, suggesting that the BK channel knock-out does not impair working memory. In the Morris water maze knock-out mice showed significantly slower acquisition of the task, but normal memory once the task was learned. Thus, we propose a crucial role of the BK channels in learning, but not in memory storage or recollection.

  18. Mice with deficient BK channel function show impaired prepulse inhibition and spatial learning, but normal working and spatial reference memory.

    Directory of Open Access Journals (Sweden)

    Marei Typlt

    Full Text Available Genetic variations in the large-conductance, voltage- and calcium activated potassium channels (BK channels have been recently implicated in mental retardation, autism and schizophrenia which all come along with severe cognitive impairments. In the present study we investigate the effects of functional BK channel deletion on cognition using a genetic mouse model with a knock-out of the gene for the pore forming α-subunit of the channel. We tested the F1 generation of a hybrid SV129/C57BL6 mouse line in which the slo1 gene was deleted in both parent strains. We first evaluated hearing and motor function to establish the suitability of this model for cognitive testing. Auditory brain stem responses to click stimuli showed no threshold differences between knockout mice and their wild-type littermates. Despite of muscular tremor, reduced grip force, and impaired gait, knockout mice exhibited normal locomotion. These findings allowed for testing of sensorimotor gating using the acoustic startle reflex, as well as of working memory, spatial learning and memory in the Y-maze and the Morris water maze, respectively. Prepulse inhibition on the first day of testing was normal, but the knockout mice did not improve over the days of testing as their wild-type littermates did. Spontaneous alternation in the y-maze was normal as well, suggesting that the BK channel knock-out does not impair working memory. In the Morris water maze knock-out mice showed significantly slower acquisition of the task, but normal memory once the task was learned. Thus, we propose a crucial role of the BK channels in learning, but not in memory storage or recollection.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  2. 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......-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...... and localization of both mRNA and protein expression of the BK(Ca) channel in the smooth muscle cell layer in rat basilar, middle cerebral, and middle meningeal arteries....

  3. 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

    and localize the BK channels in the distal colon epithelium by iberiotoxin (IbTX) binding using the radiolabeled iberiotoxin analogue (125)I-IbTX-D19Y/Y36F, by autoradiography and by immunohistochemical studies. The results showed that the surface cells, responsible for Na(+) absorption, contained a high...

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

    Science.gov (United States)

    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.

  5. The role of potassium BK channels in anticonvulsant effect of cannabidiol in pentylenetetrazole and maximal electroshock models of seizure in mice.

    Science.gov (United States)

    Shirazi-zand, Zahra; Ahmad-Molaei, Leila; Motamedi, Fereshteh; Naderi, Nima

    2013-07-01

    Cannabidiol is a nonpsychoactive member of phytocannabinoids that produces various pharmacological effects that are not mediated through putative CB1/CB2 cannabinoid receptors and their related effectors. In this study, we examined the effect of the i.c.v. administration of potassium BK channel blocker paxilline alone and in combination with cannabidiol in protection against pentylenetetrazol (PTZ)- and maximal electroshock (MES)-induced seizure in mice. In the PTZ-induced seizure model, i.c.v. administration of cannabidiol caused a significant increase in seizure threshold compared with the control group. Moreover, while i.c.v. administration of various doses of paxilline did not produce significant change in the PTZ-induced seizure threshold in mice, coadministration of cannabidiol and paxilline attenuated the antiseizure effect of cannabidiol in PTZ-induced tonic seizures. In the MES model of seizure, both cannabidiol and paxilline per se produced significant increase in percent protection against electroshock-induced seizure. However, coadministration of cannabidiol and paxilline did not produce significant interaction in their antiseizure effect in the MES test. The results of the present study showed a protective effect of cannabidiol in both PTZ and MES models of seizure. These results suggested a BK channel-mediated antiseizure action of cannabidiol in PTZ model of seizure. However, such an interaction might not exist in MES-induced convulsion. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Local Transfer Coefficient, Smooth Channel

    Directory of Open Access Journals (Sweden)

    R. T. Kukreja

    1998-01-01

    Full Text Available Naphthalene sublimation technique and the heat/mass transfer analogy are used to determine the detailed local heat/mass transfer distributions on the leading and trailing walls of a twopass square channel with smooth walls that rotates about a perpendicular axis. Since the variation of density is small in the flow through the channel, buoyancy effect is negligible. Results show that, in both the stationary and rotating channel cases, very large spanwise variations of the mass transfer exist in he turn and in the region immediately downstream of the turn in the second straight pass. In the first straight pass, the rotation-induced Coriolis forces reduce the mass transfer on the leading wall and increase the mass transfer on the trailing wall. In the turn, rotation significantly increases the mass transfer on the leading wall, especially in the upstream half of the turn. Rotation also increases the mass transfer on the trailing wall, more in the downstream half of the turn than in the upstream half of the turn. Immediately downstream of the turn, rotation causes the mass transfer to be much higher on the trailing wall near the downstream corner of the tip of the inner wall than on the opposite leading wall. The mass transfer in the second pass is higher on the leading wall than on the trailing wall. A slower flow causes higher mass transfer enhancement in the turn on both the leading and trailing walls.

  7. The levosimendan metabolite OR-1896 elicits vasodilation by activating the K(ATP) and BK(Ca) channels in rat isolated arterioles.

    Science.gov (United States)

    Erdei, Nóra; Papp, Zoltán; Pollesello, Piero; Edes, István; Bagi, Zsolt

    2006-07-01

    1. We characterized the vasoactive effects of OR-1896, the long-lived metabolite of the inodilator levosimendan, in coronary and skeletal muscle microvessels. 2. The effect of OR-1896 on isolated, pressurized (80 mmHg) rat coronary and gracilis muscle arteriole (approximately 150 microm) diameters was investigated by videomicroscopy. 3. OR-1896 elicited concentration-dependent (1 nM-10 microM) dilations in coronary (maximal dilation: 66+/-6%, relative to that in Ca2+-free solutions; pD2: 7.16+/-0.42) and gracilis muscle arterioles (maximal dilation: 73+/-4%; pD2: 6.71+/-0.42), these dilations proving comparable to those induced by levosimendan (1 nM-10 microM) in coronary (maximal dilation: 83+/-6%; pD2: 7.06+/-0.14) and gracilis muscle arterioles (maximal dilation: 73+/-12%; pD2: 7.05+/-0.1). 4. The maximal dilations in response to OR-1896 were significantly (P<0.05) attenuated by the nonselective K+ channel inhibitor tetraethylammonium (1 mM) in coronary (to 34+/-9%) and gracilis muscle arterioles (to 28+/-6%). 5. Glibenclamide (5 or 10 microM), a selective ATP-sensitive K+ channel (KATP) blocker, elicited a greater reduction of OR-1896-induced dilations in skeletal muscle arterioles than in coronary microvessels. 6. Conversely, the selective inhibition of the large conductance Ca2+-activated K+ channels (BK(Ca)) with iberiotoxin (100 nM) significantly reduced the OR-1896-induced maximal dilation in coronary arterioles (to 21+/-6%), but was ineffective in skeletal muscle arterioles (72+/-8%). 7. Accordingly, OR-1896 elicits a substantial vasodilation in coronary and skeletal muscle arterioles, by activating primarily BK(Ca) and K(ATP) channels, respectively, and it is suggested that OR-1896 contributes to the long-term hemodynamic effects of levosimendan.

  8. 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

  9. Orientations and proximities of the extracellular ends of transmembrane helices S0 and S4 in open and closed BK potassium channels.

    Directory of Open Access Journals (Sweden)

    Xiaowei Niu

    Full Text Available The large-conductance potassium channel (BK α subunit contains a transmembrane (TM helix S0 preceding the canonical TM helices S1 through S6. S0 lies between S4 and the TM2 helix of the regulatory β1 subunit. Pairs of Cys were substituted in the first helical turns in the membrane of BK α S0 and S4 and in β1 TM2. One such pair, W22C in S0 and W203C in S4, was 95% crosslinked endogenously. Under voltage-clamp conditions in outside-out patches, this crosslink was reduced by DTT and reoxidized by a membrane-impermeant bis-quaternary ammonium derivative of diamide. The rate constants for this reoxidation were not significantly different in the open and closed states of the channel. Thus, these two residues are approximately equally close in the two states. In addition, 90% crosslinking of a second pair, R20C in S0 and W203C in S4, had no effect on the V50 for opening. Taken together, these findings indicate that separation between residues at the extracellular ends of S0 and S4 is not required for voltage-sensor activation. On the contrary, even though W22C and W203C were equally likely to form a disulfide in the activated and deactivated states, relative immobilization by crosslinking of these two residues favored the activated state. Furthermore, the efficiency of recrosslinking of W22C and W203C on the cell surface was greater in the presence of the β1 subunit than in its absence, consistent with β1 acting through S0 to stabilize its immobilization relative to α S4.

  10. Gentamicin blocks the ACh-induced BK current in guinea pig type II vestibular hair cells by competing with Ca²⁺ at the L-type calcium channel.

    Science.gov (United States)

    Yu, Hong; Guo, Chang-Kai; Wang, Yi; Zhou, Tao; Kong, Wei-Jia

    2014-04-22

    Type II vestibular hair cells (VHCs II) contain big-conductance Ca²⁺-dependent K⁺ channels (BK) and L-type calcium channels. Our previous studies in guinea pig VHCs II indicated that acetylcholine (ACh) evoked the BK current by triggering the influx of Ca²⁺ ions through L-type Ca²⁺ channels, which was mediated by M2 muscarinic ACh receptor (mAChRs). Aminoglycoside antibiotics, such as gentamicin (GM), are known to have vestibulotoxicity, including damaging effects on the efferent nerve endings on VHCs II. This study used the whole-cell patch clamp technique to determine whether GM affects the vestibular efferent system at postsynaptic M2-mAChRs or the membrane ion channels. We found that GM could block the ACh-induced BK current and that inhibition was reversible, voltage-independent, and dose-dependent with an IC₅₀ value of 36.3 ± 7.8 µM. Increasing the ACh concentration had little influence on GM blocking effect, but increasing the extracellular Ca²⁺ concentration ([Ca²⁺]₀) could antagonize it. Moreover, 50 µM GM potently blocked Ca²⁺ currents activated by (-)-Bay-K8644, but did not block BK currents induced by NS1619. These observations indicate that GM most likely blocks the M2 mAChR-mediated response by competing with Ca²⁺ at the L-type calcium channel. These results provide insights into the vestibulotoxicity of aminoglycoside antibiotics on mammalian VHCs II.

  11. Expression of BK Ca channels and the modulatory beta-subunits in the rat and porcine trigeminal ganglion

    DEFF Research Database (Denmark)

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

    2009-01-01

    (Ca) channel protein was visualized by western blotting and histochemistry. The presence of the modulatory beta1-beta 4 subunit mRNAs was investigated using RT-PCR. beta1-, beta2- and beta 4-subunit mRNAs were expressed in rat TG whereas beta2- and beta 4-subunits were detected in porcine TG. Western blotting...

  12. 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...

  13. Effects of amyloid β-peptide fragment 31-35 on the BK channel-mediated K⁺ current and intracellular free Ca²⁺ concentration of hippocampal CA1 neurons.

    Science.gov (United States)

    Zhang, Yu; Shi, Zhi-Gang; Wang, Zhi-Hua; Li, Jian-Guo; Chen, Jin-Yuan; Zhang, Ce

    2014-05-07

    The present study characterizes the effects of Aβ31-35, a short active fragment of amyloid β-peptide (Aβ), upon the BK channel-mediated K⁺ current and intracellular free Ca²⁺ concentration ([Ca²⁺]i) of freshly dissociated pyramidal cells from rat CA1 hippocampus by using whole-cell patch-clamp recording and single cell Ca²⁺ imaging techniques. The results show that: (1) in the presence of voltage- and ATP-gated K⁺ channel blockers application of 5.0 μM Aβ31-35 significantly diminished transient outward K⁺ current amplitudes at clamped voltages between 0 and 45mV; (2) under the same conditions [Ca²⁺]i was minimally affected by 5.0 μM but significantly increased by 12.5 μM and 25 μM Aβ31-35; and (3) when 25 μM of a larger fragment of the amyloid β-peptide, Aβ25-35, was applied, the results were similar to those obtained with the same concentration of Aβ31-35. These results indicate that Aβ31-35 is likely to be the shortest active fragment of the full Aβ sequence, and can be as effectively as the full-length Aβ peptide in suppressing BK-channel mediated K⁺ currents and significantly elevating [Ca²⁺]i in hippocampal CA1 neurons. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Advanced carrier sensing to resolve local channel congestion

    NARCIS (Netherlands)

    Schmidt, Robert K.; Brakemeier, Achim; Leinmüller, Tim; Kargl, Frank; Schäfer, Günther

    Communication performance in VANETs under high channel load is significantly degraded due to packet collisions and messages drops, also referred to as local channel congestion. So far, research was focused on the control of transmit power and the limitation of the messages rate to mitigate the

  15. Expression of BKCa 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

    (Ca) channel protein was visualized by western blotting and histochemistry. The presence of the modulatory beta1-beta 4 subunit mRNAs was investigated using RT-PCR. beta1-, beta2- and beta 4-subunit mRNAs were expressed in rat TG whereas beta2- and beta 4-subunits were detected in porcine TG. Western blotting...

  16. Decay properties of Bk24397 and Bk24497

    Science.gov (United States)

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

    2018-01-01

    Electron capture decays of 243Bk and 244Bk have been studied by measuring the γ -ray spectra of mass-separated sources and level structures of 243Cm and 244Cm have been deduced. In 243Cm, the electron capture population to the ground state, 1 /2+[631 ] , and 1 /2+[620 ] Nilsson states have been observed. The octupole Kπ=2- band was identified in 244Cm 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.

  17. Interactions of local anesthetics with voltage-gated Na+ channels.

    Science.gov (United States)

    Nau, C; Wang, G K

    2004-09-01

    Voltage-gated Na+ channels are dynamic transmembrane proteins responsible for the rising phase of the action potential in excitable membranes. Local anesthetics (LAs) and structurally related antiarrhythmic and anticonvulsant compounds target specific sites in voltage-gated Na+ channels to block Na+ currents, thus reducing excitability in neuronal, cardiac, or central nervous tissue. A high-affinity LA block is produced by binding to open and inactivated states of Na+ channels rather than to resting states and suggests a binding site that converts from a low- to a high-affinity conformation during gating. Recent findings using site-directed mutagenesis suggest that multiple S6 segments together form an LA binding site within the Na+ channel. While the selectivity filter may form the more extracellular-located part of this binding site, the role of the fast inactivation gate in LA binding has not yet been resolved. The receptor of the neurotoxin batrachotoxin (BTX) is adjacent to or even overlaps with the LA binding site. The close proximity of the LA and BTX binding sites to residues critical for inactivation, together with gating transitions through S6 segments, might explain the strong impact of LAs and BTX on inactivation of voltage-gated Na+ channels and might help elucidate the mechanisms underlying voltage- and frequency-dependent LA block.

  18. Local anesthetic block of batrachotoxin-resistant muscle Na+ channels.

    Science.gov (United States)

    Wang, G K; Quan, C; Wang, S Y

    1998-08-01

    Local anesthetics (LAs) are noncompetitive antagonists of batrachotoxin (BTX) in voltage-gated Na+ channels. The putative LA receptor has been delineated within the transmembrane segment S6 in domain IV of voltage-gated Na+ channels, whereas the putative BTX receptor is within segment S6 in domain I. In this study, we created BTX-resistant muscle Na+ channels at segment I-S6 (micro1-N434K, micro1-L437K) to test whether these residues modulate LA binding. These mutant channels were expressed in transiently transfected human embryonic kidney 293T cells, and their sensitivity to lidocaine, QX-314, etidocaine, and benzocaine was assayed under whole-cell, voltage-clamp conditions. Our results show that LA binding in BTX-resistant micro1 Na+ channels was reduced significantly. At -100 mV holding potential, the reduction in LA affinity was maximal for QX-314 (by 17-fold) and much less for neutral benzocaine (by 2-fold). Furthermore, this reduction was residue specific; substitution of positively charged lysine with negatively charged aspartic acid (micro1-N434D) restored or even enhanced the LA affinity. We conclude that micro1-N434K and micro1-L437K residues located near the middle of the I-S6 segment of Na+ channels can reduce the LA binding affinity without BTX. Thus, this reduction of the LA affinity by point mutations at the BTX binding site is not caused by gating changes induced by BTX alone. We surmise that the BTX receptor and the LA receptor within segments I-S6 and IV-S6, respectively, may align near or within the Na+ permeation pathway.

  19. [BK virus and renal transplantation].

    Science.gov (United States)

    Liu, Hang; Shi, Yi; Li, Chao-yang; Wang, Jian-li

    2009-06-01

    BK virus (BKV) is a subtype of papovaviridae. The latent and asymptomatic infection of BKV is common among healthy people. The incidence of BKV re-activation in renal transplant recipients ranges 10%-68%. About 1%-7% of renal transplant recipients will suffer from BKV-associated nephropathy (BKVAN), and half of them will experience graft failure. This paper summarizes the re-activation mechanism of BKV as well as the risk factors, pathology, diagnosis, and treatment of BKVAN.

  20. Innate Immunity and BK Virus: Prospective Strategies.

    Science.gov (United States)

    Kariminik, Ashraf; Yaghobi, Ramin; Dabiri, Shahriar

    2016-03-01

    Recent information demonstrated that BK virus reactivation is a dominant complication after kidney transplantation, which occurs because of immunosuppression. BK virus reactivation is the main reason of transplanted kidney losing. Immune response against BK virus is the major inhibitor of the virus reactivation. Therefore, improving our knowledge regarding the main parameters that fight against BK viruses can shed light on to direct new treatment strategies to suppress BK infection. Innate immunity consists of numerous cell systems and also soluble molecules, which not only suppress virus replication, but also activate adaptive immunity to eradicate the infection. Additionally, it appears that immune responses against reactivated BK virus are the main reasons for induction of BK virus-associated nephropathy (BKAN). Thus, improving our knowledge regarding the parameters and detailed mechanisms of innate immunity and also the status of innate immunity of the patients with BK virus reactivation and its complications can introduce new prospective strategies to either prevent or as therapy of the complication. Therefore, this review was aimed to collate the most recent data regarding the roles played by innate immunity against BK virus and also the status of innate immunity in the patients with reactivation BK virus and BKAN.

  1. Streamwise decay of localized states in channel flow

    Science.gov (United States)

    Zammert, Stefan; Eckhardt, Bruno

    2016-10-01

    Channel flow, the pressure driven flow between parallel plates, has exact coherent structures that show various degrees of localization. For states which are localized in streamwise direction but extended in spanwise direction, we show that they are exponentially localized, with decay constants that are different on the upstream and downstream sides. We extend the analysis of Brand and Gibson [J. Fluid Mech. 750, R1 (2014)], 10.1017/jfm.2014.285 for stationary states to the case of advected structures that is needed here, and derive expressions for the decay in terms of eigenvalues and eigenfunctions of certain second order differential equations. The results are in very good agreement with observations on exact coherent structures of different transversal wavelengths.

  2. Electrically tunable localized tunneling channels in silicene nanoribbons

    International Nuclear Information System (INIS)

    Saari, Timo; Huang, Cheng-Yi; Tsai, Wei-Feng; Nieminen, Jouko; Lin, Hsin; Bansil, Arun

    2014-01-01

    The topological phase of a silicene nanoribbon holding edge states in the bulk energy gap can be easily broken by an external electric field. Here, we show through low-energy Green's function calculations that it is possible to localize conducting channels anywhere in a silicene nanoribbon by applying an inhomogeneous electric field. The spin degeneracy of these channels can also be broken in the same manner, allowing conduction of spin as well as charge. On this basis, we suggest design of a ternary logic device, which could be used in low-power circuits. Our study demonstrates that silicene and related group IV elements with honeycomb structure could provide a platform for efficient manipulation of spin currents via external electric fields, without the need to switch magnetic fields for spintronics applications

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

    Science.gov (United States)

    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).

  4. Localization of Sodium Channels in Intercalated Disks Modulates Cardiac Conduction

    Science.gov (United States)

    Kucera, Jan P.; Rohr, Stephan; Rudy, Yoram

    2007-01-01

    It is well known that the sodium current (INa) and the degree of gap-junctional electrical coupling are the key determinants of action potential (AP) conduction in cardiac tissue. Immunohistochemical studies have shown that sodium channels (NaChs) are preferentially located in intercalated disks (IDs). Using dual immunocytochemical staining, we confirmed the colocalization of NaChs with connexin43 in cultures of neonatal rat ventricular myocytes. In mathematical simulations of conduction using the Luo-Rudy dynamic model of the ventricular AP, we assessed the hypothesis that conduction could be modulated by the preferential localization of NaChs in IDs. Localization of INa at the ID caused a large negative potential in the intercellular cleft, which influenced conduction in two opposing ways, depending on the degree of electrical coupling: (1) for normal and moderately reduced coupling, the negative cleft potential led to a large overshoot of the transmembrane potential resulting in a decreased driving force for INa itself (self-attenuation), which slowed conduction; (2) for greatly reduced coupling (<10%), the negative cleft potential induced by INa in the prejunctional membrane led to suprathreshold depolarization of the postjunctional membrane, which facilitated and accelerated conduction. When cleft potential effects were not incorporated, conduction was not significantly affected by the ID localization of INa. By enhancing conduction through the establishment of cleft potentials, the localization of NaChs in IDs might protect the myocardium from conduction block, very slow conduction, and microreentry under conditions of greatly reduced coupling. Conversely, by supporting moderately slow conduction, this mechanism could also promote arrhythmias PMID:12480819

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

    Directory of Open Access Journals (Sweden)

    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

  6. BK and JC virus: a review.

    Science.gov (United States)

    Pinto, Michelle; Dobson, Simon

    2014-01-01

    Polyomaviruses are ubiquitous, species-specific viruses belonging to the family Papovaviridae. The two most commonly known human polyomaviruses, BK virus and JC virus were first described in the 1970s. Newer human polyomaviruses, namely KI polyoma virus, WU polyoma virus and Merkel cell polyoma virus were identified in the last five years. Most humans encounter BK and JC virus during childhood, causing mild illness. However, when reactivated or acquired in the immunocompromised host, BK and JC virus have been implicated in a number of human clinical disease states. BK is most commonly associated with renal involvement, such as ureteral stenosis, hemorrhagic cystitis and nephropathy. Less commonly, it is associated with pneumonitis, retinitis, liver disease and meningoencephalitis. JC virus is most well known for its association with progressive multifocal leukoencephalopathy, and is possibly implicated in the development of various human neoplasms. The following chapter will outline the basic virology, epidemiology and clinical manifestations of BK and JC virus and discuss relevant diagnostic and treatment options. Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  7. 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

  8. Local growth laws for channels cut by springs

    Science.gov (United States)

    Petroff, A. P.; Devauchelle, O.; Abrams, D. M.; Rothman, D.

    2009-12-01

    The growth of a river network records the interplay between flowing water and flowing sediment. A complete interpretation of a river network therefore requires an understanding of how water is focused toward different parts of the network, how the topography responds, and how this response depends on the environment. In many networks, the interplay between flowing water and flowing sediment is obscured by the strong influence of the initial topography. However, when a ravine is cut by a spring, groundwater is focused due to variations in the shape of the water table rather than variations in the topography. Thus, in a seepage channel, sediment flux is only coupled to water flux at the channel. Here we report comparisons of theoretical predictions with field observation and analysis from a high-resolution LIDAR map to reveal the dependence of sediment flux on water flux in a kilometer-scale, seepage-channel network near Bristol, Florida. A comparison between predicted and observed fluxes demonstrates that the focusing of water depends only on the two-dimensional shape of the network. Thus, Darcy's law gives the flux of groundwater into each section of the network. The flux of water focused to a point shows a strong linear relationship with the slope of the channel wall at that point. Assuming linear diffusion, seepage channels remove sediment at a rate proportional to the flux of water. Moreover, small variations in the proportionality coefficient over the scale of the network are themselves proportional to variations in the average solar radiation, suggesting that the diffusion coefficient of the topography is higher in areas that receive more sunlight. Abrams, D. M., Lobkovsky, A. E., Petroff, A. P., Straub, K. M., McElroy, B., Mohrig, D. C., Kudrolli, A, and Rothman, D. H., Growth laws for channel networks incised by groundwater flow, Nature Geoscience 2, 193-196, March 2009.

  9. BK nephropathy in the native kidneys of patients with organ transplants: Clinical spectrum of BK infection

    Science.gov (United States)

    Vigil, Darlene; Konstantinov, Nikifor K; Barry, Marc; Harford, Antonia M; Servilla, Karen S; Kim, Young Ho; Sun, Yijuan; Ganta, Kavitha; Tzamaloukas, Antonios H

    2016-01-01

    Nephropathy secondary to BK virus, a member of the Papoviridae family of viruses, has been recognized for some time as an important cause of allograft dysfunction in renal transplant recipients. In recent times, BK nephropathy (BKN) of the native kidneys has being increasingly recognized as a cause of chronic kidney disease in patients with solid organ transplants, bone marrow transplants and in patients with other clinical entities associated with immunosuppression. In such patients renal dysfunction is often attributed to other factors including nephrotoxicity of medications used to prevent rejection of the transplanted organs. Renal biopsy is required for the diagnosis of BKN. Quantitation of the BK viral load in blood and urine are surrogate diagnostic methods. The treatment of BKN is based on reduction of the immunosuppressive medications. Several compounds have shown antiviral activity, but have not consistently shown to have beneficial effects in BKN. In addition to BKN, BK viral infection can cause severe urinary bladder cystitis, ureteritis and urinary tract obstruction as well as manifestations in other organ systems including the central nervous system, the respiratory system, the gastrointestinal system and the hematopoietic system. BK viral infection has also been implicated in tumorigenesis. The spectrum of clinical manifestations from BK infection and infection from other members of the Papoviridae family is widening. Prevention and treatment of BK infection and infections from other Papovaviruses are subjects of intense research. PMID:27683628

  10. Reconstruction of lightning channel geometry by localizing thunder sources

    Science.gov (United States)

    Bodhika, J. A. P.; Dharmarathna, W. G. D.; Fernando, Mahendra; Cooray, Vernon

    2013-09-01

    Thunder is generated as a result of a shock wave created by sudden expansion of air in the lightning channel due to high temperature variations. Even though the highest amplitudes of thunder signatures are generated at the return stroke stage, thunder signals generated at other events such as preliminary breakdown pulses also can be of amplitudes which are large enough to record using a sensitive system. In this study, it was attempted to reconstruct the lightning channel geometry of cloud and ground flashes by locating the temporal and spatial variations of thunder sources. Six lightning flashes were reconstructed using the recorded thunder signatures. Possible effects due to atmospheric conditions were neglected. Numerical calculations suggest that the time resolution of the recorded signal and 10 ms-1error in speed of sound leads to 2% and 3% errors, respectively, in the calculated coordinates. Reconstructed channel geometries for cloud and ground flashes agreed with the visual observations. Results suggest that the lightning channel can be successfully reconstructed using this technique.

  11. 32 channel DQPSK DWDM-PON for local area network using dispersion compensation fiber

    Directory of Open Access Journals (Sweden)

    Fazea Yousef

    2017-01-01

    Full Text Available In the contest to improving optical channel rates in dense wavelength multiplexing (DWDM service to realize 40Gb/s, different adjustment and coherent detection plans are being investigated. In this paper, we present differential quaternary phase-shift keying (DQPSK balance for the arrangement of a 32-channel DWDM in a Local Area Network (LAN.

  12. 32 channel DQPSK DWDM-PON for local area network using dispersion compensation fiber

    Science.gov (United States)

    Fazea, Yousef; Amphawan, Angela

    2017-11-01

    In the contest to improving optical channel rates in dense wavelength multiplexing (DWDM) service to realize 40Gb/s, different adjustment and coherent detection plans are being investigated. In this paper, we present differential quaternary phase-shift keying (DQPSK) balance for the arrangement of a 32-channel DWDM in a Local Area Network (LAN).

  13. Measurements of local two-phase flow parameters in a boiling flow channel

    International Nuclear Information System (INIS)

    Yun, Byong Jo; Park, Goon-CherI; Chung, Moon Ki; Song, Chul Hwa

    1998-01-01

    Local two-phase flow parameters were measured lo investigate the internal flow structures of steam-water boiling flow in an annulus channel. Two kinds of measuring methods for local two-phase flow parameters were investigated. These are a two-conductivity probe for local vapor parameters and a Pitot cube for local liquid parameters. Using these probes, the local distribution of phasic velocities, interfacial area concentration (IAC) and void fraction is measured. In this study, the maximum local void fraction in subcooled boiling condition is observed around the heating rod and the local void fraction is smoothly decreased from the surface of a heating rod to the channel center without any wall void peaking, which was observed in air-water experiments. The distributions of local IAC and bubble frequency coincide with those of local void fraction for a given area-averaged void fraction. (author)

  14. Variability of bed mobility in natural, gravel-bed channels and adjustments to sediment load at local and reach scales

    Science.gov (United States)

    Thomas E. Lisle; Jonathan M. Nelson; John Pitlick; Mary Ann Madej; Brent L. Barkett

    2000-01-01

    Abstract - Local variations in boundary shear stress acting on bed-surface particles control patterns of bed load transport and channel evolution during varying stream discharges. At the reach scale a channel adjusts to imposed water and sediment supply through mutual interactions among channel form, local grain size, and local flow dynamics that govern bed mobility...

  15. Potassium channels in the central nervous system of the snail, Helix pomatia: localization and functional characterization.

    Science.gov (United States)

    Battonyai, I; Krajcs, N; Serfőző, Z; Kiss, T; Elekes, K

    2014-05-30

    The distribution and functional presence of three voltage-dependent potassium channels, Kv2.1, Kv3.4, Kv4.3, respectively, were studied in the central nervous system of the snail Helix pomatia by immunohistochemical and electrophysiological methods. Cell clusters displaying immunoreactivity for the different channels were observed in all parts of the CNS, although their localization and number partly varied. Differences were also found in their intracellular, perikaryonal and axonal localization, as well as in their presence in non-neuronal tissues nearby the CNS, such as the perineurium and the aorta wall. At ultrastructural level Kv4.3 channel immunolabeling was observed in axon profiles containing large 80-100nm granular vesicles. Blotting analyses revealed specific signals for the Kv2.1, Kv3.4 and Kv4.3 channels, confirming the presence of the channels in the Helix CNS. Voltage-clamp recordings proved that outward currents obtained from neurons displaying Kv3.4 or Kv4.3 immunoreactivity contained transient components while Kv2.1 immunoreactive cells were characterized by delayed currents. The distribution of the K(+)-channels containing neurons suggests specific roles in intercellular signaling processes in the Helix CNS, most probably related to well-defined, partly local events. The cellular localization of the K(+)-channels studied supports their involvement in both pre- and postsynaptic events at perikaryonal and axonal levels. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. Localization and function of ATP-sensitive potassium channels in human skeletal muscle

    DEFF Research Database (Denmark)

    Nielsen, Jens Jung; Kristensen, Michael; Hellsten, Ylva

    2003-01-01

    The present study investigated the localization of ATP-sensitive K+ (KATP) channels in human skeletal muscle and the functional importance of these channels for human muscle K+ distribution at rest and during muscle activity. Membrane fractionation based on the giant vesicle technique...... or the sucrose-gradient technique in combination with Western blotting demonstrated that the KATP channels are mainly located in the sarcolemma. This localization was confirmed by immunohistochemical measurements. With the microdialysis technique, it was demonstrated that local application of the KATP channel...... inhibitor glibenclamide reduced (P approximately 4.5 to 4.0 mM, whereas the concentration in the control leg remained constant. Glibenclamide had no effect on the interstitial K+ accumulation during knee-extensor exercise at a power output of 60 W. In contrast...

  17. 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....... 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...... that stretch and volume sensitivity can be considered two independent regulatory mechanisms....

  18. 'Butamben, a specific local anesthetic and aspecific ion channel modulator'

    NARCIS (Netherlands)

    Beekwilder, Jeroen Petrus

    2008-01-01

    Butamben is a local anesthetic with some unusual characteristics. Epidural application in the form of a suspension leads to long-term selective pain suppression, leaving the motor system intact. The mechanism behind this selective behavior is not understood. In order to see whether this selectivity

  19. 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

    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...... channels were determined by a isotope flux assay where up to 44% of the total K+ channel activity could be inhibited by iberiotoxin indicating that BK channels are widely present in kidney epithelia. Consistent with these functional studies, 125I-IbTX-D19Y/Y36F binds to membrane vesicles from outer cortex...

  20. Deformation localization and dislocation channel dynamics in neutron-irradiated austenitic stainless steels

    Science.gov (United States)

    Gussev, Maxim N.; Field, Kevin G.; Busby, Jeremy T.

    2015-05-01

    The dynamics of deformation localization and dislocation channel formation were investigated in situ in a neutron-irradiated AISI 304 austenitic stainless steel and a model 304-based austenitic alloy by combining several analytical techniques including optic microscopy and laser confocal microscopy, scanning electron microscopy, electron backscatter diffraction, and transmission electron microscopy (TEM). Channel formation was observed at ∼70% of the polycrystalline yield stress of the irradiated materials (σ0.2). It was shown that triple junction points do not always serve as a source of dislocation channels; at stress levels below the σ0.2, channels often formed near the middle of the grain boundary. For a single grain, the role of elastic stiffness value (Young's modulus) in channel formation was analyzed; it was shown that in the irradiated 304 steels the initial channels appeared in "soft" grains with a high Schmid factor located near "stiff" grains with high elastic stiffness. The spatial organization of channels in a single grain was analyzed; it was shown that secondary channels operating in the same slip plane as primary channels often appeared at the middle or at one-third of the way between primary channels. The twinning nature of dislocation channels was analyzed for grains of different orientation using TEM. In the AISI 304 steel, channels in grains oriented close to 〈0 0 1〉||TA (tensile axis) and 〈1 0 1〉||TA were twin free and grain with 〈1 1 1〉||TA and grains oriented close to a Schmid factor maximum contained deformation twins.

  1. A novel crystallization method for visualizing the membrane localization of potassium channels.

    OpenAIRE

    Lopatin, A N; Makhina, E N; Nichols, C G

    1998-01-01

    The high permeability of K+ channels to monovalent thallium (Tl+) ions and the low solubility of thallium bromide salt were used to develop a simple yet very sensitive approach to the study of membrane localization of potassium channels. K+ channels (Kir1.1, Kir2.1, Kir2.3, Kv2.1), were expressed in Xenopus oocytes and loaded with Br ions by microinjection. Oocytes were then exposed to extracellular thallium. Under conditions favoring influx of Tl+ ions (negative membrane potential under volt...

  2. Hole mobility enhancement of p-MOSFETs using global and local Ge-channel technologies

    International Nuclear Information System (INIS)

    Takagi, Shinichi; Tezuka, T.; Irisawa, T.; Nakaharai, S.; Maeda, T.; Numata, T.; Ikeda, K.; Sugiyama, N.

    2006-01-01

    Mobility enhancement technologies have currently been recognized as mandatory for future scaled MOSFETs. In this paper, we review our recent results on high hole mobility p-MOSFETs using global/local SiGe or Ge channels. There are two directions for introducing SiGe or Ge channels into Si CMOS platform. One is to use SiGe or Ge global substrates and the other is to form SiGe or Ge-channel regions locally on Si wafers. In both cases, the Ge condensation technique, where Ge-channel layers are formed by oxidizing SiGe films on SOI substrates, are effectively utilized. As for the global technologies, ultrathin GOI substrates are prepared and used to fabricate high mobility GOI p-MOSFETs. As for the local technologies, SGOI or GOI channels are formed locally in the active area of p-MOSFETs on SOI wafers. It is shown that the hole mobility enhancement factor of as high as 10 is obtained in locally fabricated p-MOSFETs through the effects of high-Ge content and the compressive strain. Furthermore, the local Ge-channel technologies are combined with global SiGe or Ge substrates for pursuing the optimal and individual design of n-MOSFETs and p-MOSFETs on a single Si wafer. The CMOS device composed of strained-Si n-MOSFETs and SGOI p-MOSFETs is successfully integrated on a same wafer, which is a promising CMOS structure under deep sub 100 nm technology nodes

  3. LOCAL HEAT TRANSFER AT THE END FACES CHANNEL PROFILES OF TURBINE NOZZLES FOR INTENSE SECONDARY FLOWS

    Directory of Open Access Journals (Sweden)

    A. Kashchenko

    2015-07-01

    Full Text Available Results of experimental study of local heat transfer at the end surfaces of channel profiles of turbine nozzles in secondary currents, the intensity of which was varied by reducing the height of the profiles are presented. The thickness of the boundary layer on the inlet in the channel profiles was reduced to the minimum possible in the experiment. The data characterizing the distribution of local heat transfer coefficients on the end surface in a wide range of characteristic parameters change is obtained.

  4. 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...

  5. Influence of Global and Local Membrane Curvature on Mechanosensitive Ion Channels: A Finite Element Approach

    Directory of Open Access Journals (Sweden)

    Omid Bavi

    2016-02-01

    Full Text Available Mechanosensitive (MS channels are ubiquitous molecular force sensors that respond to a number of different mechanical stimuli including tensile, compressive and shear stress. MS channels are also proposed to be molecular curvature sensors gating in response to bending in their local environment. One of the main mechanisms to functionally study these channels is the patch clamp technique. However, the patch of membrane surveyed using this methodology is far from physiological. Here we use continuum mechanics to probe the question of how curvature, in a standard patch clamp experiment, at different length scales (global and local affects a model MS channel. Firstly, to increase the accuracy of the Laplace’s equation in tension estimation in a patch membrane and to be able to more precisely describe the transient phenomena happening during patch clamping, we propose a modified Laplace’s equation. Most importantly, we unambiguously show that the global curvature of a patch, which is visible under the microscope during patch clamp experiments, is of negligible energetic consequence for activation of an MS channel in a model membrane. However, the local curvature (RL < 50 and the direction of bending are able to cause considerable changes in the stress distribution through the thickness of the membrane. Not only does local bending, in the order of physiologically relevant curvatures, cause a substantial change in the pressure profile but it also significantly modifies the stress distribution in response to force application. Understanding these stress variations in regions of high local bending is essential for a complete understanding of the effects of curvature on MS channels.

  6. A functional nuclear localization sequence in the C. elegans TRPV channel OCR-2.

    Directory of Open Access Journals (Sweden)

    Meredith J Ezak

    Full Text Available The ability to modulate gene expression in response to sensory experience is critical to the normal development and function of the nervous system. Calcium is a key activator of the signal transduction cascades that mediate the process of translating a cellular stimulus into transcriptional changes. With the recent discovery that the mammalian Ca(v1.2 calcium channel can be cleaved, enter the nucleus and act as a transcription factor to control neuronal gene expression, a more direct role for the calcium channels themselves in regulating transcription has begun to be appreciated. Here we report the identification of a nuclear localization sequence (NLS in the C. elegans transient receptor potential vanilloid (TRPV cation channel OCR-2. TRPV channels have previously been implicated in transcriptional regulation of neuronal genes in the nematode, although the precise mechanism remains unclear. We show that the NLS in OCR-2 is functional, being able to direct nuclear accumulation of a synthetic cargo protein as well as the carboxy-terminal cytosolic tail of OCR-2 where it is endogenously found. Furthermore, we discovered that a carboxy-terminal portion of the full-length channel can localize to the nucleus of neuronal cells. These results suggest that the OCR-2 TRPV cation channel may have a direct nuclear function in neuronal cells that was not previously appreciated.

  7. Fear conditioning suppresses large-conductance calcium-activated potassium channels in lateral amygdala neurons.

    Science.gov (United States)

    Sun, P; Zhang, Q; Zhang, Y; Wang, F; Wang, L; Yamamoto, R; Sugai, T; Kato, N

    2015-01-01

    It was previously shown that depression-like behavior is accompanied with suppression of the large-conductance calcium activated potassium (BK) channel in cingulate cortex pyramidal cells. To test whether BK channels are also involved in fear conditioning, we studied neuronal properties of amygdala principal cells in fear conditioned mice. After behavior, we made brain slices containing the amygdala, the structure critically relevant to fear memory. The resting membrane potential in lateral amygdala (LA) neurons obtained from fear conditioned mice (FC group) was more depolarized than in neurons from naïve controls. The frequencies of spikes evoked by current injections were higher in neurons from FC mice, demonstrating that excitability of LA neurons was elevated by fear conditioning. The depolarization in neurons from FC mice was shown to depend on BK channels by using the BK channel blocker charybdotoxin. Suppression of BK channels in LA neurons from the FC group was further confirmed on the basis of the spike width, since BK channels affect the descending phase of spikes. Spikes were broader in the FC group than those in the naïve control in a manner dependent on BK channels. Consistently, quantitative real-time PCR revealed a decreased expression of BK channel mRNA. The present findings suggest that emotional disorder manifested in the forms of fear conditioning is accompanied with BK channel suppression in the amygdala, the brain structure critical to this emotional disorder. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Distribution of Fecal Indicator Bacteria in Sediment of Local Open Channels Receiving Johkasou Effluent

    Directory of Open Access Journals (Sweden)

    Joni Aldilla Fajri

    2017-07-01

    Full Text Available Onsite wastewater treatment system named Johkasou has been widely applied in the Japanese rural areas, which the effluent is mainly discharged into stream channels. However, Johkasou effluent would potentially be a source of contamination that can deteriorate water and sediment quality of the receiving downstream network. In order to identify the effect of Johkasou effluent particularly in sediment, a study on the distribution of fecal indicators (F-RNA bacteriophages, total coliform (TC, and Escherichia coli [E. coli] in several sediment spots of local open channels receiving Johkasou effluent was conducted. The results showed that the contents of F-RNA bacteriophages, TC and E. coli in the sediment of open channels were detected in high levels while those contents in the sediment of Johkasou drainage channel were up to two orders magnitude higher than in the open channel. A high number of fecal bacteria in the receiving open channels was majorly influenced by the number of domestic households. Moderate correlations of fecal bacteria indicator with solid sediment and volatile sediment indicate that the sediment particles can be carriers of microbes to the downstream water networks. Therefore, water flushing and hydraulic events are suggested to reduce sediment depth that contained fecal bacteria indicator in the open channel.

  9. A basic design of microcontroller based data processor and local display for digital logarithmic power channel

    International Nuclear Information System (INIS)

    Nur Khasan; Syahrudin Yusuf

    2009-01-01

    A data processor and its local display for a digital logarithmic power channel, which will be used as a complement and diversification of nuclear reactor instrument, has been designed using micro controller base circuit. This power channel has been designed using TTL device and microcontroller. The roll of the microcontroller will be as data acquisition, data processing for the measurement of percentage reactor power, period and the trip decision. In this design has beer; created display of numerical value will be display on the local display in on-line mode for 1 nV to 10 10 nV neutron flux measurement range. This logarithmic power channel is expected to support the existing instrument which uses analog system in Instrumentation and Control System of nuclear reactor. (author)

  10. Strength tests of cold-formed channel sections undergoing local and distortional buckling

    Science.gov (United States)

    Kwon, Y. B.; Hancock, G. J.

    1991-06-01

    In this report, the results of compression tests of thin-walled channel section columns formed by brake-precessing are described. Two different section geometries, a simple lipped channel and a lipped channel with an intermediate stiffener in the web, were tested between fixed-ended boundary conditions. The geometries and yield strength were chosen to ensure that a substantial post-buckling strength reserve occurred in the distortional mode and that local buckling might occur simultaneously at a shorter wavelength. The deformations were measured using a movable frame on which linear displacement transducers were mounted. The residual stresses and material properties were also measured. Distortional or mixed local distortional buckling stresses obtained from testing are compared with theoretical buckling stresses. Design curves for the maximum strength of the columns undergoing distortional or mixed modes of buckling are proposed and compared with the test results.

  11. 76 FR 60729 - Special Local Regulations for Marine Events, Wrightsville Channel; Wrightsville Beach, NC

    Science.gov (United States)

    2011-09-30

    ..., Wrightsville Channel; Wrightsville Beach, NC AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast Guard is establishing temporary special local regulations for the swim portions of ``Beach 2 Battleship Full and Half Iron Distance Triathlon'', to be held on the waters adjacent to Wrightsville Beach...

  12. Local visible-light induced modification of the inside of glass and COC microfluidic channels

    NARCIS (Netherlands)

    Carvalho, R.R.; Pujari, S.P.; Vrouwe, E.X.; Zuilhof, H.

    2016-01-01

    The ability to locally modify the inside of microfluidic channels with functional groups that allow coupling of biologically-relevant molecules is of ever-rising relevance. We report the first example of visible-light induced hydrosilylation on hydrogen-terminated silanized glass (H-?-Glass) and

  13. Molecular mechanism of allosteric modification of voltage-dependent sodium channels by local anesthetics.

    Science.gov (United States)

    Arcisio-Miranda, Manoel; Muroi, Yukiko; Chowdhury, Sandipan; Chanda, Baron

    2010-11-01

    The hallmark of many intracellular pore blockers such as tetra-alkylammonium compounds and local anesthetics is their ability to allosterically modify the movement of the voltage sensors in voltage-dependent ion channels. For instance, the voltage sensor of domain III is specifically stabilized in the activated state when sodium currents are blocked by local anesthetics. The molecular mechanism underlying this long-range interaction between the blocker-binding site in the pore and voltage sensors remains poorly understood. Here, using scanning mutagenesis in combination with voltage clamp fluorimetry, we systematically evaluate the role of the internal gating interface of domain III of the sodium channel. We find that several mutations in the S4-S5 linker and S5 and S6 helices dramatically reduce the stabilizing effect of lidocaine on the activation of domain III voltage sensor without significantly altering use-dependent block at saturating drug concentrations. In the wild-type skeletal muscle sodium channel, local anesthetic block is accompanied by a 21% reduction in the total gating charge. In contrast, point mutations in this critical intracellular region reduce this charge modification by local anesthetics. Our analysis of a simple model suggests that these mutations in the gating interface are likely to disrupt the various coupling interactions between the voltage sensor and the pore of the sodium channel. These findings provide a molecular framework for understanding the mechanisms underlying allosteric interactions between a drug-binding site and voltage sensors.

  14. Semi-local scaling and turbulence modulation in variable property turbulent channel flows

    NARCIS (Netherlands)

    Patel, A.; Peeters, J.W.R.; Boersma, B.J.; Pecnik, R.

    2015-01-01

    We theoretically and numerically investigate the effect of temperature dependent density and viscosity on turbulence in channel flows. First, a mathematical framework is developed to support the validity of the semi-local scaling as proposed based on heuristic arguments by Huang, Coleman, and

  15. [Reconstitution of large conductance calcium-activated potassium channels into artificial planar lipid bilayers].

    Science.gov (United States)

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

    2017-06-25

    This study was aimed to establish a method to create a stable planar lipid bilayer membranes (PLBMs), in which large conductance calcium-activated potassium channels (BK Ca ) were reconstituted. Using spreading method, PLBMs were prepared by decane lipid fluid consisting of N 2 -weathered mixture of phosphatidylcholine and cholesterol at 3:1 ratio. After successful incorporation of BK Ca channel into PLBMs, single channel characteristics of BK Ca were studied by patch clamp method. The results showed that i) the single channel conductance of BK Ca was (206.8 ± 16.9) pS; ii) the activities of BK Ca channel were voltage dependent; iii) in the bath solution without Ca 2+ , there was almost no BK Ca channel activities regardless of under hyperpolarization or repolarization conditions; iv) under the condition of +40 mV membrane potential, BK Ca channels were activated in a Ca 2+ concentration dependent manner; v) when [Ca 2+ ] was increased from 1 μmol/L to 100 μmol/L, both the channel open probability and the average open time were increased, and the average close time was decreased from (32.2 ± 2.8) ms to (2.1 ± 1.8) ms; vi) the reverse potential of the reconstituted BK Ca was -30 mV when [K + ] was at 40/140 mmol/L (Cis/Trans). These results suggest that the spreading method could serve as a new method for preparing PLBMs and the reconstituted BK Ca into PLBMs showed similar electrophysiological characteristics to natural BK Ca channels, so the PLBMs with incorporated BK Ca can be used in the studies of pharmacology and dynamics of BK Ca channel.

  16. 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

  17. The use of kernel local Fisher discriminant analysis for the channelization of the Hotelling model observer

    Science.gov (United States)

    Wen, Gezheng; Markey, Mia K.

    2015-03-01

    It is resource-intensive to conduct human studies for task-based assessment of medical image quality and system optimization. Thus, numerical model observers have been developed as a surrogate for human observers. The Hotelling observer (HO) is the optimal linear observer for signal-detection tasks, but the high dimensionality of imaging data results in a heavy computational burden. Channelization is often used to approximate the HO through a dimensionality reduction step, but how to produce channelized images without losing significant image information remains a key challenge. Kernel local Fisher discriminant analysis (KLFDA) uses kernel techniques to perform supervised dimensionality reduction, which finds an embedding transformation that maximizes betweenclass separability and preserves within-class local structure in the low-dimensional manifold. It is powerful for classification tasks, especially when the distribution of a class is multimodal. Such multimodality could be observed in many practical clinical tasks. For example, primary and metastatic lesions may both appear in medical imaging studies, but the distributions of their typical characteristics (e.g., size) may be very different. In this study, we propose to use KLFDA as a novel channelization method. The dimension of the embedded manifold (i.e., the result of KLFDA) is a counterpart to the number of channels in the state-of-art linear channelization. We present a simulation study to demonstrate the potential usefulness of KLFDA for building the channelized HOs (CHOs) and generating reliable decision statistics for clinical tasks. We show that the performance of the CHO with KLFDA channels is comparable to that of the benchmark CHOs.

  18. Residues in Na(+) channel D3-S6 segment modulate both batrachotoxin and local anesthetic affinities.

    Science.gov (United States)

    Wang, S Y; Nau, C; Wang, G K

    2000-09-01

    Batrachotoxin (BTX) alters the gating of voltage-gated Na(+) channels and causes these channels to open persistently, whereas local anesthetics (LAs) block Na(+) conductance. The BTX and LA receptors have been mapped to several common residues in D1-S6 and D4-S6 segments of the Na(+) channel alpha-subunit. We substituted individual residues with lysine in homologous segment D3-S6 of the rat muscle mu1 Na(+) channel from F1274 to N1281 to determine whether additional residues are involved in BTX and LA binding. Two mutant channels, mu1-S1276K and mu1-L1280K, when expressed in mammalian cells, become completely resistant to 5 microM BTX during repetitive pulses. The activation and/or fast inactivation gating of these mutants is substantially different from that of wild type. These mutants also display approximately 10-20-fold reduction in bupivacaine affinity toward their inactivated state but show only approximately twofold affinity changes toward their resting state. These results demonstrate that residues mu1-S1276 and mu1-L1280 in D3-S6 are critical for both BTX and LA binding interactions. We propose that LAs interact readily with these residues from D3-S6 along with those from D1-S6 and D4-S6 in close proximity when the Na(+) channel is in its inactivated state. Implications of this state-dependent binding model for the S6 alignment are discussed.

  19. New data processing of local heat transfer coefficient inside a rectangular channel

    Science.gov (United States)

    Gramazio, P.; Vitali, L.; Fustinoni, D.; Niro, A.

    2017-11-01

    In this paper, we critically reconsider and discuss the models used in one of our previous work to calculate the local convective heat flux for forced air-flows inside narrow rectangular channel, in order to evaluate the limitations which may be inherent with them. To this end, several numerical FEM models have been developed in COMSOL™ and used to analyze in depth previous data processing procedures; furthermore, experimental tests are made on the channel materials, to determine their thermal conductivities and radiative properties. Here, the results of this analysis are presented and discussed.

  20. A theory of local learning, the learning channel, and the optimality of backpropagation.

    Science.gov (United States)

    Baldi, Pierre; Sadowski, Peter

    2016-11-01

    In a physical neural system, where storage and processing are intimately intertwined, the rules for adjusting the synaptic weights can only depend on variables that are available locally, such as the activity of the pre- and post-synaptic neurons, resulting in local learning rules. A systematic framework for studying the space of local learning rules is obtained by first specifying the nature of the local variables, and then the functional form that ties them together into each learning rule. Such a framework enables also the systematic discovery of new learning rules and exploration of relationships between learning rules and group symmetries. We study polynomial local learning rules stratified by their degree and analyze their behavior and capabilities in both linear and non-linear units and networks. Stacking local learning rules in deep feedforward networks leads to deep local learning. While deep local learning can learn interesting representations, it cannot learn complex input-output functions, even when targets are available for the top layer. Learning complex input-output functions requires local deep learning where target information is communicated to the deep layers through a backward learning channel. The nature of the communicated information about the targets and the structure of the learning channel partition the space of learning algorithms. For any learning algorithm, the capacity of the learning channel can be defined as the number of bits provided about the error gradient per weight, divided by the number of required operations per weight. We estimate the capacity associated with several learning algorithms and show that backpropagation outperforms them by simultaneously maximizing the information rate and minimizing the computational cost. This result is also shown to be true for recurrent networks, by unfolding them in time. The theory clarifies the concept of Hebbian learning, establishes the power and limitations of local learning rules

  1. Bedform migration in steep channels: from local avalanches to large scale changes

    Science.gov (United States)

    Mettra, F.; Heyman, J.; Ancey, C.

    2013-12-01

    flume angles and produced intense solid discharge pulses. Moreover, small avalanches occurred on the steep lee sides of antidunes. From these results, we infer a mechanism of steep channel evolution. The time- and space-averaged profile of the bed in the streamwise direction depends on the experimental parameters. Variations in the profile result mainly from bedform migration. The instantaneous global state of the bed (which can be characterized by the global channel slope) controls the growth of bedforms, which can be seen as local instabilities. When the global channel slope approaches its critical value, local instabilities of higher amplitude can develop and create intense bedload transport pulses, leading to a less steep, but more stable bed profile.

  2. Dual channel rank-based intensity weighting for quantitative co-localization of microscopy images

    LENUS (Irish Health Repository)

    Singan, Vasanth R

    2011-10-21

    Abstract Background Accurate quantitative co-localization is a key parameter in the context of understanding the spatial co-ordination of molecules and therefore their function in cells. Existing co-localization algorithms consider either the presence of co-occurring pixels or correlations of intensity in regions of interest. Depending on the image source, and the algorithm selected, the co-localization coefficients determined can be highly variable, and often inaccurate. Furthermore, this choice of whether co-occurrence or correlation is the best approach for quantifying co-localization remains controversial. Results We have developed a novel algorithm to quantify co-localization that improves on and addresses the major shortcomings of existing co-localization measures. This algorithm uses a non-parametric ranking of pixel intensities in each channel, and the difference in ranks of co-localizing pixel positions in the two channels is used to weight the coefficient. This weighting is applied to co-occurring pixels thereby efficiently combining both co-occurrence and correlation. Tests with synthetic data sets show that the algorithm is sensitive to both co-occurrence and correlation at varying levels of intensity. Analysis of biological data sets demonstrate that this new algorithm offers high sensitivity, and that it is capable of detecting subtle changes in co-localization, exemplified by studies on a well characterized cargo protein that moves through the secretory pathway of cells. Conclusions This algorithm provides a novel way to efficiently combine co-occurrence and correlation components in biological images, thereby generating an accurate measure of co-localization. This approach of rank weighting of intensities also eliminates the need for manual thresholding of the image, which is often a cause of error in co-localization quantification. We envisage that this tool will facilitate the quantitative analysis of a wide range of biological data sets

  3. Mefloquine inhibits voltage dependent Nav1.4 channel by overlapping the local anaesthetic binding site.

    Science.gov (United States)

    Paiz-Candia, Bertin; Islas, Angel A; Sánchez-Solano, Alfredo; Mancilla-Simbro, Claudia; Scior, Thomas; Millan-PerezPeña, Lourdes; Salinas-Stefanon, Eduardo M

    2017-02-05

    Mefloquine constitutes a multitarget antimalaric that inhibits cation currents. However, the effect and the binding site of this compound on Na + channels is unknown. To address the mechanism of action of mefloquine, we employed two-electrode voltage clamp recordings on Xenopus laevis oocytes, site-directed mutagenesis of the rat Na + channel, and a combined in silico approach using Molecular Dynamics and docking protocols. We found that mefloquine: i) inhibited Na v 1.4 currents (IC 50 =60μM), ii) significantly delayed fast inactivation but did not affect recovery from inactivation, iii) markedly the shifted steady-state inactivation curve to more hyperpolarized potentials. The presence of the β1 subunit significantly reduced mefloquine potency, but the drug induced a significant frequency-independent rundown upon repetitive depolarisations. Computational and experimental results indicate that mefloquine overlaps the local anaesthetic binding site by docking at a hydrophobic cavity between domains DIII and DIV that communicates the local anaesthetic binding site with the selectivity filter. This is supported by the fact that mefloquine potency significantly decreased on mutant Na v 1.4 channel F1579A and significantly increased on K1237S channels. In silico this compound docked above F1579 forming stable π-π interactions with this residue. We provide structure-activity insights into how cationic amphiphilic compounds may exert inhibitory effects by docking between the local anaesthetic binding site and the selectivity filter of a mammalian Na + channel. Our proposed synergistic cycle of experimental and computational studies may be useful for elucidating binding sites of other drugs, thereby saving in vitro and in silico resources. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Effect of Local Junction Losses in the Optimization of T-shaped Flow Channels

    Science.gov (United States)

    Kosaraju, Srinivas

    2015-11-01

    T-shaped channels are extensively used in flow distribution applications such as irrigation, chemical dispersion, gas pipelines and space heating and cooling. The geometry of T-shaped channels can be optimized to reduce the overall pressure drop in stem and branch sections. Results of such optimizations are in the form of geometric parameters such as the length and diameter ratios of the stem and branch sections. The traditional approach of this optimization accounts for the pressure drop across the stem and branch sections, however, ignores the pressure drop in the T-junction. In this paper, we conduct geometry optimization while including the effect of local junction losses in laminar flows. From the results, we are able to identify a non-dimensional parameter that can be used to predict the optimal geometric configurations. This parameter can also be used to identify the conditions in which the local junction losses can be ignored during the optimization.

  5. Synaptic Ribbons Require Ribeye for Electron Density, Proper Synaptic Localization, and Recruitment of Calcium Channels

    Directory of Open Access Journals (Sweden)

    Caixia Lv

    2016-06-01

    Full Text Available Synaptic ribbons are structures made largely of the protein Ribeye that hold synaptic vesicles near release sites in non-spiking cells in some sensory systems. Here, we introduce frameshift mutations in the two zebrafish genes encoding for Ribeye and thus remove Ribeye protein from neuromast hair cells. Despite Ribeye depletion, vesicles collect around ribbon-like structures that lack electron density, which we term “ghost ribbons.” Ghost ribbons are smaller in size but possess a similar number of smaller vesicles and are poorly localized to synapses and calcium channels. These hair cells exhibit enhanced exocytosis, as measured by capacitance, and recordings from afferent neurons post-synaptic to hair cells show no significant difference in spike rates. Our results suggest that Ribeye makes up most of the synaptic ribbon density in neuromast hair cells and is necessary for proper localization of calcium channels and synaptic ribbons.

  6. 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.)

  7. Agnoprotein Is an Essential Egress Factor during BK Polyomavirus Infection

    Directory of Open Access Journals (Sweden)

    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.

  8. 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.

  9. Single-thread channels resulting from a localization process driven by vegetation

    Science.gov (United States)

    Narteau, C.; Tal, M.

    2009-12-01

    The unpredictable manner in which braided rivers evolve is in stark contrast to the orderly migration pattern of meandering rivers driven by erosion along outer bends and deposition along inner banks. Braided channels are the default pattern that develops when an unbounded water flow interacts with noncohesive sediment. A series of laboratory experiments demonstrated that plants alone are able to achieve the two key mechanisms to developing meandering: slowing the rate of widening and discouraging channel cutoffs. Plants initially colonized braid-bars that were emergent during low flow. By adding cohesion to the sediment and increasing roughness, vegetation deterred the flow from reoccupying areas which were colonized. By decreasing erosion rates, plants made it possible for deposition along the inner bank to match the rate of erosion along the outer bank. This enabled the channel to develop sinuosity and migrate laterally while suppressing channel splitting and the creation of new channel width. Areas with established vegetation provided stable conditions which promoted new seedling establishment and expansion of the vegetated area. A generic mechanism of width production in the braided state is the opportunistic creation of new channels. As existing flow paths become slightly less favorable, for example by bar deposition or an increase in sinuosity, new ones are readily created in areas that are not currently occupied by flow. By making it more difficult for flow to occupy vegetated areas, plants in effect decouple the transition between wet and dry areas, making it harder for areas that are dry (vegetated) to turn wet (reoccupied by flow) and less likely for areas that are wet to become dry. The net effect is localization of the flow into a single-thread channel with transitions between wet and dry occurring predominantly along the channel margin and driving lateral migration while a single-thread channel remains intact. We are using a 1D cellular automata model

  10. Novel molecular determinants in the pore region of sodium channels regulate local anesthetic binding.

    Science.gov (United States)

    Yamagishi, Toshio; Xiong, Wei; Kondratiev, Andre; Vélez, Patricio; Méndez-Fitzwilliam, Ailsa; Balser, Jeffrey R; Marbán, Eduardo; Tomaselli, Gordon F

    2009-10-01

    The pore of the Na+ channel is lined by asymmetric loops formed by the linkers between the fifth and sixth transmembrane segments (S5-S6). We investigated the role of the N-terminal portion (SS1) of the S5-S6 linkers in channel gating and local anesthetic (LA) block using site-directed cysteine mutagenesis of the rat skeletal muscle (Na(V)1.4) channel. The mutants examined have variable effects on voltage dependence and kinetics of fast inactivation. Of the cysteine mutants immediately N-terminal to the putative DEKA selectivity filter in four domains, only Q399C in domain I and F1236C in domain III exhibit reduced use-dependent block. These two mutations also markedly accelerated the recovery from use-dependent block. Moreover, F1236C and Q399C significantly decreased the affinity of QX-314 for binding to its channel receptor by 8.5- and 3.3-fold, respectively. Oddly enough, F1236C enhanced stabilization of slow inactivation by both hastening entry into and delaying recovery from slow inactivation states. It is noteworthy that symmetric applications of QX-314 on both external and internal sides of F1236C mutant channels reduced recovery from use-dependent block, indicating an allosteric effect of external QX-314 binding on the recovery of availability of F1236C. These observations suggest that cysteine mutation in the SS1 region, particularly immediate adjacent to the DEKA ring, may lead to a structural rearrangement that alters binding of permanently charged QX-314 to its receptor. The results lend further support for a role for the selectivity filter region as a structural determinant for local anesthetic block.

  11. RING finger protein 121 facilitates the degradation and membrane localization of voltage-gated sodium channels

    Science.gov (United States)

    Ogino, Kazutoyo; Low, Sean E.; Yamada, Kenta; Saint-Amant, Louis; Zhou, Weibin; Muto, Akira; Asakawa, Kazuhide; Nakai, Junichi; Kawakami, Koichi; Kuwada, John Y.; Hirata, Hiromi

    2015-01-01

    Following their synthesis in the endoplasmic reticulum (ER), voltage-gated sodium channels (NaV) are transported to the membranes of excitable cells, where they often cluster, such as at the axon initial segment of neurons. Although the mechanisms by which NaV channels form and maintain clusters have been extensively examined, the processes that govern their transport and degradation have received less attention. Our entry into the study of these processes began with the isolation of a new allele of the zebrafish mutant alligator, which we found to be caused by mutations in the gene encoding really interesting new gene (RING) finger protein 121 (RNF121), an E3-ubiquitin ligase present in the ER and cis-Golgi compartments. Here we demonstrate that RNF121 facilitates two opposing fates of NaV channels: (i) ubiquitin-mediated proteasome degradation and (ii) membrane localization when coexpressed with auxiliary NaVβ subunits. Collectively, these results indicate that RNF121 participates in the quality control of NaV channels during their synthesis and subsequent transport to the membrane. PMID:25691753

  12. Real-time image dehazing using local adaptive neighborhoods and dark-channel-prior

    Science.gov (United States)

    Valderrama, Jesus A.; Díaz-Ramírez, Víctor H.; Kober, Vitaly; Hernandez, Enrique

    2015-09-01

    A real-time algorithm for single image dehazing is presented. The algorithm is based on calculation of local neighborhoods of a hazed image inside a moving window. The local neighborhoods are constructed by computing rank-order statistics. Next the dark-channel-prior approach is applied to the local neighborhoods to estimate the transmission function of the scene. By using the suggested approach there is no need for applying a refining algorithm to the estimated transmission such as the soft matting algorithm. To achieve high-rate signal processing the proposed algorithm is implemented exploiting massive parallelism on a graphics processing unit (GPU). Computer simulation results are carried out to test the performance of the proposed algorithm in terms of dehazing efficiency and speed of processing. These tests are performed using several synthetic and real images. The obtained results are analyzed and compared with those obtained with existing dehazing algorithms.

  13. Characteristics of single large-conductance Ca2+-activated K+ channels and their regulation of action potentials and excitability in parasympathetic cardiac motoneurons in the nucleus ambiguus.

    Science.gov (United States)

    Lin, Min; Hatcher, Jeff T; Wurster, Robert D; Chen, Qin-Hui; Cheng, Zixi Jack

    2014-01-15

    Large-conductance Ca2(+)-activated K+ channels (BK) regulate action potential (AP) properties and excitability in many central neurons. However, the properties and functional roles of BK channels in parasympathetic cardiac motoneurons (PCMNs) in the nucleus ambiguus (NA) have not yet been well characterized. In this study, the tracer X-rhodamine-5 (and 6)-isothiocyanate (XRITC) was injected into the pericardial sac to retrogradely label PCMNs in FVB mice at postnatal 7-9 days. Two days later, XRITC-labeled PCMNs in brain stem slices were identified. Using excised patch single-channel recordings, we identified voltage-gated and Ca(2+)-dependent BK channels in PCMNs. The majority of BK channels exhibited persistent channel opening during voltage holding. These BK channels had a conductance of 237 pS and a 50% opening probability at +27.9 mV, the channel open time constant was 3.37 ms at +20 mV, and dwell time increased exponentially as the membrane potential depolarized. At the +20-mV holding potential, the [Ca2+]50 was 15.2 μM with a P0.5 of 0.4. Occasionally, some BK channels showed a transient channel opening and fast inactivation. Using whole cell voltage clamp, we found that BK channel mediated outward currents and afterhyperpolarization currents (IAHP). Using whole cell current clamp, we found that application of BK channel blocker iberiotoxin (IBTX) increased spike half-width and suppressed fast afterhyperpolarization (fAHP) amplitude following single APs. In addition, IBTX application increased spike half-width and reduced the spike frequency-dependent AP broadening in trains and spike frequency adaption (SFA). Furthermore, BK channel blockade decreased spike frequency. Collectively, these results demonstrate that PCMNs have BK channels that significantly regulate AP repolarization, fAHP, SFA, and spike frequency. We conclude that activation of BK channels underlies one of the mechanisms for facilitation of PCMN excitability.

  14. Bisphenol A binds to the local anesthetic receptor site to block the human cardiac sodium channel.

    Directory of Open Access Journals (Sweden)

    Andrias O O'Reilly

    Full Text Available Bisphenol A (BPA has attracted considerable public attention as it leaches from plastic used in food containers, is detectable in human fluids and recent epidemiologic studies link BPA exposure with diseases including cardiovascular disorders. As heart-toxicity may derive from modified cardiac electrophysiology, we investigated the interaction between BPA and hNav1.5, the predominant voltage-gated sodium channel subtype expressed in the human heart. Electrophysiology studies of heterologously-expressed hNav1.5 determined that BPA blocks the channel with a K(d of 25.4±1.3 µM. By comparing the effects of BPA and the local anesthetic mexiletine on wild type hNav1.5 and the F1760A mutant, we demonstrate that both compounds share an overlapping binding site. With a key binding determinant thus identified, an homology model of hNav1.5 was generated based on the recently-reported crystal structure of the bacterial voltage-gated sodium channel NavAb. Docking predictions position both ligands in a cavity delimited by F1760 and contiguous with the DIII-IV pore fenestration. Steered molecular dynamics simulations used to assess routes of ligand ingress indicate that the DIII-IV pore fenestration is a viable access pathway. Therefore BPA block of the human heart sodium channel involves the local anesthetic receptor and both BPA and mexiletine may enter the closed-state pore via membrane-located side fenestrations.

  15. Local indigenous knowledge about some medicinal plants in and around Kakamega forest in western Kenya [v2; ref status: indexed, http://f1000r.es/UDNyBK

    Directory of Open Access Journals (Sweden)

    Nickson Erick Otieno

    2012-12-01

    Full Text Available Kakamega forest is Kenya’s only rainforest and is distinguishably rich in biodiversity but threatened by agricultural encroachment and other forms of human activity. It is also one of Kenya’s Important Bird Areas and a significant source of natural products to neighboring rural communities, such as medicinal plants, food, wood and other fibers. By using structured questionnaires for direct interviews, local indigenous knowledge was tapped through involvement of a focal group of elderly key informants in three blocks of the forest. Forty key species of medicinal plants used by local people were identified and recorded. Fifty-five percent of these were shrubs, thirty-two percent trees, seven-and-a-half percent lower plants such as herbs or forbs while five percent were climbers. About seventy percent of the medicinal plants occurred inside the forest itself and thirty percent around the edge and the immediate surroundings outside the forest. Thirty-eight (95% of the plants were indigenous to Kenya and two (5% exotic. Such extensive indigenous knowledge of the medicinal uses of the plants, including their distribution trends in the forest, may be tapped for decision support in rural health service planning, policy formulation for conserving the forest, tracking and mitigation of climate change impacts.

  16. Disparate role of Na(+) channel D2-S6 residues in batrachotoxin and local anesthetic action.

    Science.gov (United States)

    Wang, S Y; Barile, M; Wang, G K

    2001-05-01

    Batrachotoxin (BTX) stabilizes the voltage-gated Na(+) channels in their open conformation, whereas local anesthetics (LAs) block Na(+) conductance. Site-directed mutagenesis has identified clusters of common residues at D1-S6, D3-S6, and D4-S6 segments within the alpha-subunit Na(+) channel that are critical for binding of these two types of ligands. In this report, we address whether segment D2-S6 is similarly involved in both BTX and LA actions. Thirteen amino acid positions from G783 to L795 of the rat skeletal muscle Na(+) channel ((mu)1/Skm1) were individually substituted with a lysine residue. Four mutants (N784K, L785K, V787K, and L788K) expressed sufficient Na(+) currents for further studies. Activation and/or inactivation gating was altered in mutant channels; in particular, mu1-V787K displays enhanced slow inactivation and exhibited use-dependent inhibition of peak Na(+) currents during repetitive pulses. Two of these four mutants, (mu)1-N784K and (mu)1-L788K, were completely resistant to 5 microM BTX. This BTX-resistant phenotype could be caused by structural perturbations induced by a lysine point mutation in the D2-S6 segment. However, these two BTX-resistant mutants remained quite sensitive to bupivacaine block with affinity for inactivated Na(+) channels (K(I)) of approximately 10 microM or less, which suggests that (mu)1-N784 and (mu)1-L788 residues are not in close proximity to the LA binding site.

  17. 77 FR 25077 - Special Local Regulation; Wy-Hi Rowing Regatta, Trenton Channel; Detroit River, Wyandotte, MI

    Science.gov (United States)

    2012-04-27

    ...-AA08 Special Local Regulation; Wy-Hi Rowing Regatta, Trenton Channel; Detroit River, Wyandotte, MI..., during, and immediately after the Wy-Hi Rowing Regatta. This special local regulation will establish....35T09-0342 Special Local Regulation; Wy-Hi Rowing Regatta, Wyandotte, MI. (a) Regulated Area. A...

  18. 78 FR 25572 - Special Local Regulation; Wy-Hi Rowing Regatta, Trenton Channel; Detroit River, Wyandotte, MI

    Science.gov (United States)

    2013-05-02

    ...-AA08 Special Local Regulation; Wy-Hi Rowing Regatta, Trenton Channel; Detroit River, Wyandotte, MI..., during, and immediately after the Wy-Hi Rowing Regatta. This special local regulation will establish... to read as follows: Sec. 100.T09-0287 Special Local Regulation; Wy-Hi Rowing Regatta, Wyandotte, MI...

  19. Dual channel rank-based intensity weighting for quantitative co-localization of microscopy images

    Directory of Open Access Journals (Sweden)

    Curran Kathleen M

    2011-10-01

    Full Text Available Abstract Background Accurate quantitative co-localization is a key parameter in the context of understanding the spatial co-ordination of molecules and therefore their function in cells. Existing co-localization algorithms consider either the presence of co-occurring pixels or correlations of intensity in regions of interest. Depending on the image source, and the algorithm selected, the co-localization coefficients determined can be highly variable, and often inaccurate. Furthermore, this choice of whether co-occurrence or correlation is the best approach for quantifying co-localization remains controversial. Results We have developed a novel algorithm to quantify co-localization that improves on and addresses the major shortcomings of existing co-localization measures. This algorithm uses a non-parametric ranking of pixel intensities in each channel, and the difference in ranks of co-localizing pixel positions in the two channels is used to weight the coefficient. This weighting is applied to co-occurring pixels thereby efficiently combining both co-occurrence and correlation. Tests with synthetic data sets show that the algorithm is sensitive to both co-occurrence and correlation at varying levels of intensity. Analysis of biological data sets demonstrate that this new algorithm offers high sensitivity, and that it is capable of detecting subtle changes in co-localization, exemplified by studies on a well characterized cargo protein that moves through the secretory pathway of cells. Conclusions This algorithm provides a novel way to efficiently combine co-occurrence and correlation components in biological images, thereby generating an accurate measure of co-localization. This approach of rank weighting of intensities also eliminates the need for manual thresholding of the image, which is often a cause of error in co-localization quantification. We envisage that this tool will facilitate the quantitative analysis of a wide range of biological

  20. Subcellular localization of the delayed rectifier K(+) channels KCNQ1 and ERG1 in the rat heart

    DEFF Research Database (Denmark)

    Rasmussen, Hanne Borger; Møller, Morten; Knaus, Hans-Günther

    2003-01-01

    In the heart, several K(+) channels are responsible for the repolarization of the cardiac action potential, including transient outward and delayed rectifier K(+) currents. In the present study, the cellular and subcellular localization of the two delayed rectifier K(+) channels, KCNQ1 and ether...

  1. Measurement of the local void fraction at high pressures in a heating channel

    International Nuclear Information System (INIS)

    Martin, R.

    1969-01-01

    Void fraction measurements were made in two phase flow boiling systems at high pressures in a uniformly heated, rectangular channel with a high aspect ratio. The local void fraction values were calculated from measurements of the absorption of a thin collimated X-ray beam (2 mm x 0.05 mm). The mean void fraction in a horizontal section results from integration of the local values across the section. At a fixed measuring station the quality and- void fraction were varied by changing the heat flux, flow rate and pressure systematically. Two channels were used differing in length and thickness (150.8 cm x 5.3 cm x 0.2 cm and the significant features of this study are: -1) The void fraction measurements are among the first obtained at such high pressure (80 to 140 kg/cm 2 ); -2) In the experimental region under consideration the measurements are systematic and numerous enough to allow accurate interpolations: mass velocity from 50 to 220 g/cm 2 .s, heat flux from 40 to 170 W/cm 2 and calculated steam quality from -0.2 to 0.2; -3) Many tests were performed under local boiling conditions with the mean temperature of the fluid below the saturation temperature; and -4) These results were compared to the predictions of certain models presented in the literature and simple empirical formulae were developed to fit the experimental results. (author) [fr

  2. Immunohistochemical Localization of the Water Channels AQP4 and AQP5 in the Rat Pituitary Gland

    International Nuclear Information System (INIS)

    Matsuzaki, Toshiyuki; Inahata, Yuki; Sawai, Nobuhiko; Yang, Chun-Ying; Kobayashi, Makito; Takata, Kuniaki; Ozawa, Hitoshi

    2011-01-01

    The pituitary gland is composed of the adenohypophysis and neurohypophysis. The adenohypophysis contains endocrine cells, folliculo-stellate (FS) cells, and marginal layer cells, whereas the neurohypophysis mainly comprises axons and pituicytes. To understand the molecular nature of water transfer in the pituitary gland, we examined the immunohistochemical localization of the membrane water channels aquaporin-4 (AQP4) and AQP5 in rat tissue. Double immunofluorescence analysis of AQP4 and S100 protein, a known marker for FS cells, marginal layer cells, and pituicytes, clearly revealed that FS cells and marginal layer cells in the adenohypophysis and the pituicytes in pars nervosa are positive for AQP4. AQP5 was found to be localized at the apical membrane in some marginal layer cells surrounding the Rathke’s residual pouch, in which AQP4 was observed to be localized on the basolateral membranes. These results suggest the following possibilities: 1) FS cells especially require water for their functions and 2) transepithelial water transfer could occur between the lumen of Rathke’s residual pouch and the interstitial fluid in the adenohypophysis through the AQP4 and AQP5 channels in the marginal layer cells

  3. Profil Siswa Agresif dan Peranan Guru BK

    Directory of Open Access Journals (Sweden)

    Hafiz Hidayat

    2013-06-01

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

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

    Directory of Open Access Journals (Sweden)

    manon edekeyser

    2015-06-01

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

  5. Numerical study of cell performance and local transport phenomena in PEM fuel cells with various flow channel area ratios

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xiao-Dong [Department of Thermal Engineering, School of Mechanical Engineering, University of Science and Technology Beijing, Beijing 100083 (China); Duan, Yuan-Yuan [Key Laboratory of Thermal Science and Power Engineering of MOE, Tsinghua University, Beijing 100084 (China); Yan, Wei-Mon [Department of Mechatronic Engineering, Huafan University, Shih-Ting 22305 (China)

    2007-10-11

    Three-dimensional models of proton exchange membrane fuel cells (PEMFCs) with parallel and interdigitated flow channel designs were developed including the effects of liquid water formation on the reactant gas transport. The models were used to investigate the effects of the flow channel area ratio and the cathode flow rate on the cell performance and local transport characteristics. The results reveal that at high operating voltages, the cell performance is independent of the flow channel designs and operating parameters, while at low operating voltages, both significantly affect cell performance. For the parallel flow channel design, as the flow channel area ratio increases the cell performance improves because fuel is transported into the diffusion layer and the catalyst layer mainly by diffusion. A larger flow channel area ratio increases the contact area between the fuel and the diffusion layer, which allows more fuel to directly diffuse into the porous layers to participate in the electrochemical reaction which enhances the reaction rates. For the interdigitated flow channel design, the baffle forces more fuel to enter the cell and participate in the electrochemical reaction, so the flow channel area ratio has less effect. Forced convection not only increases the fuel transport rates but also enhances the liquid water removal, thus interdigitated flow channel design has higher performance than the parallel flow channel design. The optimal performance for the interdigitated flow channel design occurs for a flow channel area ratio of 0.4. The cell performance also improves as the cathode flow rate increases. The effects of the flow channel area ratio and the cathode flow rate on cell performance are analyzed based on the local current densities, oxygen flow rates and liquid water concentrations inside the cell. (author)

  6. Using a Modified Lane’s Relation in Local Bed Scouring Studies in the Laboratory Channel

    Directory of Open Access Journals (Sweden)

    Marta Kiraga

    2016-01-01

    Full Text Available Numerous approaches to local scour forming studies have been developed. This paper presents different scientific approaches to the scour phenomenon using Lane’s relation [1] in its modified form during laboratory studies. The original Lane’s relation is applicable in dynamic balance conditions in alluvial rivers context, and it is not an equation, but a qualitative expression which cannot be directly used to estimate the influence of a change in one parameter on the magnitude of others. Lane's relation, despite its qualitative and simplified character, serves well to describe the nature of the process of forming alluvial stream channels, while modified relation allows transforming it into an equation for laboratory studies of local scour forming in prearranged clear-water equilibrium conditions and gives a new opportunity for this principle application.

  7. Amplification of disturbances generated by localized body forces in channel flows of viscoelastic fluids

    Science.gov (United States)

    Hariharan, Gokul; Jovanovic, Mihailo; Kumar, Satish

    2017-11-01

    The study of non-modal amplification of distributed body forces in channel flows of viscoelastic fluids has provided useful insight into the mechanisms that may govern the initial stages of transition to elastic turbulence. However, distributed body forces are not easy to implement in experiments and there is a need to examine amplification of localized body forces. In this work, we use the linearized governing equations to examine such amplification in plane Poiseuille flow of FENE-CR fluids. We first identify the location at which the impulsive excitations experience the largest amplification and then analyze the energy of the fluctuations and resulting flow structures. For both a Newtonian fluid at high Reynolds number and a viscoelastic fluid at low Reynolds number, the largest amplification occurs for disturbances that are located near the channel wall. Analysis of the energy evolution shows that the localized point force directed in the spanwise direction has the largest impact and that the streamwise velocity is most affected. For viscoelastic fluids we observe the development of vortical structures away from the source of impulsive excitation, a feature absent in Newtonian fluids that may provide a mechanism for the initial stages of transition to elastic turbulence.

  8. Requirement of subunit co-assembly and ankyrin-G for M-channel localization at the axon initial segment

    DEFF Research Database (Denmark)

    Rasmussen, Hanne B; Frøkjaer-Jensen, Christian; Jensen, Camilla Stampe

    2007-01-01

    The potassium channel subunits KCNQ2 and KCNQ3 are believed to underlie the M current of hippocampal neurons. The M-type potassium current plays a key role in the regulation of neuronal excitability; however, the subcellular location of the ion channels underlying this regulation has been...... assembly of the channel complex favours localization to the axon initial segment, deletion of the ankyrin-G-binding motif in KCNQ2 alone does not alter the subcellular localization of KCNQ2/3 heteromers. By contrast, deletion of the ankyrin-G-binding motif in KCNQ3 significantly reduces AIS enrichment...... of the complex, implicating KCNQ3 as a major determinant of M channel localization to the AIS. Udgivelsesdato: 2007-Mar-15...

  9. Experimental evaluation of local bubble parameters of subcooled boiling flow in a pressurized vertical annulus channel

    Energy Technology Data Exchange (ETDEWEB)

    Chu, In-Cheol, E-mail: chuic@kaeri.re.kr; Lee, Seung-Jun; Youn, Young Jung; Park, Jong Kuk; Choi, Hae Seob; Euh, Dong-Jin; Song, Chul-Hwa

    2017-02-15

    Experiments were performed to quantify the local bubble parameters such as void fraction, bubble velocity, interfacial area concentration, and Sauter mean diameter for the subcooled boiling flow of a refrigerant R-134a in a pressurized vertical annulus channel. Optical fiber void probe and double pressure boundary visualization windows were installed at four measurement stations with different elevations, thus enabling the quantification of local bubble parameters and observation of global boiling structure. Using high-resolution traverse systems for the optical fiber void probes and the heating tube, the radial profiles of the bubble parameters and their axial propagation can be evaluated at any elevation of the whole heating region. At this first phase of the experiments, three tests were conducted by varying the pressure, heat flux, mass flux, and local liquid subcooling. The radial profiles of the bubble parameters were obtained at seven elevations. The pressure condition of the present experiments covered the normal operating pressure of PWRs according to the similarity criteria. The present experimental data will be useful for thorough validation and improvement of the CMFD (Computation Multi-Fluid Dynamics) codes and constitutive relations.

  10. Cholesterol modulates the cellular localization of Orai1 channels and its disposition among membrane domains.

    Science.gov (United States)

    Bohórquez-Hernández, A; Gratton, Enrico; Pacheco, Jonathan; Asanov, Alexander; Vaca, Luis

    2017-12-01

    Store Operated Calcium Entry (SOCE) is one of the most important mechanisms for calcium mobilization in to the cell. Two main proteins sustain SOCE: STIM1 that acts as the calcium sensor in the endoplasmic reticulum (ER) and Orai1 responsible for calcium influx upon depletion of ER. There are many studies indicating that SOCE is modulated by the cholesterol content of the plasma membrane (PM). However, a myriad of questions remain unanswered concerning the precise molecular mechanism by which cholesterol modulates SOCE. In the present study we found that reducing PM cholesterol results in the internalization of Orai1 channels, which can be prevented by overexpressing caveolin 1 (Cav1). Furthermore, Cav1 and Orai1 associate upon SOCE activation as revealed by FRET and coimmunoprecipitation assays. The effects of reducing cholesterol were not limited to an increased rate of Orai1 internalization, but also, affects the lateral movement of Orai1, inducing movement in a linear pattern (unobstructed diffusion) opposite to basal cholesterol conditions were most of Orai1 channels moves in a confined space, as assessed by Fluorescence Correlation Spectroscopy, Cav1 overexpression inhibited these alterations maintaining Orai1 into a confined and partially confined movement. These results not only highlight the complex effect of cholesterol regulation on SOCE, but also indicate a direct regulatory effect on Orai1 localization and compartmentalization by this lipid. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Local temperature rise due to a 6-channel blockage in a 7-pin bundle

    International Nuclear Information System (INIS)

    Daigo, Y.; Haga, K.; Ohtsubo, A.; Kikuchi, Y.

    1975-09-01

    An experimental study was performed of local temperature rises due to a non-heat-generating blockage in an electrically heated 7-pin bundle. Each pin was 6.5 mm in diameter and had a 450 mm heated length. The pitch-to-diameter ratio (P/D) was 1.22. The bundle was inserted in a hexagonal duct. The central six channels in the bundle were blocked by a 0.5 mm thick stainless steel plate at 350 mm downstream from the start of the heated section. The temperature distributions were measured by the thermocouples which were mostly located downstream from the blockage. The experimental conditions were as follows; Coolant velocity : 0.37 -- 5,00 m/s Linear heat rate : 8.5 -- 127.2 w/cm Inlet coolant temperature : 298 -- 296 0 C. The hottest surface temperature of the central pin was observed immediately downstream from the blockage. The measured temperature rise was approximately two thirds of the predicted value by the LOCK code, in which the presence of a stagnation behind the blockage was assumed. When applied the experimental results to reactor conditions, the temperature rise due to a 6-channel blockage is considered to be less than 130 0 C. (auth.)

  12. Fire detection and incidents localization based on public information channels and social media

    Science.gov (United States)

    Thanos, Konstantinos-Georgios; Skroumpelou, Katerina; Rizogiannis, Konstantinos; Kyriazanos, Dimitris M.; Astyakopoulos, Alkiviadis; Thomopoulos, Stelios C. A.

    2017-05-01

    In this paper a solution is presented aiming to assist the early detection and localization of a fire incident by exploiting crowdsourcing and unofficial civilian online reports. It consists of two components: (a) the potential fire incident detection and (b) the visualization component. The first component comprises two modules that run in parallel and aim to collect reports posted on public platforms and conclude to potential fire incident locations. It collects the public reports, distinguishes reports that refer to a potential fire incident and store the corresponding information in a structured way. The second module aggregates all these stored reports and conclude to a probable fire location, based on the amount of reports per area, the time and location of these reports. In further the result is entered to a fusion module which combines it with information collected by sensors if available in order to provide a more accurate fire event detection capability. The visualization component is a fully - operational public information channel which provides accurate and up-to-date information about active and past fires, raises awareness about forest fires and the relevant hazards among citizens. The channel has visualization capabilities for presenting in an efficient way information regarding detected fire incidents fire expansion areas, and relevant information such as detecting sensors and reporting origin. The paper concludes with insight to current CONOPS end user with regards to the inclusion of the proposed solution to the current CONOPS of fire detection.

  13. The opioid methadone induces a local anaestheticlike inhibition of the cardiac Na+ channel, Nav1.5

    Science.gov (United States)

    Schulze, V; Stoetzer, C; O'Reilly, AO; Eberhardt, E; Foadi, N; Ahrens, J; Wegner, F; Lampert, A; Roche, J; Leffler, A

    2014-01-01

    Background and Purpose: Treatment with methadone is associated with severe cardiac arrhythmias, a side effect that seems to result from an inhibition of cardiac hERG K+ channels. However, several other opioids are inhibitors of voltage-gated Na+ channels. Considering the common assumption that an inhibition of the cardiac Na+ channel Nav1.5, is the primary mechanism for local anaesthetic (LA)-induced cardiotoxicity, we hypothesized that methadone has LA-like properties leading to a modulation of Nav1.5 channels. Experimental Approach: The whole-cell patch clamp technique was applied to investigate the effects of methadone on wild-type and mutant human Nav1.5 channels expressed in HEK293 cells. A homology model of human Nav1.5 channels was used to perform automated ligand-docking studies. Key Results: Methadone inhibited Nav1.5 channels in a state-dependent manner, that is, tonic block was stronger with inactivated channels than with resting channels and a use-dependent block at 10 Hz. Methadone induced a concentration-dependent shift of the voltage dependency of both fast and slow inactivation towards more hyperpolarized potentials, and impaired recovery from fast and slow inactivation. The LA-insensitive mutants N406K and F1760A exhibited reduced tonic and use-dependent block by methadone, and docking predictions positioned methadone in a cavity that was delimited by the residue F1760. Dextromethadone and levomethadone induced discrete stereo-selective effects on Nav1.5 channels. Conclusions and Implications: Methadone interacted with the LA-binding site to inhibit Nav1.5 channels. Our data suggest that these channels are a hitherto unrecognized molecular component contributing to cardiac arrhythmias induced by methadone. PMID:24117196

  14. dTULP, the Drosophila melanogaster homolog of tubby, regulates transient receptor potential channel localization in cilia.

    Directory of Open Access Journals (Sweden)

    Jina Park

    Full Text Available Mechanically gated ion channels convert sound into an electrical signal for the sense of hearing. In Drosophila melanogaster, several transient receptor potential (TRP channels have been implicated to be involved in this process. TRPN (NompC and TRPV (Inactive channels are localized in the distal and proximal ciliary zones of auditory receptor neurons, respectively. This segregated ciliary localization suggests distinct roles in auditory transduction. However, the regulation of this localization is not fully understood. Here we show that the Drosophila Tubby homolog, King tubby (hereafter called dTULP regulates ciliary localization of TRPs. dTULP-deficient flies show uncoordinated movement and complete loss of sound-evoked action potentials. Inactive and NompC are mislocalized in the cilia of auditory receptor neurons in the dTulp mutants, indicating that dTULP is required for proper cilia membrane protein localization. This is the first demonstration that dTULP regulates TRP channel localization in cilia, and suggests that dTULP is a protein that regulates ciliary neurosensory functions.

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Strain Localization during Equal-Channel Angular Pressing Analyzed by Finite Element Simulations

    Directory of Open Access Journals (Sweden)

    Tobias Daniel Horn

    2018-01-01

    Full Text Available Equal-Channel Angular Pressing (ECAP is a method used to introduce severe plastic deformation into a metallic billet without changing its geometry. In special cases, strain localization occurs and a pattern consisting of regions with high and low deformation (so-called shear and matrix bands can emerge. This paper studies this phenomenon numerically adopting two-dimensional finite element simulations of one ECAP pass. The mechanical behavior of aluminum is modeled using phenomenological plasticity theory with isotropic or kinematic hardening. The effects of the two different strain hardening types are investigated numerically by systematic parameter studies: while isotropic hardening only causes minor fluctuations in the plastic strain fields, a material with high initial hardening rate and sufficient strain hardening capacity can exhibit pronounced localized deformation after ECAP. The corresponding finite element simulation results show a regular pattern of shear and matrix bands. This result is confirmed experimentally by ECAP-processing of AA6060 material in a severely cold worked condition, where microstructural analysis also reveals the formation of shear and matrix bands. Excellent agreement is found between the experimental and numerical results in terms of shear and matrix band width and length scale. The simulations provide additional insights regarding the evolution of the strain and stress states in shear and matrix bands.

  18. The interpretation of resonance formation in coupled-channel models of positron scattering by atomic hydrogen using localized optical potentials

    International Nuclear Information System (INIS)

    Bransden, B.H.; Hewitt, R.N.

    1997-01-01

    Above-threshold resonances can occur in coupled-channel models of the e + + H system when Ps formation is taken into account (although it should be pointed out that, in this specific system, resonances do not occur in an exact theory). In general, to understand the mechanism of resonance formation it is useful to obtain the exact optical potential in a given channel in a localized form. The methods of achieving this localization are discussed with reference to a specific application to the resonance found in the two-state approximation for the l = 0 partial wave. (author)

  19. Patch clamp and perfusion techniques for studying ion channels expressed in Xenopus oocytes.

    Science.gov (United States)

    Yang, Junqiu; Delaloye, Kelli; Lee, Urvi S; Cui, Jianmin

    2011-01-10

    The protocol presented here is designed to study the activation of the large conductance, voltage- and Ca(2+)-activated K(+) (BK) channels. The protocol may also be used to study the structure-function relationship for other ion channels and neurotransmitter receptors. BK channels are widely expressed in different tissues and have been implicated in many physiological functions, including regulation of smooth muscle contraction, frequency tuning of inner hair cells and regulation of neurotransmitter release. BK channels are activated by membrane depolarization and by intracellular Ca(2+) and Mg(2+). Therefore, the protocol is designed to control both the membrane voltage and the intracellular solution. In this protocol, messenger RNA of BK channels is injected into Xenopus laevis oocytes (stage V-VI) followed by 2-5 days of incubation at 18°C. Membrane patches that contain single or multiple BK channels are excised with the inside-out configuration using patch clamp techniques. The intracellular side of the patch is perfused with desired solutions during recording so that the channel activation under different conditions can be examined. To summarize, the mRNA of BK channels is injected into Xenopus laevis oocytes to express channel proteins on the oocyte membrane; patch clamp techniques are used to record currents flowing through the channels under controlled voltage and intracellular solutions.

  20. T-type Ca(2+) channels and Autoregulation of Local Blood Flow

    DEFF Research Database (Denmark)

    Jensen, Lars Jørn; Nielsen, Morten Schak; Salomonsson, Max

    2017-01-01

    L-type voltage gated Ca(2+) channels are considered to be the primary source of calcium influx during the myogenic response. However, many vascular beds also express T-type voltage gated Ca(2+) channels. Recent studies suggest that these channels may also play a role in autoregulation. At low...... pressures (40-80 mm Hg) T-type channels affect myogenic responses in cerebral and mesenteric vascular beds. T-type channels also seem to be involved in skeletal muscle autoregulation. This review discusses the expression and role of T-type voltage gated Ca(2+) channels in the autoregulation of several...... different vascular beds. Lack of specific pharmacological inhibitors has been a huge challenge in the field. Now the research has been strengthened by genetically modified models such as mice lacking expression of T-type voltage gated Ca(2+) channels (CaV3.1 and CaV3.2). Hopefully, these new tools will help...

  1. Effects of large conductance Ca(2+)-activated K(+) channels on nitroglycerin-mediated vasorelaxation in humans

    DEFF Research Database (Denmark)

    Gruhn, Nicolai; Boesgaard, Søren; Eiberg, Jonas

    2002-01-01

    Nitric oxide (NO)-induced vasorelaxation and the regulation of endothelial superoxide anion levels is partly mediated by vascular large conductance Ca(2+)-activated K(+) (BK(Ca)) channels. Nitroglycerin acts through the release of NO and its effect is modulated by changes in endothelial superoxide...... levels. This study examines the effect of BK(Ca) channel blockade on nitroglycerin-induced vasorelaxation in human arterial and venous vascular segments and whether responses to BK(Ca) channel blockade are influenced by the development of venous nitroglycerin tolerance. Dose-relaxation curves...... in human venous nitroglycerin tolerance development....

  2. A study of the low-luminosity Type II-Plateau supernova 2008bk

    Science.gov (United States)

    Lisakov, S. M.; Dessart, Luc; Hillier, D. John; Waldman, Roni; Livne, Eli

    2017-04-01

    Supernova (SN) 2008bk is a well-observed low-luminosity Type II event visually associated with a low-mass red-supergiant progenitor. To model SN 2008bk, we evolve a 12 M⊙ star from the main sequence until core collapse, when it has a total mass of 9.88 M⊙, a He-core mass of 3.22 M⊙ and a radius of 502 R⊙. We then artificially trigger an explosion that produces 8.29 M⊙ of ejecta with a total energy of 2.5 × 1050 erg and ˜0.009 M⊙ of 56Ni. We model the subsequent evolution of the ejecta with non-local thermodynamic equilibrium time-dependent radiative transfer. Although somewhat too luminous and energetic, this model reproduces satisfactorily the multiband light curves and multi-epoch spectra of SN 2008bk, confirming the suitability of a low-mass massive star progenitor. As in other low-luminosity SNe II, the structured Hα profile at the end of the plateau phase is probably caused by Ba II 6496.9 Å rather than asphericity. We discuss the sensitivity of our results to changes in progenitor radius and mass, as well as chemical mixing. A 15 per cent increase in progenitor radius causes a 15 per cent increase in luminosity and a 0.2 mag V-band brightening of the plateau but leaves its length unaffected. An increase in ejecta mass by 10 per cent lengthens the plateau by ˜10 d. Chemical mixing introduces slight changes to the bolometric light curve, limited to the end of the plateau, but has a large impact on colours and spectra at nebular times.

  3. Localization and pharmacological characterization of voltage dependent calcium channels in cultured neocortical neurons

    DEFF Research Database (Denmark)

    Timmermann, D B; Lund, Trine Meldgaard; Belhage, B

    2001-01-01

    The physiological significance and subcellular distribution of voltage dependent calcium channels was defined using calcium channel blockers to inhibit potassium induced rises in cytosolic calcium concentration in cultured mouse neocortical neurons. The cytosolic calcium concentration was measured...... channels were differentially distributed in somata, neurites and nerve terminals. omega-conotoxin MVIIC (omega-CgTx MVIIC) inhibited approximately 40% of the Ca(2+)-rise in both somata and neurites and 60% of the potassium induced [3H]GABA release, indicating that the Q-type channel is the quantitatively...... using the fluorescent calcium chelator fura-2. The types of calcium channels present at the synaptic terminal were determined by the inhibitory action of calcium channel blockers on potassium-induced [3H]GABA release in the same cell preparation. L-, N-, P-, Q- and R-/T-type voltage dependent calcium...

  4. Valley and channel networks extraction based on local topographic curvature and k-means clustering of contours

    Science.gov (United States)

    Hooshyar, Milad; Wang, Dingbao; Kim, Seoyoung; Medeiros, Stephen C.; Hagen, Scott C.

    2016-10-01

    A method for automatic extraction of valley and channel networks from high-resolution digital elevation models (DEMs) is presented. This method utilizes both positive (i.e., convergent topography) and negative (i.e., divergent topography) curvature to delineate the valley network. The valley and ridge skeletons are extracted using the pixels' curvature and the local terrain conditions. The valley network is generated by checking the terrain for the existence of at least one ridge between two intersecting valleys. The transition from unchannelized to channelized sections (i.e., channel head) in each first-order valley tributary is identified independently by categorizing the corresponding contours using an unsupervised approach based on k-means clustering. The method does not require a spatially constant channel initiation threshold (e.g., curvature or contributing area). Moreover, instead of a point attribute (e.g., curvature), the proposed clustering method utilizes the shape of contours, which reflects the entire cross-sectional profile including possible banks. The method was applied to three catchments: Indian Creek and Mid Bailey Run in Ohio and Feather River in California. The accuracy of channel head extraction from the proposed method is comparable to state-of-the-art channel extraction methods.

  5. Functional coupling between large-conductance potassium channels and Cav3.2 voltage-dependent calcium channels participates in prostate cancer cell growth

    Directory of Open Access Journals (Sweden)

    Florian Gackière

    2013-07-01

    It is strongly suspected that potassium (K+ channels are involved in various aspects of prostate cancer development, such as cell growth. However, the molecular nature of those K+ channels implicated in prostate cancer cell proliferation and the mechanisms through which they control proliferation are still unknown. This study uses pharmacological, biophysical and molecular approaches to show that the main voltage-dependent K+ current in prostate cancer LNCaP cells is carried by large-conductance BK channels. Indeed, most of the voltage-dependent current was inhibited by inhibitors of BK channels (paxillin and iberiotoxin and by siRNA targeting BK channels. In addition, we reveal that BK channels constitute the main K+ channel family involved in setting the resting membrane potential in LNCaP cells at around −40 mV. This consequently promotes a constitutive calcium entry through T-type Cav3.2 calcium channels. We demonstrate, using single-channel recording, confocal imaging and co-immunoprecipitation approaches, that both channels form macromolecular complexes. Finally, using flow cytometry cell cycle measurements, cell survival assays and Ki67 immunofluorescent staining, we show that both BK and Cav3.2 channels participate in the proliferation of prostate cancer cells.

  6. Molecular insights into the local anesthetic receptor within voltage-gated sodium channels using hydroxylated analogues of mexiletine

    Directory of Open Access Journals (Sweden)

    Jean-François eDesaphy

    2012-02-01

    Full Text Available We previously showed that the β-adrenoceptor modulators, clenbuterol and propranolol, directly blocked voltage-gated sodium channels, whereas salbutamol and nadolol did not (Desaphy et al., 2003, suggesting the presence of two hydroxyl groups on the aromatic moiety of the drugs as a molecular requisite for impeding sodium channel block. To verify such an hypothesis, we synthesized five new mexiletine analogues by adding one or two hydroxyl groups to the aryl moiety of the sodium channel blocker and tested these compounds on hNav1.4 channels expressed in HEK293 cells. Concentration-response relationships were constructed using an holding potential of -120 mV at 0.1 Hz (tonic block and 10 Hz (use-dependent block stimulation frequencies. The half-maximum inhibitory concentrations (IC50 were linearly correlated to drug lipophilicity: the less lipophilic the drug, minor was the block. The same compounds were also tested on F1586C and Y1593C hNav1.4 channel mutants, to gain further information on the molecular interactions of mexiletine with its receptor within the sodium channel pore. Alteration of tonic block suggests that the aryl moiety of mexiletine may interact either directly or indirectly with Phe1586 in the closed sodium channel to produce low-affinity binding block, and that this interaction depends on the electrostatic potential of the drug aromatic tail. Alteration of use-dependent block suggests that addition of hydroxyl groups to the aryl moiety may modify high-affinity binding of the drug ammine terminal to Phe1586 through cooperativity between the two pharmacophores, this effect being mainly related to drug lipophilicity. Mutation of Tyr1593 further impaired such cooperativity. In conclusion, these results confirm our former hypothesis showing that the presence of hydroxyl groups to the aryl moiety of mexiletine greatly reduced sodium channel block, and provide molecular insights into the intimate interaction of local anesthetics with

  7. Drosophila TRPN(=NOMPC channel localizes to the distal end of mechanosensory cilia.

    Directory of Open Access Journals (Sweden)

    Jeongmi Lee

    Full Text Available BACKGROUND: A TRPN channel protein is essential for sensory transduction in insect mechanosensory neurons and in vertebrate hair cells. The Drosophila TRPN homolog, NOMPC, is required to generate mechanoreceptor potentials and currents in tactile bristles. NOMPC is also required, together with a TRPV channel, for transduction by chordotonal neurons of the fly's antennal ear, but the TRPN or TRPV channels have distinct roles in transduction and in regulating active antennal mechanics. The evidence suggests that NOMPC is a primary mechanotransducer channel, but its subcellular location-key for understanding its exact role in transduction-has not yet been established. METHODOLOGY/PRINCIPAL FINDINGS: Here, by immunostaining, we locate NOMPC at the tips of mechanosensory cilia in both external and chordotonal sensory neurons, as predicted for a mechanotransducer channel. In chordotonal neurons, the TRPN and TRPV channels are respectively segregated into distal and proximal ciliary zones. This zonal separation is demarcated by and requires the ciliary dilation, an intraciliary assembly of intraflagellar transport (IFT proteins. CONCLUSIONS: Our results provide a strong evidence for NOMPC as a primary transduction channel in Drosophila mechansensory organs. The data also reveals a structural basis for the model of auditory chordotonal transduction in which the TRPN and TRPV channels play sequential roles in generating and amplifying the receptor potential, but have opposing roles in regulating active ciliary motility.

  8. Localization Improvement in Wireless Sensor Networks Using a New Statistical Channel Model

    DEFF Research Database (Denmark)

    Karimi Alavijeh, Amir; Ramezani, Hossein; Karimi Alavijeh, Ali

    2018-01-01

    In this paper, a statistical channel model is proposed based on the second moment of Received Signal Strength Indicator (RSSI) in an outdoor communication channel. The medium under study is a grass field where the RSSI data are collected in different distances and orientations using a set of in-h...

  9. Calculation of the evaporation residue cross sections for the synthesis of the superheavy element Z=119 via the 50Ti+249Bk hot fusion reaction

    Science.gov (United States)

    Liu, Zu-Hua; Bao, Jing-Dong

    2011-09-01

    The evaporation residue (ER) cross sections for 3n and 4n evaporation channels in the 50Ti + 249Bk reaction leading the formation of 296119 and 295119 isotopes are evaluated by means of a modified fusion-by-diffusion model. In the model, the dynamic evolution from dinucleus to mononucleus is taken into account with the two-dimensional coupled Langenvin equations. The calculated maximum ER cross sections in 3n and 4n evaporation channels of the 50Ti + 249Bk reaction are 0.17 and 0.57 pb, respectively. The cross section of 0.57 pb is close to the present experimental limit for the registration of the evaporation residual nuclei. Therefore, superheavy element 119 may be the most hopeful new element with Z>118 to be synthesized under somehow improved experimental conditions in the near future.

  10. Local anesthetic interaction with human ether-a-go-go-related gene (HERG) channels: role of aromatic amino acids Y652 and F656

    DEFF Research Database (Denmark)

    Siebrands, Cornelia C; Schmitt, Nicole; Friederich, Patrick

    2005-01-01

    BACKGROUND: Human ether-a-go-go-related gene (HERG) potassium channels constitute a potential target involved in cardiotoxic side effects of amino-amide local anesthetics. The molecular interaction site of these low-affinity blockers with HERG channels is currently unknown. The aim of this study...... (r > 0.9). CONCLUSIONS: These results indicate that local anesthetics specifically but not exclusively interact with the aromatic residues Y652 and F656 in S6 of HERG channels....

  11. Bs⁎BK vertex from QCD sum rules

    International Nuclear Information System (INIS)

    Cerqueira, A.; Osório Rodrigues, B.; Bracco, M.E.

    2012-01-01

    The form factors and the coupling constant of the B s ⁎ BK vertex are calculated using the QCD sum rules method. Three-point correlation functions are computed considering both K and B mesons off-shell and, after an extrapolation of the QCDSR results, we obtain the coupling constant of the vertex. We study the uncertainties in our result by calculating a third form factor obtained when the B s ⁎ is the off-shell meson, considering other acceptable structures and computing the variations of the sum rules' parameters. The form factors obtained have different behaviors but their simultaneous extrapolations reach to the same value of the coupling constant g B s ⁎ BK =10.6±1.7. We compare our result with other theoretical estimates.

  12. Functional role of BK virus tumor antigens in transformation.

    OpenAIRE

    Nakshatri, H; Pater, M M; Pater, A

    1988-01-01

    We have examined the role of the human papovavirus BK virus (BKV) tumor (T) antigen(s) in the maintenance of transformation and have identified the domain of T antigen essential for transformation. BKV-transformed BHK 21 and NIH 3T3 cells expressing antisense T-antigen RNA lose their ability to grow in soft agar, indicating the need for the continued expression of T antigen for the maintenance of the transformed phenotype. Experiments using translation termination linker insertion and deletio...

  13. Serine-401 as a batrachotoxin- and local anesthetic-sensing residue in the human cardiac Na+ channel.

    Science.gov (United States)

    Wang, Sho-Ya; Tikhonov, Denis B; Zhorov, Boris S; Mitchell, Jane; Wang, Ging Kuo

    2007-05-01

    Sequence alignment of four S6 segments in the human cardiac Na+ channel suggests that serine-401 (hNav1.5-S401) at D1S6 along with asparagine-927 (N927) at D2S6, serine-1458 (S1458) at D3S6, and phenylalanine-1760 (F1760) at D4S6 may jointly form a pore-facing S(401)N(927)S(1458)F(1760) ring. Importantly, this pore-facing structure is adjacent to the putative gating-hinge (G(400)G(926)G(1457)S(1759)) and close to the selectivity filter. Within this SNSF ring, only S401 has not yet been identified as a batrachotoxin (BTX) sensing residue. We therefore created S401 mutants with 12 substitutions (S401C,W,P,A,K,F,R,E,L,N,D,G) and assayed their BTX sensitivity. All S401 mutants expressed Na+ currents but often with altered gating characteristics. Ten mutants were found sensitive to 5 muM BTX, which eliminated Na+ channel fast inactivation after repetitive pulses. However, S401K and S401R became BTX resistant. In addition, the block of open and inactivated hNav1.5-S401K Na+ channels by local anesthetic bupivacaine was reduced by approximately 8-10-fold, but not the block of resting Na+ channels. Qualitatively, these ligand-sensing phenotypes of hNav1.5-S401K channels resemble those of S1458K and F1760K channels reported earlier. Together, our results support that residue hNav1.5-S401 at D1S6 is facing the inner cavity and is in close proximity to the receptor sites for BTX and for local anesthetics.

  14. 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.

  15. Methadone is a local anaesthetic-like inhibitor of neuronal Na+ channels and blocks excitability of mouse peripheral nerves.

    Science.gov (United States)

    Stoetzer, C; Kistner, K; Stüber, T; Wirths, M; Schulze, V; Doll, T; Foadi, N; Wegner, F; Ahrens, J; Leffler, A

    2015-01-01

    Opioids enhance and prolong analgesia when applied as adjuvants to local anaesthetics (LAs). A possible molecular mechanism for this property is a direct inhibition of voltage-gated Na(+) channels which was reported for some opioids. Methadone is an effective adjuvant to LA and was recently reported to inhibit cardiac Na(+) channels. Here, we explore and compare LA properties of methadone and bupivacaine on neuronal Na(+) channels, excitability of peripheral nerves, and cell viability. Effects of methadone were explored on compound action potentials (CAP) of isolated mouse saphenous nerves. Patch clamp recordings were performed on Na(+) channels in ND7/23 cells, the α-subunits Nav1.2, Nav1.3, Nav1.7, and Nav1.8, and the hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2). Cytotoxicity was determined using flow cytometry. Methadone (IC50 86-119 µM) is a state-dependent and unselective blocker on Nav1.2, Nav1.3, Nav1.7, and Nav1.8 with a potency comparable with that of bupivacaine (IC50 177 µM). Both bupivacaine and methadone also inhibit C- and A-fibre CAPs in saphenous nerves in a concentration-dependent manner. Tonic block of Nav1.7 revealed a discrete stereo-selectivity with a higher potency for levomethadone than for dextromethadone. Methadone is also a weak blocker of HCN2 channels. Both methadone and bupivacaine induce a pronounced cytotoxicity at concentrations required for LA effects. Methadone induces typical LA effects by inhibiting Na(+) channels with a potency similar to that of bupivacaine. This hitherto unknown property of methadone might contribute to its high efficacy when applied as an adjuvant to LA. © The Author 2014. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Effects of large conductance Ca(2+)-activated K(+) channels on nitroglycerin-mediated vasorelaxation in humans

    DEFF Research Database (Denmark)

    Gruhn, Nicolai; Boesgaard, Søren; Eiberg, Jonas

    2002-01-01

    Nitric oxide (NO)-induced vasorelaxation and the regulation of endothelial superoxide anion levels is partly mediated by vascular large conductance Ca(2+)-activated K(+) (BK(Ca)) channels. Nitroglycerin acts through the release of NO and its effect is modulated by changes in endothelial superoxide...... levels. This study examines the effect of BK(Ca) channel blockade on nitroglycerin-induced vasorelaxation in human arterial and venous vascular segments and whether responses to BK(Ca) channel blockade are influenced by the development of venous nitroglycerin tolerance. Dose-relaxation curves...... to nitroglycerin (10(-10)-10(-4) M) were obtained in segments of the saphenous vein and the left mammary artery. Studies were performed with and without pre-incubation with the BK(Ca) channel blocker iberiotoxin (10(-7) M) and venous tolerance to nitroglycerin were induced by a 24-h i.v. infusion (0.5 microg...

  17. Localization of transient receptor potential ion channels in primary and motile cilia of the female murine reproductive organs

    DEFF Research Database (Denmark)

    Teilmann, Stefan C.; Byskov, Anne Grete; Pedersen, Per Amstrup

    2005-01-01

    We have examined the subcellular localization of transient receptor potential (TRP) ion channels and the potential sensory role of cilia in murine female reproductive organs using confocal laser scanning microscopy analysis on ovary and oviduct tissue sections as well as on primary cultures of fo...... differentiation and in development and maturation of ovarian follicles. In the oviduct both TRPV4 and polycystins could be important in relaying physiochemical changes in the oviduct upon ovulation. Mol. Reprod. Dev. © 2005 Wiley-Liss, Inc....

  18. 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.

  19. Pannexin2 oligomers localize into endosomal vesicles in mammalian cells while Pannexin1 channels traffic to the plasma membrane

    Directory of Open Access Journals (Sweden)

    Daniela eBoassa

    2015-02-01

    Full Text Available Pannexin2 (Panx2 is the largest of three members of the pannexin proteins. Pannexins are topologically related to connexins and innexins, but serve different functional roles than forming gap junctions. We previously showed that pannexins form oligomeric channels but unlike connexins and innexins, they form only single membrane channels. High levels of Panx2 mRNA and protein in the Central Nervous System (CNS have been documented. Whereas Pannexin1 (Panx1 is fairly ubiquitous and Pannexin3 (Panx3 is found in skin and connective tissue, both are fully glycosylated, traffic to the plasma membrane and have functions correlated with extracellular ATP release. Here, we describe trafficking and subcellular localizations of exogenous Panx2 and Panx1 protein expression in MDCK, HeLa and HEK293T cells as well as endogenous Panx1 and Panx2 patterns in the CNS. Panx2 was found in intracellular localizations, was partially N-glycosylated, and localizations were non-overlapping with Panx1. Confocal images of hippocampal sections immunolabeled for the astrocytic protein GFAP, Panx1 and Panx2 demonstrated that the two isoforms, Panx1 and Panx2, localized at different subcellular compartments in both astrocytes and neurons. Using recombinant fusions of Panx2 with appended genetic tags developed for correlated light and electron microscopy and then expressed in different cell lines, we determined that Panx2 is localized in the membrane of intracellular vesicles and not in the endoplasmic reticulum as initially indicated by calnexin colocalization experiments. Dual immunofluorescence imaging with protein markers for specific vesicle compartments showed that Panx2 vesicles are early endosomal in origin. In electron tomographic volumes, cross-sections of these vesicles displayed fine structural details and close proximity to actin filaments. Thus, pannexins expressed at different subcellular compartments likely exert distinct functional roles, particularly in the

  20. Inhalation of the BK(Ca-opener NS1619 attenuates right ventricular pressure and improves oxygenation in the rat monocrotaline model of pulmonary hypertension.

    Directory of Open Access Journals (Sweden)

    Marc Revermann

    Full Text Available Right heart failure is a fatal consequence of chronic pulmonary hypertension (PH. The development of PH is characterized by increased proliferation of vascular cells, in particular pulmonary artery smooth muscle cells (PASMCs and pulmonary artery endothelial cells. In the course of PH, an escalated right ventricular (RV afterload occurs, which leads to increased perioperative morbidity and mortality. BK(Ca channels are ubiquitously expressed in vascular smooth muscle cells and their opening induces cell membrane hyperpolarization followed by vasodilation. Moreover, BK activation induces anti-proliferative effects in a multitude of cell types. On this basis, we hypothesized that treatment with the nebulized BK channel opener NS1619 might be a therapy option for pulmonary hypertension and tested this in rats.(1 Rats received monocrotaline injection for PH induction. Twenty-four days later, rats were anesthetized and NS1619 or the solvent was administered by inhalation. Systemic hemodynamic parameters, RV hemodynamic parameters, and blood gas analyses were measured before as well as 30 and 120 minutes after inhalation. (2 Rat PASMCs were stimulated with PDGF-BB in the presence and absence of NS1619. AKT, ERK1 and ERK2 activation were investigated by western blot analyses, and relative cell number was determined 48 hours after stimulation.Inhalation of a 12 µM and 100 µM NS1619 solution significantly reduced RV pressure without affecting systemic arterial pressure. Blood gas analyses demonstrated significantly reduced carbon dioxide and improved oxygenation in NS1619-treated animals pointing towards a considerable pulmonary shunt-reducing effect. In PASMC's, NS1619 (100 µM significantly attenuated PASMC proliferation by a pathway independent of AKT and ERK1/2 activation.NS1619 inhalation reduces RV pressure and improves oxygen supply and its application inhibits PASMC proliferation in vitro. Hence, BK opening might be a novel option for the

  1. Analysis of photon-scanning tunneling microscope images of inhomogeneous samples: Determination of the local refractive index of channel waveguides

    International Nuclear Information System (INIS)

    Bourillot, E.; Fornel, F. de.; Goudonnet, J.P.

    1995-01-01

    Channel waveguides are imaged by a photon-scanning tunneling microscope (PSTM). The polarization of the light and its orientation with respect to the guide aids are shown to be very important parameters in the analysis of the images of such samples. We simulated image formation for the plane of incidence parallel to the axis of the guide. Our theoretical results are qualitatively in agreement with our measurements. These results show the ability of the PSTM to give information about the local refractive-index variations of a sample. 21 refs., 14 figs

  2. Local anesthetics QX 572 and benzocaine act at separate sites on the batrachotoxin-activated sodium channel

    OpenAIRE

    1981-01-01

    We have studied the effect of local anesthetics QX 572, which is permanently charged, and benzocaine, which is neutral, on batrachotoxin- activated sodium channels in mouse neuroblastoma N18 cells. The dose- response curves for each drug suggest that QX 752 and benzocaine each act on a single class of binding sites. The dissociation constants are 3.15 X 10(-5) M for QX 572 and 2.65 X 10(-4) M for benzocaine. Equilibrium and kinetic experiments indicate that both drugs are competitive inhibito...

  3. 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)

  4. 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 $\\hat B_K =0.789 \\pm 0.046$.

  5. Acid-sensing ion channel (ASIC) 4 predominantly localizes to an early endosome-related organelle upon heterologous expression.

    Science.gov (United States)

    Schwartz, Verena; Friedrich, Katharina; Polleichtner, Georg; Gründer, Stefan

    2015-12-15

    Acid-sensing ion channels (ASICs) are voltage-independent proton-gated amiloride sensitive sodium channels, belonging to the DEG/ENaC gene family. Six different ASICs have been identified (ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3, ASIC4) that are activated by a drop in extracellular pH, either as homo- or heteromers. An exception is ASIC4, which is not activated by protons as a homomer and which does not contribute to functional heteromeric ASICs. Insensitivity of ASIC4 to protons and its comparatively low sequence identity to other ASICs (45%) raises the question whether ASIC4 may have different functions than other ASICs. In this study, we therefore investigated the subcellular localization of ASIC4 in heterologous cell lines, which revealed a surprising accumulation of the channel in early endosome-related vacuoles. Moreover, we identified an unique amino-terminal motif as important for forward-trafficking from the ER/Golgi to the early endosome-related compartment. Collectively, our results show that heterologously expressed ASIC4 predominantly resides in an intracellular endosomal compartment.

  6. Observation of multi-channel non-local transport in J-TEXT plasmas

    Science.gov (United States)

    Shi, Yuejiang; Chen, Zhongyong; Yang, Zhoujun; Shi, Peng; Zhao, Kaijun; Diamond, Patrick H.; Kwon, JaeMin; Yan, Wei; Zhou, Hao; Pan, Xiaoming; Cheng, Zhifeng; Chen, Zhiping; Yang, SeongMoo; Zhang, Chi; Li, Da; Dong, Yunbo; Wang, Lu; Ding, YongHua; Liang, Yunfeng; Hahn, SangHee; Jhang, HoGun; Na, Yong-Su

    2018-04-01

    In cold pulse experiments in J-TEXT, not only are rapid electron temperature increases in the core observed, but also steep rises in the inner density are found. Moreover, some evidence of acceleration of the core toroidal rotation is also observed during the non-local transport process of electron temperature. These new findings of cold pulse experiments in J-TEXT suggest that turbulence spreading is a possible mechanism for the non-local transport dynamics.

  7. Generalized non-Local Resistance Expression and its Application in F/N/F Spintronic Structure with Graphene Channel

    Science.gov (United States)

    Wei, Huazhou; Fu, Shiwei

    We report our work on the spin transport properties in the F/N/F(ferromagnets/normal metal/ferromagnets) spintronic structure from a new theoretical perspective. A significant problem in the field is to explain the inferior measured order of magnitude for spin lifetime. Based on the known non-local resistance formula and the mechanism analysis of spin-flipping within the interfaces between F and N, we analytically derive a broadly applicable new non-local resistance expression and a generalized Hanle curve formula. After employing them in the F/N/F structure under different limits, especially in the case of graphene channel, we find that the fitting from experimental data would yield a longer spin lifetime, which approaches its theoretical predicted value in graphene. The authors acknowledge the financial support by China University of Petroleum-Beijing and the Key Laboratory of Optical Detection Technology for Oil and Gas in this institution.

  8. Localization of receptor site on insect sodium channel for depressant β-toxin BmK IT2.

    Directory of Open Access Journals (Sweden)

    Huiqiong He

    Full Text Available BACKGROUND: BmK IT2 is regarded as a receptor site-4 modulator of sodium channels with depressant insect toxicity. It also displays anti-nociceptive and anti-convulsant activities in rat models. In this study, the potency and efficacy of BmK IT2 were for the first time assessed and compared among four sodium channel isoforms expressed in Xenopus oocytes. Combined with molecular approach, the receptor site of BmK IT2 was further localized. PRINCIPAL FINDINGS: 2 µM BmK IT2 strongly shifted the activation of DmNa(v1, the sodium channel from Drosophila, to more hyperpolarized potentials; whereas it hardly affected the gating properties of rNa(v1.2, rNa(v1.3 and mNa(v1.6, three mammalian central neuronal sodium channel subtypes. (1 Mutations of Glu(896, Leu(899, Gly(904 in extracellular loop Domain II S3-S4 of DmNa(v1 abolished the functional action of BmK IT2. (2 BmK IT2-preference for DmNa(v1 could be conferred by Domain III. Analysis of subsequent DmNa(v1 mutants highlighted the residues in Domain III pore loop, esp. Ile(1529 was critical for recognition and binding of BmK IT2. CONCLUSIONS/SIGNIFICANCE: In this study, BmK IT2 displayed total insect-selectivity. Two binding regions, comprising domains II and III of DmNa(v1, play separated but indispensable roles in the interaction with BmK IT2. The insensitivity of Na(v1.2, Na(v1.3 and Na(v1.6 to BmK IT2 suggests other isoforms or mechanism might be involved in the suppressive activity of BmK IT2 in rat pathological models.

  9. Localization of MIWC and GLIP water channel homologs in neuromuscular, epithelial and glandular tissues.

    Science.gov (United States)

    Frigeri, A; Gropper, M A; Umenishi, F; Kawashima, M; Brown, D; Verkman, A S

    1995-09-01

    It was shown recently that water channel homologs MIWC (mercurial insensitive water channel) and GLIP (glycerol intrinsic protein) colocalized in basolateral membranes of kidney collecting duct, tracheal and colonic epithelia, and in brain pia mater. We report here an extensive immunolocalization study of MIWC and GLIP in non-epithelial and glandular epithelial tissues in rat. Immunogold electron microscopy confirmed colocalization of MIWC and GLIP in basolateral membrane of principal cells in kidney collecting duct. However, in other epithelia, MIWC but not GLIP was expressed in basolateral membrane of parietal cells in stomach, and in excretory tubules of salivary and lacrimal glands; GLIP but not MIWC was expressed in transitional epithelium of urinary bladder and skin epidermis. In the central nervous system, MIWC was strongly expressed in the ependymal layer lining the aqueductal system, and in astrocytes throughout the spinal cord and in selected regions of brain. MIWC was also expressed in a plasma membrane pattern in skeletal, but not smooth or cardiac muscle. Neither protein was expressed in small intestine, testis, liver, spleen and nerve. The tissue-specific expression of MIWC suggests a role in fluid transport and/or cell volume regulation in stomach and glandular epithelia. The functional role of MIWC expression in the neuromuscular system and of GLIP expression in skin and urinary bladder is uncertain. The specific cellular sites of MIWC expression (astrocytes, trachea, sarcolemma, gastric parietal cells and kidney principal cells) correspond exactly to sites where orthogonal arrays of particles (OAPs) have been visualized by freeze-fracture electron microscopy, suggesting that MIWC may be the OAP protein.

  10. 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

    , whereas low-conductance (SK) K+ channels could not be detected. To investigate the role of K+ and Cl- channels in secretion, intact rabbit submandibular glands were vascularly perfused and secretion induced by 10 microM ACh. Secretion was inhibited by 34+/-3% following perfusion with the general K...... abolished, while 10 microM NPPB, 20 microM NS1652 and 20 microM NS3623 reduced secretion by 34+/-3%, 23+/-3% and 59+/-4%, respectively. In conclusion, although high expression levels of BK channels were demonstrated, pharmacological tools failed to demonstrate any role for BK, IK or SK channels in salivary...

  11. Search for the Decay B+-->K+ tau-/+ mu+/-.

    Science.gov (United States)

    Aubert, B; Bona, M; Boutigny, D; Karyotakis, Y; Lees, J P; Poireau, V; Prudent, X; Tisserand, V; Zghiche, A; Garra Tico, J; Grauges, E; Lopez, L; Palano, A; Pappagallo, M; Eigen, G; Stugu, B; Sun, L; Abrams, G S; Battaglia, M; Brown, D N; Button-Shafer, J; Cahn, R N; Groysman, Y; Jacobsen, R G; Kadyk, J A; Kerth, L T; Kolomensky, Yu G; Kukartsev, G; Lopes Pegna, D; Lynch, G; Mir, L M; Orimoto, T J; Osipenkov, I L; Ronan, M T; Tackmann, K; Tanabe, T; Wenzel, W A; del Amo Sanchez, P; Hawkes, C M; Watson, A T; Held, T; Koch, H; Pelizaeus, M; Schroeder, T; Steinke, M; Walker, D; Asgeirsson, D J; Cuhadar-Donszelmann, T; Fulsom, B G; Hearty, C; Mattison, T S; McKenna, J A; Khan, A; Saleem, M; Teodorescu, L; Blinov, V E; Bukin, A D; Druzhinin, V P; Golubev, V B; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Bondioli, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Martin, E C; Stoker, D P; Abachi, S; Buchanan, C; Foulkes, S D; Gary, J W; Liu, F; Long, O; Shen, B C; Zhang, L; Paar, H P; Rahatlou, S; Sharma, V; Berryhill, J W; Campagnari, C; Cunha, A; Dahmes, B; Hong, T M; Kovalskyi, D; Richman, J D; Beck, T W; Eisner, A M; Flacco, C J; Heusch, C A; Kroseberg, J; Lockman, W S; Schalk, T; Schumm, B A; Seiden, A; Wilson, M G; Winstrom, L O; Chen, E; Cheng, C H; Fang, F; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Andreassen, R; Mancinelli, G; Meadows, B T; Mishra, K; Sokoloff, M D; Blanc, F; Bloom, P C; Chen, S; Ford, W T; Hirschauer, J F; Kreisel, A; Nagel, M; Nauenberg, U; Olivas, A; Smith, J G; Ulmer, K A; Wagner, S R; Zhang, J; Gabareen, A M; Soffer, A; Toki, W H; Wilson, R J; Winklmeier, F; Altenburg, D D; Feltresi, E; Hauke, A; Jasper, H; Merkel, J; Petzold, A; Spaan, B; Wacker, K; Klose, V; Kobel, M J; Lacker, H M; Mader, W F; Nogowski, R; Schubert, J; Schubert, K R; Schwierz, R; Sundermann, J E; Volk, A; Bernard, D; Bonneaud, G R; Latour, E; Lombardo, V; Thiebaux, Ch; Verderi, M; Clark, P J; Gradl, W; Muheim, F; Playfer, S; Robertson, A I; Watson, J E; Xie, Y; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cecchi, A; Cibinetto, G; Franchini, P; Luppi, E; Negrini, M; Petrella, A; Piemontese, L; Prencipe, E; Santoro, V; Anulli, F; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Pacetti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Rama, M; Zallo, A; Buzzo, A; Contri, R; Lo Vetere, M; Macri, M M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Santroni, A; Tosi, S; Chaisanguanthum, K S; Morii, M; Wu, J; Dubitzky, R S; Marks, J; Schenk, S; Uwer, U; Bard, D J; Dauncey, P D; Flack, R L; Nash, J A; Panduro Vazquez, W; Tibbetts, M; Behera, P K; Chai, X; Charles, M J; Mallik, U; Ziegler, V; Cochran, J; Crawley, H B; Dong, L; Eyges, V; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Gao, Y Y; Gritsan, A V; Guo, Z J; Lae, C K; Denig, A G; Fritsch, M; Schott, G; Arnaud, N; Béquilleux, J; D'Orazio, A; Davier, M; Grosdidier, G; Höcker, A; Lepeltier, V; Le Diberder, F; Lutz, A M; Pruvot, S; Rodier, S; Roudeau, P; Schune, M H; Serrano, J; Sordini, V; Stocchi, A; Wang, W F; Wormser, G; Lange, D J; Wright, D M; Bingham, I; Burke, J P; Chavez, C A; Forster, I J; Fry, J R; Gabathuler, E; Gamet, R; Hutchcroft, D E; Payne, D J; Schofield, K C; Touramanis, C; Bevan, A J; George, K A; Di Lodovico, F; Menges, W; Sacco, R; Cowan, G; Flaecher, H U; Hopkins, D A; Paramesvaran, S; Salvatore, F; Wren, A C; Brown, D N; Davis, C L; Allison, J; Barlow, N R; Barlow, R J; Chia, Y M; Edgar, C L; Lafferty, G D; West, T J; Yi, J I; Anderson, J; Chen, C; Jawahery, A; Roberts, D A; Simi, G; Tuggle, J M; Blaylock, G; Dallapiccola, C; Hertzbach, S S; Li, X; Moore, T B; Salvati, E; Saremi, S; Cowan, R; Dujmic, D; Fisher, P H; Koeneke, K; Sciolla, G; Sekula, S J; Spitznagel, M; Taylor, F; Yamamoto, R K; Zhao, M; Zheng, Y; Mclachlin, S E; Patel, P M; Robertson, S H; Lazzaro, A; Palombo, F; Bauer, J M; Cremaldi, L; Eschenburg, V; Godang, R; Kroeger, R; Sanders, D A; Summers, D J; Zhao, H W; Brunet, S; Côté, D; Simard, M; Taras, P; Viaud, F B; Nicholson, H; De Nardo, G; Fabozzi, F; Lista, L; Monorchio, D; Sciacca, C; Baak, M A; Raven, G; Snoek, H L; Jessop, C P; Knoepfel, K J; LoSecco, J M; Benelli, G; Corwin, L A; Honscheid, K; Kagan, H; Kass, R; Morris, J P; Rahimi, A M; Regensburger, J J; Wong, Q K; Blount, N L; Brau, J; Frey, R; Igonkina, O; Kolb, J A; Lu, M; Rahmat, R; Sinev, N B; Strom, D; Strube, J; Torrence, E; Gagliardi, N; Gaz, A; Margoni, M; Morandin, M; Pompili, A; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; Ben-Haim, E; Briand, H; Calderini, G; Chauveau, J; David, P; Del Buono, L; de la Vaissière, Ch; Hamon, O; Leruste, Ph; Malclès, J; Ocariz, J; Perez, A; Prendki, J; Gladney, L; Biasini, M; Covarelli, R; Manoni, E; Angelini, C; Batignani, G; Bettarini, S; Carpinelli, M; Cenci, R; Cervelli, A; Forti, F; Giorgi, M A

    2007-11-16

    We present a search for the lepton flavor violating decay B+-->K+ tau-/+ mu+/- using 383 x 10;{6} BB[over ] events collected by the BABAR experiment. The branching fraction for this decay can be substantially enhanced in new physics models. The kinematics of the tau from the signal B decay are inferred from the K+, mu, and other B in the event, which is fully reconstructed in one of a variety of hadronic decay modes, allowing the signal B candidate to be fully reconstructed. We observe no excess of events over the expected background and set a limit of B(B+-->K+ tau mu)<7.7 x 10(-5) at 90% confidence level, where the branching fraction is for the sum of the K+ tau- mu+ and K+ tau+mu- final states. We use this result to improve a model-independent bound on the energy scale of flavor-changing new physics.

  12. Non-local coupled-channels optical calculation of electron scattering by atomic hydrogen at 54.42 eV

    International Nuclear Information System (INIS)

    Ratnavelu, K.; McCarthy, I.E.

    1990-01-01

    The present study incorporates the non-local optical potentials for the continuum within the coupled-channels optical framework to study electron scattering from atomic hydrogen at 54.42 eV. Nine-state coupled-channels calculations with non-local and local continuum optical potentials were performed. The results for differential, total and ionization cross sections as well as the 2p angular correlation parameters λ and R are comparable with other non-perturbative calculations. There are still discrepancies between theory and experiment, particularly for λ and R at larger angles. (author)

  13. On locality of Generalized Reed-Muller codes over the broadcast erasure channel

    KAUST Repository

    Alloum, Amira

    2016-07-28

    One to Many communications are expected to be among the killer applications for the currently discussed 5G standard. The usage of coding mechanisms is impacting broadcasting standard quality, as coding is involved at several levels of the stack, and more specifically at the application layer where Rateless, LDPC, Reed Slomon codes and network coding schemes have been extensively studied, optimized and standardized in the past. Beyond reusing, extending or adapting existing application layer packet coding mechanisms based on previous schemes and designed for the foregoing LTE or other broadcasting standards; our purpose is to investigate the use of Generalized Reed Muller codes and the value of their locality property in their progressive decoding for Broadcast/Multicast communication schemes with real time video delivery. Our results are meant to bring insight into the use of locally decodable codes in Broadcasting. © 2016 IEEE.

  14. Hyperbolic Positioning with Antenna Arrays and Multi-Channel Pseudolite for Indoor Localization

    Directory of Open Access Journals (Sweden)

    Kenjirou Fujii

    2015-09-01

    Full Text Available A hyperbolic positioning method with antenna arrays consisting of proximately-located antennas and a multi-channel pseudolite is proposed in order to overcome the problems of indoor positioning with conventional pseudolites (ground-based GPS transmitters. A two-dimensional positioning experiment using actual devices is conducted. The experimental result shows that the positioning accuracy varies centimeter- to meter-level according to the geometric relation between the pseudolite antennas and the receiver. It also shows that the bias error of the carrier-phase difference observables is more serious than their random error. Based on the size of the bias error of carrier-phase difference that is inverse-calculated from the experimental result, three-dimensional positioning performance is evaluated by computer simulation. In addition, in the three-dimensional positioning scenario, an initial value convergence analysis of the non-linear least squares is conducted. Its result shows that initial values that can converge to a right position exist at least under the proposed antenna setup. The simulated values and evaluation methods introduced in this work can be applied to various antenna setups; therefore, by using them, positioning performance can be predicted in advance of installing an actual system.

  15. Local gas- and liquid-phase measurements for air-water two-phase flows in a rectangular channel

    International Nuclear Information System (INIS)

    Zhou, X.; Sun, X.; Williams, M.; Fu, Y.; Liu, Y.

    2014-01-01

    Local gas- and liquid-phase measurements of various gas-liquid two-phase flows, including bubbly, cap-bubbly, slug, and churn-turbulent flows, were performed in an acrylic vertical channel with a rectangular cross section of 30 mm x 10 mm and height of 3.0 m. All the measurements were carried out at three measurement elevations along the flow channel, with z/D h = 9, 72, and 136, respectively, to study the flow development. The gas-phase velocity, void fraction, and bubble number frequency were measured using a double-sensor conductivity probe. A high-speed imaging system was utilized to perform the flow regime visualization and to provide additional quantitative information of the two-phase flow structure. An image processing scheme was developed to obtain the gas-phase velocity, void fraction, Sauter mean diameter, bubble number density, and interfacial area concentration. The liquid-phase velocity and turbulence measurements were conducted using a particle image velocimetry-planar laser-induced fluorescence (PIV-PLIF) system, which enables whole-field and high-resolution data acquisition. An optical phase separation method, which uses fluorescent particles and optical filtration technique, is adopted to extract the velocity information of the liquid phase. An image pre-processing scheme is imposed on the raw PIV images acquired to remove noises due to the presence of bubble residuals and optically distorted particles in the images captured by the PIV-PLIF system. Due to the better light access and less bubble distortion in the narrow rectangular channel, the PIV-PLIF system were able to perform reasonably well in flows of even higher void fractions as compared to the situations with circular pipe test sections. The flow conditions being studied covered various flow regime transitions, void fractions, and liquid-phase flow Reynolds numbers. The obtained experimental data can also be used to validate two-phase CFD results. (author)

  16. Modeling the thermal behavior of fluid flow inside channels using an artificial locally linear neuro-fuzzy approach

    Directory of Open Access Journals (Sweden)

    Azadeh Hashemian

    2008-06-01

    Full Text Available Enhanced surface heat exchangers are commonly used all worldwide. If applicable, due to their complicated geometry, simulating corrugated plate heat exchangers is a time-consuming process. In the present study, first we simulate the heat transfer in a sharp V-shape corrugation cell with constant temperature walls; then, we use a Locally Linear Neuro-Fuzzy method based on a radial basis function (RBFs to model the temperature field in the whole channel. New approach is developed to deal with fast computational and low memory resources that can be used with the largest available data sets. The purpose of the research is to reveal the advantages of proposed Neuro-Fuzzy model as a powerful modeling system designed for predicting and to make a fair comparison between it and the successful FLUENT simulated approaches in its best structures.

  17. Local anesthetics QX 572 and benzocaine act at separate sites on the batrachotoxin-activated sodium channel.

    Science.gov (United States)

    Huang, L M; Ehrenstein, G

    1981-02-01

    We have studied the effect of local anesthetics QX 572, which is permanently charged, and benzocaine, which is neutral, on batrachotoxin-activated sodium channels in mouse neuroblastoma N18 cells. The dose-response curves for each drug suggest that QX 752 and benzocaine each act on a single class of binding sites. The dissociation constants are 3.15 X 10(-5) M for QX 572 and 2.65 X 10(-4) M for benzocaine. Equilibrium and kinetic experiments indicate that both drugs are competitive inhibitors of batrachotoxin. When benzocaine and QX 572 are present with batrachotoxin, they are much more effective at inhibiting Na+ flux than would be predicted by a one-site model. Our results indicate that QX 572 and benzocaine bind to separate sites, each of which interacts competitively with batrachotoxin.

  18. Toward Standardization of BK Virus Monitoring: Evaluation of the BK Virus R-gene Kit for Quantification of BK Viral Load in Urine, Whole-Blood, and Plasma Specimens

    OpenAIRE

    Sueur, Charlotte; Solis, Morgane; Meddeb, Mariam; Soulier, Eric; Domingo-Calap, Pilar; Lepiller, Quentin; Freitag, Rachel; Bahram, Seiamak; Caillard, Sophie; Barth, Heidi; Stoll-Keller, Françoise; Fafi-Kremer, Samira

    2014-01-01

    Screening of BK virus (BKV) replication is recommended to identify patients at increased risk of BKV-associated diseases. However, the heterogeneity of molecular techniques hinders the establishment of universal guidelines for BKV monitoring. Here we aimed to compare the performance of the CE-marked BK virus R-gene kit (R-gene) to the performance of our in-house assay for quantification of BKV DNA loads (BKVL). A 12-specimen panel from the Quality Control for Molecular Diagnostics (QCMD) orga...

  19. Predictive model for local scour downstream of hydrokinetic turbines in erodible channels

    Science.gov (United States)

    Musa, Mirko; Heisel, Michael; Guala, Michele

    2018-02-01

    A modeling framework is derived to predict the scour induced by marine hydrokinetic turbines installed on fluvial or tidal erodible bed surfaces. Following recent advances in bridge scour formulation, the phenomenological theory of turbulence is applied to describe the flow structures that dictate the equilibrium scour depth condition at the turbine base. Using scaling arguments, we link the turbine operating conditions to the flow structures and scour depth through the drag force exerted by the device on the flow. The resulting theoretical model predicts scour depth using dimensionless parameters and considers two potential scenarios depending on the proximity of the turbine rotor to the erodible bed. The model is validated at the laboratory scale with experimental data comprising the two sediment mobility regimes (clear water and live bed), different turbine configurations, hydraulic settings, bed material compositions, and migrating bedform types. The present work provides future developers of flow energy conversion technologies with a physics-based predictive formula for local scour depth beneficial to feasibility studies and anchoring system design. A potential prototype-scale deployment in a large sandy river is also considered with our model to quantify how the expected scour depth varies as a function of the flow discharge and rotor diameter.

  20. METODE GURU BK DALAM MENGATASI PROBLEM PENYESUAIAN DIRI PADA ANAK BERKEBUTUHAN KHUSUS

    Directory of Open Access Journals (Sweden)

    Fitri Lestari

    2015-12-01

    Full Text Available Penelitian ini bertujuan untuk mengetahui serta menjelaskan metode yang dilakukan guru BK dalam mengatasi problem penyesuaian diri pada sisiwa tunarungu SD LB di SLB Purwokerto. Penelitian ini merupakan penelitian lapangan dengan jenis penelitian kualitatif (studi kasus. Subjek penelitiannya kepala sekolah, guru BK, dan siswa tunarungu, sedangkan objek penelitiannya adalah problem penyesuaian diri pada siswa tunarungu SD LB dab metode guru BK dalam mengatasinya di SLB Purwokerto. Hasil penelitian ini menunjukkan bahwa problem penyesuainan diri pada siswa tunarungu meliputi kurang percaya diri, kurang mandiri, cenderung kaku, dan egoisentris. Metode yang digunakan oleh guru BK dalam mengatasi problem penyesuaian diri tersebut yaitu dengan metode bimbingan khusus. Metode bimbingan khusus dibagi menjadi 2 kelompok besar yaitu metode kelompok (metode ceramah, metode demonstrasi/praktik, metode drill, dan karyawisata dan metode individu (metode tanya jawab dan metode penugasan.

  1. OSR1 and SPAK Sensitivity of Large-Conductance Ca2+ Activated K+ Channel

    Directory of Open Access Journals (Sweden)

    Bernat Elvira

    2016-04-01

    Full Text Available Background/Aims: The oxidative stress-responsive kinase 1 (OSR1 and the serine/threonine kinases SPAK (SPS1-related proline/alanine-rich kinase are under the control of WNK (with-no-K [Lys] kinases. OSR1 and SPAK participate in diverse functions including cell volume regulation and neuronal excitability. Cell volume and neuronal excitation are further modified by the large conductance Ca2+-activated K+ channels (maxi K+ channel or BK channels. An influence of OSR1 and/or SPAK on BK channel activity has, however, never been shown. The present study thus explored whether OSR1 and/or SPAK modify the activity of BK channels. Methods: cRNA encoding the Ca2+ insensitive BK channel mutant BKM513I+Δ899-903 was injected into Xenopus laevis oocytes without or with additional injection of cRNA encoding wild-type OSR1 or wild-type SPAK, constitutively active T185EOSR1, catalytically inactive D164AOSR1, constitutively active T233ESPAK or catalytically inactive D212ASPAK. K+ channel activity was measured utilizing dual electrode voltage clamp. Results: BK channel activity in BKM513I+Δ899-903 expressing oocytes was significantly decreased by co-expression of OSR1 or SPAK. The effect of wild-type OSR1/SPAK was mimicked by T185EOSR1 and T233ESPAK, but not by D164AOSR1 or D212ASPAK. Conclusions: OSR1 and SPAK suppress BK channels, an effect possibly contributing to cell volume regulation and neuroexcitability.

  2. Complications post renal transplantation: literature focus on BK virus nephropathy and diagnostic tools actually available

    Directory of Open Access Journals (Sweden)

    Miglio Umberto

    2008-03-01

    Full Text Available Abstract Clinical diagnosis of kidney transplants related illnesses is not a simple task. Several studies were conducted to define diseases and complications after renal transplantation, but there are no comprehensive guidelines about diagnostic tools for their prevention and detection. The Authors of this review looked for the medical literature and pertinent publications in particular to understand the role of Human Polyomavirus BK (BKV in renal failure and to recognize analytical techniques for BK virus associated nephropathy (BKVAN detection.

  3. Conformal barrier and hidden local symmetry constraints: Walking technirhos in LHC diboson channels

    Directory of Open Access Journals (Sweden)

    Hidenori S. Fukano

    2016-03-01

    Full Text Available We expand the previous analyses of the conformal barrier on the walking technirho for the 2 TeV diboson excesses reported by the ATLAS Collaboration, with a special emphasis on the hidden local symmetry (HLS constraints. We first show that the Standard Model (SM Higgs Lagrangian is equivalent to the scale-invariant nonlinear chiral Lagrangian, which is further gauge equivalent to the scale-invariant HLS model, with the scale symmetry realized nonlinearly via SM Higgs as a (pseudo-dilaton. The scale symmetry forbids the new vector boson decay to the 125 GeV Higgs plus W/Z boson, in sharp contrast to the conventional “equivalence theorem” which is invalidated by the conformality. The HLS forbids mixing between the iso-triplet technirho's, ρΠ and ρP, of the one-family walking technicolor (with four doublets ND=NF/2=4, which, without the HLS, would be generated when switching on the standard model gauging. We also present updated analyses of the walking technirho's for the diboson excesses by fully incorporating the constraints from the conformal barrier and the HLS as well as possible higher order effects: still characteristic of the one-family walking technirho is its smallness of the decay width, roughly of order Γ/Mρ∼[3/NC×1/ND]×[Γ/Mρ]QCD≃70 GeV/2 TeV (ND=NC=4, in perfect agreement with the expected diboson resonance with Γ<100 GeV. The model is so sharply distinguishable from other massive spin 1 models without the conformality and HLS that it is clearly testable at the LHC Run II. If the 2 TeV boson decay to WH/ZH is not observed in the ongoing Run II, then the conformality is operative on the 125 GeV Higgs, strongly suggesting that the 2 TeV excess events are responsible for the walking technirhos and the 125 GeV Higgs is the technidilaton.

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

    Directory of Open Access Journals (Sweden)

    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

  5. Local Nusselt number enhancement during gas-liquid Taylor bubble flow in a square mini-channel: An experimental study

    International Nuclear Information System (INIS)

    Majumder, Abhik; Mehta, Balkrishna; Khandekar, Sameer

    2013-01-01

    Taylor bubble flow takes place when two immiscible fluids (liquid-liquid or gas-liquid) flow inside a tube of capillary dimensions within specific range of volume flow ratios. In the slug flows where gas and liquid are two different phases, liquid slugs are separated by elongated Taylor bubbles. This singular flow pattern is observed in many engineering mini-/micro-scale devices like pulsating heat pipes, gas-liquid-solid monolithic reactors, micro-two-phase heat exchangers, digital micro-fluidics, micro-scale mass transfer process, fuel cells, etc. The unique and complex flow characteristics require understanding on local, as well as global, spatio-temporal scales. In the present work, the axial stream-wise profile of the fluid and wall temperature for air-water (i) isolated single Taylor bubble and, (ii) a train of Taylor bubbles, in a horizontal square channel of size 3.3 mm x 3.3 mm x 350 mm, heated from the bottom (heated length = 175 mm), with the other three sides kept insulated, are reported at different gas volume flow ratios. The primary aim is to study the enhancement of heat transfer due to the Taylor bubble train flow, in comparison with thermally developing single-phase flows. Intrusion of a bubble in the liquid flow drastically changes the local temperature profiles. The axial distribution of time-averaged local Nusselt number (Nu z ) shows that Taylor bubble train regime increases the transport of heat up to 1.2-1.6 times more as compared with laminar single-phase liquid flow. In addition, for a given liquid flow Reynolds number, the heat transfer enhancement is a function of the geometrical parameters of the unit cell, i.e., the length of adjacent gas bubble and water plug. (authors)

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Modes of operation of the BKCa channel beta2 subunit.

    Science.gov (United States)

    Savalli, Nicoletta; Kondratiev, Andrei; de Quintana, Sarah Buxton; Toro, Ligia; Olcese, Riccardo

    2007-07-01

    The beta(2) subunit of the large conductance Ca(2+)- and voltage-activated K(+) channel (BK(Ca)) modulates a number of channel functions, such as the apparent Ca(2+)/voltage sensitivity, pharmacological and kinetic properties of the channel. In addition, the N terminus of the beta(2) subunit acts as an inactivating particle that produces a relatively fast inactivation of the ionic conductance. Applying voltage clamp fluorometry to fluorescently labeled human BK(Ca) channels (hSlo), we have investigated the mechanisms of operation of the beta(2) subunit. We found that the leftward shift on the voltage axis of channel activation curves (G(V)) produced by coexpression with beta(2) subunits is associated with a shift in the same direction of the fluorescence vs. voltage curves (F(V)), which are reporting the voltage dependence of the main voltage-sensing region of hSlo (S4-transmembrane domain). In addition, we investigated the inactivating mechanism of the beta(2) subunits by comparing its properties with the ones of the typical N-type inactivation process of Shaker channel. While fluorescence recordings from the inactivated Shaker channels revealed the immobilization of the S4 segments in the active conformation, we did not observe a similar feature in BK(Ca) channels coexpressed with the beta(2) subunit. The experimental observations are consistent with the view that the beta(2) subunit of BK(Ca) channels facilitates channel activation by changing the voltage sensor equilibrium and that the beta(2)-induced inactivation process does not follow a typical N-type mechanism.

  8. Local anesthetic interaction with human ether-a-go-go-related gene (HERG) channels: role of aromatic amino acids Y652 and F656

    DEFF Research Database (Denmark)

    Siebrands, Cornelia C; Schmitt, Nicole; Friederich, Patrick

    2005-01-01

    by bupivacaine, ropivacaine, and mepivacaine. Whole cell patch clamp recordings were performed at room temperature. RESULTS: Inhibition of HERG wild-type and mutant channels by the different local anesthetics was concentration dependent, stereoselective, and reversible. The sensitivity decreased in the order...

  9. Local Multi-Channel RF Surface Coil versus Body RF Coil Transmission for Cardiac Magnetic Resonance at 3 Tesla: Which Configuration Is Winning the Game?

    Science.gov (United States)

    Weinberger, Oliver; Winter, Lukas; Dieringer, Matthias A; Els, Antje; Oezerdem, Celal; Rieger, Jan; Kuehne, Andre; Cassara, Antonino M; Pfeiffer, Harald; Wetterling, Friedrich; Niendorf, Thoralf

    2016-01-01

    The purpose of this study was to demonstrate the feasibility and efficiency of cardiac MR at 3 Tesla using local four-channel RF coil transmission and benchmark it against large volume body RF coil excitation. Electromagnetic field simulations are conducted to detail RF power deposition, transmission field uniformity and efficiency for local and body RF coil transmission. For both excitation regimes transmission field maps are acquired in a human torso phantom. For each transmission regime flip angle distributions and blood-myocardium contrast are examined in a volunteer study of 12 subjects. The feasibility of the local transceiver RF coil array for cardiac chamber quantification at 3 Tesla is demonstrated. Our simulations and experiments demonstrate that cardiac MR at 3 Tesla using four-channel surface RF coil transmission is competitive versus current clinical CMR practice of large volume body RF coil transmission. The efficiency advantage of the 4TX/4RX setup facilitates shorter repetition times governed by local SAR limits versus body RF coil transmission at whole-body SAR limit. No statistically significant difference was found for cardiac chamber quantification derived with body RF coil versus four-channel surface RF coil transmission. Our simulation also show that the body RF coil exceeds local SAR limits by a factor of ~2 when driven at maximum applicable input power to reach the whole-body SAR limit. Pursuing local surface RF coil arrays for transmission in cardiac MR is a conceptually appealing alternative to body RF coil transmission, especially for patients with implants.

  10. Troponin T3 regulates nuclear localization of the calcium channel Cavβ1a subunit in skeletal muscle.

    Science.gov (United States)

    Zhang, Tan; Taylor, Jackson; Jiang, Yang; Pereyra, Andrea S; Messi, Maria Laura; Wang, Zhong-Min; Hereñú, Claudia; Delbono, Osvaldo

    2015-08-15

    The voltage-gated calcium channel (Cav) β1a subunit (Cavβ1a) plays an important role in excitation-contraction coupling (ECC), a process in the myoplasm that leads to muscle-force generation. Recently, we discovered that the Cavβ1a subunit travels to the nucleus of skeletal muscle cells where it helps to regulate gene transcription. To determine how it travels to the nucleus, we performed a yeast two-hybrid screening of the mouse fast skeletal muscle cDNA library and identified an interaction with troponin T3 (TnT3), which we subsequently confirmed by co-immunoprecipitation and co-localization assays in mouse skeletal muscle in vivo and in cultured C2C12 muscle cells. Interacting domains were mapped to the leucine zipper domain in TnT3 COOH-terminus (160-244 aa) and Cavβ1a NH2-terminus (1-99 aa), respectively. The double fluorescence assay in C2C12 cells co-expressing TnT3/DsRed and Cavβ1a/YFP shows that TnT3 facilitates Cavβ1a nuclear recruitment, suggesting that the two proteins play a heretofore unknown role during early muscle differentiation in addition to their classical role in ECC regulation. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. 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

    IK/rSK3 and hBK channels suggest that the significant stimulation of hIK and rSK3 channels during swelling is not mediated by changes in intracellular Ca2+, but rather through interactions with the cytoskeleton, provided that a sufficient basal concentration of intracellular Ca2+ or Cd2+ is present....

  12. 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...

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

    Directory of Open Access Journals (Sweden)

    Nirianne Marie Q Palacpac

    Full Text Available BACKGROUND: 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. METHODS: 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. RESULTS: 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

  14. VP-1 quasispecies in human infection with polyomavirus BK.

    Science.gov (United States)

    Luo, Chunqing; Hirsch, Hans H; Kant, Jeffrey; Randhawa, Parmjeet

    2012-01-01

    Polyomavirus BK is a recognized cause of nephropathy and hemorrhagic cystitis in kidney or allogeneic hematopoietic stem cell transplant recipients. This study explored a role of genetic variations in capsid protein VP-1 gene as a factor in viral pathogenesis. VP-1 was amplified from 7 healthy subjects with viruria, 7 transplant patients with viruria, and 11 patients with viremia or nephropathy. PCR products were cloned and a total of 558 clonal sequences were subjected to phylogenetic analysis using standard methods. VP-1 quasispecies were found in 25/25 and coinfection with different genotypes in 12/25 subjects. Genotype II was found as an unexpected minority species in 5/25 individuals. Recombinant strains of uncertain biologic significance, which frequently contained genotype II and IV sequences were identified in 9/25 subjects. Viremia/nephropathy group was characterized by (a) greater sequence complexity in whole VP-1 versus BC loop and BC loop compared to the HI loop, (b) greater intra-strain genetic diversity in the BC loop compared to whole VP-1 protein and HI loop, (c) more non-synonymous substitutions (dN) in the BC loop compared to whole VP-1 and HI loop, (e) fewer synonymous substitutions (dS) compared to healthy-viruria group, and (f) selection pressure (dN/dS >1.0) exerted on VP-1. In conclusion, this study documents frequent occurrence of quasispecies in a host DNA polymerase dependent virus, which is theoretically expected to show high replication fidelity. Quasispecies occur even in healthy subjects with viruria, but evolutionary selection pressure directed at the viral capsid protein (VP-1) is seen only in patients with viremia or nephropathy. Copyright © 2011 Wiley Periodicals, Inc.

  15. Kv3.3 Channels Bind Hax-1 and Arp2/3 to Assemble a Stable Local Actin Network that Regulates Channel Gating.

    Science.gov (United States)

    Zhang, Yalan; Zhang, Xiao-Feng; Fleming, Matthew R; Amiri, Anahita; El-Hassar, Lynda; Surguchev, Alexei A; Hyland, Callen; Jenkins, David P; Desai, Rooma; Brown, Maile R; Gazula, Valeswara-Rao; Waters, Michael F; Large, Charles H; Horvath, Tamas L; Navaratnam, Dhasakumar; Vaccarino, Flora M; Forscher, Paul; Kaczmarek, Leonard K

    2016-04-07

    Mutations in the Kv3.3 potassium channel (KCNC3) cause cerebellar neurodegeneration and impair auditory processing. The cytoplasmic C terminus of Kv3.3 contains a proline-rich domain conserved in proteins that activate actin nucleation through Arp2/3. We found that Kv3.3 recruits Arp2/3 to the plasma membrane, resulting in formation of a relatively stable cortical actin filament network resistant to cytochalasin D that inhibits fast barbed end actin assembly. These Kv3.3-associated actin structures are required to prevent very rapid N-type channel inactivation during short depolarizations of the plasma membrane. The effects of Kv3.3 on the actin cytoskeleton are mediated by the binding of the cytoplasmic C terminus of Kv3.3 to Hax-1, an anti-apoptotic protein that regulates actin nucleation through Arp2/3. A human Kv3.3 mutation within a conserved proline-rich domain produces channels that bind Hax-1 but are impaired in recruiting Arp2/3 to the plasma membrane, resulting in growth cones with deficient actin veils in stem cell-derived neurons. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. 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.

  17. 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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    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...

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Troponin T3 regulates nuclear localization of the calcium channel Cavβ1a subunit in skeletal muscle

    International Nuclear Information System (INIS)

    Zhang, Tan; Taylor, Jackson; Jiang, Yang; Pereyra, Andrea S.; Messi, Maria Laura; Wang, Zhong-Min; Hereñú, Claudia; Delbono, Osvaldo

    2015-01-01

    The voltage-gated calcium channel (Ca v ) β 1a subunit (Ca v β 1a ) plays an important role in excitation–contraction coupling (ECC), a process in the myoplasm that leads to muscle-force generation. Recently, we discovered that the Ca v β 1a subunit travels to the nucleus of skeletal muscle cells where it helps to regulate gene transcription. To determine how it travels to the nucleus, we performed a yeast two-hybrid screening of the mouse fast skeletal muscle cDNA library and identified an interaction with troponin T3 (TnT3), which we subsequently confirmed by co-immunoprecipitation and co-localization assays in mouse skeletal muscle in vivo and in cultured C2C12 muscle cells. Interacting domains were mapped to the leucine zipper domain in TnT3 COOH-terminus (160–244 aa) and Ca v β 1a NH 2 -terminus (1–99 aa), respectively. The double fluorescence assay in C2C12 cells co-expressing TnT3/DsRed and Ca v β 1a /YFP shows that TnT3 facilitates Ca v β 1a nuclear recruitment, suggesting that the two proteins play a heretofore unknown role during early muscle differentiation in addition to their classical role in ECC regulation. - Highlights: • Previously, we demonstrated that Ca v β 1a is a gene transcription regulator. • Here, we show that TnT3 interacts with Ca v β 1a . • We mapped TnT3 and Ca v β 1a interaction domain. • TnT3 facilitates Ca v β 1a nuclear enrichment. • The two proteins play a heretofore unknown role during early muscle differentiation

  1. 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.

  2. 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

  3. BK virus encephalitis: case report, review of the literature, and description of a novel treatment modality.

    Science.gov (United States)

    Chittick, Paul; Williamson, John C; Ohl, Christopher A

    2013-09-01

    To describe a case of BK virus encephalitis with attempted direct antiviral therapy, review the reported cases of BK virus in the central nervous system, and report the novel use of intravenous cimetidine in place of oral probenecid to minimize the toxicities of intravenous cidofovir. A 36-year-old male with acute myelomonocytic leukemia and subsequent myelodysplastic syndrome underwent allogeneic hematopoietic stem cell transplant. His course was complicated by severe graft-versus-host disease involving his skin and gastrointestinal tract. Five weeks after transplantation, he developed fever and confusion. Magnetic resonance imaging was suggestive of limbic encephalitis and cerebrospinal fluid tested positive for BK virus. Therapy with intravenous cidofovir was thought to be indicated. Although probenecid is commonly used to minimize the toxicities of cidofovir, the patient's severe graft-versus-host disease raised concerns about absorption of oral medications. Based on animal models and pharmacokinetic data, intravenous cimetidine was used in place of oral probenecid. Despite these therapies, the patient's mental status did not improve. He developed progressive organ system failure, and care was ultimately withdrawn. BK virus is increasingly described as a cause of encephalitis. The majority of reported cases have occurred in immunocompromised patients and have generally had a poor outcome. This case describes attempted antiviral therapy using cidofovir, the antiviral agent used most frequently in other syndromes due to BK virus. Intravenous cimetidine is a novel modality used to minimize ocular and renal toxicities frequently seen with cidofovir, and we believe this warrants further investigation. BK virus may be a cause of encephalitis in immunocompromised hosts, and cidofovir represents a possible treatment option. Intravenous cimetidine can be considered to minimize toxicities associated with cidofovir use in patients unable to tolerate or absorb oral

  4. Cloning and Immunocytochemical Localization of a Cyclic Nucleotide–Gated Channel α-Subunit to All Cone Photoreceptors in the Mouse Retina

    Science.gov (United States)

    HIRANO, ARLENE A.; HACK, IRIS; WÄSSLE, HEINZ; DUVOISIN, ROBERT M.

    2010-01-01

    Cyclic nucleotide–gated channels (CNGC) are ligand-gated ion channels that open and close in response to changes in the intracellular concentration of the second messengers, 3′,5′-cyclic adenosine monophosphate and 3′,5′-cyclic guanosine monophosphate. Most notably, they transduce the chemical signal produced by the absorption of light in photoreceptors into a membrane potential change, which is then transmitted to the ascending visual pathway. CNGCs have also been implicated in the signal transduction of other neurons downstream of the photoreceptors, in particular the ON-bipolar cells, as well as in other areas of the central nervous system. We therefore undertook a search for additional cyclic nucleotide–gated channels expressed in the retina. Following a degenerate reverse transcription polymerase chain reaction approach to amplify low-copy number messages, a cDNA encoding a new splice variant of CNGC α-subunit was isolated from mouse retina and classified as mCNG3. An antiserum raised against the carboxy-terminal sequence identified the retinal cell type expressing mCNG3 as cone photoreceptors. Preembedding immunoelectron microscopy demonstrated its membrane localization in the outer segments, consistent with its role in phototransduction. Double-labeling experiments with cone-specific markers indicated that all cone photoreceptors in the murid retina use the same or a highly conserved cyclic nucleotide–gated channel. Therefore, defects in this channel would be predicted to severely impair photopic vision. PMID:10813773

  5. Automated parallel recordings of topologically identified single ion channels.

    Science.gov (United States)

    Kawano, Ryuji; Tsuji, Yutaro; Sato, Koji; Osaki, Toshihisa; Kamiya, Koki; Hirano, Minako; Ide, Toru; Miki, Norihisa; Takeuchi, Shoji

    2013-01-01

    Although ion channels are attractive targets for drug discovery, the systematic screening of ion channel-targeted drugs remains challenging. To facilitate automated single ion-channel recordings for the analysis of drug interactions with the intra- and extracellular domain, we have developed a parallel recording methodology using artificial cell membranes. The use of stable lipid bilayer formation in droplet chamber arrays facilitated automated, parallel, single-channel recording from reconstituted native and mutated ion channels. Using this system, several types of ion channels, including mutated forms, were characterised by determining the protein orientation. In addition, we provide evidence that both intra- and extracellular amyloid-beta fragments directly inhibit the channel open probability of the hBK channel. This automated methodology provides a high-throughput drug screening system for the targeting of ion channels and a data-intensive analysis technique for studying ion channel gating mechanisms.

  6. 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

  7. 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.

  8. 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)

  9. 75 FR 66657 - Airworthiness Directives; Eurocopter Deutschland GmbH Model MBB-BK 117 C-2 Helicopters

    Science.gov (United States)

    2010-10-29

    ... Airworthiness Directives; Eurocopter Deutschland GmbH Model MBB- BK 117 C-2 Helicopters AGENCY: Federal Aviation... (AD) for the Eurocopter Deutschland GmbH (ECD) Model MBB BK 117 C-2 helicopters. This amendment...: 2010-22-07 Eurocopter Deutschland GmbH: Amendment 39-16486; Docket No. FAA-2010-0780; Directorate...

  10. The Role of L- and T-Type Calcium Channels in Local and Remote Calcium Responses in Rat Mesenteric Terminal Arterioles

    DEFF Research Database (Denmark)

    Braunstein, Thomas Hartig; Inoue, Ryuji; Cribbs, Leanne

    2009-01-01

    to local (DeltaR = 0.54) and remote (DeltaR = 0.17 at 500 mum) increases in intracellular Ca(2+). Remote Ca(2+) responses were inhibited by the gap junction uncouplers carbenoxolone and palmitoleic acid. Ca(V)1.2, Ca(V)3.1 and Ca(V)3.2 channels were immunolocalized in vascular smooth muscle cells and Ca...

  11. Exploring the Structure of the Voltage-gated Na+ Channel by an Engineered Drug Access Pathway to the Receptor Site for Local Anesthetics*

    Science.gov (United States)

    Lukacs, Peter; Gawali, Vaibhavkumar S.; Cervenka, Rene; Ke, Song; Koenig, Xaver; Rubi, Lena; Zarrabi, Touran; Hilber, Karlheinz; Stary-Weinzinger, Anna; Todt, Hannes

    2014-01-01

    Despite the availability of several crystal structures of bacterial voltage-gated Na+ channels, the structure of eukaryotic Na+ channels is still undefined. We used predictions from available homology models and crystal structures to modulate an external access pathway for the membrane-impermeant local anesthetic derivative QX-222 into the internal vestibule of the mammalian rNaV1.4 channel. Potassium channel-based homology models predict amino acid Ile-1575 in domain IV segment 6 to be in close proximity to Lys-1237 of the domain III pore-loop selectivity filter. The mutation K1237E has been shown previously to increase the diameter of the selectivity filter. We found that an access pathway for external QX-222 created by mutations of Ile-1575 was abolished by the additional mutation K1237E, supporting the notion of a close spatial relationship between sites 1237 and 1575. Crystal structures of bacterial voltage-gated Na+ channels predict that the side chain of rNaV1.4 Trp-1531 of the domain IV pore-loop projects into the space between domain IV segment 6 and domain III pore-loop and, therefore, should obstruct the putative external access pathway. Indeed, mutations W1531A and W1531G allowed for exceptionally rapid access of QX-222. In addition, W1531G created a second non-selective ion-conducting pore, bypassing the outer vestibule but probably merging into the internal vestibule, allowing for control by the activation gate. These data suggest a strong structural similarity between bacterial and eukaryotic voltage-gated Na+ channels. PMID:24947510

  12. Exploring the structure of the voltage-gated Na+ channel by an engineered drug access pathway to the receptor site for local anesthetics.

    Science.gov (United States)

    Lukacs, Peter; Gawali, Vaibhavkumar S; Cervenka, Rene; Ke, Song; Koenig, Xaver; Rubi, Lena; Zarrabi, Touran; Hilber, Karlheinz; Stary-Weinzinger, Anna; Todt, Hannes

    2014-08-01

    Despite the availability of several crystal structures of bacterial voltage-gated Na(+) channels, the structure of eukaryotic Na(+) channels is still undefined. We used predictions from available homology models and crystal structures to modulate an external access pathway for the membrane-impermeant local anesthetic derivative QX-222 into the internal vestibule of the mammalian rNaV1.4 channel. Potassium channel-based homology models predict amino acid Ile-1575 in domain IV segment 6 to be in close proximity to Lys-1237 of the domain III pore-loop selectivity filter. The mutation K1237E has been shown previously to increase the diameter of the selectivity filter. We found that an access pathway for external QX-222 created by mutations of Ile-1575 was abolished by the additional mutation K1237E, supporting the notion of a close spatial relationship between sites 1237 and 1575. Crystal structures of bacterial voltage-gated Na(+) channels predict that the side chain of rNaV1.4 Trp-1531 of the domain IV pore-loop projects into the space between domain IV segment 6 and domain III pore-loop and, therefore, should obstruct the putative external access pathway. Indeed, mutations W1531A and W1531G allowed for exceptionally rapid access of QX-222. In addition, W1531G created a second non-selective ion-conducting pore, bypassing the outer vestibule but probably merging into the internal vestibule, allowing for control by the activation gate. These data suggest a strong structural similarity between bacterial and eukaryotic voltage-gated Na(+) channels. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. 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.

  14. Active zone protein Bassoon co-localizes with presynaptic calcium channel, modifies channel function, and recovers from aging related loss by exercise.

    Science.gov (United States)

    Nishimune, Hiroshi; Numata, Tomohiro; Chen, Jie; Aoki, Yudai; Wang, Yonghong; Starr, Miranda P; Mori, Yasuo; Stanford, John A

    2012-01-01

    The P/Q-type voltage-dependent calcium channels (VDCCs) are essential for synaptic transmission at adult mammalian neuromuscular junctions (NMJs); however, the subsynaptic location of VDCCs relative to active zones in rodent NMJs, and the functional modification of VDCCs by the interaction with active zone protein Bassoon remain unknown. Here, we show that P/Q-type VDCCs distribute in a punctate pattern within the NMJ presynaptic terminals and align in three dimensions with Bassoon. This distribution pattern of P/Q-type VDCCs and Bassoon in NMJs is consistent with our previous study demonstrating the binding of VDCCs and Bassoon. In addition, we now show that the interaction between P/Q-type VDCCs and Bassoon significantly suppressed the inactivation property of P/Q-type VDCCs, suggesting that the Ca(2+) influx may be augmented by Bassoon for efficient synaptic transmission at NMJs. However, presynaptic Bassoon level was significantly attenuated in aged rat NMJs, which suggests an attenuation of VDCC function due to a lack of this interaction between VDCC and Bassoon. Importantly, the decreased Bassoon level in aged NMJs was ameliorated by isometric strength training of muscles for two months. The training increased Bassoon immunoreactivity in NMJs without affecting synapse size. These results demonstrated that the P/Q-type VDCCs preferentially accumulate at NMJ active zones and play essential role in synaptic transmission in conjunction with the active zone protein Bassoon. This molecular mechanism becomes impaired by aging, which suggests altered synaptic function in aged NMJs. However, Bassoon level in aged NMJs can be improved by muscle exercise.

  15. Purification and characterization of a new bioscouring pectate lyase from Bacillus pumilus BK2

    NARCIS (Netherlands)

    Klug-Santner, Barbara G.; Schnitzhofer, Wolfgang; Vrsanska, Maria; Weber, Jörg; Agrawal, Pramod; Nierstrasz, Vincent; Guebitz, Georg M.

    2006-01-01

    An alkalophilic bacterium was isolated based on the potential of extra-cellular enzymes for bioscouring. The bacterium was identified as a new strain of Bacillus pumilus BK2 producing an extra-cellular endo-pectate lyase PL (EC 4.2.2.2). PL was purified to homogeneity in three steps and has a

  16. The making of BK City : The ultimate laboratory for a faculty of architecture

    NARCIS (Netherlands)

    Den Heijer, A.

    2009-01-01

    This article in The Architecture Annual 2007-2008 describes the process of the making of BK city - after the fire that destroyed TU Delft's Faculty of Architecture building in May 2008 - and is written by one of the members of the project team (Alexandra den Heijer, chair brief team), who was

  17. Aryl hydrocarbon receptor expression by macrophages and lymphocytes within infiltrates in BK polyomavirus associated nephropathy

    NARCIS (Netherlands)

    Bouatou, Yassine; Stokman, Geurt; Claessen, Nike; Roelofs, Joris J. T. H.; Bemelman, Frédérike; Kers, Jesper; Florquin, Sandrine

    2018-01-01

    BK virus nephropathy (BKPyVN) is a major complication after renal transplantation. Little is known about the intra renal immune response during BKPyVN. The role of macrophages remains elusive. The activation of aryl hydrocarbon receptor (AHR) - a transcription factor involved in drug metabolism -

  18. 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.)

  19. Evaluation of polyomavirus BK reactivation in lupus patients who underwent kidney transplantation

    Directory of Open Access Journals (Sweden)

    Cristina Costa

    2012-06-01

    Full Text Available Background. A pathogenic role for polyomavirus BK in systemic lupus erythematosus (SLE has been proposed, however no study evaluated the occurrence of BK replication in renal transplant recipients according to the underlying disease leading to transplantation and its potential impact. Methods. The occurrence of BK reactivation was serially evaluated in 468 renal transplant recipients, including 11 patients with SLE as underlying disease (overall, 2370 serum and 2370 urine specimens; 65 from SLE patients. Results. Considering the overall occurrence of viral reactivation (viremia and/or viruria, 26/65 (40% specimens were positive in four SLE patients (36.3% versus 331/2143 (15.4% in 130/227 (57.3% non-SLE patients. A patient transplanted for class III lupus nephritis evidenced sustained BK viremia and viruria (with viremia values potentially indicative of polyomavirus-associated nephropathy in the absence of clinical features of renal dysfunction or recurrence of lupus nephritis. Conclusions. Further studies on larger populations and for a longer follow-up should be required to evaluate the impact of BKV reactivation in renal transplant patients with SLE as underlying disease, as well as the potential therapeutic implications.

  20. Test du Module BECKHOFF (BK7420) Entrées/Sorties deportees sur FIPIO de SCHNEIDER

    CERN Document Server

    Palluel, J; CERN. Geneva. AB Department

    2004-01-01

    Cette note présente le test du nouveau coupleur I/O déporté sur FIPIO de Beckhoff référencé BK7420 (voir photo ci-dessous), et notamment son évaluation sur différentes longueurs par rapport à un module semblable de Schneider (Momentum 170 FNT 110 01).

  1. 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.

  2. Activities of Different Classes of Acyclic Nucleoside Phosphonates against BK Virus in Primary Human Renal Cells

    Czech Academy of Sciences Publication Activity Database

    Topalis, D.; Lebeau, I.; Krečmerová, Marcela; Andrei, G.; Snoeck, R.

    2011-01-01

    Roč. 55, č. 5 (2011), s. 1961-1967 ISSN 0066-4804 Institutional research plan: CEZ:AV0Z40550506 Keywords : polyomavirus * BK virus * nephropathy * acyclic nucleoside phosphonates * HPMP-5-azaC Subject RIV: CC - Organic Chemistry Impact factor: 4.841, year: 2011

  3. Activation of acid-sensing ion channels by localized proton transient reveals their role in proton signaling

    Science.gov (United States)

    Zeng, Wei-Zheng; Liu, Di-Shi; Liu, Lu; She, Liang; Wu, Long-Jun; Xu, Tian-Le

    2015-01-01

    Extracellular transients of pH alterations likely mediate signal transduction in the nervous system. Neuronal acid-sensing ion channels (ASICs) act as sensors for extracellular protons, but the mechanism underlying ASIC activation remains largely unknown. Here, we show that, following activation of a light-activated proton pump, Archaerhodopsin-3 (Arch), proton transients induced ASIC currents in both neurons and HEK293T cells co-expressing ASIC1a channels. Using chimera proteins that bridge Arch and ASIC1a by a glycine/serine linker, we found that successful coupling occurred within 15 nm distance. Furthermore, two-cell sniffer patch recording revealed that regulated release of protons through either Arch or voltage-gated proton channel Hv1 activated neighbouring cells expressing ASIC1a channels. Finally, computational modelling predicted the peak proton concentration at the intercellular interface to be at pH 6.7, which is acidic enough to activate ASICs in vivo. Our results highlight the pathophysiological role of proton signalling in the nervous system. PMID:26370138

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

    Directory of Open Access Journals (Sweden)

    Cristina Costa

    2012-03-01

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

  5. Relationship between the field local quadrature and the quantum discord of a photon-added correlated channel under the influence of scattering and phase fluctuation noise

    Science.gov (United States)

    Domínguez-Serna, Francisco A.; Mendieta-Jimenez, Francisco J.; Rojas, Fernando

    2017-10-01

    We study quantum correlations and discord in a bipartite continuous variable hybrid system formed by linear combinations of coherent states {|{α }\\rangle } and single photon-added coherent states of the form {|{ψ }\\rangle }_{ {dp(pa)}}= N/√{2} (\\hat{a}^\\dagger {|{α }\\rangle }_a{|{α }\\rangle }_b ± \\hat{b}^\\dagger {|{α }\\rangle }_a{|{α }\\rangle }_b). We stablish a relationship between the quantum discord with a local observable (the quadrature variance for one subsystem) under the influence of scattering and phase fluctuation noise. For the pure states the quantum correlations are characterized by means of measurement induced disturbance (MID) with simultaneous quadrature measurements. In a scenario where homodyne conditional measurements are available we show that the MID provides an easy way to select optimal phases to obtain information of the maximal correlations in the channels. The quantum correlations of these entangled states with channel losses are quantitatively characterized with the quantum discord (QD) with a displaced qubit projector. We observe that as scattering increases, QD decreases monotonically. At the same time for the state {|{ψ }\\rangle }_{ {dp}}, QD is more resistant to high phase fluctuations when the average photon number n_0 is bigger than zero, but if phase fluctuations are low, QD is more resistant if n_0=0. For the dp model with scattering, we obtain an analytical expression of the QD as a function of the observable quadrature variance in a local subsystem. This relation allows us to have a way to obtain the degree of QD in the channel by just measuring a local property observable such as the quadrature variance. For the other model this relation still exists but is explored numerically. This relation is an important result that allows to identify quantum processing capabilities in terms of just local observables.

  6. The Effect of Inclination Angle on Critical Heat Flux in a Locally Heated Liquid Film Moving Under the Action of Gas Flow in a Mini-Channel

    Directory of Open Access Journals (Sweden)

    Tkachenko Egor M.

    2016-01-01

    Full Text Available Intensively evaporating liquid films moving under the action of the cocurrent gas flow in a microchannel are promising for the use in modern cooling systems of semiconductor devices with high local heat release. This work has studied the dependence of the critical heat flux on the inclination angle of the channel. It has been found that the inclination angle in the plane parallel to the flow has no significant effect on the critical heat flux. Whereas the inclination angle in the plane perpendicular to the flow, on the contrary, significantly changes the value of the critical heat flux. However, for a given flow rate of fluid there is a threshold gas velocity at which the critical heat flux does not differ from the case of zero inclination of the channel. Thus, it can be concluded that the cooling system based on shear-driven liquid films can be potentially used when direction of the gravity changes.

  7. Fluoroquinolone prophylaxis in preventing BK polyomavirus infection after renal transplant: A systematic review and meta-analysis.

    Science.gov (United States)

    Song, Tu-Run; Rao, Zheng-Sheng; Qiu, Yang; Liu, Jin-Peng; Huang, Zhong-Li; Wang, Xian-Ding; Lin, Tao

    2016-03-01

    Previous studies regarding the prevention of BK viremia following renal transplantation with fluoroquinolone have yielded conflicting results. The purpose of this systematic review was to examine the evidence regarding the efficacy of fluoroquinolone in preventing BK polyomavirus infection following renal transplantation. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for research articles published prior to January 2015 using keywords such as "fluoroquinolone," "BK viremia," and "renal transplantation." We extracted all types of study published in English. The primary outcome was BK viremia and viruria at 1 year post-transplantation. Secondary outcomes were BK virus-associated nephropathy (BKVN), graft failure, and fluoroquinolone-resistant infection. We identified eight trials, including a total of 1477 participants with a mean duration of fluoroquinolone prophylaxis of >1 month. At 1 year, fluoroquinolone prophylaxis was not associated with a decreased incidence of BK viremia [risk ratio (RR), 0.84; 95% confidence interval (95% CI), 0.58-1.20). No significant differences in BKVN (RR, 0.88; 95% CI, 0.37-2.11), risk of graft failure due to BKVN (RR, 0.68; 95% CI, 0.29-1.59), or fluoroquinolone-resistant infection (RR, 1.08; 95% CI, 0.64-1.83) were observed between the fluoroquinolone prophylaxis and control groups. The results of this study suggest that fluoroquinolone is ineffective in preventing BK polyomavirus infection following renal transplantation. Copyright © 2016. Published by Elsevier Taiwan.

  8. Channel flow and localized fault bounded slice tectonics (LFBST): Insights from petrological, structural, geochronological and geospeedometric studies in the Sikkim Himalaya, NE India

    Science.gov (United States)

    Chakraborty, Sumit; Mukhopadhyay, Dilip K.; Chowdhury, Priyadarshi; Rubatto, Daniela; Anczkiewicz, Robert; Trepmann, Claudia; Gaidies, Fred; Sorcar, Nilanjana; Dasgupta, Somnath

    2017-06-01

    One of the enduring debates in the study of the Himalayan orogen (and continental collision zones in general) is whether the salient observed features are explained (a) by localized deformation along discrete, narrow fault zones/ductile shear zones separating individual blocks or slices (e.g. critical taper or wedge tectonic models), or (b) by distributed deformation dominated by wide zones of visco-plastic flow in the solid or a partially molten state (e.g. channel flow models). A balanced cross-section from Sikkim in the eastern Himalaya that is based on structural data and is drawn to satisfy petrological and geophysical constraints as well, is used in combination with information from petrology, geochronology, geospeedometry and microstructural data to address this question. We discuss that any tectonic model needs to be thermally, rheologically, geometrically and temporally viable in order to qualify as a suitable description of a system; models such as channel flow and critical taper are considered in this context. It is shown that channel flow models may operate with or without an erosional porthole (channel with tunnel and funnel mode vs. channels with only the tunnel mode) and that the predicted features differ significantly between the two. Subsequently, we consider a large body of data from Sikkim to show that a channel flow type model (in the tunneling without funneling mode), such as the ones of Faccenda et al. (2008), describes features formed at high temperatures very well, while features formed at lower temperatures are more consistent with the operation of localized, fault-bounded, slice tectonics, (LFBST, be it in the form of critical taper, wedge tectonics, or something else). Thus, the two modes are not competing, but collaborating, processes and both affect a given rock unit at different points of time during burial, metamorphism and exhumation. A transitional stage separates the two end-member styles of tectonic evolution. The proposed models

  9. Interaction of batrachotoxin with the local anesthetic receptor site in transmembrane segment IVS6 of the voltage-gated sodium channel.

    Science.gov (United States)

    Linford, N J; Cantrell, A R; Qu, Y; Scheuer, T; Catterall, W A

    1998-11-10

    The voltage-gated sodium channel is the site of action of more than six classes of neurotoxins and drugs that alter its function by interaction with distinct, allosterically coupled receptor sites. Batrachotoxin (BTX) is a steroidal alkaloid that binds to neurotoxin receptor site 2 and causes persistent activation. BTX binding is inhibited allosterically by local anesthetics. We have investigated the interaction of BTX with amino acid residues I1760, F1764, and Y1771, which form part of local anesthetic receptor site in transmembrane segment IVS6 of type IIA sodium channels. Alanine substitution for F1764 (mutant F1764A) reduces tritiated BTX-A-20-alpha-benzoate binding affinity, causing a 60-fold increase in Kd. Alanine substitution for I1760, which is adjacent to F1764 in the predicted IVS6 transmembrane alpha helix, causes only a 4-fold increase in Kd. In contrast, mutant Y1771A shows no change in BTX binding affinity. For wild-type and mutant Y1771A, BTX shifted the voltage for half-maximal activation approximately 40 mV in the hyperpolarizing direction and increased the percentage of noninactivating sodium current to approximately 60%. In contrast, these BTX effects were eliminated completely for the F1764A mutant and were reduced substantially for mutant I1760A. Our data suggest that the BTX receptor site shares overlapping but nonidentical molecular determinants with the local anesthetic receptor site in transmembrane segment IVS6 as well as having unique molecular determinants in transmembrane segment IS6, as demonstrated in previous work. Evidently, BTX conforms to a domain-interface allosteric model of ligand binding and action, as previously proposed for calcium agonist and antagonist drugs acting on L-type calcium channels.

  10. Pannexin2 oligomers localize in the membranes of endosomal vesicles in mammalian cells while Pannexin1 channels traffic to the plasma membrane.

    Science.gov (United States)

    Boassa, Daniela; Nguyen, Phuong; Hu, Junru; Ellisman, Mark H; Sosinsky, Gina E

    2014-01-01

    Pannexin2 (Panx2) is the largest of three members of the pannexin proteins. Pannexins are topologically related to connexins and innexins, but serve different functional roles than forming gap junctions. We previously showed that pannexins form oligomeric channels but unlike connexins and innexins, they form only single membrane channels. High levels of Panx2 mRNA and protein in the Central Nervous System (CNS) have been documented. Whereas Pannexin1 (Panx1) is fairly ubiquitous and Pannexin3 (Panx3) is found in skin and connective tissue, both are fully glycosylated, traffic to the plasma membrane and have functions correlated with extracellular ATP release. Here, we describe trafficking and subcellular localizations of exogenous Panx2 and Panx1 protein expression in MDCK, HeLa, and HEK 293T cells as well as endogenous Panx1 and Panx2 patterns in the CNS. Panx2 was found in intracellular localizations, was partially N-glycosylated, and localizations were non-overlapping with Panx1. Confocal images of hippocampal sections immunolabeled for the astrocytic protein GFAP, Panx1 and Panx2 demonstrated that the two isoforms, Panx1 and Panx2, localized at different subcellular compartments in both astrocytes and neurons. Using recombinant fusions of Panx2 with appended genetic tags developed for correlated light and electron microscopy and then expressed in different cell lines, we determined that Panx2 is localized in the membrane of intracellular vesicles and not in the endoplasmic reticulum as initially indicated by calnexin colocalization experiments. Dual immunofluorescence imaging with protein markers for specific vesicle compartments showed that Panx2 vesicles are early endosomal in origin. In electron tomographic volumes, cross-sections of these vesicles displayed fine structural details and close proximity to actin filaments. Thus, pannexins expressed at different subcellular compartments likely exert distinct functional roles, particularly in the nervous system.

  11. Neuropatía por virus BK post trasplante renal diagnostico y seguimiento por PCR en tiempo real BK virus nephropathy after renal transplantation: Diagnosis and prognosis by real time PCR

    Directory of Open Access Journals (Sweden)

    Marcela Echavarria

    2007-12-01

    Full Text Available La nefropatía producida por el virus BK puede llevar a la pérdida del trasplante renal. El diagnóstico etiológico es importante debido a que la clínica no permite diferenciar entre nefropatía por virus BK y rechazo agudo, en donde los tratamientos de estas dos entidades son diametralmente opuestos. El desarrollo reciente de métodos moleculares muy sensibles y específicos como PCR y PCR en tiempo real para virus BK permiten un diagnóstico de certeza en forma rápida y cuantificar la carga viral presente. El diagnóstico de nefropatía por virus BK se realiza por inmunohistoquímica en una biopsia renal, pero dada la naturaleza multifocal de las lesiones, la sensibilidad no siempre es del 100%. Los nuevos métodos de PCR para detectar virus BK en sangre y orina contribuyen al diagnóstico de nefropatía de una manera más normatizada y menos invasiva. Más aún, la cuantificación del virus BK en sangre por PCR en tiempo real, ha demostrado ser útil en el diagnóstico y monitoreo de esta enfermedad. En este trabajo se presenta el caso de una paciente transplantada renal con nefropatía por virus BK y el desarrollo de un método de PCR en tiempo real para la detección de virus BK en sangre y orina. Esta nueva metodología confirmó el diagnóstico de nefropatía por virus BK lo que permitió un cambio en el esquema de inmunosupresión y la instauración de un tratamiento que pudo ser monitorizado utilizando la carga viral.BK virus nephropathy may lead to kidney transplant failure. BK infection and acute rejection are clinically undistinguishable, therefore diagnosis of these entities is critical to establish the correct treatment. The new molecular methods using PCR and real time PCR have significantly contributed to the rapid and sensitive diagnosis of BK virus. Furthermore, viral load determination in plasma has significantly been associated with BK virus nephropathy. Definite diagnosis of nephropathy requires renal biopsy, although

  12. Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation

    DEFF Research Database (Denmark)

    Nassini, Romina; Pedretti, Pamela; Moretto, Nadia

    2012-01-01

    and fibroblasts, acrolein and CS extract evoked IL-8 release, a response selectively reduced by TRPA1 antagonists. Capsaicin, agonist of the transient receptor potential vanilloid 1 (TRPV1), a channel co-expressed with TRPA1 by airway sensory nerves, and acrolein or CS (TRPA1 agonists), or the neuropeptide...... substance P (SP), which is released from sensory nerve terminals by capsaicin, acrolein or CS), produced neurogenic inflammation in mouse airways. However, only acrolein and CS, but not capsaicin or SP, released the keratinocyte chemoattractant (CXCL-1/KC, IL-8 analogue) in bronchoalveolar lavage (BAL...

  13. Polar Localization of the NIP5;1 Boric Acid Channel Is Maintained by Endocytosis and Facilitates Boron Transport in Arabidopsis Roots.

    Science.gov (United States)

    Wang, Sheliang; Yoshinari, Akira; Shimada, Tomoo; Hara-Nishimura, Ikuko; Mitani-Ueno, Namiki; Feng Ma, Jian; Naito, Satoshi; Takano, Junpei

    2017-04-01

    Boron uptake in Arabidopsis thaliana is mediated by nodulin 26-like intrinsic protein 5;1 (NIP5;1), a boric acid channel that is located preferentially on the soil side of the plasma membrane in root cells. However, the mechanism underlying this polar localization is poorly understood. Here, we show that the polar localization of NIP5;1 in epidermal and endodermal root cells is mediated by the phosphorylation of Thr residues in the conserved TPG (ThrProGly) repeat in the N-terminal region of NIP5;1. Although substitutions of Ala for three Thr residues in the TPG repeat did not affect lateral diffusion in the plasma membrane, these substitutions inhibited endocytosis and strongly compromised the polar localization of GFP-NIP5;1. Consistent with this, the polar localization was compromised in µ subunit mutants of the clathrin adaptor AP2. The Thr-to-Ala substitutions did not affect the boron transport activity of GFP-NIP5;1 in Xenopus laevis oocytes but did inhibit the ability to complement boron translocation to shoots and rescue growth defects in nip5;1-1 mutant plants under boron-limited conditions. These results demonstrate that the polar localization of NIP5;1 is maintained by clathrin-mediated endocytosis, is dependent on phosphorylation in the TPG repeat, and is necessary for the efficient transport of boron in roots. © 2017 American Society of Plant Biologists. All rights reserved.

  14. Intersubject local SAR variation for 7T prostate MR imaging with an eight-channel single-side adapted dipole antenna array.

    Science.gov (United States)

    Ipek, Ozlem; Raaijmakers, Alexander J; Lagendijk, Jan J; Luijten, Peter R; van den Berg, Cornelis A T

    2014-04-01

    Surface transmit arrays used in ultra-high field body MRI require local specific absorption rate (SAR) assessment. As local SAR cannot be measured directly, local SAR is determined by simulations using dielectric patient models. In this study, the inter-patient local SAR variation is investigated for 7T prostate imaging with the single-side adapted dipole antenna array. Four-dedicated dielectric models were created by segmenting Dixon water-fat separated images that were obtained from four subjects with a 1.5T scanner and the surface array in place. Electromagnetic simulations were performed to calculate the SAR distribution for each model. Radio frequency (RF) exposure variations were determined by analyzing the SAR(10g) distributions (1) with one element active, (2) using a Q-matrix eigenvalue/eigenvector approach, (3) with the maximum potential SAR in each voxel, and (4) for a phase shimmed prostate measurement. Maximum potential local SAR levels for 1 W time-averaged accepted power per transmit channel range from 4.1 to 7.1 W/kg. These variations show that one model is not sufficient to determine safe scan settings. For the operation of the surface array conservative power settings were derived based on a worst-case SAR evaluation and the most SAR-sensitive body model. Copyright © 2013 Wiley Periodicals, Inc.

  15. 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

  16. Numerical and experimental modelling of turbulent flow in curved channels and diffusers

    Czech Academy of Sciences Publication Activity Database

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

    2005-01-01

    Roč. 12, č. 6 (2005), s. 429-440 ISSN 1802-1484 R&D Projects: GA ČR(CZ) GA103/02/0545 Institutional research plan: CEZ:AV0Z20760514 Keywords : turbulent flow * curved channels and diffusers Subject RIV: BK - Fluid Dynamics

  17. 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

  18. 75 FR 48617 - Airworthiness Directives; Eurocopter Deutschland GmbH (ECD) Model MBB-BK 117 C-2 Helicopters

    Science.gov (United States)

    2010-08-11

    ... Deutschland GmbH (ECD) Model MBB-BK 117 C-2 Helicopters AGENCY: Federal Aviation Administration (FAA), DOT... 13679, dated March 23, 2007) and adding the following new AD: Eurocopter Deutschland GmbH: Docket No...

  19. Kv2 Ion Channels Determine the Expression and Localization of the Associated AMIGO-1 Cell Adhesion Molecule in Adult Brain Neurons

    Directory of Open Access Journals (Sweden)

    Hannah I. Bishop

    2018-01-01

    Full Text Available Voltage-gated K+ (Kv channels play important roles in regulating neuronal excitability. Kv channels comprise four principal α subunits, and transmembrane and/or cytoplasmic auxiliary subunits that modify diverse aspects of channel function. AMIGO-1, which mediates homophilic cell adhesion underlying neurite outgrowth and fasciculation during development, has recently been shown to be an auxiliary subunit of adult brain Kv2.1-containing Kv channels. We show that AMIGO-1 is extensively colocalized with both Kv2.1 and its paralog Kv2.2 in brain neurons across diverse mammals, and that in adult brain, there is no apparent population of AMIGO-1 outside of that colocalized with these Kv2 α subunits. AMIGO-1 is coclustered with Kv2 α subunits at specific plasma membrane (PM sites associated with hypolemmal subsurface cisternae at neuronal ER:PM junctions. This distinct PM clustering of AMIGO-1 is not observed in brain neurons of mice lacking Kv2 α subunit expression. Moreover, in heterologous cells, coexpression of either Kv2.1 or Kv2.2 is sufficient to drive clustering of the otherwise uniformly expressed AMIGO-1. Kv2 α subunit coexpression also increases biosynthetic intracellular trafficking and PM expression of AMIGO-1 in heterologous cells, and analyses of Kv2.1 and Kv2.2 knockout mice show selective loss of AMIGO-1 expression and localization in neurons lacking the respective Kv2 α subunit. Together, these data suggest that in mammalian brain neurons, AMIGO-1 is exclusively associated with Kv2 α subunits, and that Kv2 α subunits are obligatory in determining the correct pattern of AMIGO-1 expression, PM trafficking and clustering.

  20. Effect of biological and synthetic polymers on BK virus infectivity and hemagglutination.

    Science.gov (United States)

    Sinibaldi, L; Pietropaolo, V; Goldoni, P; Di Taranto, C; Orsi, N

    1992-02-01

    The effect of several biological and synthetic polymers, chosen on the basis of different physical and chemical properties, was investigated on BK virus infectivity and hemagglutination. It was observed that polyanions like mucin, dextran sulfate and heparin depressed the viral binding, whereas polycations had no significant activity, with the exception of poly-L-lysine, which enhanced it. The effect of the active polymers was studied in different experimental conditions and the results obtained suggested that polyanions may act directly on the virus particle, whereas the target of polycations could be at the level of cell membranes. However, the effect shown by the active compounds did not appear to be simply related to the electric charge since neutral compounds, such as tamarind gum and locust bean gum, showed a marked inhibitory effect on BK virus binding to the cells.

  1. Inhibition of cellular proliferation and induction of apoptosis in human lung adenocarcinoma A549 cells by T-type calcium channel antagonist.

    Science.gov (United States)

    Choi, Doo Li; Jang, Sun Jeong; Cho, Sehyeon; Choi, Hye-Eun; Rim, Hong-Kun; Lee, Kyung-Tae; Lee, Jae Yeol

    2014-03-15

    The anti-proliferative and apoptotic activities of new T-type calcium channel antagonist, 6e (BK10040) on human lung adenocarcinoma A549 cells were investigated. The MTT assay results indicated that BK10040 was cytotoxic against human lung adenocarcinoma (A549) and pancreatic cancer (MiaPaCa2) cells in a dose-dependent manner with IC50 of 2.25 and 0.93μM, respectively, which is ca. 2-fold more potent than lead compound KYS05090 despite of its decreased T-type calcium channel blockade. As a mode of action for cytotoxic effect of BK10040 on lung cancer (A549) cells, this cancer cell death was found to have the typical features of apoptosis, as evidenced by the accumulation of positive cells for annexin V. In addition, BK10040 triggered the activations of caspases 3 and 9, and the cleavages of poly (ADP-ribose) polymerase (PARP). Moreover, the treatment with z-VAD-fmk (a broad spectrum caspase inhibitor) significantly prevented BK10040-induced apoptosis. Based on these results, BK10040 may be used as a potential therapeutic agent for human lung cancer via the potent apoptotic activity. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    OpenAIRE

    Le Calloch, R.; Ianotto, J. C.; Berthou, C.; Tempescul, A.

    2011-01-01

    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. Reactivat...

  3. Measurement of B(K+ → π+ ν νbar)

    International Nuclear Information System (INIS)

    Kettell, S.H.

    2000-01-01

    The experimental measurement of K + → π + νbar ν is reviewed. New results from experiment E787 at BNL are presented: with data from 1995-97 the branching ratio has been measured to be B(K + → π + νbar ν) = (1.5 -1.2 +3.4 ) x 10 -10 . The future prospects for additional data in this mode are examined

  4. 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.

  5. Search for a new element Z=117 among the ^249Bk + ^48Ca reaction products

    Science.gov (United States)

    Rykaczewski, K.; Oganessian, Yu; Dmitriev, S.; Utyonkov, V.; Hamilton, J.; Ramayya, A.; Henderson, R.; Moody, K.; Shaughnessy, D.; Al, M. Stoyer Et; Al, J. Roberto Et; Al, M. Ryabinin Et; et al.

    2009-10-01

    Following irradiation of Am and Cm seed isotopes at the ORNL High Flux Isotope Reactor, the ^249Bk activity (T1/2=320 d) has been separated at the ORNL Radiochemical Engineering Development Center [1] to be used as target material for a search for element Z=117 using an intense ^48 Ca beam from the U-400 cyclotron at JINR Dubna. The targets will be made from Bk nitrate at the IAR Dmitrovgrad. The search for the A=294 and A=293 isotopes of the new element Z=117 and their decay products, see [2], is scheduled to begin at the Dubna Gas Filled Recoil Separator at JINR Flerov Laboratory of Nuclear Reactions in August 2009. Details of the ^249Bk separation and experiment will be reported. [1] C.Alexander, P.Bailey, J.Ezold, M.Ferren, C.Porter, F.Riley et al., HFIR/REDC campaign 74, 2009. [2] Yu. Oganessian, J.Phys.G 34, R164,2007.

  6. Silver-enhanced in situ hybridization for detection of polyomavirus DNA in patients with BK virus nephropathy.

    Science.gov (United States)

    Fritzsche, Florian R; Pianca, Silvio; Gaspert, Ariana; Varga, Zsuzsanna; Wang, Lin; Farrell, Michael P; Chen, Xiao-Bo; Hirsch, Hans H; Springer, Erik; Fehr, Thomas; Myles, Jonathan; Tubbs, Raymond; Moch, Holger

    2011-06-01

    BK virus nephropathy is not an infrequent complication of renal transplantation associated with high rates of graft loss. Although antibodies against SV40 antigen detect different viruses of the polyomavirus family, immunohistochemistry is widely used to confirm the diagnosis of BK virus nephropathy in renal biopsies. Here we aimed to validate the novel silver-enhanced in situ hybridization (SISH) technique for the automated detection of BK virus in renal transplant biopsies. Two different patient cohorts were included. Twenty-nine consecutive patients suspicious for BK virus infection were investigated by SISH and chromogenic in situ hybridization. An additional 26 renal biopsies positive by SV40 immunohistochemistry from 19 patients were analyzed by SISH. Polyomavirus DNA serum levels, as determined by nested PCR analysis, were available for all of these patients. The presence of BK virus DNA in renal tubular cells was identified in 5 of the suspicious cases by both, SISH and chromogenic in situ hybridization . One additional patient was only positive in the SISH. In the second cohort, SISH was positive in all SV40 positive biopsies, but SISH signals were less extensive than SV40 immunohistochemistry. Our results show that the BK virus SISH is an ancillary tool for the detection of polyomavirus DNA in renal biopsies using bright-field microscopy. However, its diagnostic value in comparison with standard immunohistochemistry seems to be limited.

  7. 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.

  8. A recurrent KCNQ2 pore mutation causing early onset epileptic encephalopathy has a moderate effect on M current but alters subcellular localization of Kv7 channels.

    Science.gov (United States)

    Abidi, Affef; Devaux, Jérôme J; Molinari, Florence; Alcaraz, Gisèle; Michon, François-Xavier; Sutera-Sardo, Julie; Becq, Hélène; Lacoste, Caroline; Altuzarra, Cécilia; Afenjar, Alexandra; Mignot, Cyril; Doummar, Diane; Isidor, Bertrand; Guyen, Sylvie N; Colin, Estelle; De La Vaissière, Sabine; Haye, Damien; Trauffler, Adeline; Badens, Catherine; Prieur, Fabienne; Lesca, Gaetan; Villard, Laurent; Milh, Mathieu; Aniksztejn, Laurent

    2015-08-01

    Mutations in the KCNQ2 gene encoding the voltage-dependent potassium M channel Kv7.2 subunit cause either benign epilepsy or early onset epileptic encephalopathy (EOEE). It has been proposed that the disease severity rests on the inhibitory impact of mutations on M current density. Here, we have analyzed the phenotype of 7 patients carrying the p.A294V mutation located on the S6 segment of the Kv7.2 pore domain (Kv7.2(A294V)). We investigated the functional and subcellular consequences of this mutation and compared it to another mutation (Kv7.2(A294G)) associated with a benign epilepsy and affecting the same residue. We report that all the patients carrying the p.A294V mutation presented the clinical and EEG characteristics of EOEE. In CHO cells, the total expression of Kv7.2(A294V) alone, assessed by western blotting, was only 20% compared to wild-type. No measurable current was recorded in CHO cells expressing Kv7.2(A294V) channel alone. Although the total Kv7.2(A294V) expression was rescued to wild-type levels in cells co-expressing the Kv7.3 subunit, the global current density was still reduced by 83% compared to wild-type heteromeric channel. In a configuration mimicking the patients' heterozygous genotype i.e., Kv7.2(A294V)/Kv7.2/Kv7.3, the global current density was reduced by 30%. In contrast to Kv7.2(A294V), the current density of homomeric Kv7.2(A294G) was not significantly changed compared to wild-type Kv7.2. However, the current density of Kv7.2(A294G)/Kv7.2/Kv7.3 and Kv7.2(A294G)/Kv7.3 channels were reduced by 30% and 50% respectively, compared to wild-type Kv7.2/Kv7.3. In neurons, the p.A294V mutation induced a mislocalization of heteromeric mutant channels to the somato-dendritic compartment, while the p.A294G mutation did not affect the localization of the heteromeric channels to the axon initial segment. We conclude that this position is a hotspot of mutation that can give rise to a severe or a benign epilepsy. The p.A294V mutation does not exert a

  9. N-terminal arginines modulate plasma-membrane localization of Kv7.1/KCNE1 channel complexes.

    Directory of Open Access Journals (Sweden)

    Zenawit Girmatsion

    Full Text Available BACKGROUND AND OBJECTIVE: The slow delayed rectifier current (I(Ks is important for cardiac action potential termination. The underlying channel is composed of Kv7.1 α-subunits and KCNE1 β-subunits. While most evidence suggests a role of KCNE1 transmembrane domain and C-terminus for the interaction, the N-terminal KCNE1 polymorphism 38G is associated with reduced I(Ks and atrial fibrillation (a human arrhythmia. Structure-function relationship of the KCNE1 N-terminus for I(Ks modulation is poorly understood and was subject of this study. METHODS: We studied N-terminal KCNE1 constructs disrupting structurally important positively charged amino-acids (arginines at positions 32, 33, 36 as well as KCNE1 constructs that modify position 38 including an N-terminal truncation mutation. Experimental procedures included molecular cloning, patch-clamp recording, protein biochemistry, real-time-PCR and confocal microscopy. RESULTS: All KCNE1 constructs physically interacted with Kv7.1. I(Ks resulting from co-expression of Kv7.1 with non-atrial fibrillation '38S' was greater than with any other construct. Ionic currents resulting from co-transfection of a KCNE1 mutant with arginine substitutions ('38G-3xA' were comparable to currents evoked from cells transfected with an N-terminally truncated KCNE1-construct ('Δ1-38'. Western-blots from plasma-membrane preparations and confocal images consistently showed a greater amount of Kv7.1 protein at the plasma-membrane in cells co-transfected with the non-atrial fibrillation KCNE1-38S than with any other construct. CONCLUSIONS: The results of our study indicate that N-terminal arginines in positions 32, 33, 36 of KCNE1 are important for reconstitution of I(Ks. Furthermore, our results hint towards a role of these N-terminal amino-acids in membrane representation of the delayed rectifier channel complex.

  10. HLA-A01-, -A03-, and -A024-binding nanomeric epitopes in polyomavirus BK large T antigen.

    Science.gov (United States)

    Ramaswami, Bala; Popescu, Iulia; Macedo, Camila; Metes, Diana; Bueno, Marta; Zeevi, Adriana; Shapiro, Ron; Viscidi, Raphael; Randhawa, Parmjeet S

    2009-09-01

    Polyomavirus BK (BKV) infections are increasingly recognized. The development of immune-monitoring strategies against BKV requires definition of antigenic epitopes. Bioinformatic algorithms were used to identify 60 BKV large T-antigen (LT-Ag) peptides predicted to bind HLA class I alleles. In vitro peptide binding was used to select a subset of 19 peptides for interferon (IFN)-gamma ELISPOT assays in 13 healthy subjects and 12 kidney transplant recipients. Four A01-, nine A03-, and five A24-binding immunogenic peptides were identified in 1 to 3 (14-67%) tested subjects in each group. BKV epitope sequences were identical to homologous JC virus sequences for 3 of 19 peptides and homologous SV40 sequences for 5 of 19 peptides. Homology modeling localized these epitopes to the helicase, origin of DNA binding, or J domains, respectively. In conclusion, we have identified multiple 9-mer BKV LT-Ag-derived immunogenic epitopes that bind HLA-A01, -A03, or -A24 molecules. Sequence alignments indicate that two epitopes, FLICKGVNK and RYWLFKGPI, are common to BKV, JC virus, and SV40 virus.

  11. Autoradiographic localization of voltage-dependent sodium channels on the mouse neuromuscular junction using 125I-alpha scorpion toxin. I. Preferential labeling of glial cells on the presynaptic side

    International Nuclear Information System (INIS)

    Boudier, J.L.; Jover, E.; Cau, P.

    1988-01-01

    Alpha-scorpion toxins bind specifically to the voltage-sensitive sodium channel in excitable membranes, and binding is potential-dependent. The radioiodinated toxin II from the scorpion Androctonus australis Hector (alpha ScTx) was used to localize voltage-sensitive sodium channels on the presynaptic side of mouse neuromuscular junctions (NMJ) by autoradiography using both light and electron microscopy. Silver grain localization was analyzed by the cross-fire method. At the light-microscopic level, grain density over NMJ appeared 6-8x higher than over nonjunctional muscle membrane. The specificity of labeling was verified by competition/displacement with an excess of native alpha ScTx. Labeling was also inhibited by incubation in depolarizing conditions, showing its potential-dependence. At the electron-microscopic level, analysis showed that voltage-sensitive sodium channels labeled with alpha ScTx were almost exclusively localized on membranes, as expected. Due to washout after incubation, appreciable numbers of binding sites were not found on the postsynaptic membranes. However, on the presynaptic side, alpha ScTx-labeled voltage-sensitive sodium channels were localized on the membrane of non-myelin-forming Schwann cells covering NMJ. The axonal presynaptic membrane was not labeled. These results show that voltage-sensitive sodium channels are present on glial cells in vivo, as already demonstrated in vitro. It is proposed that these glial channels could be indirectly involved in the ionic homeostasis of the axonal environment

  12. 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

  13. Channelling and channelling radiation

    International Nuclear Information System (INIS)

    Soerensen, A.H.; Uggerhoej, E.

    1987-01-01

    The study of channelling phenomena has developed rapidly since the early 1960s and today channelling has found many applications. The radiation emitted by channelled megaelectronvolt and gigaelectronvolt electrons and positrons has been investigated extensively and the possibility of, for example, constructing intense tunable X- and γ-ray sources is being explored. Multi-gigaelectronvolt radiation and pair-creation processes in single crystals show similarities with strong-field effects and are of particular interest because of high production rates that persist far beyond the channelling regime. (author)

  14. Enhanced K+-channel-mediated endothelium-dependent local and conducted dilation of small mesenteric arteries from ApoE−/− mice

    Science.gov (United States)

    Beleznai, Timea; Takano, Hiromichi; Hamill, Claire; Yarova, Polina; Douglas, Gillian; Channon, Keith; Dora, Kim

    2011-01-01

    Aims Agonists that evoke smooth muscle cell hyperpolarization have the potential to stimulate both local and conducted dilation. We investigated whether the endothelium-dependent vasodilators acetylcholine (ACh) and SLIGRL stimulated conducted dilation and whether this was altered by deficiency in apolipoprotein E (ApoE−/−). Methods and results Isolated mesenteric arteries were cannulated, pressurized, and precontracted with phenylephrine. Agonists were either added to the bath to study local dilation or were restricted to one end of arteries to study conducted dilation. An enhanced sensitivity to both ACh and SLIGRL was observed in mesenteric arteries from ApoE−/− mice compared with wild-type controls. Inhibition of nitric oxide (NO) synthase blocked ACh responses, but had no effect on maximum dilation to SLIGRL. SLIGRL increased endothelial cell Ca2+, hyperpolarized smooth muscle cells, and fully dilated arteries. The NO-independent dilation to SLIGRL was blocked with high [KCl] or Ca2+-activated K+-channel blockers. The hyperpolarization and dilation to SLIGRL passed through the artery to at least 2.5 mm upstream. The conducted dilation was not affected by a deficit in ApoE and could also be stimulated by ACh, suggesting NO itself could stimulate conducted dilation. Conclusion In small mesenteric arteries of ApoE−/− mice, NO-independent dilation is enhanced. Since both NO-dependent and -independent pathways can stimulate local and conducted dilation, the potential for reducing vascular resistance is improved in these vessels. PMID:21690174

  15. Gap junctions in the ovary of Drosophila melanogaster: localization of innexins 1, 2, 3 and 4 and evidence for intercellular communication via innexin-2 containing channels

    Directory of Open Access Journals (Sweden)

    Zimmermann Jennifer

    2008-11-01

    Full Text Available Abstract Background In the Drosophila ovary, germ-line and soma cells are interconnected via gap junctions. The main gap-junction proteins in invertebrates are members of the innexin family. In order to reveal the role that innexins play in cell-cell communication during oogenesis, we investigated the localization of innexins 1, 2, 3 and 4 using immunohistochemistry, and analyzed follicle development following channel blockade. Results We found innexin 1 predominantly localized to the baso-lateral domain of follicle cells, whereas innexin 2 is positioned apico-laterally as well as apically between follicle cells and germ-line cells. Innexin 3 was observed laterally in follicle cells and also in nurse cells, and innexin 4 was detected in the oolemma up to stage 8 and in nurse-cell membranes up to stage 12. In order to test whether innexins form channels suitable for intercellular communication, we microinjected innexin antibodies in combination with a fluorescent tracer into the oocyte of stage-10 follicles. We found that dye-coupling between oocyte and follicle cells was largely reduced by innexin-2 antibodies directed against the intracellular C-terminus as well as against the intracellular loop. Analyzing in vitro, between stages 10 and 14, the developmental capacities of follicles following microinjections of innexin-2 antibodies revealed defects in follicle-cell differentiation, nurse-cell regression, oocyte growth and choriogenesis. Conclusion Our results suggest that all analyzed innexins are involved in the formation of gap junctions in the ovary. While innexins 2 and 3 are colocalized between soma cells, innexins 2 and 4 are colocalized between soma and germ-line cells. Innexin 2 is participating in cell-cell communication via hemichannels residing in the oolemma. It is obvious that gap-junctional communication between germ-line and soma cells is essential for several processes during oogenesis.

  16. 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

  17. On development of analytical closure relationships for local wall friction, heat and mass transfer coefficients for sub-channel codes

    International Nuclear Information System (INIS)

    Kornienko, Y.

    2000-01-01

    The purpose has been to describe an approach suggested for constructing generalized closure relationships for local and subchannel wall friction, heat and mass transfer coefficients, with not only axial and transversal parameters taken into account, but azimuthal substance transfer effects as well. These constitutive relations that are primary for description of one- and two-phase one-dimensional flow models can be derived from the initial 3-D drift flux formulation. The approach is based on the Reynolds flux, boundary layer and generalized coefficient of substance transfer. One more task has been to illustrate the validity of the 'conformity principle' for the limiting cases. The method proposed is based on the similarity theory, boundary layer model, and a phenomenological description of the regularities of the substance transfer (momentum, heat, and mass), as well as on an adequate simulation of the forms of flow structure by a generalized approach to build (an integrated in form and semi-empirical in maintenance structure) analytical relationships for wall friction, heat and mass transfer coefficients. (author)

  18. Nephritic-nephrotic syndrome as a presentation of BK virus infection

    Directory of Open Access Journals (Sweden)

    Nima Derakhshan

    2011-01-01

    Full Text Available BK virus (BKV is increasingly found as an important cause of allograft nephro-pathy. Nephrotic syndrome is not a usual manifestation of BKV nephropathy. Here, we report a 12-year-old boy, a case of end-stage renal disease due to nephronophthisis, who got the kidney trans-planted from a 16-year-old cadaver, and after 18 months of uneventful transplantation on triple immunosuppressive therapy (Mycophenolate mofetil (MMF, cyclosporin and prednisolone, pre-sented with nephrotic feature (edema, heavy proteinuria, hypoalbuminemia and hyperlipidema. Kidney biopsy was in favor of BKV infection and eventually ended in graft failure.

  19. Nephritic-nephrotic syndrome as a presentation of BK virus infection.

    Science.gov (United States)

    Derakhshan, Nima; Derakhshan, Dorna; Torabinejad, Simin; Derakhshan, Ali

    2011-01-01

    BK virus (BKV) is increasingly found as an important cause of allograft nephropathy. Nephrotic syndrome is not a usual manifestation of BKV nephropathy. Here, we report a 12-year-old boy, a case of end-stage renal disease due to nephronophthisis, who got the kidney transplanted from a 16-year-old cadaver, and after 18 months of uneventful transplantation on triple immunosuppressive therapy (mycophenolate mofetil (MMF), cyclosporin and prednisolone), presented with nephrotic feature (edema, heavy proteinuria, hypoalbuminemia and hyperlipidemia). Kidney biopsy was in favor of BKV infection and eventually ended in graft failure.

  20. Decay properties of Bk97243 and Bk97244

    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

  1. 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.

  2. Localization and functional modification of L-type voltage-gated calcium channels in equine spermatozoa from fresh and frozen semen.

    Science.gov (United States)

    Albrizio, M; Moramarco, A M; Nicassio, M; Micera, E; Zarrilli, A; Lacalandra, G M

    2015-02-01

    It is well known that insemination of cryopreserved semen always results in lower fertility when compared with fresh semen, but there is an increased interest and demand for frozen equine semen by the major breeder associations because of the utility arising from semen already "on hand" at breeding time. In this article, we report that equine sperm cells express L-type voltage-gated calcium channels; their localization is restricted to sperm neck and to the principal piece of the tail in both fresh and frozen-thawed spermatozoa. We also studied the causes of cryoinjury at the membrane level focusing on the function of L-type calcium channels. We report that in cryopreserved spermatozoa the mean basal value of [Ca(2+)]i is higher than that of spermatozoa from fresh semen (447.130 vs. 288.3 nM; P antagonist in relation to semen condition (fresh or frozen-thawed). We found that on addition of agonist to the culture medium, the increase in intracellular calcium concentrations ([Ca(2+)]i) was greater in frozen semen than in fresh semen (Δ[Ca(2+)]i = 124.59 vs. 16.04 nM; P antagonist the decrease in [Ca(2+)]i was lower in frozen semen than in fresh semen (Δ[Ca(2+)]i = 32.5 vs. 82.5 nM; P < 0.001). In this article, we also discuss the impact of cryopreservation on sperm physiology. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Jaione Simon-Santamaria

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

  4. Altered gating and local anesthetic block mediated by residues in the I-S6 and II-S6 transmembrane segments of voltage-dependent Na+ channels.

    Science.gov (United States)

    Kondratiev, Andrei; Tomaselli, Gordon F

    2003-09-01

    The cytoplasmic side of the voltage-dependent Na+ channel pore is putatively formed by the S6 segments of domains I to IV. The role of amino acid residues of I-S6 and II-S6 in channel gating and local anesthetic (LA) block was investigated using the cysteine scanning mutagenesis of the rat skeletal muscle Na+ channel (Nav1.4). G428C uniquely reduced sensitivity to rested state or first-pulse block by lidocaine without alterations in the voltage dependence or kinetics of gating that would otherwise account for the increase in the IC50 for block. Mutations in I-S6 (N434C and I436C) and in II-S6 (L785C and V787C) increased sensitivity to first-pulse block by lidocaine. Enhanced inactivation accounted for the increased sensitivity of N434C to lidocaine and hastening of inactivation of I436C in the absence of drug could account for higher affinity first-pulse block. Mutations in I-S6 (I424C, I425C, and F430C) and in II-S6 (I782C and V786C) reduced the use-dependent lidocaine block. The reduction in use-dependent block of F430C was consistent with alterations in inactivation gating; the other mutants did not exhibit gating changes that could explain the reduced sensitivity to lidocaine. Therefore, several amino acids (I424, I425, G428, I782, and V786), in addition to those previously identified (Yarov-Yarovoy et al., 2002), alter the sensitivity of Nav1.4 to lidocaine, independent of mutation-induced changes in gating. The magnitude of the change in the IC50 values, the isoform, and LA dependence of the changes in affinity suggest that the determinants of binding in I-S6 and II-S6 are subsidiary to those in IV-S6.

  5. 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.

  6. Adjuvant Ciprofloxacin for Persistent BK Polyomavirus Infection in Kidney Transplant Recipients

    Directory of Open Access Journals (Sweden)

    David Arroyo

    2014-01-01

    Full Text Available Background. BK virus (BKV infection is a common complication following kidney transplantation. Immunosuppression reduction is the cornerstone of treatment while adjuvant drugs have been tried in small uncontrolled studies. We sought to examine our center’s experience with the use of ciprofloxacin in patients with persistent BKV infection. Methods. Retrospective evaluation of the effect of a 30-day ciprofloxacin course (250 mg twice daily on BKV infection in kidney transplant recipients who had been diagnosed with BK viruria ≥106 copies/mL and viremia ≥500 copies/mL and in whom the infection did not resolve after immunosuppression reduction and/or treatment with other adjuvant agents. BKV in plasma and urine was evaluated after 3 months following treatment with ciprofloxacin. Results. Nine kidney transplant recipients received ciprofloxacin at a median of 130 days following the initial reduction in immunosuppression. Three patients showed complete viral clearance and another 3 had a ≥50% decrease in plasma viral load. No serious adverse events secondary to ciprofloxacin were reported and no grafts were lost due to BKV up to 1 year after treatment. Conclusion. Ciprofloxacin may be a useful therapy for persistent BKV infection despite conventional treatment. Randomized trials are required to evaluate the potential benefit of this adjuvant therapy.

  7. [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.

  8. 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)

  9. HIPPI and Fibre Channel

    International Nuclear Information System (INIS)

    Tolmie, D.E.

    1992-01-01

    The High-Performance Parallel Interface (HIPPI) and Fibre Channel are near-gigabit per second data communications interfaces being developed in ANSI standards Task Group X3T9.3. HIPPI is the current interface of choice in the high-end and supercomputer arena, and Fibre Channel is a follow-on effort. HIPPI came from a local area network background, and Fibre Channel came from a mainframe to peripheral interface background

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Starburst Channels

    Science.gov (United States)

    2007-01-01

    [figure removed for brevity, see original site] Figure 1 Translucent carbon dioxide ice covers the polar regions of Mars seasonally. It is warmed and sublimates (evaporates) from below, and escaping gas carves a numerous channel morphologies. In this example (figure 1) the channels form a 'starburst' pattern, radiating out into feathery extensions. The center of the pattern is being buried with dust and new darker dust fans ring the outer edges. This may be an example of an expanding morphology, where new channels are formed as the older ones fill and are no longer efficiently channeling the subliming gas out. Observation Geometry Image PSP_003443_0980 was taken by the High Resolution Imaging Science Experiment (HiRISE) camera onboard the Mars Reconnaissance Orbiter spacecraft on 21-Apr-2007. The complete image is centered at -81.8 degrees latitude, 76.2 degrees East longitude. The range to the target site was 247.1 km (154.4 miles). At this distance the image scale is 24.7 cm/pixel (with 1 x 1 binning) so objects 74 cm across are resolved. The image shown here has been map-projected to 25 cm/pixel. The image was taken at a local Mars time of 04:52 PM and the scene is illuminated from the west with a solar incidence angle of 71 degrees, thus the sun was about 19 degrees above the horizon. At a solar longitude of 223.4 degrees, the season on Mars is Northern Autumn.

  12. Neural network-based multiuser detection for SDMA-OFDM system over IEEE 802.11n indoor wireless local area network channel models

    Science.gov (United States)

    Praveen Bagadi, Kala; Das, Susmita

    2013-10-01

    Space division multiple access - orthogonal frequency division multiplexing-based wireless communication has the potential to offer high-spectral efficiency, system performance and capacity. This article proposes an efficient blind multiuser detection (MUD) scheme using artificial neural network models such as the radial basis function. The proposed MUD technique is consistently outperforming the existing minimum mean square error and minimum bit error rate (MBER) MUDs with the performance close to the optimal maximum likelihood (ML) detector. Besides that, the computational complexity of the proposed one is comparatively lower than both the MBER and ML detectors. Further, it can also outperform MBER MUD in the overload scenario, where the number of users is more than that of the number of receiving antennas simulation-based study showing BER performance and complexity are carried out to prove the efficiency of the proposed techniques. This analysis is carried through the IEEE 802.11n standard channel models, which are designed for indoor wireless local area network applications of bandwidth up to 100 MHz at frequencies 2 and 5 GHz.

  13. The role of Ca2+-dependent K+- channels at the rat corticostriatal synapses revealed by paired pulse stimulation.

    Science.gov (United States)

    Robles Gómez, Angel A; Vega, Ana V; Gónzalez-Sandoval, Carolina; Barral, Jaime

    2018-02-01

    Potassium channels play an important role in modulating synaptic activity both at presynaptic and postsynaptic levels. We have shown before that presynaptically located K V and K IR channels modulate the strength of corticostriatal synapses in rat brain, but the role of other types of potassium channels at these synapses remains largely unknown. Here, we show that calcium-dependent potassium channels BK-type but not SK-type channels are located presynaptically in corticostriatal synapses. We stimulated cortical neurons in rat brain slices and recorded postsynaptic excitatory potentials (EPSP) in medium spiny neurons (MSN) in dorsal neostriatum. By using a paired pulse protocol, we induced synaptic facilitation before applying either BK- or SK-specific toxins. Thus, we found that blockage of BK Ca with iberiotoxin (10 nM) reduces synaptic facilitation and increases the amplitude of the EPSP, while exposure to SK-blocker apamin (100 nM) has no effect. Additionally, we induced train action potentials on striatal MSN by current injection before and after the exposure to K Ca toxins. We found that the action potential becomes broader when the MSN is exposed to iberiotoxin, although it has no impact on frequency. In contrast, exposure to apamin results in loss of afterhyperpolarization phase and an increase of spike frequency. Therefore, we concluded that postsynaptic SK channels are involved in afterhyperpolarization and modulation of spike frequency while the BK channels are involved on the late repolarization phase of the action potential. Altogether, our results show that calcium-dependent potassium channels modulate both input towards and output from the striatum. © 2017 Wiley Periodicals, Inc.

  14. Voltage-dependent conformational changes in human Ca(2+)- and voltage-activated K(+) channel, revealed by voltage-clamp fluorometry.

    Science.gov (United States)

    Savalli, Nicoletta; Kondratiev, Andrei; Toro, Ligia; Olcese, Riccardo

    2006-08-15

    Large conductance voltage- and Ca(2+)-activated K(+) (BK(Ca)) channels regulate important physiological processes such as neurotransmitter release and vascular tone. BK(Ca) channels possess a voltage sensor mainly represented by the S4 transmembrane domain. Changes in membrane potential displace the voltage sensor, producing a conformational change that leads to channel opening. By site-directed fluorescent labeling of residues in the S3-S4 region and by using voltage clamp fluorometry, we have resolved the conformational changes the channel undergoes during activation. The voltage dependence of these conformational changes (detected as changes in fluorescence emission, fluorescence vs. voltage curves) always preceded the channel activation curves, as expected for protein rearrangements associated to the movement of the voltage sensor. Extremely slow conformational changes were revealed by fluorescent labeling of position 202, elicited by a mutual interaction of the fluorophore with the adjacent tryptophan 203.

  15. 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.

  16. Urinary exosomal viral microRNA as a marker of BK virus nephropathy in kidney transplant recipients.

    Directory of Open Access Journals (Sweden)

    Myeong Hee Kim

    Full Text Available Bkv-miR-B1-5p, one of the microRNAs encoded by BK virus, was recently reported to be elevated in the blood among the patients with BK virus nephropathy (BKVN. Urinary exosome was suggested to be a possible source of biomarker for kidney diseases, but it was unknown whether it could contain viral microRNA as well as human microRNAs. The aim of this study was to evaluate whether urinary exosomal BK viral microRNA were expressed during replication and could be used to diagnose BKVN in kidney transplant recipients.In a cross-sectional multicenter study, we collected and analyzed 458 graft biopsies from 385 kidney transplant recipients. Urine samples were collected at the time of graft biopsy, and microRNAs in urinary exosome were measured once. For 13 patients with BKVN and 67 age, sex-matched kidney transplant recipients, we measured BK viral microRNA B1-5p, 3p and human microRNA-16 in urinary exosomal fraction and compared the diagnostic value with BK viral load in plasma and urine.Pathology proven BKVN was diagnosed in 13 patients (2.8%. High levels of bkv-miR-B1-5p and bkv-miR-B1-3p were shown in all patients with BKVN. Meanwhile, plasma BK viral load assay (cut-off value of ≥ 4.0 log10 copies/mL showed false negative in 3 cases and urinary BK viral load assay (cut-off value of ≥ 7.0 log10 copies/mL showed false negative in 1 case among these 13 patients. The receiver operator characteristics curve analysis for bkv-miR-B1-5p and bkv-miR-B1-5p/miR-16 showed excellent discriminative power for the diagnosis of BKVN, with area under the curve values of 0.989 and 0.985, respectively.This study suggests that urinary exosomal bkv-miR-B1-5p and bkv-miR-B1-5p/miR-16 could be surrogate markers for the diagnosis of BKVN.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Le Calloch, R; Ianotto, J C; Berthou, C; Tempescul, A

    2011-01-01

    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.

  19. Surface Damage Characteristics of BK7 Glass in Ultrasonic Vibration Machining Based on Scratching Experiment

    Science.gov (United States)

    Rui, Gao; Hong-xiang, Wang; Jun-liang, Liu; Chu, Wang; Wen-jie, Zhai

    2017-11-01

    To further explore the material removal mechanism in ultrasonic vibration machining, a diamond Vickers indenter was used to carry out scratching experiment for BK7 glass specimen. The morphologies of scratches and removal mechanism of material were analysed under different conditions. The results showed that the damage mode of scratch was plastic deformation when the scratching depth was small enough, and no crack was observed. With increase of scratching depth, the intermittent and continuous scratches appeared in plastic removal area, and plastic flow phenomenon was obvious. With further increase of scratching depth, the median/radial cracks and lateral cracks were induced, and the material was removed by plastic flow and brittle-plastic mixed mode. When the indenter arrived at the brittle fracture removal area, cracks in scratched surface became denser, the lateral cracks extended from inside of material to workpiece surface, and the material was removed by brittle fracture.

  20. Analysis of Surface and Subsurface Damage Morphology in Rotary Ultrasonic Machining of BK7 Glass

    Science.gov (United States)

    Hong-xiang, Wang; Chu, Wang; Jun-liang, Liu; Shi, Gao; Wen-Jie, Zhai

    2017-11-01

    This paper investigates the formation process of surface/subsurface damage in the rotary ultrasonic machining of BK7 glass. The results show that during the milling using the end face of the tool, the cutting depth and the residual height between the abrasive grains constantly change with the high-frequency vibration, generating lots of cracks on both sides of the scratches. The high-frequency vibration accelerates the chips falling from the surface, so that the chips and thermal damage are reduced, causing the grinding surface quality better. A plastic deformation area is formed during the grinding, due to the non-uniform cutting force on the material surface, and the residual stress is produced in the deformation area, inducing the median/lateral cracks.

  1. Study of 249BkBr3 dimorphism by absorption spectrometry and X ray diffraction

    International Nuclear Information System (INIS)

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

    1977-01-01

    The phase transformation that occurs in solid BkBr 3 was studied by absorption spectroscopy and X-ray diffraction. Both techniques were applied to each 2-12 microgram sample at ambient and elevated temperatures. Significant increases in the f-f transition intensities were observed when the crystal structure was changed from the AlCl 3 -type monoclinic to the PuBr 3 -type orthorhombic form. The high-temperature monoclinic form can be maintained at room temperature by quenching the sample from above 350 deg C. By following the absorption intensity changes, it is also possible to study the kinetics of the phase transformation in the temperature range of 200-350 deg C [fr

  2. The Effect of Discharge Ratio and Confluence Angle on Local Scouring at 60 Degree Erodible Open Channel with SSIIM1 Model

    Directory of Open Access Journals (Sweden)

    R. Ghobadian

    2016-10-01

    Full Text Available Introduction: Flow and sediment transport has an important role in entrance deformation of open channel junctions. As water moved through a drainage network, it forced to converge at confluence. Due to increasing of water discharge and collision of converging flows, a complex three-dimensional and most highly turbulent location were occurred in the vicinity of the junction. Therefore a deep scour hole and point bar has developed in this area that caused the change in rivers morphology. Despite the large amount of research carried out on flow patterns in river confluences, only a few researches have focused on sediment transport. Materials and methods: In this research three dimensional model (SSIIM1 was used to study of flow pattern and sediment and erosion pattern at 60 degree Junction .the Navier-Stockes equation of turbulent flow in a general three-dimensional geometry are solved to obtain the water velocity: , (1 Where U is average velocity, ρ is density of water, is pressure, the Kronecker delta, which is 1 if i is equal to j and 0 otherwise and general space dimension. The last term is Reynolds stress, often modeled with the following equation: (2 Where and k are eddy viscosity and turbulent kinetic energy respectively. Van Rijn's relations were used to calculate sediment suspended and bed load transport. Dirichlet and zero gradients boundary conditions were used at inflow and outflow boundary respectively. fixed-lid approach was used to computed free surface by using zero gradient for all variables. The wall law for rough boundaries was also used as a boundary condition for bed and wall. In equilibrium situation, The sediment concentration for the cell closet to the bed was specified as the bed boundary condition. Specified value was used for sediment concentration of other boundary conditions at upstream boundary and zero gradients for the water surface, outlet, and the sides. the only simulation of local scouring and sedimentation at

  3. Occurrence of BK Virus and Human Papilloma Virus in colorectal cancer.

    Science.gov (United States)

    Jarzyński, Adrian; Zając, Przemysław; Żebrowski, Remigiusz; Boguszewska, Anastazja; Polz-Dacewicz, Małgorzata

    2017-09-21

    Colorectal cancer is one of the most common cancers worldwide. In Poland, it is the second most common cancer, regardless of gender. The aim of study was to analyze the incidence of HPV and BKV in the tissue of colorectal cancer and to determine the relationship between the presence of these viruses and the development of this cancer. The experiments were conducted using 50 colorectal cancer tissues collected from histological sections. The clinical material was embedded in paraffin blocks. Next, DNA extraction was performed. Isolates of colorectal cancer tissue were tested for the presence of HPV DNA. BKV DNA was detected by PCR using specific primers and then differentiated from JCV by digestion with BamHI enzyme. In clinical specimens taken from patients with colorectal cancer, HPV DNA was detected in 20% of cases. In 10% of cases the presence of HPV type 18 was confirmed, in the other 90% of the samples HPV type 16 was detected, while the presence of BKV was confirmed in 30% of cases. Coinfection with HPV and BKV was shown in 12% of patients. In one case, BK virus coexisted with HPV type 18, in the remaining 5 cases with HPV type 16. Developing colorectal cancer can show no symptoms, even for many years. This is why it is so important to become familiar with as many etiological factors as possible. The development of many human neoplasms is often initiated by exposure to infectious agents - such as bacterial or viral infections. Similar to the human papillomavirus, the BK virus was detected in clinical specimens. It seems that HPV and BKV infections can contribute to the neoplastic process, which requires detailed studies on a larger group of patients.

  4. Cloning, chromosomal localization, and functional expression of the alpha 1 subunit of the L-type voltage-dependent calcium channel from normal human heart

    NARCIS (Netherlands)

    Schultz, D; Mikala, G; Yatani, A; Engle, D B; Iles, D E; Segers, B; Sinke, R J; Weghuis, D O; Klöckner, U; Wakamori, M

    1993-01-01

    A unique structural variant of the cardiac L-type voltage-dependent calcium channel alpha 1 subunit cDNA was isolated from libraries derived from normal human heart mRNA. The deduced amino acid sequence shows significant homology to other calcium channel alpha 1 subunits. However, differences from

  5. Local heat/mass transfer distributions around sharp 180 deg turns in two-pass smooth and rib-roughened channels

    Science.gov (United States)

    Han, J. C.; Chandra, P. R.; Lau, S. C.

    1988-01-01

    The napthalene sublimation technique was employed to study the detailed mass transfer distributions around the sharp 180 deg turns in a two-pass, square, smooth channel and in an identical channel with two rib-roughened opposite walls. Experiments conducted for Reynolds numbers of 15,000, 30,000, and 60,000 indicate that the Sherwood numbers on the top, outer, and inner walls around the turn in the rib-roughened channel are higher than the corresponding Sherwood numbers around the turn in the smooth channel. Sherwood numbers after the sharp turn are found to be higher than those before the turn for both the smooth and the ribbed channels.

  6. 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

    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......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...... could be a potential drug target....

  7. 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

  8. Troponin T3 regulates nuclear localization of the calcium channel Ca{sub v}β{sub 1a} subunit in skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Tan; Taylor, Jackson; Jiang, Yang [Department of Internal Medicine-Gerontology, Wake Forest School of Medicine, Winston-Salem, NC 27157 (United States); Pereyra, Andrea S. [Department of Histology, National University of La Plata, 1900 La Plata (Argentina); Messi, Maria Laura; Wang, Zhong-Min [Department of Internal Medicine-Gerontology, Wake Forest School of Medicine, Winston-Salem, NC 27157 (United States); Hereñú, Claudia [Department of Histology, National University of La Plata, 1900 La Plata (Argentina); Delbono, Osvaldo, E-mail: odelbono@wakehealth.edu [Department of Internal Medicine-Gerontology, Wake Forest School of Medicine, Winston-Salem, NC 27157 (United States); Neuroscience Program, Wake Forest School of Medicine, Winston-Salem, NC 27157 (United States)

    2015-08-15

    The voltage-gated calcium channel (Ca{sub v}) β{sub 1a} subunit (Ca{sub v}β{sub 1a}) plays an important role in excitation–contraction coupling (ECC), a process in the myoplasm that leads to muscle-force generation. Recently, we discovered that the Ca{sub v}β{sub 1a} subunit travels to the nucleus of skeletal muscle cells where it helps to regulate gene transcription. To determine how it travels to the nucleus, we performed a yeast two-hybrid screening of the mouse fast skeletal muscle cDNA library and identified an interaction with troponin T3 (TnT3), which we subsequently confirmed by co-immunoprecipitation and co-localization assays in mouse skeletal muscle in vivo and in cultured C2C12 muscle cells. Interacting domains were mapped to the leucine zipper domain in TnT3 COOH-terminus (160–244 aa) and Ca{sub v}β{sub 1a} NH{sub 2}-terminus (1–99 aa), respectively. The double fluorescence assay in C2C12 cells co-expressing TnT3/DsRed and Ca{sub v}β{sub 1a}/YFP shows that TnT3 facilitates Ca{sub v}β{sub 1a} nuclear recruitment, suggesting that the two proteins play a heretofore unknown role during early muscle differentiation in addition to their classical role in ECC regulation. - Highlights: • Previously, we demonstrated that Ca{sub v}β{sub 1a} is a gene transcription regulator. • Here, we show that TnT3 interacts with Ca{sub v}β{sub 1a}. • We mapped TnT3 and Ca{sub v}β{sub 1a} interaction domain. • TnT3 facilitates Ca{sub v}β{sub 1a} nuclear enrichment. • The two proteins play a heretofore unknown role during early muscle differentiation.

  9. Fate of the Urinary Tract Virus BK Human Polyomavirus in Source-Separated Urine.

    Science.gov (United States)

    Goetsch, Heather E; Zhao, Linbo; Gnegy, Mariah; Imperiale, Michael J; Love, Nancy G; Wigginton, Krista R

    2018-04-01

    Human polyomaviruses are emerging pathogens that infect a large percentage of the human population and are excreted in urine. Consequently, urine that is collected for fertilizer production often has high concentrations of polyomavirus genes. We studied the fate of infectious double-stranded DNA (dsDNA) BK human polyomavirus (BKPyV) in hydrolyzed source-separated urine with infectivity assays and quantitative PCR (qPCR). Although BKPyV genomes persisted in the hydrolyzed urine for long periods of time ( T 90 [time required for 90% reduction in infectivity or gene copies] of >3 weeks), the viruses were rapidly inactivated ( T 90 of 1.1 to 11 h) in most of the tested urine samples. Interestingly, the infectivity of dsDNA bacteriophage surrogate T3 ( T 90 of 24 to 46 days) was much more persistent than that of BKPyV, highlighting a major shortcoming of using bacteriophages as human virus surrogates. Pasteurization and filtration experiments suggest that BKPyV virus inactivation was due to microorganism activity in the source-separated urine, and SDS-PAGE Western blots showed that BKPyV protein capsid disassembly is concurrent with inactivation. Our results imply that stored urine does not pose a substantial risk of BKPyV transmission, that qPCR and infectivity of the dsDNA surrogate do not accurately depict BKPyV fate, and that microbial inactivation is driven by structural elements of the BKPyV capsid. IMPORTANCE We demonstrate that a common urinary tract virus has a high susceptibility to the conditions in hydrolyzed urine and consequently would not be a substantial exposure route to humans using urine-derived fertilizers. The results have significant implications for understanding virus fate. First, by demonstrating that the dsDNA (double-stranded DNA) genome of the polyomavirus lasts for weeks despite infectivity lasting for hours to days, our work highlights the shortcomings of using qPCR to estimate risks from unculturable viruses. Second, commonly used ds

  10. Viral DNA replication-dependent DNA damage response activation during BK polyomavirus infection.

    Science.gov (United States)

    Verhalen, Brandy; Justice, Joshua L; Imperiale, Michael J; Jiang, Mengxi

    2015-05-01

    BK polyomavirus (BKPyV) reactivation is associated with severe human disease in kidney and bone marrow transplant patients. The interplay between viral and host factors that regulates the productive infection process remains poorly understood. We have previously reported that the cellular DNA damage response (DDR) is activated upon lytic BKPyV infection and that its activation is required for optimal viral replication in primary kidney epithelial cells. In this report, we set out to determine what viral components are responsible for activating the two major phosphatidylinositol 3-kinase-like kinases (PI3KKs) involved in the DDR: ataxia telangiectasia mutated (ATM) kinase and ATM and Rad3-related (ATR) kinase. Using a combination of UV treatment, lentivirus transduction, and mutant virus infection experiments, our results demonstrate that neither the input virus nor the expression of large T antigen (TAg) alone is sufficient to trigger the activation of ATM or ATR in our primary culture model. Instead, our data suggest that the activation of both the ATM- and ATR-mediated DDR pathways is linked to viral DNA replication. Intriguingly, a TAg mutant virus that is unable to activate the DDR causes substantial host DNA damage. Our study provides insight into how DDRs are activated by polyomaviruses in primary cells with intact cell cycle checkpoints and how the activation might be linked to the maintenance of host genome stability. Polyomaviruses are opportunistic pathogens that are associated with several human diseases under immunosuppressed conditions. BK polyomavirus (BKPyV) affects mostly kidney and bone marrow transplant patients. The detailed replication mechanism of these viruses remains to be determined. We have previously reported that BKPyV activates the host DNA damage response (DDR), a response normally used by the host cell to combat genotoxic stress, to aid its own replication. In this study, we identified that the trigger for DDR activation is viral

  11. 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

  12. BK virus-associated urinary bladder carcinoma in transplant recipients: report of 2 cases, review of the literature, and proposed pathogenetic model.

    Science.gov (United States)

    Alexiev, Borislav A; Randhawa, Parmjeet; Vazquez Martul, Eduardo; Zeng, Gang; Luo, Chunqing; Ramos, Emilio; Drachenberg, Cinthia B; Papadimitriou, John C

    2013-05-01

    Despite strong experimental evidence, BK polyomavirus involvement in human cancers has been controversial. We report 2 cases of kidney ± pancreas transplant recipients with evidence of BK polyomavirus reactivation, who developed aggressive urinary bladder urothelial carcinomas with adenocarcinomatous and/or micropapillary differentiation. Diffuse strong nuclear positivity for viral T antigen, p53, Ki-67, and p16 was observed in both malignancies. The BK polyomavirus role in promoting urothelial neoplasia in transplant recipients may be partly indirect, based on the demonstration by polymerase chain reaction in both tumors of BK polyomavirus with intact open reading frames and close phylogenetic clustering with known replication-competent strains, and viral capsid protein VP1 messenger RNA and intranuclear virions by electron microscopy in 1 tumor. No unique cancer-associated mutations were found, but some viral T antigen mutations were potentially associated with increased rate of viral replication and risk for "rare" carcinogenic events. The BK polyomavirus-induced profound effects on cell activation, cell cycle shift to proliferation, and apoptosis inhibition, in the context of marked immunosuppression, constitute a potentially ideal background for malignant transformation. The long time lapse between transplantation and tumor manifestation, 7 and 11 years, respectively, further supports the concept of multistep carcinogenesis cascade and long-term risk for these patients. We propose a model of changes ranging from viral reactivation to dysplasia to invasive carcinoma. Clinical vigilance is warranted for early diagnosis of BK polyomavirus-related urothelial malignancies in transplant recipients. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. 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

  14. 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.

  15. Do polyomavirus hominis strains BK and JC play a role in oral squamous cell carcinoma?

    Directory of Open Access Journals (Sweden)

    Dorota Polz

    2015-02-01

    Full Text Available Introduction. Head and neck cancers are the most common cancers worldwide. It is estimated that approximately 90% of all head and neck cancers are represented by squamous cell carcinoma (SCC. There are many risk factors causing this type of cancer, including environmental factors and lifestyle choices, such as tobacco smoking or abusing alcohol. Other important risk factor include infectious factors. [b]Objective[/b]. The aim of this study was to analyze the prevalence of BK and JC virus infections among patients with oral squamous cell carcinoma (OSCC. [b]Materials and method[/b]. The correlation between BKV infection and OSCC, and correlation between BKV, OSCC, alcohol abuse, tobacco smoking, demographic data, pre-treatment staging, metastases of lymph node evidence, and grading, was analyzed. The study group consisted of 92 patients with squamous cell carcinoma (OSCC, 75 males, and 17 females, aged between 40 – 87 (average 56.8. All the patients underwent surgery and were not subjected to chemotherapy or radiotherapy prior to treatment. The analyzed samples were collected from paraffin sections. [b]Results[/b]. BKV DNA was detected in 18.5% of patients with OSCC. In the control group, BKV DNA was detected in 3.3%. BKV DNA was statistically more frequently detected among patients with squamous carcinoma, compared to the control group (p<0.05. [b]Conclusions[/b]. The obtained results suggest that the BKV virus may play an important role in the development of oral squamous cell carcinoma.

  16. 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

  17. 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

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    Raquel Burger-Calderon

    2015-07-01

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

  20. 47 CFR 76.57 - Channel positioning.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Channel positioning. 76.57 Section 76.57... CABLE TELEVISION SERVICE Carriage of Television Broadcast Signals § 76.57 Channel positioning. (a) At... choice of channel position when it requests carriage. Channel positioning requests from local commercial...

  1. Planar channeling observed by radiography

    International Nuclear Information System (INIS)

    Delsarte, Guy

    1970-06-01

    Radiographies of crystals by means of channeled particles exhibit channeling patterns. The origin of these patterns is studied, The role played by planar channeling is demonstrated. It is shown that these patterns are local amplifications of the process generating the images of a crystal on the radiography. It is deduced that planar channeling plays a determining role in the formation of these images. An orientation chamber using transmitted planar channels is described. The orientation of very small grains in a polycrystal can be very easily obtained, (author) [fr

  2. Limited Variation in BK Virus T-Cell Epitopes Revealed by Next-Generation Sequencing

    Science.gov (United States)

    Sahoo, Malaya K.; Tan, Susanna K.; Chen, Sharon F.; Kapusinszky, Beatrix; Concepcion, Katherine R.; Kjelson, Lynn; Mallempati, Kalyan; Farina, Heidi M.; Fernández-Viña, Marcelo; Tyan, Dolly; Grimm, Paul C.; Anderson, Matthew W.; Concepcion, Waldo

    2015-01-01

    BK virus (BKV) infection causing end-organ disease remains a formidable challenge to the hematopoietic cell transplant (HCT) and kidney transplant fields. As BKV-specific treatments are limited, immunologic-based therapies may be a promising and novel therapeutic option for transplant recipients with persistent BKV infection. Here, we describe a whole-genome, deep-sequencing methodology and bioinformatics pipeline that identify BKV variants across the genome and at BKV-specific HLA-A2-, HLA-B0702-, and HLA-B08-restricted CD8 T-cell epitopes. BKV whole genomes were amplified using long-range PCR with four inverse primer sets, and fragmentation libraries were sequenced on the Ion Torrent Personal Genome Machine (PGM). An error model and variant-calling algorithm were developed to accurately identify rare variants. A total of 65 samples from 18 pediatric HCT and kidney recipients with quantifiable BKV DNAemia underwent whole-genome sequencing. Limited genetic variation was observed. The median number of amino acid variants identified per sample was 8 (range, 2 to 37; interquartile range, 10), with the majority of variants (77%) detected at a frequency of <5%. When normalized for length, there was no statistical difference in the median number of variants across all genes. Similarly, the predominant virus population within samples harbored T-cell epitopes similar to the reference BKV strain that was matched for the BKV genotype. Despite the conservation of epitopes, low-level variants in T-cell epitopes were detected in 77.7% (14/18) of patients. Understanding epitope variation across the whole genome provides insight into the virus-immune interface and may help guide the development of protocols for novel immunologic-based therapies. PMID:26202116

  3. The kinetics of urinary shedding of BK virus in children with renal disease.

    Science.gov (United States)

    Yamamoto, Yasuto; Morooka, Masashi; Ihira, Masaru; Yoshikawa, Tetsushi

    2015-01-01

    Children with renal diseases are typically treated with immunosuppressive drugs, which place them at high risk of reactivation of the BK virus (BKV). Currently, little is known about the impact of immunosuppressive drugs on the kinetics of urinary shedding of BKV and viral reactivation in pediatric patients with renal diseases. Urine samples were collected monthly for 1 year from 20 children (median age, 9 years; range, 4-15 years) with renal diseases and subjected to real-time PCR. Urinary shedding of BKV was detected in 35% (7/20) of the patients, three of these patients having persistent viral DNA excretion (two cases, twelve times; one case, four times) and four having intermittent viral DNA excretion. Thirty-four of the 240 urine samples contained BKV DNA (median copy numbers, 5.66 log copies/mL; range, 2.45-7.69 log copies/mL). In two of the cases with persistent viral shedding, high copy numbers (range, 4.57-7.69 log copies/mL) of BKV DNA were detected in all 12 urine samples collected. In the other case with persistent viral excretion, a range of 2.45-3.98 log copies/mL of BKV DNA was detected in the four urine samples collected between the 9th and 12th sampling time points. Additionally, high copy numbers (range, 3.12-4.36 log copies/mL) of BKV DNA were detected intermittently in the urine samples of the other four cases. No remarkable correlations were found between the kinetics of BKV DNA loads and urinary findings such as proteinuria and hematuria. The present data demonstrate the kinetics of urinary BKV shedding in pediatric patients with renal diseases. Additionally, no pathogenic role for BKV infection was identified. © 2014 The Societies and Wiley Publishing Asia Pty Ltd.

  4. Cidofovir for BK virus-associated hemorrhagic cystitis: a retrospective study.

    Science.gov (United States)

    Cesaro, Simone; Hirsch, Hans H; Faraci, Maura; Owoc-Lempach, Joanna; Beltrame, Angela; Tendas, Andrea; Baltadakis, Ioannis; Dalle, Jean-Hughes; Koc, Yener; Toporski, Jacek; Styczynski, Jan; Yesilipek, M Akif; Heinz, Werner; Caniglia, Maurizio; Rascon, Jelena; Fauser, Axel A; Michallet, Mauricette; Lopez-Corral, Lucia; Neuburger, Stefan; Tridello, Gloria; Einsele, Herman

    2009-07-15

    BK virus-associated hemorrhagic cystitis (BKV-HC) is a severe complication after allogeneic hematopoietic stem cell transplantation (HSCT), but antiviral treatment for this condition has not been evaluated. We conducted a retrospective survey on the safety and outcome of cidofovir treatment for patients with BKV-HC in centers affiliated with the European Group for Blood and Marrow Transplantation. From 1 April 2004 to 31 December 2007, 62 patients received a diagnosis of BKV-HC after a median interval of 35 days after HSCT (range, 3-577 days). Fifty-seven patients (92%) received intravenous cidofovir, whereas 5 patients received cidofovir intravesically. Complete response (CR) was recorded in 38 (67%) of 57 patients with HC treated with intravenous cidofovir, whereas partial response (PR) was documented in 7 patients (12%). CR was documented in 3 patients and PR in 1 patient with HC treated with intravesical cidofovir. A reduction of 1-3 logs in BKV load was documented in 8 of the 10 patients achieving CR. Mild-to-moderate toxic effects were recorded in 18 of 57 patients who received intravenous cidofovir administration. In a multivariate analysis, the factors significantly associated with response to cidofovir were the stem cell source (P = .01) and the use of total body irradiation (P = .03). After a median follow-up of 287 days, overall survival and total treatment-related mortality rates were 63% and 40% for patients achieving CR, compared with 14% and 72% for patients with PR or no response to cidofovir, respectively (P = .001 and P = .001, respectively). Cidofovir may be a potentially effective therapy for BKV-HC, but evidence supporting its use requires randomized controlled trials.

  5. 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.

  6. Development of Energy Efficient, Multi-Channel, Pulsed Plasma Generator for High-Speed Flow Control by Localized Arc Filament Plasma Actuators, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The research team at The Ohio State University has been developing technologies to suppress jet noise using localized arc filament plasma actuators and are in the...

  7. Characterization of the Divergent sacBK and sacAR Operons, Involved in Sucrose Utilization by Lactococcus lactis

    OpenAIRE

    Luesink, Evert J.; Marugg, Joey D.; Kuipers, Oscar P.; Vos, Willem M. de

    1999-01-01

    The divergently transcribed sacBK and sacAR operons, which are involved in the utilization of sucrose by Lactococcus lactis NZ9800, were examined by transcriptional and gene inactivation studies. Northern analyses of RNA isolated from cells grown at the expense of different carbon sources revealed three sucrose-inducible transcripts: one of 3.2 kb containing sacB and sacK, a second of 3.4 kb containing sacA and sacR, and a third of 1.8 kb containing only sacR. The inactivation of the sacR gen...

  8. 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.

  9. Detection of BK virus and JC virus in urine and brain tissue by the polymerase chain reaction.

    OpenAIRE

    Arthur, R R; Dagostin, S; Shah, K V

    1989-01-01

    DNAs of the human polyomaviruses BK virus (BKV) and JC virus (JCV) were amplified by the polymerase chain reaction (PCR) by using a single pair of 20-base oligonucleotide primers that were complementary to the same regions of both viruses. The sequences flanked by the primers were unique for each virus and could be differentiated by hybridization with 40-base, 32P-labeled oligonucleotide probes or by cleavage with BamHI. The DNA fragments resulting from amplification of BKV and JCV were 176 a...

  10. Impact of low-level BK polyomavirus viremia on intermediate-term renal allograft function.

    Science.gov (United States)

    Korth, Johannes; Widera, Marek; Dolff, Sebastian; Guberina, Hana; Bienholz, Anja; Brinkhoff, Alexandra; Anastasiou, Olympia Evdoxia; Kribben, Andreas; Dittmer, Ulf; Verheyen, Jens; Wilde, Benjamin; Witzke, Oliver

    2018-02-01

    BK polyomavirus (BKPyV)-associated nephropathy (PyVAN) is a significant cause of premature renal transplant failure. High-level BKPyV viremia is predictive for PyVAN; however, low-level BKPyV viremia does not necessarily exclude the presence of PyVAN. As data are limited regarding whether or not low-level BKPyV viremia has an effect on intermediate-term graft outcome, this study analyzes the impact of low-level BKPyV viremia on intermediate-term graft function and outcome compared with high-level viremia and non-viremic patients. All renal transplant patients received follow-up examinations at the Department of Nephrology, University Hospital Essen. Patients were screened for BKPyV viremia and stratified into three groups according to their maximum BKPyV load in serum (low-level viremia, high-level viremia, and no viremia). In 142 of 213 (67%) patients, BKPyV was never detected in serum; 42 of 213 (20%) patients were found positive for low-level viremia (≤10 4 copies/mL); and 29 of 213 (13%) patients showed high-level viremia (>10 4 copies/mL). No significant differences regarding transplant function and graft failure were observed between patients without BKPyV viremia (delta estimated glomerular filtration rate [eGFR] +0.1 mL/min [month 1 vs last visit at month 44]) and patients with low-level BKPyV viremia (delta eGFR -1.7 mL/min). In patients with high-level viremia, transplant function was significantly restricted (delta eGFR -6.5 mL/min) compared with low-level viremia until the last visit at 44 ± 9.7 months after transplantation. Although the graft function and graft loss were worse in the high-level viremia group compared with no viremia (eGFR 37 vs 45 mL/min), the difference was not significant. High-level viremia was associated with impaired graft function. In contrast, low-level BKPyV viremia had no significant impact on intermediate-term graft function. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    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

  12. Sub-cellular Electrical Heterogeneity Revealed by Loose Patch Recording Reflects Differential Localization of Sarcolemmal Ion Channels in Intact Rat Hearts

    Directory of Open Access Journals (Sweden)

    Igor V. Kubasov

    2018-02-01

    Full Text Available The cardiac action potential (AP is commonly recoded as an integral signal from isolated myocytes or ensembles of myocytes (with intracellular microelectrodes and extracellular macroelectrodes, respectively. These signals, however, do not provide a direct measure of activity of ion channels and transporters located in two major compartments of a cardiac myocyte: surface sarcolemma and the T-tubule system, which differentially contribute to impulse propagation and excitation-contraction (EC coupling. In the present study we investigated electrical properties of myocytes within perfused intact rat heart employing loose patch recording with narrow-tip (2 μm diameter extracellular electrodes. Using this approach, we demonstrated two distinct types of electric signals with distinct waveforms (single peak and multi-peak AP; AP1 and AP2, respectively during intrinsic pacemaker activity. These two types of waveforms depend on the position of the electrode tip on the myocyte surface. Such heterogeneity of electrical signals was lost when electrodes of larger pipette diameter were used (5 or 10 μm, which indicates that the electric signal was assessed from a region of <5 μm. Importantly, both pharmacological and mathematical simulation based on transverse (T-tubular distribution suggested that while the AP1 and the initial peak of AP2 are predominantly attributable to the fast, inward Na+ current in myocyte's surface sarcolemma, the late components of AP2 are likely representative of currents associated with L-type Ca2+ channel and Na+/Ca2+ exchanger (NCX currents which are predominantly located in T-tubules. Thus, loose patch recording with narrow-tip pipette provides a valuable tool for studying cardiac electric activity on the subcellular level in the intact heart.

  13. Social stress alters expression of large conductance calcium-activated potassium channel subunits in mouse adrenal medulla and pituitary glands.

    Science.gov (United States)

    Chatterjee, O; Taylor, L A; Ahmed, S; Nagaraj, S; Hall, J J; Finckbeiner, S M; Chan, P S; Suda, N; King, J T; Zeeman, M L; McCobb, D P

    2009-03-01

    Large conductance calcium-activated potassium (BK) channels are very prominently expressed in adrenal chromaffin and many anterior pituitary cells, where they shape intrinsic excitability complexly. Stress- and sex-steroids regulate alternative splicing of Slo-alpha, the pore-forming subunit of BK channels, and chronic behavioural stress has been shown to alter Slo splicing in tree shrew adrenals. In the present study, we focus on mice, measuring the effects of chronic behavioural stress on total mRNA expression of the Slo-alpha gene, two key BK channel beta subunit genes (beta2 and beta4), and the 'STREX' splice variant of Slo-alpha. As a chronic stressor, males of the relatively aggressive SJL strain were housed with a different unfamiliar SJL male every 24 h for 19 days. This 'social-instability' paradigm stressed all individuals, as demonstrated by reduced weight gain and elevated corticosterone levels. Five quantitative reverse transcriptase-polymerase chain assays were performed in parallel, including beta-actin, each calibrated against a dilution series of its corresponding cDNA template. Stress-related changes in BK expression were larger in mice tested at 6 weeks than 9 weeks. In younger animals, Slo-alpha mRNA levels were elevated 44% and 116% in the adrenal medulla and pituitary, respectively, compared to individually-housed controls. beta2 and beta4 mRNAs were elevated 162% and 194% in the pituitary, but slightly reduced in the adrenals of stressed animals. In the pituitary, dominance scores of stressed animals correlated negatively with alpha and beta subunit expression, with more subordinate individuals exhibiting levels that were three- to four-fold higher than controls or dominant individuals. STREX variant representation was lower in the subordinate subset. Thus, the combination of subunits responding to stress differs markedly between adrenal and pituitary glands. These data suggest that early stress will differentially affect neuroendocrine cell

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. The secretory KCa1.1 channel localises to crypts of distal mouse colon: functional and molecular evidence

    DEFF Research Database (Denmark)

    Sørensen, Mads Vaarby; Strandsby, Anne Bystrup; Larsen, Casper Kornbech

    2011-01-01

    Na+ absorption is mediated by epithelial Na+ channel (ENaC) in surface cells. Previously, we identified the large conductance Ca2+-activated K+ channel, KCa1.1 or big potassium (BK) channel, as the only relevant K+ secretory pathway in mouse distal colon. The exact localisation of K(Ca)1.1 channels...... along the crypt axis is, however, still controversial. The aim of this project was to further define the localisation of the K(Ca)1.1 channel in mouse distal colonic epithelium. Through quantification of mRNA extracted from micro-dissected surface and crypt cells, we confirmed that Na+/K+/2Cl- (NKCC1......-ENaC and KCa1.1 α-subunit were, however, under these circumstances substantially augmented (KCa1.1 α-subunit, twofold; NKCC1, twofold and ENaC, tenfold). Functionally, we show that ENaC-mediated Na+ absorption and BK channel-mediated K+ secretion are two independent processes. These findings show that KCa1...

  17. MARKETING CHANNELS

    Directory of Open Access Journals (Sweden)

    Ljiljana Stošić Mihajlović

    2014-07-01

    Full Text Available Marketing channel is a set of entities and institutions, completion of distribution and marketing activities, attend the efficient and effective networking of producers and consumers. Marketing channels include the total flows of goods, money and information taking place between the institutions in the system of marketing, establishing a connection between them. The functions of the exchange, the physical supply and service activities, inherent in the system of marketing and trade. They represent paths which products and services are moving after the production, which will ultimately end up buying and eating by the user.

  18. Cell Cycle-dependent Changes in Localization and Phosphorylation of the Plasma Membrane Kv2.1 K+ Channel Impact Endoplasmic Reticulum Membrane Contact Sites in COS-1 Cells.

    Science.gov (United States)

    Cobb, Melanie M; Austin, Daniel C; Sack, Jon T; Trimmer, James S

    2015-12-04

    The plasma membrane (PM) comprises distinct subcellular domains with diverse functions that need to be dynamically coordinated with intracellular events, one of the most impactful being mitosis. The Kv2.1 voltage-gated potassium channel is conditionally localized to large PM clusters that represent specialized PM:endoplasmic reticulum membrane contact sites (PM:ER MCS), and overexpression of Kv2.1 induces more exuberant PM:ER MCS in neurons and in certain heterologous cell types. Localization of Kv2.1 at these contact sites is dynamically regulated by changes in phosphorylation at one or more sites located on its large cytoplasmic C terminus. Here, we show that Kv2.1 expressed in COS-1 cells undergoes dramatic cell cycle-dependent changes in its PM localization, having diffuse localization in interphase cells, and robust clustering during M phase. The mitosis-specific clusters of Kv2.1 are localized to PM:ER MCS, and M phase clustering of Kv2.1 induces more extensive PM:ER MCS. These cell cycle-dependent changes in Kv2.1 localization and the induction of PM:ER MCS are accompanied by increased mitotic Kv2.1 phosphorylation at several C-terminal phosphorylation sites. Phosphorylation of exogenously expressed Kv2.1 is significantly increased upon metaphase arrest in COS-1 and CHO cells, and in a pancreatic β cell line that express endogenous Kv2.1. The M phase clustering of Kv2.1 at PM:ER MCS in COS-1 cells requires the same C-terminal targeting motif needed for conditional Kv2.1 clustering in neurons. The cell cycle-dependent changes in localization and phosphorylation of Kv2.1 were not accompanied by changes in the electrophysiological properties of Kv2.1 expressed in CHO cells. Together, these results provide novel insights into the cell cycle-dependent changes in PM protein localization and phosphorylation. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Local upregulation of transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 ion channels in rectosigmoid deep infiltrating endometriosis.

    Science.gov (United States)

    Bohonyi, Noémi; Pohóczky, Krisztina; Szalontai, Bálint; Perkecz, Anikó; Kovács, Krisztina; Kajtár, Béla; Orbán, Lajos; Varga, Tamás; Szegedi, Sarolta; Bódis, József; Helyes, Zsuzsanna; Koppán, Miklós

    2017-01-01

    evidence for the presence of non-neuronal TRPA1 receptor in the healthy human endometrium and confirm the expression of TRPV1 channels. Their upregulations in rectosigmoid deep infiltrating endometriosis lesions and correlations with pain intensity suggest potential roles in pathophysiological mechanisms of the disease.

  20. Comparing information about arm movement direction in single channels of local and epicortical field potentials from monkey and human motor cortex.

    Science.gov (United States)

    Mehring, Carsten; Nawrot, Martin Paul; de Oliveira, Simone Cardoso; Vaadia, Eilon; Schulze-Bonhage, Andreas; Aertsen, Ad; Ball, Tonio

    2004-01-01

    Cortical field potentials have been used for decades in neurophysiological studies to probe spatio-temporal activity patterns of local populations of neurons. Recently, however, interest in these signals was spurred as they were proposed as potential control signals for neuronal motor prostheses, i.e., for devices fit to record and decode brain activity to restore motor functions in paralyzed patients. Little is known, however, about the functional significance of these cortical field potentials. Here we compared information about arm movement direction in two types of movement related cortical field potentials, obtained during a four direction center-out arm reaching paradigm: local field potentials (LFPs) recorded with intracortical micro-electrodes from monkey motor cortex, and epicortical field potentials (EFPs) recorded with macro-electrode arrays subdurally implanted on the surface of the human cerebral cortex. While monkey LFPs showed a typical sequence of positive and negative potential peaks, an initial negative peak was the most salient feature of human EFPs. Individual contralateral LFPs from the monkey motor cortex carried approximately twice as much decoded information (DI) about arm movement direction (median 0.27 bit) as did individual EFPs from the contralateral hand/arm area of primary motor cortex in humans (median 0.12 bit). This relation was similar to the relation between median peak signal-to-noise ratios for directional modulation of movement related potentials (MRPs) of both types of signals. We discuss possible reasons for the observed differences, amongst them epi- vs. intracortical recording and the different electrode dimensions used to measure EFPs and LFPs.

  1. Preliminary Studies of Acute Cadmium Administration Effects on the Calcium-Activated Potassium (SKCa and BKCa) Channels and Na+/K+-ATPase Activity in Isolated Aortic Rings of Rats.

    Science.gov (United States)

    Vassallo, Dalton V; Almenara, Camila C P; Broseghini-Filho, Gilson Brás; Teixeira, Ariane Calazans; da Silva, David Chaves F; Angeli, Jhuli K; Padilha, Alessandra S

    2017-09-13

    Cadmium is an environmental pollutant closely linked with cardiovascular diseases that seems to involve endothelium dysfunction and reduced nitric oxide (NO) bioavailability. Knowing that NO causes dilatation through the activation of potassium channels and Na + /K + -ATPase, we aimed to determine whether acute cadmium administration (10 μM) alters the participation of K + channels, voltage-activated calcium channel, and Na + /K + -ATPase activity in vascular function of isolated aortic rings of rats. Cadmium did not modify the acetylcholine-induced relaxation. After L-NAME addition, the relaxation induced by acetylcholine was abolished in presence or absence of cadmium, suggesting that acutely, this metal did not change NO release. However, tetraethylammonium (a nonselective K + channels blocker) reduced acetylcholine-induced relaxation but this effect was lower in the preparations with cadmium, suggesting a decrease of K + channels function in acetylcholine response after cadmium incubation. Apamin (a selective blocker of small Ca 2+ -activated K + channels-SK Ca ), iberiotoxin (a selective blocker of large-conductance Ca 2+ -activated K + channels-BK Ca ), and verapamil (a blocker of calcium channel) reduced the endothelium-dependent relaxation only in the absence of cadmium. Finally, cadmium decreases Na + /K + -ATPase activity. Our results provide evidence that the cadmium acute incubation unaffected the calcium-activated potassium channels (SK Ca and BK Ca ) and voltage-calcium channels on the acetylcholine vasodilatation. In addition, acute cadmium incubation seems to reduce the Na + /K + -ATPase activity.

  2. The secretory KCa1.1 channel localises to crypts of distal mouse colon: functional and molecular evidence

    DEFF Research Database (Denmark)

    Sørensen, Mads Vaarby; Strandsby, Anne Bystrup; Larsen, Casper Kornbech

    2011-01-01

    The colonic epithelium absorbs and secretes electrolytes and water. Ion and water absorption occurs primarily in surface cells, whereas crypt cells perform secretion. Ion transport in distal colon is regulated by aldosterone, which stimulates both Na+ absorption and K+ secretion. The electrogenic...... Na+ absorption is mediated by epithelial Na+ channel (ENaC) in surface cells. Previously, we identified the large conductance Ca2+-activated K+ channel, KCa1.1 or big potassium (BK) channel, as the only relevant K+ secretory pathway in mouse distal colon. The exact localisation of K(Ca)1.1 channels...... along the crypt axis is, however, still controversial. The aim of this project was to further define the localisation of the K(Ca)1.1 channel in mouse distal colonic epithelium. Through quantification of mRNA extracted from micro-dissected surface and crypt cells, we confirmed that Na+/K+/2Cl- (NKCC1...

  3. Analysis of decay chains of superheavy nuclei produced in the 249Bk+48Ca and 243Am+48Ca reactions

    International Nuclear Information System (INIS)

    Zlokazov, V B; Utyonkov, V K

    2017-01-01

    The analysis of decay chains starting at superheavy nuclei 293 Ts and 289 Mc is presented. The spectroscopic properties of nuclei identified during the experiments using the 249 Bk+ 48 Ca and 243 Am+ 48 Ca reactions studied at the gas-filled separators DGFRS, TASCA and BGS are considered. We present the analysis of decay data using widely adopted statistical methods and applying them to the short decay chains of parent odd- Z nuclei. We find out that the recently suggested method of analyzing decay chains by Forsberg et al may lead to questionable conclusions when applied for the analysis of radioactive decays. Our discussion demonstrates reasonable congruence of α -particle energies and decay times of nuclei assigned to isotopes 289 Mc, 285 Nh and 281 Rg observed in both reactions. (paper)

  4. Analysis of decay chains of superheavy nuclei produced in the 249Bk+48Ca and 243Am+48Ca reactions

    Science.gov (United States)

    Zlokazov, V. B.; Utyonkov, V. K.

    2017-07-01

    The analysis of decay chains starting at superheavy nuclei 293Ts and 289Mc is presented. The spectroscopic properties of nuclei identified during the experiments using the 249Bk+48Ca and 243Am+48Ca reactions studied at the gas-filled separators DGFRS, TASCA and BGS are considered. We present the analysis of decay data using widely adopted statistical methods and applying them to the short decay chains of parent odd-Z nuclei. We find out that the recently suggested method of analyzing decay chains by Forsberg et al may lead to questionable conclusions when applied for the analysis of radioactive decays. Our discussion demonstrates reasonable congruence of α-particle energies and decay times of nuclei assigned to isotopes 289Mc, 285Nh and 281Rg observed in both reactions.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.

  7. 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.

  8. A fast BK-type KCa current acts as a postsynaptic modulator of temporal selectivity for communication signals

    Directory of Open Access Journals (Sweden)

    Tsunehiko eKohashi

    2014-09-01

    Full Text Available Temporal patterns of spiking often convey behaviorally relevant information. Various synaptic mechanisms and intrinsic membrane properties can influence neuronal selectivity to temporal patterns of input. However, little is known about how synaptic mechanisms and intrinsic properties together determine the temporal selectivity of neuronal output. We tackled this question by recording from midbrain electrosensory neurons in mormyrid fish, in which the processing of temporal intervals between communication signals can be studied in a reduced in vitro preparation. Mormyrids communicate by varying interpulse intervals (IPIs between electric pulses. Within the midbrain posterior exterolateral nucleus (ELp, the temporal patterns of afferent spike trains are filtered to establish single-neuron IPI tuning. We performed whole-cell recording from ELp neurons in a whole-brain preparation and examined the relationship between intrinsic excitability and IPI tuning. We found that spike frequency adaptation of ELp neurons was highly variable. Postsynaptic potentials (PSPs of strongly adapting (phasic neurons were more sharply tuned to IPIs than weakly adapting (tonic neurons. Further, the synaptic filtering of IPIs by tonic neurons was more faithfully converted into variation in spiking output, particularly at short IPIs. Pharmacological manipulation under current- and voltage-clamp revealed that tonic firing is mediated by a fast, large-conductance Ca2+-activated K+ (KCa current (BK that speeds up action potential repolarization. These results suggest that BK currents can shape the temporal filtering of sensory inputs by modifying both synaptic responses and PSP-to-spike conversion. Slow SK-type KCa currents have previously been implicated in temporal processing. Thus, both fast and slow KCa currents can fine-tune temporal selectivity.

  9. Local topology via the invariants of the velocity gradient tensor within vortex clusters and intense Reynolds stress structures in turbulent channel flow

    Science.gov (United States)

    Buchner, Abel-John; Lozano-Durán, Adrián; Kitsios, Vassili; Atkinson, Callum; Soria, Julio

    2016-04-01

    Previous works have shown that momentum transfer in the wall-normal direction within turbulent wall-bounded flows occurs primarily within coherent structures defined by regions of intense Reynolds stress [1]. Such structures may be classified into wall-attached and wall-detached structures with the latter being typically weak, small-scale, and isotropically oriented, while the former are larger and carry most of the Reynolds stresses. The mean velocity fluctuation within each structure may also be used to separate structures by their dynamic properties. This study aims to extract information regarding the scales, kinematics and dynamics of these structures within the topological framework of the invariants of the velocity gradient tensor (VGT). The local topological characteristics of these intense Reynolds stress structures are compared to the topological characteristics of vortex clusters defined by the discriminant of the velocity gradient tensor. The alignment of vorticity with the principal strain directions within these structures is also determined, and the implications of these findings are discussed.

  10. 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

  11. 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.

  12. Blockade of ATP-sensitive potassium channels prevents the attenuation of the exercise pressor reflex by tempol in rats with ligated femoral arteries.

    Science.gov (United States)

    Yamauchi, Katsuya; Stone, Audrey J; Stocker, Sean D; Kaufman, Marc P

    2012-08-01

    We reported previously that tempol attenuated the exercise pressor and muscle mechanoreceptor reflexes in rats whose femoral arteries were ligated, whereas tempol did not attenuate these reflexes in rats whose femoral arteries were freely perfused. Although the mechanism whereby tempol attenuated these reflexes in rats whose femoral artery was ligated was independent of its ability to scavenge reactive oxygen species, its nature remains unclear. An alternative explanation for the tempol-induced attenuation of these reflexes involves ATP-sensitive potassium channels (K(ATP)) and calcium-activated potassium channels (BK(Ca)), both of which are opened by tempol. We tested the likelihood of this explanation by measuring the effects of either glibenclamide (0.1 mg/kg), which blocks K(ATP) channels, or iberiotoxin (20 or 40 μg/kg), which blocks BK(Ca) channels, on the tempol-induced attenuation of the exercise pressor and muscle mechanoreceptor reflexes in decerebrated rats whose femoral arteries were ligated. We found that glibenclamide prevented the tempol-induced attenuation of both reflexes, whereas iberiotoxin did not. We also found that the amount of protein comprising the pore of the K(ATP) channel in the dorsal root ganglia innervating hindlimbs whose femoral artery was ligated was significantly greater than that in the dorsal root ganglia innervating hindlimbs whose femoral arteries were freely perfused. In contrast, the amounts of protein comprising the BK(Ca) channel in the dorsal root ganglia innervating the ligated and freely perfused hindlimbs were not different. We conclude that tempol attenuated both reflexes by opening K(ATP) channels, an effect that hyperpolarized muscle afferents stimulated by static contraction or tendon stretch.

  13. Stabilization of diastolic calcium signal via calcium pump regulation of complex local calcium releases and transient decay in a computational model of cardiac pacemaker cell with individual release channels.

    Directory of Open Access Journals (Sweden)

    Alexander V Maltsev

    2017-08-01

    Full Text Available Intracellular Local Ca releases (LCRs from sarcoplasmic reticulum (SR regulate cardiac pacemaker cell function by activation of electrogenic Na/Ca exchanger (NCX during diastole. Prior studies demonstrated the existence of powerful compensatory mechanisms of LCR regulation via a complex local cross-talk of Ca pump, release and NCX. One major obstacle to study these mechanisms is that LCR exhibit complex Ca release propagation patterns (including merges and separations that have not been characterized. Here we developed new terminology, classification, and computer algorithms for automatic detection of numerically simulated LCRs and examined LCR regulation by SR Ca pumping rate (Pup that provides a major contribution to fight-or-flight response. In our simulations the faster SR Ca pumping accelerates action potential-induced Ca transient decay and quickly clears Ca under the cell membrane in diastole, preventing premature releases. Then the SR generates an earlier, more synchronized, and stronger diastolic LCR signal activating an earlier and larger inward NCX current. LCRs at higher Pup exhibit larger amplitudes and faster propagation with more collisions to each other. The LCRs overlap with Ca transient decay, causing an elevation of the average diastolic [Ca] nadir to ~200 nM (at Pup = 24 mM/s. Background Ca (in locations lacking LCRs quickly decays to resting Ca levels (<100 nM at high Pup, but remained elevated during slower decay at low Pup. Release propagation is facilitated at higher Pup by a larger LCR amplitude, whereas at low Pup by higher background Ca. While at low Pup LCRs show smaller amplitudes, their larger durations and sizes combined with longer transient decay stabilize integrals of diastolic Ca and NCX current signals. Thus, the local interplay of SR Ca pump and release channels regulates LCRs and Ca transient decay to insure fail-safe pacemaker cell operation within a wide range of rates.

  14. Co-expression of mCysLT1 receptors and IK channels in Xenopus laevis oocytes elicits LTD4-stimulated IK current, independent of an increase in [Ca2+]i

    DEFF Research Database (Denmark)

    Wulff, Tune; Hougaard, Charlotte; Klaerke, Dan A

    2004-01-01

    Addition of LTD4 (10 nM) to Xenopus laevis oocytes expressing the mCysLT1 receptor together with hBK or hIK channels resulted in the activation of both channels secondary to an LTD4-induced increase in [Ca2+]i. In addition, the hIK channel is activated by low concentrations of LTD4 (0.1 nM), which...... to LTD4. Neither hTBAK1 nor hTASK2 was activated following stimulations with LTD4 (0.1 and 100 nM)....

  15. Incidence and outcome of BK polyomavirus infection in a multicenter randomized controlled trial with renal transplant patients receiving cyclosporine-, mycophenolate sodium-, or everolimus-based low-dose immunosuppressive therapy

    NARCIS (Netherlands)

    van Doesum, Willem B.; Gard, Lilli; Bemelman, Frederike J.; de Fijter, Johan W.; van der Heide, Jaap J. Homan; Niesters, Hubert G.; van Son, Willem J.; Stegeman, Coen A.; Groen, Henk; Riezebos-Brilman, Annelies; Sanders, Jan Stephan F.

    Background: It remains unclear whether overall degree of immunosuppression or specific effects of individual immunosuppressive agents are causal for increased occurrence of BK polyomavirus (BKPyV) infection in renal transplant recipients (RTR). Methods: A prospective, multicenter, open-label

  16. Incidence and outcome of BK polyomavirus infection in a multicenter randomized controlled trial with renal transplant patients receiving cyclosporine-, mycophenolate sodium-, or everolimus-based low-dose immunosuppressive therapy

    NARCIS (Netherlands)

    van Doesum, Willem B.; Gard, Lilli; Bemelman, Frederike J.; de Fijter, Johan W.; Homan van der Heide, Jaap J.; Niesters, Hubert G.; van Son, Willem J.; Stegeman, Coen A.; Groen, Henk; Riezebos-Brilman, Annelies; Sanders, Jan Stephan F.

    2017-01-01

    Background: It remains unclear whether overall degree of immunosuppression or specific effects of individual immunosuppressive agents are causal for increased occurrence of BK polyomavirus (BKPyV) infection in renal transplant recipients (RTR). Methods: A prospective, multicenter, open-label

  17. 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

  18. 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....

  19. Evaluation of the Genetic Variation of Non Coding Control Region of BK Virus Using Nested-PCR Sequencing Method in Renal Graft Patients

    Directory of Open Access Journals (Sweden)

    A Emami

    2015-05-01

    Full Text Available Background & aim: Polyomaviruses (BK is a comprehensive infection with more than of 80% prevalence in the world. One of the most important reasons of BK virus nephropathy is in the renal transplant recipients and rejection of transplanted tissue between them. Non Coding region of this virus play a regulatory role in replication and amplification of the virus. The aim of this study was to evaluate the genetic patterns of this area in renal graft at Namazi Transplantation Center, Shiraz, Iran. Methods: In the present experimental study, 380 renal allograft serums were collected. DNAs of 129 eligible samples were extracted and evaluated using a virus genome. The presence of the virus was determined by qualitative and sequencing. Of these, 129 samples were tested for the presence of virus according to the condition study, using quantitative, qualitative genomic amplification and sequencing. Results: The study showed symptoms of nephropathy, 76 (58.9% of them were males and 46 (35.7% were females with the mean age 38.0±.089 years of age. In general, 46 patients (35.7% percent were positive for BK Polyomaviruses. After comparing the genomic sequence with applications of molecular they were categorized in three groups and then recorded in gene bank. Conclusion: About 35% of renal transplant recipients with high creatinine levels were positive for the presence of BK virus. Non-coding region of respondents in the sample survey revealed that among patients with the most common genotypes were rearranged the entire transplant patients were observed at this tranplant center. Examination of these sequences indicated that this rearrangments had a specific pattern, different from the standard strain of archaea type.

  20. Growth of bultfonteinite and hydrogarnet in metasomatized basalt xenoliths in the B/K9 kimberlite, Damtshaa, Botswana: insights into hydrothermal metamorphism in kimberlite pipes

    Science.gov (United States)

    Buse, Ben; Schumacher, John C.; Sparks, R. Stephen J.; Field, Matthew

    2010-10-01

    Metamorphic assemblages within Karoo basalt xenoliths, found within volcaniclastic kimberlite of the B/K9 pipe, Damtshaa, Botswana, constrain conditions of kimberlite alteration. Bultfonteinite and chlorite partially replace the original augite-plagioclase assemblage, driven by the serpentinisation of the kimberlite creating strong chemical potential gradients for Si and Mg. Hydrogarnet and serpentine replace these earlier metamorphic assemblages as the deposits cool. The bultfonteinite (ideally Ca2SiO2[OH,F]4) and hydrogarnet assemblages require a water-rich fluid containing F-, and imply hydrothermal alteration dominated by external fluids rather than autometamorphism from deuteric fluids. Bultfonteinite and hydrogarnet are estimated to form at temperatures of ca. 350-250°C, which are similar to those for serpentinisation. Alteration within the B/K9 kimberlite predominantly occurs between 250 and 400°C. We attribute these conditions to increased efficiency of mass transfer and chemical reactions below the critical point of water and a consequence of volume-increasing serpentinisation and metasomatic reactions that take place over this temperature range. A comparison of the B/K9 kimberlite with kimberlites from Venetia, South Africa suggests that the composition and mineralogy of included xenoliths affects the alteration assemblages within kimberlite deposits.

  1. Development of a clone from established Bovine Kidney (BK cell line and evaluation of its sensitivity to Parainfluenza type 3 and Herpes Simplex type 1 viruses.

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    Yashar Mohammadzadeh sedigh

    2009-09-01

    Full Text Available Background: Application of continuous cell lines has got a special place in the virological researches. These cells are immortal and their chromosomes are aneuploid. Therefore, they can be passage without any limitation. The aim of this research was to choose the best way of producing clone of cells. Methods: in this study, Bovine Kidney (BK cell line was used to be cloned through limiting dilution method in which Vero cells were used as feeder layer. Vero cells were first cultured in DMEM supplimented with 7% heat inactivated calf serum and after a monolayer were formed, their growth was arrested by Mitomycin C. The cloned cells after incubation were separated and cultured in a new flask. After several experiments different clones were obtained and cultured for further studies. Results: Karyotype of clone cells were determined and compared with original cells. It was shown that cloned cells were more homogenous in early passages and their karyotypes showed less variability than original ones. Cloned and original cells were inoculated with HSV-1 and Parainfluenza virus 3 in order to evaluate its biological abilities. Tissue culture of infectious dose 50 (TCID50 of each virus was calculated and it was shown that there was no significant different between the HSV-1 titers before and after cloning whereas the titer of the Parainfluenza virus 3 was significantly higher in the original cells. Conclusions: Cloned cells of BK showed more stable karyotype and were less sensitive to parainfluenza type-3 virus infection than original BK cells.

  2. Incidence and outcome of BK polyomavirus infection in a multicenter randomized controlled trial with renal transplant patients receiving cyclosporine-, mycophenolate sodium-, or everolimus-based low-dose immunosuppressive therapy.

    Science.gov (United States)

    van Doesum, Willem B; Gard, Lilli; Bemelman, Frederike J; de Fijter, Johan W; Homan van der Heide, Jaap J; Niesters, Hubert G; van Son, Willem J; Stegeman, Coen A; Groen, Henk; Riezebos-Brilman, Annelies; Sanders, Jan Stephan F

    2017-06-01

    It remains unclear whether overall degree of immunosuppression or specific effects of individual immunosuppressive agents are causal for increased occurrence of BK polyomavirus (BKPyV) infection in renal transplant recipients (RTR). A prospective, multicenter, open-label randomized controlled trial in 361 de novo RTR was performed. A total of 224 RTR were randomized at 6 months into three treatment groups with dual therapy consisting of prednisolone (Pred) plus either cyclosporine (CsA), mycophenolate sodium (MPS), or everolimus (EVL). Primary outcomes were incidence of BK viruria, BK viremia, and BKPyV-associated nephropathy (BKVAN). From 6 months, incidence of BK viruria in the MPS group (43.6%) was significantly higher than in the other groups (CsA: 16.9%, EVL: 19.8%) (P=.003). BKVAN was diagnosed in 3 patients, all treated with MPS (7.8%, P=.001). Longitudinal data analysis showed a lower BKPyV load and a significantly faster clearance of BK viruria in the CsA group compared to the MPS group (P=.03). Treatment with MPS was associated with an increased incidence of BK viruria. Dual immunosuppressive therapy with CsA and Pred was associated with the lowest rate of BKPyV replication and the fastest clearance of the virus. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. High-frequency vibration effects on hole entrance chipping in rotary ultrasonic drilling of BK7 glass.

    Science.gov (United States)

    Lv, Dongxi; Zhang, Yuanming; Peng, Yunfeng

    2016-12-01

    This present investigation exhibited some fundamental information about the influence of the high-frequency vibration on the hole entrance chipping formation involved in rotary ultrasonic drilling (RUD) of BK7 glass process. The entrance chipping morphologies, produced with and without ultrasonic, were observed and evaluated with respect to the fracture mechanics of brittle material. Giving consideration to the variation characteristics of the plastic deformation region in the interior material induced by the specific kinematics principles of the abrasive, the ultrasonic effects on the chipping formation mechanisms were investigated by assessing the groove morphologies obtained in the scratching experiment utilizing the formation mechanisms of the lateral cracking. Furthermore, the formal confirmatory tests with and without ultrasonic were performed to validate these chipping formation mechanisms. It was found that the plastic deformed region reached its maximum at the trajectory bottom. Moreover, the propagation of the lateral cracking initially nucleated at the bottom of the ductile deformation zone resulted in the formation of the entrance chipping in formal RUD process. The slight deformation of the material at the two terminals of each groove produced with ultrasonic would provide the inhibitory effects to the further extending of the lateral cracks, which would shrink with the increased spindle speed, and the inhibitory effect dominated in determining the improvement effects on the hole entrance quality. Additionally, a theoretical relationship between the nucleation depth and the propagation length of the lateral cracking was developed for the conventional drilling (CD) process. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Prevalence of JC and BK polyomavirus excretion in the urine of HIV-infected patients from Serbia

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    Karalić Danijela

    2014-01-01

    Full Text Available BK virus (BKV and JC virus (JCV persist as latent infection in the kidneys. Reactivation of both viruses may be linked to immunodeficiency. The aims of this study were to determine the prevalence of BKV and JCV viruria and to evaluate the relationship between immunodeficiency and viruria in a cohort of HIV-infected patients. Urine samples from 93 HIV-infected patients were collected and tested for the presence of BKV and JCV DNA by PCR. The overall prevalence of polyomavirus DNA in urine was 74.2%. BKV DNA was detected in 30.1% urine samples and JCV DNA in 23.7% samples. Both BKV and JCV DNA were detected in 20.4% samples. There was no association between BKV/JCV urinary shedding and the degree of immunosuppression measured by CD4+ cell count. However, taking into account the severity of disease resulting from reactivation of BKV and JCV, patients with HIV/polyomavirus co-infection should be kept under frequent and regular supervision. [Projekat Ministarstva nauke Republike Srbije, br. 175073

  5. 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.

  6. 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.

  7. Analysis of the action of lidocaine on insect sodium channels

    OpenAIRE

    Song, Weizhong; Silver, Kristopher S.; Du, Yuzhe; Liu, Zhiqi; Dong, Ke

    2010-01-01

    A new class of sodium channel blocker insecticides (SCBIs), which include indoxacarb, its active metabolite, DCJW, and metaflumizone, preferably block inactivated states of both insect and mammalian sodium channels in a manner similar to that by which local anesthetic (LA) drugs block mammalian sodium channels. A recent study showed that two residues in the cockroach sodium channel, F1817 and Y1824, corresponding to two key LA-interacting residues identified in mammalian sodium channels are n...

  8. Angioedema attacks in patients with hereditary angioedema: Local manifestations of a systemic activation process.

    Science.gov (United States)

    Hofman, Zonne L M; Relan, Anurag; Zeerleder, Sacha; Drouet, Christian; Zuraw, Bruce; Hack, C Erik

    2016-08-01

    Hereditary angioedema (HAE) caused by a deficiency of functional C1-inhibitor (C1INH) becomes clinically manifest as attacks of angioedema. C1INH is the main inhibitor of the contact system. Poor control of a local activation process of this system at the site of the attack is believed to lead to the formation of bradykinin (BK), which increases local vasopermeability and mediates angioedema on interaction with BK receptor 2 on the endothelium. However, several observations in patients with HAE are difficult to explain from a pathogenic model claiming a local activation process at the site of the angioedema attack. Therefore we postulate an alternative model for angioedema attacks in patients with HAE, which assumes a systemic, fluid-phase activation of the contact system to generate BK and its breakdown products. Interaction of these peptides with endothelial receptors that are locally expressed in the affected tissues rather than with receptors constitutively expressed by the endothelium throughout the whole body explains that such a systemic activation process results in local manifestations of an attack. In particular, BK receptor 1, which is induced on the endothelium by inflammatory stimuli, such as kinins and cytokines, meets the specifications of the involved receptor. The pathogenic model discussed here also provides an explanation for why angioedema can occur at multiple sites during an attack and why HAE attacks respond well to modest increases of circulating C1INH activity levels because inhibition of fluid-phase Factor XIIa and kallikrein requires lower C1INH levels than inhibition of activator-bound factors. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  9. 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.

  10. Dynamic Channel Allocation

    Science.gov (United States)

    2003-09-01

    21 9. Beowulf Ethernet Channel Bonding.................................................22 F. SUMMARY...on demand, hybrid channel allocation in wireless networks, and 3 Beowulf Ethernet channel bonding. The background information presented in this...channels are available for dynamic allocation [Ref 32]. 9. Beowulf Ethernet Channel Bonding A by-product of using older computers in a NASA research lab

  11. Upregulation of the sodium channel NaVβ4 subunit and its contributions to mechanical hypersensitivity and neuronal hyperexcitability in a rat model of radicular pain induced by local DRG inflammation

    Science.gov (United States)

    Xie, Wenrui; Tan, Zhi-Yong; Barbosa, Cindy; Strong, Judith A.; Cummins, Theodore R.; Zhang, Jun-Ming

    2016-01-01

    High frequency spontaneous firing in myelinated sensory neurons plays a key role in initiating pain behaviors in several different models, including the radicular pain model in which the rat lumbar dorsal root ganglia (DRG) are locally inflamed. The sodium channel isoform NaV1.6 contributes to pain behaviors and spontaneous activity in this model. Among all the isoforms in adult DRG, NaV1.6 is the main carrier of TTX-sensitive resurgent Na currents that allow high-frequency firing. Resurgent currents flow after a depolarization or action potential, as a blocking particle exits the pore. In most neurons the regulatory β4 subunit is potentially the endogenous blocker. We used in vivo siRNA mediated knockdown of NaVβ4 to examine its role in the DRG inflammation model. NaVβ4 but not control siRNA almost completely blocked mechanical hypersensitivity induced by DRG inflammation. Microelectrode recordings in isolated whole DRGs showed that NaVβ4 siRNA blocked the inflammation-induced increase in spontaneous activity of Aβ neurons, and reduced repetitive firing and other measures of excitability. NaVβ4 was preferentially expressed in larger diameter cells; DRG inflammation increased its expression and this was reversed by NaVβ4 siRNA, based on immunohistochemistry and Western blotting. NaVβ4 siRNA also reduced immunohistochemical NaV1.6 expression. Patch clamp recordings of TTX-sensitive Na currents in acutely cultured medium diameter DRG neurons showed that DRG inflammation increased transient and especially resurgent current; effects blocked by NaVβ4 siRNA. NaVβ4 may represent a more specific target for pain conditions that depend on myelinated neurons expressing NaV1.6. PMID:26785322

  12. Upregulation of the sodium channel NaVβ4 subunit and its contributions to mechanical hypersensitivity and neuronal hyperexcitability in a rat model of radicular pain induced by local dorsal root ganglion inflammation.

    Science.gov (United States)

    Xie, Wenrui; Tan, Zhi-Yong; Barbosa, Cindy; Strong, Judith A; Cummins, Theodore R; Zhang, Jun-Ming

    2016-04-01

    High-frequency spontaneous firing in myelinated sensory neurons plays a key role in initiating pain behaviors in several different models, including the radicular pain model in which the rat lumbar dorsal root ganglia (DRG) are locally inflamed. The sodium channel isoform NaV1.6 contributes to pain behaviors and spontaneous activity in this model. Among all isoforms in adult DRG, NaV1.6 is the main carrier of tetrodotoxin-sensitive resurgent Na currents that allow high-frequency firing. Resurgent currents flow after a depolarization or action potential, as a blocking particle exits the pore. In most neurons, the regulatory β4 subunit is potentially the endogenous blocker. We used in vivo siRNA-mediated knockdown of NaVβ4 to examine its role in the DRG inflammation model. NaVβ4 but not control siRNA almost completely blocked mechanical hypersensitivity induced by DRG inflammation. Microelectrode recordings in isolated whole DRG showed that NaVβ4 siRNA blocked the inflammation-induced increase in spontaneous activity of Aβ neurons and reduced repetitive firing and other measures of excitability. NaVβ4 was preferentially expressed in larger diameter cells; DRG inflammation increased its expression, and this was reversed by NaVβ4 siRNA, based on immunohistochemistry and Western blotting. NaVβ4 siRNA also reduced immunohistochemical NaV1.6 expression. Patch-clamp recordings of tetrodotoxin-sensitive Na currents in acutely cultured medium diameter DRG neurons showed that DRG inflammation increased transient and especially resurgent current, effects blocked by NaVβ4 siRNA. NaVβ4 may represent a more specific target for pain conditions that depend on myelinated neurons expressing NaV1.6.

  13. Human polyomaviruses JC and BK in the urine of Brazilian children and adolescents vertically infected by HIV

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    Daisy Maria Machado

    2011-12-01

    Full Text Available The aim of this study was to characterize the urinary excretion of the BK (BKV and JC (JCV human polyomaviruses in a cohort of human immunodeficiency virus (HIV-infected children and adolescents. One hundred and fifty-six patients were enrolled: Group I included 116 HIV-infected children and adolescents [median age = 11.4 years (y; range 1-22 y]; Group II included 40 non-HIV-infected healthy controls (median age = 11.37 y; range 7-16 y. Single urine samples from both groups were screened for the presence of JCV and BKV DNA by polymerase chain reaction at enrolment. The overall rate of JCV and BKV urinary excretion was found to be 24.4% and 40.4%, respectively (n = 156. Group I had urinary excretion of JCV and BKV in 27.6% and 54.3% of subjects, respectively. In contrast, Group II showed positive results for JCV in 17.5% of subjects and for BKV in 12.5% of subjects (p Pearson JCV = 0.20; p Pearson BKV < 0.0001. In Group I, there was no association between JCV/BKV shedding and age, gender or CD4 values. Patients with an HIV viral load < 50 copies/mL had a lower excretion of BKV (p < 0.001 and a trend of lower JCV excretion (p = 0.07. One patient in Group I (1/116, 0.9% showed clinical and radiological features consistent with progressive multifocal leukoencephalopathy, suggesting that children with HIV/polyomavirus coinfection should be kept under surveillance.

  14. Computed Tomography Findings of Human Polyomavirus BK (BKV)-Associated Cystitis in Allogeneic Hematopoietic Stem Cell Transplant Recipients

    International Nuclear Information System (INIS)

    Schulze, M.; Beck, R.; Igney, A.; Vogel, M.; Maksimovic, O.; Claussen, C.D.; Faul, C.; Horger, M.

    2008-01-01

    Background: Over 70% of the general population worldwide is positive for antibodies against polyomavirus hominis type 1 (BKV). Polyomavirus can be reactivated in immunocompromised patients and thereby induce urogenital tract infection, including cystitis. Purpose: To describe the computed tomography (CT) findings of human polyomavirus-induced cystitis in adult patients after allogeneic hematopoietic stem cell transplantation (allogeneic HCT). Material and Methods: The study population was a retrospective cohort of 11 consecutive adult patients (eight men, three women; age range 22-59 years, mean 42.9 years) who received allogeneic HCT between December 2003 and December 2007 and were tested positive for urinary BKV infection. All CT scans were evaluated with regard to bladder wall thickness, mucosal enhancement, distinct layering of thickened bladder wall, and presence of intravesical clots, perivesical stranding as well as attenuation values of intravesical urine. Clinical data concerning transplant and conditioning regimen variables and laboratory parameters were correlated with degree and extent of imaging findings. Results: All patients had clinical signs of cystitis with different degrees of thickening of the urinary bladder wall. Well-delineated urinary bladder layers were present in six patients. Thickening of the urinary bladder wall was continuous in nine of 11 patients. Increased attenuation of intravesical urine was found in seven patients with hemorrhagic cystitis. Four patients had intraluminal clots. Perivesical stranding was not a major CT finding, occurring in a mild fashion in three of 11 patients. The clinical classification of hemorrhagic cystitis did not correlate with the analyzed imaging parameters. Patient outcome was not influenced by this infectious complication. Conclusion: CT findings in patients with polyomavirus BK cystitis consist of different degrees of bladder wall thickening usually with good delineation of all mural layers and

  15. Computed Tomography Findings of Human Polyomavirus BK (BKV)-Associated Cystitis in Allogeneic Hematopoietic Stem Cell Transplant Recipients

    Energy Technology Data Exchange (ETDEWEB)

    Schulze, M.; Beck, R.; Igney, A.; Vogel, M.; Maksimovic, O.; Claussen, C.D.; Faul, C.; Horger, M. [Dept. of Diagnostic Radiology, Dept. of Internal Medicine-Oncology, and Inst. of Medical Virology, Eberhard-Karls Univ., Tbingen (Germany)

    2008-12-15

    Background: Over 70% of the general population worldwide is positive for antibodies against polyomavirus hominis type 1 (BKV). Polyomavirus can be reactivated in immunocompromised patients and thereby induce urogenital tract infection, including cystitis. Purpose: To describe the computed tomography (CT) findings of human polyomavirus-induced cystitis in adult patients after allogeneic hematopoietic stem cell transplantation (allogeneic HCT). Material and Methods: The study population was a retrospective cohort of 11 consecutive adult patients (eight men, three women; age range 22-59 years, mean 42.9 years) who received allogeneic HCT between December 2003 and December 2007 and were tested positive for urinary BKV infection. All CT scans were evaluated with regard to bladder wall thickness, mucosal enhancement, distinct layering of thickened bladder wall, and presence of intravesical clots, perivesical stranding as well as attenuation values of intravesical urine. Clinical data concerning transplant and conditioning regimen variables and laboratory parameters were correlated with degree and extent of imaging findings. Results: All patients had clinical signs of cystitis with different degrees of thickening of the urinary bladder wall. Well-delineated urinary bladder layers were present in six patients. Thickening of the urinary bladder wall was continuous in nine of 11 patients. Increased attenuation of intravesical urine was found in seven patients with hemorrhagic cystitis. Four patients had intraluminal clots. Perivesical stranding was not a major CT finding, occurring in a mild fashion in three of 11 patients. The clinical classification of hemorrhagic cystitis did not correlate with the analyzed imaging parameters. Patient outcome was not influenced by this infectious complication. Conclusion: CT findings in patients with polyomavirus BK cystitis consist of different degrees of bladder wall thickening usually with good delineation of all mural layers and

  16. Computed Tomography Findings of Human Polyomavirus BK (BKV)-Associated Cystitis in Allogeneic Hematopoietic Stem Cell Transplant Recipients

    Energy Technology Data Exchange (ETDEWEB)

    Schulze, M.; Beck, R.; Igney, A.; Vogel, M.; Maksimovic, O.; Claussen, C.D.; Faul, C.; Horger, M. (Dept. of Diagnostic Radiology, Dept. of Internal Medicine-Oncology, and Inst. of Medical Virology, Eberhard-Karls Univ., Tbingen (Germany))

    2008-12-15

    Background: Over 70% of the general population worldwide is positive for antibodies against polyomavirus hominis type 1 (BKV). Polyomavirus can be reactivated in immunocompromised patients and thereby induce urogenital tract infection, including cystitis. Purpose: To describe the computed tomography (CT) findings of human polyomavirus-induced cystitis in adult patients after allogeneic hematopoietic stem cell transplantation (allogeneic HCT). Material and Methods: The study population was a retrospective cohort of 11 consecutive adult patients (eight men, three women; age range 22-59 years, mean 42.9 years) who received allogeneic HCT between December 2003 and December 2007 and were tested positive for urinary BKV infection. All CT scans were evaluated with regard to bladder wall thickness, mucosal enhancement, distinct layering of thickened bladder wall, and presence of intravesical clots, perivesical stranding as well as attenuation values of intravesical urine. Clinical data concerning transplant and conditioning regimen variables and laboratory parameters were correlated with degree and extent of imaging findings. Results: All patients had clinical signs of cystitis with different degrees of thickening of the urinary bladder wall. Well-delineated urinary bladder layers were present in six patients. Thickening of the urinary bladder wall was continuous in nine of 11 patients. Increased attenuation of intravesical urine was found in seven patients with hemorrhagic cystitis. Four patients had intraluminal clots. Perivesical stranding was not a major CT finding, occurring in a mild fashion in three of 11 patients. The clinical classification of hemorrhagic cystitis did not correlate with the analyzed imaging parameters. Patient outcome was not influenced by this infectious complication. Conclusion: CT findings in patients with polyomavirus BK cystitis consist of different degrees of bladder wall thickening usually with good delineation of all mural layers and

  17. Treatment for presumed BK polyomavirus nephropathy and risk of urinary tract cancers among kidney transplant recipients in the United States.

    Science.gov (United States)

    Gupta, Gaurav; Kuppachi, Sarat; Kalil, Roberto S; Buck, Christopher B; Lynch, Charles F; Engels, Eric A

    2018-01-01

    Recent case series describe detection of BK polyomavirus (BKV) in urinary tract cancers in kidney transplant recipients, suggesting that BKV could contribute to the development of these cancers. We assessed risk for urinary tract cancers in kidney recipients with or without treatment for presumed BKV nephropathy (tBKVN) using data from the United States Transplant Cancer Match Study (2003-2013). Among 55 697 included recipients, 2015 (3.6%) were reported with tBKVN. Relative to the general population, incidence was similarly elevated (approximately 4.5-fold) for kidney cancer in recipients with or without tBKVN, and incidence was not increased in either group for prostate cancer. In contrast, for invasive bladder cancer, incidence was more strongly elevated in recipients with versus without tBKVN (standardized incidence ratios 4.5 vs. 1.7; N = 48 cases), corresponding to an incidence rate ratio (IRR) of 2.9 (95% confidence interval [CI] 1.0-8.2), adjusted for sex, age, transplant year, and use of polyclonal antibody induction. As a result, recipients with tBKVN had borderline increased incidence for all urothelial cancers combined (renal pelvis, ureter, and bladder cancers: adjusted IRR 2.2, 95% CI 0.9-5.4; N = 89 cases). Together with reports describing BKV detection in tumor tissues, these results support an association between BKV and urothelial carcinogenesis among kidney transplant recipients. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  18. Investigation of BK virus, Epstein-Barr virus and human papillomavirus sequences in postoperative thyroid gland specimens.

    Science.gov (United States)

    Stamatiou, Dimitris; Derdas, Stavros P; Symvoulakis, Emmanouil K; Sakorafas, Georgios H; Zoras, Odysseas; Spandidos, Demetrios A

    2015-02-24

    Although recent evidence has implicated viruses in the regulation of epithelial-to-mesenchymal transition and tumor progression, little is known regarding viral infections in thyroid malignancies. Thus the aim of this study was to detect sequences of 3 potentially oncogenic viruses - BK virus (BKV), Epstein-Barr virus (EBV) and human papillomavirus (HPV) - in a series of postoperative thyroid gland specimens. Thirty patients with thyroid nodules who underwent surgery for thyroid disease within a 3-year period were enrolled. Both nodular and adjacent normal thyroid tissue was surgically excised from each patient. Viral gene sequences of BKV (VP1), EBV (LMP1, EBNA2 and EBER1) and HPV were amplified by PCR. The PCR results were confirmed by direct sequencing analysis. VP1 gene sequences were detected in 60% (18/30) of thyroid cancer or multinodular hyperplasia lesions compared with in 43.3% (13/30) of adjacent normal thyroid tissue specimens. Fifteen of thirty (50%) of thyroid cancer or multinodular hyperplasia samples revealed LMP1 sequences compared with 46.7% (14/30) of corresponding normal thyroid tissues. EBNA2 gene sequences were detected in 90% (27/30) of thyroid cancer or multinodular hyperplasia samples, compared with 90% (27/30) of adjacent normal thyroid tissue specimens. All samples were negative for EBER1 sequences, while HPV DNA was not detected in either nodular or normal thyroid tissue. This study suggests that BKV and EBV "infection" is an early event, occurring within normal tissue. Our findings do not show a clear role for the viruses examined, instead they suggest an "endemicity" pattern rather than a causal effect.

  19. On the dynamics of the Zanzibar Channel

    Science.gov (United States)

    Zavala-Garay, J.; Theiss, J.; Moulton, M.; Walsh, C.; van Woesik, R.; Mayorga-Adame, C. G.; García-Reyes, M.; Mukaka, D. S.; Whilden, K.; Shaghude, Y. W.

    2015-09-01

    The Zanzibar Channel lies between the mainland of Tanzania and Zanzibar Island in the tropical western Indian Ocean, is about 100 km long, 40 km wide, and 40 m deep, and is essential to local socioeconomic activities. This paper presents a model of the seasonal and tidal dynamics of the Zanzibar Channel based on the Regional Ocean Modeling System (ROMS) and a comparison of the model and observations. The seasonal dynamics of the channel is forced by remote processes and the local wind. Remote forcing creates the East African Coastal Current, a portion of which flows through the channel northward with a seasonally varying magnitude. The local wind enhances this seasonality in the surface Ekman layer, resulting in a stronger northward flow during the southwest monsoon season and a weak northward or occasionally southward flow during the northeast monsoon season. The tidal flows converge and diverge in the center of the channel and reduce the transport in the channel. The remotely forced, wind-forced, and tidal dynamics contain 5%, 3%, and 92% of the total kinetic energy, respectively. Despite their low kinetic energy, the remotely forced and wind-forced flows are most relevant in advecting channel water to the open ocean, which occurs in 19 days at the peak of the southwest monsoon season. The channel is well mixed, except during brief periods in the two rainy seasons, and temporarily cools between December and February. The dispersion of passive tracers is presented as an example of potential model applications.

  20. Cross-reactivity of acid-sensing ion channel and Na+–H+ exchanger antagonists with nicotinic acetylcholine receptors

    Science.gov (United States)

    Santos-Torres, Julio; Ślimak, Marta A; Auer, Sebastian; Ibañez-Tallon, Inés

    2011-01-01

    Abstract Nicotinic acetylcholine receptors (nAChRs) are widely distributed throughout the mammalian central and peripheral nervous systems, where they contribute to neuronal excitability and synaptic communication. It has been reported that nAChRs are modulated by BK channels and that BK channels, in turn, are inhibited by acid-sensing ion channels (ASICs). Here we investigate the possible functional interaction between these channels in medial habenula (MHb) neurones. We report that selective antagonists of large-conductance calcium-activated potassium channels and ASIC1a channels, paxilline and psalmotoxin 1, respectively, did not induce detectable changes in nicotine-evoked currents. In contrast, the non-selective ASIC and Na+–H+ exchanger (NHE1) antagonists, amiloride and its analogues, suppressed nicotine-evoked responses in MHb neurones of wild-type and ASIC2 null mice, excluding a possible involvement of ASIC2 in the nAChR inhibition by amiloride. Zoniporide, a more selective inhibitor of NHE1, reversibly inhibited α3β4-, α7- and α4-containing (*) nAChRs in Xenopus oocytes and in brain slices, as well as in PS120 cells deficient in NHE1 and virally transduced with nAChRs, suggesting a generalized effect of zoniporide in most neuronal nAChR subtypes. Independently from nAChR antagonism, zoniporide profoundly blocked synaptic transmission onto MHb neurones without affecting glutamatergic and GABA receptors. Taken together, these results indicate that amiloride and zoniporide, which are clinically used to treat hypertension and cardiovascular disease, have an inhibitory effect on neuronal nAChRs when used experimentally at high doses. The possible cross-reactivity of these compounds with nAChRs in vivo will require further investigation. PMID:21911609

  1. VKCDB: Voltage-gated potassium channel database

    Directory of Open Access Journals (Sweden)

    Gallin Warren J

    2004-01-01

    Full Text Available Abstract Background The family of voltage-gated potassium channels comprises a functionally diverse group of membrane proteins. They help maintain and regulate the potassium ion-based component of the membrane potential and are thus central to many critical physiological processes. VKCDB (Voltage-gated potassium [K] Channel DataBase is a database of structural and functional data on these channels. It is designed as a resource for research on the molecular basis of voltage-gated potassium channel function. Description Voltage-gated potassium channel sequences were identified by using BLASTP to search GENBANK and SWISSPROT. Annotations for all voltage-gated potassium channels were selectively parsed and integrated into VKCDB. Electrophysiological and pharmacological data for the channels were collected from published journal articles. Transmembrane domain predictions by TMHMM and PHD are included for each VKCDB entry. Multiple sequence alignments of conserved domains of channels of the four Kv families and the KCNQ family are also included. Currently VKCDB contains 346 channel entries. It can be browsed and searched using a set of functionally relevant categories. Protein sequences can also be searched using a local BLAST engine. Conclusions VKCDB is a resource for comparative studies of voltage-gated potassium channels. The methods used to construct VKCDB are general; they can be used to create specialized databases for other protein families. VKCDB is accessible at http://vkcdb.biology.ualberta.ca.

  2. 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.

  3. 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.

  4. New Channels, New Possibilities

    DEFF Research Database (Denmark)

    Pieterson, Willem; Ebbers, Wolfgang; Østergaard Madsen, Christian

    2017-01-01

    In this contribution we discuss the characteristics of what we call the fourth generation of public sector service channels: social robots. Based on a review of relevant literature we discuss their characteristics and place into multi-channel models of service delivery. We argue that social robots...... is not one homogenous type of channels, but rather breaks down in different (sub)types of channels, each with different characteristics and possibilities to supplement and/or replace existing channels. Given the variety of channels, we foresee challenges in incorporating these new channels in multi-channel...... models of service delivery. This is especially relevant given the current lack of evaluations of such models, the broad range of channels available, and their different stages of deployment at governments around the world. Nevertheless, social robots offer an potentially very relevant addition...

  5. Hadamard quantum broadcast channels

    Science.gov (United States)

    Wang, Qingle; Das, Siddhartha; Wilde, Mark M.

    2017-10-01

    We consider three different communication tasks for quantum broadcast channels, and we determine the capacity region of a Hadamard broadcast channel for these various tasks. We define a Hadamard broadcast channel to be such that the channel from the sender to one of the receivers is entanglement-breaking and the channel from the sender to the other receiver is complementary to this one. As such, this channel is a quantum generalization of a degraded broadcast channel, which is well known in classical information theory. The first communication task we consider is classical communication to both receivers, the second is quantum communication to the stronger receiver and classical communication to other, and the third is entanglement-assisted classical communication to the stronger receiver and unassisted classical communication to the other. The structure of a Hadamard broadcast channel plays a critical role in our analysis: The channel to the weaker receiver can be simulated by performing a measurement channel on the stronger receiver's system, followed by a preparation channel. As such, we can incorporate the classical output of the measurement channel as an auxiliary variable and solve all three of the above capacities for Hadamard broadcast channels, in this way avoiding known difficulties associated with quantum auxiliary variables.

  6. What controls sediment flux in dryland channels?

    Science.gov (United States)

    Michaelides, K.; Singer, M. B.

    2010-12-01

    Theories for the development of longitudinal and grain size profiles in perennial fluvial systems are well developed, allowing for generalization of sediment flux and sorting in these fluvial systems over decadal to millennial time scales under different forcings (e.g., sediment supply, climate changes, etc). However, such theoretical frameworks are inadequate for understanding sediment flux in dryland channels subject to spatially and temporally discontinuous streamflow, where transport capacity is usually much lower than sediment supply. In such fluvial systems, channel beds are poorly sorted with weak vertical layering, poorly defined bar forms, minimal downstream fining, and straight longitudinal profiles. Previous work in dryland channels has documented sediment flux at higher rates than their humid counterparts once significant channel flow develops, pulsations in bed material transport under constant discharge, and oscillations in dryland channel width that govern longitudinal patterns in erosion and deposition. These factors point to less well appreciated controls on sediment flux in dryland valley floors that invite further study. This paper investigates the relative roles of hydrology, bed material grain size, and channel width on sediment flux rates in the Rambla de Nogalte in southeastern Spain. Topographic valley cross sections and hillslope and channel particle sizes were collected from an ephemeral-river reach. Longitudinal grain-size variation on the hillslopes and on the channel bed were analysed in order to determine the relationship between hillslope supply characteristics and channel grain-size distribution and longitudinal changes. Local fractional estimates of bed-material transport in the channel were calculated using a range of channel discharge scenarios in order to examine the effect of channel hydrology on sediment transport. Numerical modelling was conducted to investigate runoff connectivity from hillslopes to channel and to examine the

  7. Calcium Channel Blockers

    Science.gov (United States)

    ... conditions, such as Raynaud's disease For people of African heritage and older people, calcium channel blockers might ... high-blood-pressure/in-depth/calcium-channel-blockers/ART-20047605 . Mayo Clinic Footer Legal Conditions and Terms ...

  8. 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

  9. Anestésicos locais: interação com membranas biológicas e com o canal de sódio voltagem-dependente Local anesthetics: interaction with biological membranes and with the voltage-gated sodium channel

    Directory of Open Access Journals (Sweden)

    Daniele Ribeiro de Araujo

    2008-01-01

    Full Text Available Many theories about the mechanism of action of local anesthetics (LA are described in the literature. Two types of theories can be distinguished: those that focus on the direct effects of LA on their target protein in the axon membranes, i.e. the voltage-gated sodium channel and the ones that take into account the interaction of anesthetic molecules with the lipid membrane phase for the reversible nerve blockage. Since there is a direct correlation between LA hydrophobicity and potency, it is crucial to take this physico-chemical property into account to understand the mechanism of action of LA, be it on the sodium channel protein, lipid(s, or on the whole membrane phase.

  10. KV7 potassium channels

    DEFF Research Database (Denmark)

    Stott, Jennifer B; Jepps, Thomas Andrew; Greenwood, Iain A

    2014-01-01

    Potassium channels are key regulators of smooth muscle tone, with increases in activity resulting in hyperpolarisation of the cell membrane, which acts to oppose vasoconstriction. Several potassium channels exist within smooth muscle, but the KV7 family of voltage-gated potassium channels have been...

  11. 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)

  12. Channel morphology [Chapter 5

    Science.gov (United States)

    Jonathan W. Long; Alvin L. Medina; Daniel G. Neary

    2012-01-01

    Channel morphology has become an increasingly important subject for analyzing the health of rivers and associated fish populations, particularly since the popularization of channel classification and assessment methods. Morphological data can help to evaluate the flows of sediment and water that influence aquatic and riparian habitat. Channel classification systems,...

  13. Business Models for Local Foods

    DEFF Research Database (Denmark)

    Esbjerg, Lars; Pedersen, Maja; Pederson, Robert

    2014-01-01

    Interest in local foods is growing, but there has been limited research on who and why producers of local foods thrive or struggle. A particularly important problem for local food producers is how to reach end consumers, as they often find it difficult to work with the retail chains that dominate...... sales of food products (and vice versa) and therefore have to develop alternative marketing channels. The purpose of this paper is to investigate the practices of different small and medium-sized Danish producers of locally grown and/or processed foods in relation to developing marketing channels...

  14. Absolute dimensions of eclipsing binaries. XXVIII. BK Pegasi and other F-type binaries: Prospects for calibration of convective core overshoot

    Science.gov (United States)

    Clausen, J. V.; Frandsen, S.; Bruntt, H.; Olsen, E. H.; Helt, B. E.; Gregersen, K.; Juncher, D.; Krogstrup, P.

    2010-06-01

    Context. Double-lined, detached eclipsing binaries are our main source for accurate stellar masses and radii. In this paper we focus on the 1.15-1.70 M⊙ interval where convective core overshoot is gradually ramped up in theoretical evolutionary models. Aims: We aim to determine absolute dimensions and abundances for the F-type detached eclipsing binary BK Peg, and to perform a detailed comparison with results from recent stellar evolutionary models, including a sample of previously studied systems with accurate parameters. Methods: uvby light curves and uvbyβ standard photometry were obtained with the Strömgren Automatic Telescope, ESO, La Silla, and high-resolution spectra were acquired with the FIES spectrograph at the Nordic Optical Telescope, La Palma. Results: The 5 fd 49 period orbit of BK Peg is slightly eccentric (e = 0.053). The two components are quite different with masses and radii of (1.414 ± 0.007 M⊙, 1.988 ± 0.008 Rsun) and (1.257 ± 0.005 M⊙, 1.474 ± 0.017 Rsun), respectively. The measured rotational velocities are 16.6 ± 0.2 (primary) and 13.4 ± 0.2 (secondary) km s-1. For the secondary component this corresponds to (pseudo)synchronous rotation, whereas the primary component seems to rotate at a slightly lower rate. We derive an iron abundance of [Fe/H] = -0.12 ± 0.07 and similar abundances for Si, Ca, Sc, Ti, Cr and Ni. The stars have evolved to the upper half of the main-sequence band. Yonsei-Yale and Victoria-Regina evolutionary models for the observed metal abundance reproduce BK Peg at ages of 2.75 and 2.50 Gyr, respectively, but tend to predict a lower age for the more massive primary component than for the secondary. We find the same age trend for three other upper main-sequence systems in a sample of well studied eclipsing binaries with components in the 1.15-1.70 M⊙ range. We also find that the Yonsei-Yale models systematically predict higher ages than the Victoria-Regina models. The sample includes BW Aqr, and as a

  15. Energy up-conversion and trapping: Dynamics of 5f states of Bk sup 4+ in CeF sub 4

    Energy Technology Data Exchange (ETDEWEB)

    Liu, G.K.; Beitz, J.V.

    1991-01-01

    Energy transfer mechanisms of excited 5f states of Bk{sup 4+} (0.05 atom %) in CeF{sub 4} containing circa 0.95 atom % Cf{sup 4+} have been investigated at 4 K. The observed anti-Stokes fluorescence arises from both up-conversion and two-photon excitation. Nonexponential decays of Stokes fluorescence are ascribed to both excitation-excitation annihilation and site-dependent trapping processes and, therefore, are not describable by the Inokuti-Hirayama or exciton annihilation models. Based on the Forster-Dexter energy transfer theory, a new model is developed to fit the observed fluorescence decay data. 16 refs., 3 figs.

  16. 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.

  17. Cross-reactivity of acid-sensing ion channel and Na⁺-H⁺ exchanger antagonists with nicotinic acetylcholine receptors.

    Science.gov (United States)

    Santos-Torres, Julio; Ślimak, Marta A; Auer, Sebastian; Ibañez-Tallon, Inés

    2011-11-01

    Nicotinic acetylcholine receptors (nAChRs) are widely distributed throughout the mammalian central and peripheral nervous systems, where they contribute to neuronal excitability and synaptic communication. It has been reported that nAChRs are modulated by BK channels and that BK channels, in turn, are inhibited by acid-sensing ion channels (ASICs). Here we investigate the possible functional interaction between these channels in medial habenula (MHb) neurones. We report that selective antagonists of large-conductance calcium-activated potassium channels and ASIC1a channels, paxilline and psalmotoxin 1, respectively, did not induce detectable changes in nicotine-evoked currents. In contrast, the non-selective ASIC and Na(+)-H(+) exchanger (NHE1) antagonists, amiloride and its analogues, suppressed nicotine-evoked responses in MHb neurones of wild-type and ASIC2 null mice, excluding a possible involvement of ASIC2 in the nAChR inhibition by amiloride. Zoniporide, a more selective inhibitor of NHE1, reversibly inhibited α3β4-, α7- and α4-containing (*) nAChRs in Xenopus oocytes and in brain slices, as well as in PS120 cells deficient in NHE1 and virally transduced with nAChRs, suggesting a generalized effect of zoniporide in most neuronal nAChR subtypes. Independently from nAChR antagonism, zoniporide profoundly blocked synaptic transmission onto MHb neurones without affecting glutamatergic and GABA receptors. Taken together, these results indicate that amiloride and zoniporide, which are clinically used to treat hypertension and cardiovascular disease, have an inhibitory effect on neuronal nAChRs when used experimentally at high doses. The possible cross-reactivity of these compounds with nAChRs in vivo will require further investigation.

  18. "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.

  19. Local energy losses at positive and negative steps in subcritical ...

    African Journals Online (AJOL)

    Local energy losses occur when there is a transition in open channel flow. Even though local losses in subcritical open channel flow due to changes in channel width have been studied, to date no studies have been reported for losses due to changes in bed elevations. Steps are commonly used in engineering applications ...

  20. BK Virus-Hemorrhagic Cystitis Following Allogeneic Stem Cell Transplantation: Clinical Characteristics and Utility of Leflunomide Treatment

    Directory of Open Access Journals (Sweden)

    Young Hoon Park

    2016-08-01

    Full Text Available Objective: BK virus-hemorrhagic cystitis (BKV-HC is a potential cause of morbidity and mortality in patients having undergone allogeneic stem cell transplantation (Allo-SCT. We analyzed the clinical features of BKV-HC following Allo-SCT and reported the utility of leflunomide therapy for BKV-HC. Materials and methods: From January 2005 to June 2014, among the 69 patients underwent Allo-SCT in our institution, the patients who experienced BKV-HC were investigated retrospectively. Results: Hemorrhagic cystitis (HC was observed in 30 patients (43.5%, and among them, 18 patients (26.1% were identified as BKV-HC. The median age of the patients (12 males and 6 females was 45 years (range, 13-63. Patients received Allo-SCT from acute myeloid leukemia (n=11, aplastic anemia (n=4, myelodysplastic syndrome (n=2, and non-Hodgkin lymphoma (n=1.The donor types were a HLA-matched sibling donor for 6 patients, HLA-matched unrelated donor for 9, and a haploidentical familial donor for 2. The median onset and duration of BKV-HC was on day 21 (range, 7-97 after transplantation and 22 days (range, 6-107. Eleven patients (62.1% had grade I-II HC and seven patients (38.9% had grade III-IV (high-grade HC. Among the seven patients who had high-grade HC, one had complete response (CR, one partial response (PR, and five no response (NR. Among the five non-responders, one died of BKV-HC associated complications. The remaining four patients were treated with leflunomide, with achieving CR (n=2 and PR (n=2. The median duration from the start of leflunomide therapy to response was 13 days (range, 8–17 days. All patients tolerated the leflunomide treatment well, with three patients having mild gastrointestinal symptoms, including anorexia and abdominal bloating. Conclusion: BKV-HC was commonly observed in patients with HC following Allo-SCT. In high-grade BKV-HC patients who fail supportive care, leflunomide may be a feasible option without significant toxicity. Materials

  1. The large-conductance calcium-activated potassium channel holds the key to the conundrum of familial hypokalemic periodic paralysis

    Science.gov (United States)

    Kim, Sung-Jo; Kang, Sun-Yang; Yi, Jin Woong; Kim, Seung-Min

    2014-01-01

    Purpose Familial hypokalemic periodic paralysis (HOKPP) is an autosomal dominant channelopathy characterized by episodic attacks of muscle weakness and hypokalemia. Mutations in the calcium channel gene, CACNA1S, or the sodium channel gene, SCN4A, have been found to be responsible for HOKPP; however, the mechanism that causes hypokalemia remains to be determined. The aim of this study was to improve the understanding of this mechanism by investigating the expression of calcium-activated potassium (KCa) channel genes in HOKPP patients. Methods We measured the intracellular calcium concentration with fura-2-acetoxymethyl ester in skeletal muscle cells of HOKPP patients and healthy individuals. We examined the mRNA and protein expression of KCa channel genes (KCNMA1, KCNN1, KCNN2, KCNN3, and KCNN4) in both cell types. Results Patient cells exhibited higher cytosolic calcium levels than normal cells. Quantitative reverse transcription polymerase chain reaction analysis showed that the mRNA levels of the KCa channel genes did not significantly differ between patient and normal cells. However, western blot analysis showed that protein levels of the KCNMA1 gene, which encodes KCa1.1 channels (also called big potassium channels), were significantly lower in the membrane fraction and higher in the cytosolic fraction of patient cells than normal cells. When patient cells were exposed to 50 mM potassium buffer, which was used to induce depolarization, the altered subcellular distribution of BK channels remained unchanged. Conclusion These findings suggest a novel mechanism for the development of hypokalemia and paralysis in HOKPP and demonstrate a connection between disease-associated mutations in calcium/sodium channels and pathogenic changes in nonmutant potassium channels. PMID:25379045

  2. Hypoxia Sensing in Plants: On a Quest for Ion Channels as Putative Oxygen Sensors.

    Science.gov (United States)

    Wang, Feifei; Chen, Zhong-Hua; Shabala, Sergey

    2017-07-01

    Over 17 million km2 of land is affected by soil flooding every year, resulting in substantial yield losses and jeopardizing food security across the globe. A key step in resolving this problem and creating stress-tolerant cultivars is an understanding of the mechanisms by which plants sense low-oxygen stress. In this work, we review the current knowledge about the oxygen-sensing and signaling pathway in mammalian and plant systems and postulate the potential role of ion channels as putative oxygen sensors in plant roots. We first discuss the definition and requirements for the oxygen sensor and the difference between sensing and signaling. We then summarize the literature and identify several known candidates for oxygen sensing in the mammalian literature. This includes transient receptor potential (TRP) channels; K+-permeable channels (Kv, BK and TASK); Ca2+ channels (RyR and TPC); and various chemo- and reactive oxygen species (ROS)-dependent oxygen sensors. Identified key oxygen-sensing domains (PAS, GCS, GAF and PHD) in mammalian systems are used to predict the potential plant counterparts in Arabidopsis. Finally, the sequences of known mammalian ion channels with reported roles in oxygen sensing were employed to BLAST the Arabidopsis genome for the candidate genes. Several plasma membrane and tonoplast ion channels (such as TPC, AKT and KCO) and oxygen domain-containing proteins with predicted oxygen-sensing ability were identified and discussed. We propose a testable model for potential roles of ion channels in plant hypoxia sensing. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  3. Distribution Profile of Inositol 1,4,5-Trisphosphate Receptor/Ca2+ Channels in α and β Cells of Pancreas: Dominant Localization in Secretory Granules and Common Error in Identification of Secretory Granule Membranes.

    Science.gov (United States)

    Hur, Yong Suk; Yoo, Seung Hyun

    2015-01-01

    The α and β cells of pancreatic islet release important hormones in response to intracellular Ca increases that result from Ca releases through the inositol 1,4,5-trisphoshate receptor (IP3R)/Ca channels. Yet no systematic studies on distribution of IP3R/Ca channels have been done, prompting us to investigate the distribution of all 3 IP3R isoforms. Immunogold electron microscopy was performed to determine the presence and the relative concentrations of all 3 IP3R isoforms in 2 major organelles secretory granules (SGs) and the endoplasmic reticulum of α and β cells of rat pancreas. All 3 IP3R isoforms were present in SG membranes of both cells, and the IP3R concentrations in SGs were ∼2-fold higher than those in the endoplasmic reticulum. Moreover, large halos shown in the electron microscope images of insulin-containing SGs of β cells were gap spaces that resulted from separation of granule membranes from the surrounding cytoplasm. These results strongly suggest the important roles of SGs in IP3-induced, Ca-dependent regulatory secretory pathway in pancreas. Moreover, the accurate location of SG membranes of β cells was further confirmed by the location of another integral membrane protein synaptotagmin V and of membrane phospholipid PI(4,5)P2.

  4. Ion Channels in Leukocytes

    Science.gov (United States)

    1991-07-01

    be fitted to a Hodgkin - conductance. K (1.0) > Rb (0.77) > NH4 (0.10) > Cs Huxley type n4j model (17, 38). However, the rate of K0 (0.02) > Na (ɘ.01...15, 25 activated) T- and B-cells, murine B-cells? SCG, single-channel conductance under physiological ionic gradient- tfor ructif~ y ig ehannel, largest...the channel induces a confor- kat T-cell line (52). Fina:! y , single-channel recordings of mational change that ina.-tix ates the channel rather human T

  5. 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.)

  6. Nonperturbative approach to relativistic quantum communication channels

    Science.gov (United States)

    Landulfo, André G. S.

    2016-05-01

    We investigate the transmission of both classical and quantum information between two arbitrary observers in globally hyperbolic spacetimes using a quantum field as a communication channel. The field is supposed to be in some arbitrary quasifree state and no choice of representation of its canonical commutation relations is made. Both sender and receiver possess some localized two-level quantum system with which they can interact with the quantum field to prepare the input and receive the output of the channel, respectively. The interaction between the two-level systems and the quantum field is such that one can trace out the field degrees of freedom exactly and thus obtain the quantum channel in a nonperturbative way. We end the paper determining the unassisted as well as the entanglement-assisted classical and quantum channel capacities.

  7. A linearization of quantum channels

    Science.gov (United States)

    Crowder, Tanner

    2015-06-01

    Because the quantum channels form a compact, convex set, we can express any quantum channel as a convex combination of extremal channels. We give a Euclidean representation for the channels whose inverses are also valid channels; these are a subset of the extreme points. They form a compact, connected Lie group, and we calculate its Lie algebra. Lastly, we calculate a maximal torus for the group and provide a constructive approach to decomposing any invertible channel into a product of elementary channels.

  8. Entanglement-annihilating and entanglement-breaking channels

    International Nuclear Information System (INIS)

    Moravcikova, Lenka; Ziman, Mario

    2010-01-01

    We introduce and investigate a family of entanglement-annihilating channels. These channels are capable of destroying any quantum entanglement within the system they act on. We show that they are not necessarily entanglement breaking. In order to achieve this result we analyze the subset of locally entanglement-annihilating channels. In this case, the same local noise applied on each subsystem individually is less entanglement annihilating (with respect to multi-partite entanglement) as the number of subsystems is increasing. Therefore, the bipartite case provides restrictions on the set of local entanglement-annihilating channels for the multipartite case. The introduced concepts are illustrated on the family of single-qubit depolarizing channels.

  9. Intra-membrane molecular interactions of K+ channel proteins :

    Energy Technology Data Exchange (ETDEWEB)

    Moczydlowski, Edward G.

    2013-07-01

    Ion channel proteins regulate complex patterns of cellular electrical activity and ionic signaling. Certain K+ channels play an important role in immunological biodefense mechanisms of adaptive and innate immunity. Most ion channel proteins are oligomeric complexes with the conductive pore located at the central subunit interface. The long-term activity of many K+ channel proteins is dependent on the concentration of extracellular K+; however, the mechanism is unclear. Thus, this project focused on mechanisms underlying structural stability of tetrameric K+ channels. Using KcsA of Streptomyces lividans as a model K+ channel of known structure, the molecular basis of tetramer stability was investigated by: 1. Bioinformatic analysis of the tetramer interface. 2. Effect of two local anesthetics (lidocaine, tetracaine) on tetramer stability. 3. Molecular simulation of drug docking to the ion conduction pore. The results provide new insights regarding the structural stability of K+ channels and its possible role in cell physiology.

  10. DESIGN OF PARABOLIC CHANNELS

    Directory of Open Access Journals (Sweden)

    A. K. Alibekov

    2015-01-01

    Full Text Available The dependence of the apparent location of the hydraulic parameters of parabolic channels in earthen channel and volume of dredging required in their design and construction, on the basis of conditions to ensure the stability of the slope at the maximum water flow rate. 

  11. Calcium channel blocker overdose

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002580.htm Calcium-channel blocker overdose To use the sharing features on this ... vary. However, the main ingredient is called a calcium-channel antagonist. It helps decrease the heart's pumping strength, which ...

  12. CHANNEL ESTIMATION TECHNIQUE

    DEFF Research Database (Denmark)

    2015-01-01

    the communication channel. The method further includes determining a sequence of second coefficient estimates of the communication channel based on a decomposition of the first coefficient estimates in a dictionary matrix and a sparse vector of the second coefficient estimates, the dictionary matrix including...

  13. Athermalized channeled spectropolarimeter enhancement.

    Energy Technology Data Exchange (ETDEWEB)

    Jones, Julia Craven; Way, Brandyn Michael; Mercier, Jeffrey Alan; Hunt, Jeffery P.

    2013-09-01

    Channeled spectropolarimetry can measure the complete polarization state of light as a function of wavelength. Typically, a channeled spectropolarimeter uses high order retarders made of uniaxial crystal to amplitude modulate the measured spectrum with the spectrally-dependent Stokes polarization information. A primary limitation of conventional channeled spectropolarimeters is related to the thermal variability of the retarders. Thermal variation often forces frequent system recalibration, particularly for field deployed systems. However, implementing thermally stable retarders, made of biaxial crystal, results in an athermal channeled spectropolarimeter that relieves the need for frequent recalibration. This report presents experimental results for an anthermalized channeled spectropolarimeter prototype produced using potassium titanyl phosphate. The results of this prototype are compared to the current thermal stabilization state of the art. Finally, the application of the technique to the thermal infrared is studied, and the athermalization concept is applied to an infrared imaging spectropolarimeter design.

  14. Cardiac potassium channel subtypes

    DEFF Research Database (Denmark)

    Schmitt, Nicole; Grunnet, Morten; Olesen, Søren-Peter

    2014-01-01

    . The underlying posttranscriptional and posttranslational remodeling of the individual K(+) channels changes their activity and significance relative to each other, and they must be viewed together to understand their role in keeping a stable heart rhythm, also under menacing conditions like attacks of reentry......About 10 distinct potassium channels in the heart are involved in shaping the action potential. Some of the K(+) channels are primarily responsible for early repolarization, whereas others drive late repolarization and still others are open throughout the cardiac cycle. Three main K(+) channels...... that they could constitute targets for new pharmacological treatment of atrial fibrillation. The interplay between the different K(+) channel subtypes in both atria and ventricle is dynamic, and a significant up- and downregulation occurs in disease states such as atrial fibrillation or heart failure...

  15. Muon cooling channels

    CERN Document Server

    Eberhard-K-Kei

    2003-01-01

    A procedure uses the equations that govern ionization cooling, and leads to the most important parameters of a muon cooling channel that achieves assumed performance parameters. First, purely transverse cooling is considered, followed by both transverse and longitudinal cooling in quadrupole and solenoid channels. Similarities and differences in the results are discussed in detail, and a common notation is developed. Procedure and notation are applied to a few published cooling channels. The parameters of the cooling channels are derived step by step, starting from assumed values of the initial, final and equilibrium emittances, both transverse and longitudinal, the length of the cooling channel, and the material properties of the absorber. The results obtained include cooling lengths and partition numbers, amplitude functions and limits on the dispersion at the absorber, length, aperture and spacing of the absorber, parameters of the RF system that achieve the longitudinal amplitude function and bucket area ...

  16. The small molecule NS11021 is a potent and specific activator of Ca2+-activated big-conductance K+ channels

    DEFF Research Database (Denmark)

    Bentzen, Bo Hjorth; Nardi, Antonio; Calloe, Kirstine

    2007-01-01

    Large-conductance Ca(2+)- and voltage-activated K(+) channels (Kca1.1/BK/MaxiK) are widely expressed ion channels. They provide a Ca(2+)-dependent feedback mechanism for the regulation of various body functions such as blood flow, neurotransmitter release, uresis, and immunity. In addition......, a mitochondrial K(+) channel with KCa1.1-resembling properties has been found in the heart, where it may be involved in regulation of energy consumption. In the present study, the effect of a novel NeuroSearch compound, 1-(3,5-bis-trifluoromethyl-phenyl)-3-[4-bromo-2-(1H-tetrazol-5-yl)-phenyl]-thiourea (NS11021......), was investigated on cloned KCa1.1 expressed in Xenopus laevis oocytes and mammalian cells using electrophysiological methods. NS11021 at concentrations above 0.3 microM activated KCa1.1 in a concentration-dependent manner by parallel-shifting the channel activation curves to more negative potentials. Single-channel...

  17. The Internet and the Banks' Strategic Distribution Channel Decisions.

    Science.gov (United States)

    Mols, Niels Peter

    1998-01-01

    Discusses two strategic distribution channel decisions facing banks, one regarding whether to target the Internet banking segment of customers versus the branch banking segment, and the other regarding the geographical area banks aim to serve. Future distribution channels, the change process, and local, national, and international strategies are…

  18. 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.

  19. Coherifying quantum channels

    Science.gov (United States)

    Korzekwa, Kamil; Czachórski, Stanisław; Puchała, Zbigniew; Życzkowski, Karol

    2018-04-01

    Is it always possible to explain random stochastic transitions between states of a finite-dimensional system as arising from the deterministic quantum evolution of the system? If not, then what is the minimal amount of randomness required by quantum theory to explain a given stochastic process? Here, we address this problem by studying possible coherifications of a quantum channel Φ, i.e., we look for channels {{{Φ }}}{ \\mathcal C } that induce the same classical transitions T, but are ‘more coherent’. To quantify the coherence of a channel Φ we measure the coherence of the corresponding Jamiołkowski state J Φ. We show that the classical transition matrix T can be coherified to reversible unitary dynamics if and only if T is unistochastic. Otherwise the Jamiołkowski state {J}{{Φ }}{ \\mathcal C } of the optimally coherified channel is mixed, and the dynamics must necessarily be irreversible. To assess the extent to which an optimal process {{{Φ }}}{ \\mathcal C } is indeterministic we find explicit bounds on the entropy and purity of {J}{{Φ }}{ \\mathcal C }, and relate the latter to the unitarity of {{{Φ }}}{ \\mathcal C }. We also find optimal coherifications for several classes of channels, including all one-qubit channels. Finally, we provide a non-optimal coherification procedure that works for an arbitrary channel Φ and reduces its rank (the minimal number of required Kraus operators) from {d}2 to d.

  20. Evaluation channel performance in multichannel environments

    NARCIS (Netherlands)

    Gensler, S.; Dekimpe, M.; Skiera, B.

    2007-01-01

    Evaluating channel performance is crucial for actively managing multiple sales channels, and requires understanding the customers' channel preferences. Two key components of channel performance are (i) the existing customers' intrinsic loyalty to a particular channel and (ii) the channel's ability

  1. Fractional channel multichannel analyzer

    Science.gov (United States)

    Brackenbush, L.W.; Anderson, G.A.

    1994-08-23

    A multichannel analyzer incorporating the features of the present invention obtains the effect of fractional channels thus greatly reducing the number of actual channels necessary to record complex line spectra. This is accomplished by using an analog-to-digital converter in the asynchronous mode, i.e., the gate pulse from the pulse height-to-pulse width converter is not synchronized with the signal from a clock oscillator. This saves power and reduces the number of components required on the board to achieve the effect of radically expanding the number of channels without changing the circuit board. 9 figs.

  2. Cl- channels in apoptosis

    DEFF Research Database (Denmark)

    Wanitchakool, Podchanart; Ousingsawat, Jiraporn; Sirianant, Lalida

    2016-01-01

    A remarkable feature of apoptosis is the initial massive cell shrinkage, which requires opening of ion channels to allow release of K(+), Cl(-), and organic osmolytes to drive osmotic water movement and cell shrinkage. This article focuses on the role of the Cl(-) channels LRRC8, TMEM16/anoctamin......, and cystic fibrosis transmembrane conductance regulator (CFTR) in cellular apoptosis. LRRC8A-E has been identified as a volume-regulated anion channel expressed in many cell types. It was shown to be required for regulatory and apoptotic volume decrease (RVD, AVD) in cultured cell lines. Its presence also...

  3. Direct channel problems and phenomena

    International Nuclear Information System (INIS)

    Cutkosky, R.E.

    1975-01-01

    Direct channel problems and phenomena are considered covering the need for precision hadron spectroscopy, the data base for precision hadron spectroscopy, some relations between direct-channel and cross-channel effects, and spin rotation phenomena

  4. Two-Pass Channel with Angled Ribs

    Directory of Open Access Journals (Sweden)

    C. W. Park

    1999-01-01

    Full Text Available Experiments have been conducted to study the local heat (mass transfer distributions in a two-pass test model of internal turbine blade cooling passages, with 60 ribs on the leading and trailing walls. For radial outward flow in the first pass, rotation did not significantly increase the local nor the overall heat (mass transfer between consecutive ribs on the trailing wall. Rotation-induced Coriolis force lowered the relative overall heat (mass transfer on the leading wall less in the rib-roughened channel than in a smooth channel. When the rotation number was high, there were twin peaks in the local heat (mass transfer distribution between ribs on the leading wall. For radial inward flow in the second pass, the sharp turn reduced the difference between the heat (mass transfer.on the leading wall and that on the trailing wall.

  5. [Mechanisms of action of voltage-gated sodium channel ligands].

    Science.gov (United States)

    Tikhonov, D B

    2007-05-01

    The voltage-gated sodium channels play a key role in the generation of action potential in excitable cells. Sodium channels are targeted by a number of modulating ligands. Despite numerous studies, the mechanisms of action of many ligands are still unknown. The main cause of the problem is the absence of the channel structure. Sodium channels belong to the superfamily of P-loop channels that also the data abowt includes potassium and calcium channels and the channels of ionotropic glutamate receptors. Crystallization of several potassium channels has opened a possibility to analyze the structure of other members of the superfamily using the homology modeling approach. The present study summarizes the results of several recent modelling studies of such sodium channel ligands as tetrodotoxin, batrachotoxin and local anesthetics. Comparison of available experimental data with X-ray structures of potassium channels has provided a new level of understanding of the mechanisms of action of sodium channel ligands and has allowed proposing several testable hypotheses.

  6. Ion channel regulation by protein S-acylation

    Science.gov (United States)

    2014-01-01

    Protein S-acylation, the reversible covalent fatty-acid modification of cysteine residues, has emerged as a dynamic posttranslational modification (PTM) that controls the diversity, life cycle, and physiological function of numerous ligand- and voltage-gated ion channels. S-acylation is enzymatically mediated by a diverse family of acyltransferases (zDHHCs) and is reversed by acylthioesterases. However, for most ion channels, the dynamics and subcellular localization at which S-acylation and deacylation cycles occur are not known. S-acylation can control the two fundamental determinants of ion channel function: (1) the number of channels resident in a membrane and (2) the activity of the channel at the membrane. It controls the former by regulating channel trafficking and the latter by controlling channel kinetics and modulation by other PTMs. Ion channel function may be modulated by S-acylation of both pore-forming and regulatory subunits as well as through control of adapter, signaling, and scaffolding proteins in ion channel complexes. Importantly, cross-talk of S-acylation with other PTMs of both cysteine residues by themselves and neighboring sites of phosphorylation is an emerging concept in the control of ion channel physiology. In this review, I discuss the fundamentals of protein S-acylation and the tools available to investigate ion channel S-acylation. The mechanisms and role of S-acylation in controlling diverse stages of the ion channel life cycle and its effect on ion channel function are highlighted. Finally, I discuss future goals and challenges for the field to understand both the mechanistic basis for S-acylation control of ion channels and the functional consequence and implications for understanding the physiological function of ion channel S-acylation in health and disease. PMID:24821965

  7. Channel Choice: A Literature Review

    DEFF Research Database (Denmark)

    Østergaard Madsen, Christian; Kræmmergaard, Pernille

    2015-01-01

    The channel choice branch of e-government studies citizens’ and businesses’ choice of channels for interacting with government, and how government organizations can integrate channels and migrate users towards the most cost-efficient channels. In spite of the valuable contributions offered no sys...... no systematic overview exist of channel choice. We present a literature review of channel choice studies in government to citizen context identifying authors, countries, methods, concepts, units of analysis, and theories, and offer suggestionsfor future studies....

  8. Coupled channels Marchenko inversion for nucleon-nucleon potentials

    International Nuclear Information System (INIS)

    Kohlhoff, H.; Geramb, H.V. von

    1994-01-01

    Marchenko inversion is used to determine local energy independent but channel dependent potential matrices from optimum sets of experimental phase shifts. 3 SD 1 and 3 PF 2 channels of nucleon-nucleon systems contain in their off-diagonal potential matrices explicitly the tensor force for T = 0 and 1 isospin. We obtain, together with single channels, complete sets of quantitative nucleon-nucleon potential results which are ready for application in nuclear structure and reaction analyses. The historic coupled channels inversion result of Newton and Fulton is revisited. (orig.)

  9. Volume Regulated Channels

    DEFF Research Database (Denmark)

    Klausen, Thomas Kjær

    , controlled cell death and cellular migration. Volume regulatory mechanisms has long been in focus for regulating cellular proliferation and my thesis work have been focusing on the role of Cl- channels in proliferation with specific emphasis on ICl, swell. Pharmacological blockage of the ubiquitously...... 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...... understood. Potential agonist binding sites have been proposed in transmembrane domains 3 and 4, in congruence with agonist binding sites of TRPV1. However, the functional relationship between TRPV4 and agonist binding is not yet understood. In this thesis is further elaborate the structure...

  10. Sensing with Ion Channels

    CERN Document Server

    Martinac, Boris

    2008-01-01

    All living cells are able to detect and translate environmental stimuli into biologically meaningful signals. Sensations of touch, hearing, sight, taste, smell or pain are essential to the survival of all living organisms. The importance of sensory input for the existence of life thus justifies the effort made to understand its molecular origins. Sensing with Ion Channels focuses on ion channels as key molecules enabling biological systems to sense and process the physical and chemical stimuli that act upon cells in their living environment. Its aim is to serve as a reference to ion channel specialists and as a source of new information to non specialists who want to learn about the structural and functional diversity of ion channels and their role in sensory physiology.

  11. Calcium channel blocker poisoning

    Directory of Open Access Journals (Sweden)

    Miran Brvar

    2005-04-01

    Full Text Available Background: Calcium channel blockers act at L-type calcium channels in cardiac and vascular smooth muscles by preventing calcium influx into cells with resultant decrease in vascular tone and cardiac inotropy, chronotropy and dromotropy. Poisoning with calcium channel blockers results in reduced cardiac output, bradycardia, atrioventricular block, hypotension and shock. The findings of hypotension and bradycardia should suggest poisoning with calcium channel blockers.Conclusions: Treatment includes immediate gastric lavage and whole-bowel irrigation in case of ingestion of sustainedrelease products. All patients should receive an activated charcoal orally. Specific treatment includes calcium, glucagone and insulin, which proved especially useful in shocked patients. Supportive care including the use of catecholamines is not always effective. In the setting of failure of pharmacological therapy transvenous pacing, balloon pump and cardiopulmonary by-pass may be necessary.

  12. Coding for optical channels

    CERN Document Server

    Djordjevic, Ivan; Vasic, Bane

    2010-01-01

    This unique book provides a coherent and comprehensive introduction to the fundamentals of optical communications, signal processing and coding for optical channels. It is the first to integrate the fundamentals of coding theory and optical communication.

  13. 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.

  14. Tritium in the Channel

    International Nuclear Information System (INIS)

    Masson, M.; Fievet, B.; Bailly-Du-Bois, P.; Olivier, A.; Tenailleau, L.

    2009-01-01

    After having recalled that sea waters entering the Channel exhibit a natural concentration of tritium, the authors outline that spent nuclear fuel reprocessing plants are now the main sources of tritium for marine ecosystems as some oceanographic campaigns showed it. If data about the presence of tritium in water are numerous, data concerning the presence of tritiated water and of organically bound tritium in organisms are much less frequent. However, some surveys have been performed along the Channel French coasts

  15. Channelling versus inversion

    DEFF Research Database (Denmark)

    Gale, A.S.; Surlyk, Finn; Anderskouv, Kresten

    2013-01-01

    Evidence from regional stratigraphical patterns in Santonian−Campanian chalk is used to infer the presence of a very broad channel system (5 km across) with a depth of at least 50 m, running NNW−SSE across the eastern Isle of Wight; only the western part of the channel wall and fill is exposed. W......−Campanian chalks in the eastern Isle of Wight, involving penecontemporaneous tectonic inversion of the underlying basement structure, are rejected....

  16. Course on Ionic Channels

    CERN Document Server

    1986-01-01

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

  17. 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."

  18. 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.

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

    Science.gov (United States)

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

    2000-11-01

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

  20. 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.

  1. ECIL guidelines for the prevention, diagnosis and treatment of BK polyomavirus-associated haemorrhagic cystitis in haematopoietic stem cell transplant recipients.

    Science.gov (United States)

    Cesaro, Simone; Dalianis, Tina; Hanssen Rinaldo, Christine; Koskenvuo, Minna; Pegoraro, Anna; Einsele, Hermann; Cordonnier, Catherine; Hirsch, Hans H

    2018-01-01

    To define guidelines for BK polyomavirus (BKPyV)-associated haemorrhagic cystitis (BKPyV-HC) after paediatric and adult HSCT. Review of English literature and evidence-based recommendations by expert consensus. BKPyV-HC occurs in 8%-25% of paediatric and 7%-54% of adult recipients undergoing allogeneic HSCT. Diagnosis requires the triad of cystitis, macro-haematuria and high urine BKPyV loads >7 log10 copies/mL, and exclusion of other relevant aetiologies. BKPyV viraemia is frequent and may serve as a more specific semiquantitative follow-up marker. No randomized controlled trials are available to inform antiviral prophylaxis or treatment. However, hyper-hydration and/or bladder irrigation showed limited prophylactic value. Fluoroquinolones are not effective for prophylaxis or treatment, but rather increase antibiotic resistance. Hyperbaric oxygen or fibrin glue is marginally effective based on small case series from correspondingly equipped centres. Although cidofovir has been reported to improve and/or reduce BKPyV viraemia or viruria, the current data do not support its regular use. BKPyV-HC remains a disabling unmet clinical need in HSCT that requires novel approaches supported by proper clinical trials. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Neuronal trafficking of voltage-gated potassium channels

    DEFF Research Database (Denmark)

    Jensen, Camilla S; Rasmussen, Hanne Borger; Misonou, Hiroaki

    2011-01-01

    The computational ability of CNS neurons depends critically on the specific localization of ion channels in the somatodendritic and axonal membranes. Neuronal dendrites receive synaptic inputs at numerous spines and integrate them in time and space. The integration of synaptic potentials...... is regulated by voltage-gated potassium (Kv) channels, such as Kv4.2, which are specifically localized in the dendritic membrane. The synaptic potentials eventually depolarize the membrane of the axon initial segment, thereby activating voltage-gated sodium channels to generate action potentials. Specific Kv...

  3. adequacy of drainage channels f drainage channels in a small

    African Journals Online (AJOL)

    eobe

    carried out and data obtain from drainage channels. The time of concentratio version of version of Kirpich equation (new equation of time new equation of time from the drainage channels were determined using results showed that most of the drainage channels h. All the drainage channels of basin A had velocities ra.

  4. Ion channelling in diamond

    International Nuclear Information System (INIS)

    Derry, T.E.

    1978-06-01

    Diamond is one of the most extreme cases from a channelling point of view, having the smallest thermal vibration amplitude and the lowest atomic number of commonly-encountered crystals. These are the two parameters most important for determining channelling behaviour. It is of consiberable interest therefore to see how well the theories explaining and predicting the channeling properties of other substance, succeed with diamond. Natural diamond, although the best available form for these experiments, is rather variable in its physical properties. Part of the project was devoted to considering and solving the problem of obtaining reproducible results representative of the ideal crystal. Channelling studies were performed on several good crystals, using the Rutherford backscattering method. Critical angles for proton channelling were measured for incident energies from 0.6 to 4.5 MeV, in the three most open axes and three most open planes of the diamond structure, and for α-particle channelling at 0.7 and 1.0 MeV (He + ) in the same axes and planes. For 1.0 MeV protons, the crystal temperature was varied from 20 degrees Celsius to 700 degrees Celsius. The results are presented as curves of backscattered yield versus angle in the region of each axis or plane, and summarised in the form of tables and graphs. Generally the critical angles, axial minimum yields, and temperature dependence are well predicted by the accepted theories. The most valuable overall conclusion is that the mean thermal vibration amplitude of the atoms in a crytical determines the critical approach distance to the channel walls at which an ion can remain channelled, even when this distance is much smaller than the Thomas-Fermi screening distance of the atomic potential, as is the case in diamond. A brief study was made of the radiation damage caused by α-particle bombardment, via its effect on the channelling phenomenon. It was possible to hold damage down to negligible levels during the

  5. Hydraulic geometry of cohesive channels undergoing base level drop

    Science.gov (United States)

    Vachtman, Dina; Laronne, Jonathan B.

    2013-09-01

    This study extends earlier contributions on dynamic adjustments of fluvial channels to base level changes. We have investigated an in situ response of self-formed cohesive channels to a base level drop, conditions analogous to a gradual change in uplift and/or climate. Empirical hydraulic geometry equations for clayey-cohesive natural streams are presented using data from eight channels draining perennial brackish springs and discharge into the Dead Sea. Investigation of downstream variations in gradient and stream power relations suggests existence of three distinct reaches in which channel adjustment to base level drop is shared inequitably among hydraulic geometry variables. Values of the flow velocity exponent m are low (0.11 ≤ m ≤ 0.24), the mid-channel reach having the lowest exponent. The depth exponent f has the lowest value (f ≈ 0.3) for the uppermost channel reaches, the rest having higher values (f ≈ 0.4). The smallest width exponent (b = 0.35) characterizes the upper reaches. These values and their spatial distribution exhibit a regular pattern. We show that the lowermost channel reach adjusts by profile steepening and channel narrowing (f > b); the prevailing mechanism in the mid-channel reaches is lateral (width) adjustment, cross sections transiently transforming toward equilibrium; the uppermost reaches have wide and shallow channel cross sections because of series of bank collapses and resultant sediment aggradation, bringing rise to decreased local gradient, forcing further channel widening. The results of this study not only allow inference about how cohesive channels regulate their geometry, but also reveal the means by which hydraulic forces overcome substrate resistance, adjusting slope and channel dimensions and, as such, have implication for reach-scale channel morphology and models of stream power.

  6. Channel identification machines.

    Science.gov (United States)

    Lazar, Aurel A; Slutskiy, Yevgeniy B

    2012-01-01

    We present a formal methodology for identifying a channel in a system consisting of a communication channel in cascade with an asynchronous sampler. The channel is modeled as a multidimensional filter, while models of asynchronous samplers are taken from neuroscience and communications and include integrate-and-fire neurons, asynchronous sigma/delta modulators and general oscillators in cascade with zero-crossing detectors. We devise channel identification algorithms that recover a projection of the filter(s) onto a space of input signals loss-free for both scalar and vector-valued test signals. The test signals are modeled as elements of a reproducing kernel Hilbert space (RKHS) with a Dirichlet kernel. Under appropriate limiting conditions on the bandwidth and the order of the test signal space, the filter projection converges to the impulse response of the filter. We show that our results hold for a wide class of RKHSs, including the space of finite-energy bandlimited signals. We also extend our channel identification results to noisy circuits.

  7. Channel Identification Machines

    Directory of Open Access Journals (Sweden)

    Aurel A. Lazar

    2012-01-01

    Full Text Available We present a formal methodology for identifying a channel in a system consisting of a communication channel in cascade with an asynchronous sampler. The channel is modeled as a multidimensional filter, while models of asynchronous samplers are taken from neuroscience and communications and include integrate-and-fire neurons, asynchronous sigma/delta modulators and general oscillators in cascade with zero-crossing detectors. We devise channel identification algorithms that recover a projection of the filter(s onto a space of input signals loss-free for both scalar and vector-valued test signals. The test signals are modeled as elements of a reproducing kernel Hilbert space (RKHS with a Dirichlet kernel. Under appropriate limiting conditions on the bandwidth and the order of the test signal space, the filter projection converges to the impulse response of the filter. We show that our results hold for a wide class of RKHSs, including the space of finite-energy bandlimited signals. We also extend our channel identification results to noisy circuits.

  8. Channel plate for DNA sequencing

    Science.gov (United States)

    Douthart, Richard J.; Crowell, Shannon L.

    1998-01-01

    This invention is a channel plate that facilitates data compaction in DNA sequencing. The channel plate has a length, a width and a thickness, and further has a plurality of channels that are parallel. Each channel has a depth partially through the thickness of the channel plate. Additionally an interface edge permits electrical communication across an interface through a buffer to a deposition membrane surface.

  9. Nanoscale Vacuum Channel Transistor.

    Science.gov (United States)

    Han, Jin-Woo; Moon, Dong-Il; Meyyappan, M

    2017-04-12

    Vacuum tubes that sparked the electronics era had given way to semiconductor transistors. Despite their faster operation and better immunity to noise and radiation compared to the transistors, the vacuum device technology became extinct due to the high power consumption, integration difficulties, and short lifetime of the vacuum tubes. We combine the best of vacuum tubes and modern silicon nanofabrication technology here. The surround gate nanoscale vacuum channel transistor consists of sharp source and drain electrodes separated by sub-50 nm vacuum channel with a source to gate distance of 10 nm. This transistor performs at a low voltage (3 microamperes). The nanoscale vacuum channel transistor can be a possible alternative to semiconductor transistors beyond Moore's law.

  10. Chaos in quantum channels

    Science.gov (United States)

    Hosur, Pavan; Qi, Xiao-Liang; Roberts, Daniel A.; Yoshida, Beni

    2016-02-01

    We study chaos and scrambling in unitary channels by considering their entanglement properties as states. Using out-of-time-order correlation functions to diagnose chaos, we characterize the ability of a channel to process quantum information. We show that the generic decay of such correlators implies that any input subsystem must have near vanishing mutual information with almost all partitions of the output. Additionally, we propose the negativity of the tripartite information of the channel as a general diagnostic of scrambling. This measures the delocalization of information and is closely related to the decay of out-of-time-order correlators. We back up our results with numerics in two non-integrable models and analytic results in a perfect tensor network model of chaotic time evolution. These results show that the butterfly effect in quantum systems implies the information-theoretic definition of scrambling.

  11. CANDU fuel channels

    International Nuclear Information System (INIS)

    Coleman, C.E.; Cheadle, B.A.

    1997-01-01

    The service life of CANDU fuel channels is determined by the component that has to withstand the most severe conditions, the Zr-2.5Nb pressure tube. The latest fuel channels are expected to have a lifetime of over 30 years. The properties that control service life are fracture and deformation. For fracture, a defence-in-depth approach is used - preventing crack initiation and invoking leak-before-break. Confidence in the serviceability of fuel channels is based on current knowledge of the state of health of the components evaluated by surveillance. Degradation of properties with service is slow, allowing sufficient time to judge and act when end-of-life is reached. Methods for improving the properties of components are outlined. (author)

  12. TRESK potassium channel in human T lymphoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Sánchez-Miguel, Dénison Selene, E-mail: amurusk@hotmail.com [Center for Biomedical Research, University of Colima, Av. 25 de Julio 965, Villa San Sebastian, C.P. 28045 Colima (Mexico); García-Dolores, Fernando, E-mail: garciaddf@yahoo.com [Department of Pathology, Institute of Forensic Sciences, Av. Niños Héroes 130, Col. Doctores, C.P. 06720 Mexico, DF (Mexico); Rosa Flores-Márquez, María, E-mail: mariafo31@yahoo.com.mx [National Medical Center of Occident (CMNO) IMSS, Belisario Dominguez 735, Col. Independencia Oriente, C.P. 44340 Guadalajara, Jalisco (Mexico); Delgado-Enciso, Iván [University of Colima, School of Medicine, Av. Universidad 333, Col. Las Viboras, C.P. 28040 Colima (Mexico); Pottosin, Igor, E-mail: pottosin@ucol.mx [Center for Biomedical Research, University of Colima, Av. 25 de Julio 965, Villa San Sebastian, C.P. 28045 Colima (Mexico); Dobrovinskaya, Oxana, E-mail: oxana@ucol.mx [Center for Biomedical Research, University of Colima, Av. 25 de Julio 965, Villa San Sebastian, C.P. 28045 Colima (Mexico)

    2013-05-03

    Highlights: • TRESK (KCNK18) mRNA is present in different T lymphoblastic cell lines. • KCNK18 mRNA was not found in resting peripheral blood lymphocytes. • Clinical samples of T lymphoblastic leukemias and lymphomas were positive for TRESK. • TRESK in T lymphoblasts has dual localization, in plasma membrane and intracellular. -- Abstract: TRESK (TWIK-related spinal cord K{sup +}) channel, encoded by KCNK18 gene, belongs to the double-pore domain K{sup +} channel family and in normal conditions is expressed predominantly in the central nervous system. In our previous patch-clamp study on Jurkat T lymphoblasts we have characterized highly selective K{sup +} channel with pharmacological profile identical to TRESK. In the present work, the presence of KCNK18 mRNA was confirmed in T lymphoblastic cell lines (Jurkat, JCaM, H9) but not in resting peripheral blood lymphocytes of healthy donors. Positive immunostaining for TRESK was demonstrated in lymphoblastic cell lines, in germinal centers of non-tumoral lymph nodes, and in clinical samples of T acute lymphoblastic leukemias/lymphomas. Besides detection in the plasma membrane, intracellular TRESK localization was also revealed. Possible involvement of TRESK channel in lymphocyte proliferation and tumorigenesis is discussed.

  13. Seafloor classification of the mound and channel provinces of the Porcupine Seabight: An application of the multibeam angular backscatter data

    Digital Repository Service at National Institute of Oceanography (India)

    Beyer, A.; Chakraborty, B.; Schenke, H.W.

    provinces like: carbonate mounds, buried mounds, seafloor channels, and inter-channel areas. A detailed methodology is developed to produce a map of angle-invariant (normalized) backscatter data by correcting the local angular backscatter values. The present...

  14. Ionic channel mechanisms mediating the intrinsic excitability of Kenyon cells in the mushroom body of the cricket brain.

    Science.gov (United States)

    Inoue, Shigeki; Murata, Kaoru; Tanaka, Aiko; Kakuta, Eri; Tanemura, Saori; Hatakeyama, Shiori; Nakamura, Atsunao; Yamamoto, Chihiro; Hasebe, Masaharu; Kosakai, Kumiko; Yoshino, Masami

    2014-09-01

    Intrinsic neurons within the mushroom body of the insect brain, called Kenyon cells, play an important role in olfactory associative learning. In this study, we examined the ionic mechanisms mediating the intrinsic excitability of Kenyon cells in the cricket Gryllus bimaculatus. A perforated whole-cell clamp study using β-escin indicated the existence of several inward and outward currents. Three types of inward currents (INaf, INaP, and ICa) were identified. The transient sodium current (INaf) activated at -40 mV, peaked at -26 mV, and half-inactivated at -46.7 mV. The persistent sodium current (INaP) activated at -51 mV, peaked at -23 mV, and half-inactivated at -30.7 mV. Tetrodotoxin (TTX; 1 μM) completely blocked both INaf and INaP, but 10nM TTX blocked INaf more potently than INaP. Cd(2+) (50 μM) potently blocked INaP with little effect on INaf. Riluzole (>20 μM) nonselectively blocked both INaP and INaf. The voltage-dependent calcium current (ICa) activated at -30 mV, peaked at -11.3 mV, and half-inactivated at -34 mV. The Ca(2+) channel blocker verapamil (100 μM) blocked ICa in a use-dependent manner. Cell-attached patch-clamp recordings showed the presence of a large-conductance Ca(2+)-activated K(+) (BK) channel, and the activity of this channel was decreased by removing the extracellular Ca(2+) or adding verapamil or nifedipine, and increased by adding the Ca(2+) agonist Bay K8644, indicating that Ca(2+) entry via the L-type Ca(2+) channel regulates BK channel activity. Under the current-clamp condition, membrane depolarization generated membrane oscillations in the presence of 10nM TTX or 100 μM riluzole in the bath solution. These membrane oscillations disappeared with 1 μM TTX, 50 μM Cd(2+), replacement of external Na(+) with choline, and blockage of Na(+)-activated K(+) current (IKNa) with 50 μM quinidine, indicating that membrane oscillations are primarily mediated by INaP in cooperation with IKNa. The plateau potentials observed either in

  15. Local Publications.

    Science.gov (United States)

    Wilson, Yvonne; And Others

    1991-01-01

    Includes annotations for 23 local government publications that reflect the main issues confronting local communities, including AIDS, children at risk, homelessness, human rights, and environmental decline. The shift of local problem solving from the federal and state government levels to the local level is briefly discussed. (LRW)

  16. 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

    Defect-free dislocation channel formation has been reported to promote plastic instability during tensile testing via localized plastic flow, leading to a distinct loss of ductility and strain hardening in many low-temperature irradiated materials. In order to study the underlying mechanisms governing dislocation channel width and formation, the channel formation process is modeled via a simple stochastic dislocation-jog process dependent upon grain size, defect cluster density, and defect size. Dislocations traverse a field of defect clusters and jog stochastically upon defect interaction, forming channels of low defect-density. Based upon prior molecular dynamics (MD) simulations and in-situ experimental transmission electron microscopy (TEM) observations, each dislocation encounter with a dislocation loop or stacking fault tetrahedron (SFT) is assumed to cause complete absorption of the defect cluster, prompting the dislocation to jog up or down by a distance equal to half the defect cluster diameter. Channels are predicted to form rapidly and are comparable to reported TEM measurements for many materials. Predicted channel widths are found to be most strongly dependent on mean defect size and correlated well with a power law dependence on defect diameter and density, and distance from the dislocation source. Due to the dependence of modeled channel width on defect diameter and density, maximum channel width is predicted to slowly increase as accumulated dose increases. The relatively weak predicted dependence of channel formation width with distance, in accordance with a diffusion analogy, implies that after only a few microns from the source, most channels observed via TEM analyses may not appear to vary with distance because of limitations in the field-of-view to a few microns. Further, examinations of the effect of the so-called "source-broadening" mechanism of channel formation showed that its effect is simply to add a minimum thickness to the channel

  17. Local formularies

    Science.gov (United States)

    Reynolds, D John M; Fajemisin, Olubunmi; Wilds, Sara

    2012-01-01

    The widespread availability of authoritative guidance on prescribing from a wide variety of international and national bodies calls into question the need for additional local formulary advice. This article describes contemporary local formulary management in the United Kingdom and discusses the areas where local decision making remains valuable. Local formularies can fulfil important roles which justify their continued existence, including ensuring local ownership and acceptance of advice, rapid dissemination of information, responsiveness to local circumstances and service design, sensitivity to local pricing arrangements and close professional links with commissioners, pharmacists and prescribers. PMID:22420709

  18. Single-molecule denaturation mapping of DNA in nanofluidic channels

    DEFF Research Database (Denmark)

    Reisner, Walter; Larsen, Niels Bent; Silahtaroglu, Asli

    2010-01-01

    Here we explore the potential power of denaturation mapping as a single-molecule technique. By partially denaturing YOYO (R)-1-labeled DNA in nanofluidic channels with a combination of formamide and local heating, we obtain a sequence-dependent "barcode" corresponding to a series of local dips...

  19. Inhibition of Sodium Ion Channel Function with Truncated Forms of Batrachotoxin.

    Science.gov (United States)

    Toma, Tatsuya; Logan, Matthew M; Menard, Frederic; Devlin, A Sloan; Du Bois, J

    2016-10-19

    A novel family of small molecule inhibitors of voltage-gated sodium channels (Na V s) based on the structure of batrachotoxin (BTX), a well-known channel agonist, is described. Protein mutagenesis and electrophysiology experiments reveal the binding site as the inner pore region of the channel, analogous to BTX, alkaloid toxins, and local anesthetics. Homology modeling of the eukaryotic channel based on recent crystallographic analyses of bacterial Na V s suggests a mechanism of action for ion conduction block.

  20. Local formularies

    OpenAIRE

    Reynolds, D John M; Fajemisin, Olubunmi; Wilds, Sara

    2012-01-01

    The widespread availability of authoritative guidance on prescribing from a wide variety of international and national bodies calls into question the need for additional local formulary advice. This article describes contemporary local formulary management in the United Kingdom and discusses the areas where local decision making remains valuable. Local formularies can fulfil important roles which justify their continued existence, including ensuring local ownership and acceptance of advice, r...

  1. Antigen-Specificity of T Cell Infiltrates in Biopsies With T Cell-Mediated Rejection and BK Polyomavirus Viremia: Analysis by Next Generation Sequencing.

    Science.gov (United States)

    Zeng, G; Huang, Y; Huang, Y; Lyu, Z; Lesniak, D; Randhawa, P

    2016-11-01

    This study interrogates the antigen-specificity of inflammatory infiltrates in renal biopsies with BK polyomavirus (BKPyV) viremia (BKPyVM) with or without allograft nephropathy (BKPyVN). Peripheral blood mononuclear cells (PBMC) from five healthy HLA-A0101 subjects were stimulated by peptides derived from the BKPYV proteome or polymorphic regions of HLA. Next generation sequencing of the T cell-receptor complementary DNA was performed on peptide-stimulated PBMC and 23 biopsies with T cell-mediated rejection (TCMR) or BKPyVN. Biopsies from patients with BKPyVM or BKVPyVN contained 7.7732 times more alloreactive than virus-reactive clones. Biopsies with TCMR also contained BKPyV-specific clones, presumably a manifestation of heterologous immunity. The mean cumulative T cell clonal frequency was 0.1378 for alloreactive clones and 0.0375 for BKPyV-reactive clones. Samples with BKPyVN and TCMR clustered separately in dendrograms of V-family and J-gene utilization patterns. Dendrograms also revealed that V-gene, J-gene, and D-gene usage patterns were a function of HLA type. In conclusion, biopsies with BKPyVN contain abundant allospecific clones that exceed the number of virus-reactive clones. The T cell component of tissue injury in viral nephropathy appears to be mediated primarily by an "innocent bystander" mechanism in which the principal element is secondary T cell influx triggered by both antiviral and anti-HLA immunity. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

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

    Directory of Open Access Journals (Sweden)

    Bartłomiej Drop

    2017-12-01

    Full Text Available 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 viral infection, SCC, demographic parameters, evidence of metastases and grading were also investigated. Fresh-frozen tumour tissue samples were collected from 146 patients with laryngeal, oropharyngeal and oral cancer. After DNA extraction, the DNA of the studied viruses was detected using polymerase chain rection (PCR assay. Males (87.7% with a history of smoking (70.6% and alcohol abuse (59.6% prevailed in the studied group. Histological type G2 was recognized in 64.4% cases. The patients were most frequently diagnosed with T2 stage (36.3% and with N1 stage (45.8%. Infection with at least two viruses was detected in 56.2% of patients. In this group, co-infection with HPV/EBV was identified in 34.1% of cases, EBV/BKV in 23.2%, HPV/BKV in 22.0%, and HPV/EBV/BKV in 20.7%. No difference of multiple infection in different locations of cancer was observed. The prevalence of poorly differentiated tumours (G3 was more frequent in co-infection with all three viruses than EBV or BKV alone. A significant correlation was observed between tumour dimensions (T and lymph-node involvement (N in co-infected patients compared to single infection. Further studies are necessary to clarify whether co-infection plays an important role in the initiation and/or progression of oncogenic transformation of oral, oropharyngeal and laryngeal epithelial cells.

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

    Science.gov (United States)

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

    2017-12-19

    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 viral infection, SCC, demographic parameters, evidence of metastases and grading were also investigated. Fresh-frozen tumour tissue samples were collected from 146 patients with laryngeal, oropharyngeal and oral cancer. After DNA extraction, the DNA of the studied viruses was detected using polymerase chain rection (PCR) assay. Males (87.7%) with a history of smoking (70.6%) and alcohol abuse (59.6%) prevailed in the studied group. Histological type G2 was recognized in 64.4% cases. The patients were most frequently diagnosed with T2 stage (36.3%) and with N1 stage (45.8%). Infection with at least two viruses was detected in 56.2% of patients. In this group, co-infection with HPV/EBV was identified in 34.1% of cases, EBV/BKV in 23.2%, HPV/BKV in 22.0%, and HPV/EBV/BKV in 20.7%. No difference of multiple infection in different locations of cancer was observed. The prevalence of poorly differentiated tumours (G3) was more frequent in co-infection with all three viruses than EBV or BKV alone. A significant correlation was observed between tumour dimensions (T) and lymph-node involvement (N) in co-infected patients compared to single infection. Further studies are necessary to clarify whether co-infection plays an important role in the initiation and/or progression of oncogenic transformation of oral, oropharyngeal and laryngeal epithelial cells.

  4. Loss Prediction of Low Re Flow Through Quasiperiodic Serpentine Channels

    Science.gov (United States)

    Becker, Sid

    2017-11-01

    Low Re internal flow through a complex structure whose geometry is regular (periodically uniform) will experience losses that are periodically regular and may be predicted using simple correlations. In many porous media applications this is represented by Darcy's Law. This study considers the prediction of losses through a channel whose geometry is periodic but with characteristic length scales that vary in the direction of bulk flow. Asymptotic expansions of the variation in the characteristic length are implemented in flow simulations in order to determine a correlation relating local hydraulic permeability to local channel geometry. In this way the local losses may be predicted without requiring the explicit solution of the flow field for every specific channel geometry. Several test cases are presented showing that using these correlations, the local pressure losses may predicted to within 0.5% agreement with the solution to the Navier-Stokes Equations.

  5. MITOCHONDRIAL BKCa CHANNEL

    Directory of Open Access Journals (Sweden)

    Enrique eBalderas

    2015-03-01

    Full Text Available Since its discovery in a glioma cell line 15 years ago, mitochondrial BKCa channel (mitoBKCa has been studied in brain cells and cardiomyocytes sharing general biophysical properties such as high K+ conductance (~300 pS, voltage-dependency and Ca2+-sensitivity. Main advances in deciphering the molecular composition of mitoBKCa have included establishing that it is encoded by the Kcnma1 gene, that a C-terminal splice insert confers mitoBKCa ability to be targeted to cardiac mitochondria, and evidence for its potential coassembly with β subunits. Notoriously, β1 subunit directly interacts with cytochrome c oxidase and mitoBKCa can be modulated by substrates of the respiratory chain. mitoBKCa channel has a central role in protecting the heart from ischemia, where pharmacological activation of the channel impacts the generation of reactive oxygen species and mitochondrial Ca2+ preventing cell death likely by impeding uncontrolled opening of the mitochondrial transition pore. Supporting this view, inhibition of mitoBKCa with Iberiotoxin, enhances cytochrome c release from glioma mitochondria. Many tantalizing questions remain. Some of them are: how is mitoBKCa coupled to the respiratory chain? Does mitoBKCa play non-conduction roles in mitochondria physiology? Which are the functional partners of mitoBKCa? What are the roles of mitoBKCa in other cell types? Answers to these questions are essential to define the impact of mitoBKCa channel in mitochondria biology and disease.

  6. Channels of Propaganda.

    Science.gov (United States)

    Sproule, J. Michael

    Defining propaganda as "efforts by special interests to win over the public covertly by infiltrating messages into various channels of public expression ordinarily viewed as politically neutral," this book argues that propaganda has become pervasive in American life. Pointing out that the 1990s society is inundated with propaganda from…

  7. Chemistry in Microfluidic Channels

    Science.gov (United States)

    Chia, Matthew C.; Sweeney, Christina M.; Odom, Teri W.

    2011-01-01

    General chemistry introduces principles such as acid-base chemistry, mixing, and precipitation that are usually demonstrated in bulk solutions. In this laboratory experiment, we describe how chemical reactions can be performed in a microfluidic channel to show advanced concepts such as laminar fluid flow and controlled precipitation. Three sets of…

  8. Channeling through Bent Crystals

    Energy Technology Data Exchange (ETDEWEB)

    Mack, Stephanie; /Ottawa U. /SLAC

    2012-09-07

    Bent crystals have demonstrated potential for use in beam collimation. A process called channeling is when accelerated particle beams are trapped by the nuclear potentials in the atomic planes within a crystal lattice. If the crystal is bent then the particles can follow the bending angle of the crystal. There are several different effects that are observed when particles travel through a bent crystal including dechanneling, volume capture, volume reflection and channeling. With a crystal placed at the edge of a particle beam, part of the fringe of the beam can be deflected away towards a detector or beam dump, thus helping collimate the beam. There is currently FORTRAN code by Igor Yazynin that has been used to model the passage of particles through a bent crystal. Using this code, the effects mentioned were explored for beam energy that would be seen at the Facility for Advanced Accelerator Experimental Tests (FACET) at a range of crystal orientations with respect to the incoming beam. After propagating 5 meters in vacuum space past the crystal the channeled particles were observed to separate from most of the beam with some noise due to dechanneled particles. Progressively smaller bending radii, with corresponding shorter crystal lengths, were compared and it was seen that multiple scattering decreases with the length of the crystal therefore allowing for cleaner detection of the channeled particles. The input beam was then modified and only a portion of the beam sent through the crystal. With the majority of the beam not affected by the crystal, most particles were not deflected and after propagation the channeled particles were seen to be deflected approximately 5mm. After a portion of the beam travels through the crystal, the entire beam was then sent through a quadrupole magnet, which increased the separation of the channeled particles from the remainder of the beam to a distance of around 20mm. A different code, which was developed at SLAC, was used to

  9. 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...

  10. Numerical simulation of separated flows in channels

    Czech Academy of Sciences Publication Activity Database

    Louda, P.; Příhoda, Jaromír; Sváček, P.; Kozel, K.

    2012-01-01

    Roč. 21, č. 2 (2012), s. 145-153 ISSN 1003-2169 R&D Projects: GA ČR GA103/09/0977 Institutional research plan: CEZ:AV0Z20760514 Keywords : backward facing step flow * EARSM model * SST model Subject RIV: BK - Fluid Dynamics Impact factor: 0.302, year: 2012 http://www.springerlink.com/content/806t56t72787g643/fulltext.pdf

  11. Source localization using acoustic vector sensors: a music approach

    NARCIS (Netherlands)

    Wind, Jelmer; Tijs, Emiel; de Bree, H.E.

    2009-01-01

    Traditionally, a large array of microphones is used to localize multiple far field sources in acoustics. We present a sound source localization technique that requires far less channels and measurement locations (affecting data channels, setup times and cabling issues). This is achieved by using an

  12. Quantum communication under channel uncertainty

    International Nuclear Information System (INIS)

    Noetzel, Janis Christian Gregor

    2012-01-01

    This work contains results concerning transmission of entanglement and subspaces as well as generation of entanglement in the limit of arbitrary many uses of compound- and arbitrarily varying quantum channels (CQC, AVQC). In both cases, the channel is described by a set of memoryless channels. Only forward communication between one sender and one receiver is allowed. A code is said to be ''good'' only, if it is ''good'' for every channel out of the set. Both settings describe a scenario, in which sender and receiver have only limited channel knowledge. For different amounts of information about the channel available to sender or receiver, coding theorems are proven for the CQC. For the AVQC, both deterministic and randomised coding schemes are considered. Coding theorems are proven, as well as a quantum analogue of the Ahlswede-dichotomy. The connection to zero-error capacities of stationary memoryless quantum channels is investigated. The notion of symmetrisability is defined and used for both classes of channels.

  13. Learning Channels and Verbal Behavior

    Science.gov (United States)

    Lin, Fan-Yu; Kubina, Richard M., Jr.

    2004-01-01

    This article reviews the basics of learning channels and how specification of stimuli can help enhance verbal behavior. This article will define learning channels and the role of the ability matrix in training verbal behavior.

  14. ``Just Another Distribution Channel?''

    Science.gov (United States)

    Lemstra, Wolter; de Leeuw, Gerd-Jan; van de Kar, Els; Brand, Paul

    The telecommunications-centric business model of mobile operators is under attack due to technological convergence in the communication and content industries. This has resulted in a plethora of academic contributions on the design of new business models and service platform architectures. However, a discussion of the challenges that operators are facing in adopting these models is lacking. We assess these challenges by considering the mobile network as part of the value system of the content industry. We will argue that from the perspective of a content provider the mobile network is ‘just another’ distribution channel. Strategic options available for the mobile communication operators are to deliver an excellent distribution channel for content delivery or to move upwards in the value chain by becoming a content aggregator. To become a mobile content aggregator operators will have to develop or acquire complementary resources and capabilities. Whether this strategic option is sustainable remains open.

  15. Geysering in boiling channels

    Energy Technology Data Exchange (ETDEWEB)

    Aritomi, Masanori; Takemoto, Takatoshi [Tokyo Institute of Technology, Tokyo (Japan); Chiang, Jing-Hsien [Japan NUS Corp. Ltd., Toyko (Japan)] [and others

    1995-09-01

    A concept of natural circulation BWRs such as the SBWR has been proposed and seems to be promising in that the primary cooling system can be simplified. The authors have been investigating thermo-hydraulic instabilities which may appear during the start-up in natural circulation BWRs. In our previous works, geysering was investigated in parallel boiling channels for both natural and forced circulations, and its driving mechanism and the effect of system pressure on geysering occurrence were made clear. In this paper, geysering is investigated in a vertical column and a U-shaped vertical column heated in the lower parts. It is clarified from the results that the occurrence mechanism of geysering and the dependence of system pressure on geysering occurrence coincide between parallel boiling channels in circulation systems and vertical columns in non-circulation systems.

  16. Educación en la promoción de estilos de vida saludables para la prevención de recaídas en pacientes con tuberculosis pulmonar bk (+), en el hospital Carlos Monge Medrano Juliaca 2010.

    OpenAIRE

    Maldonado Zanabria, Dionicia

    2011-01-01

    El presente estudio se realizó con el objetivo de evaluar la efectividad de la Educación en la Promoción de estilos de vida saludable para la prevención de recaídas en pacientes con Tuberculosis Pulmonar BK (+) en el Hospital Carlos Monge Medran o Juliaca 2010. El estudio es de carácter Cuasi-Experimental, con diseño de pre y post test; la muestra estuvo constituida por 18 pacientes. Para recolección de datos se utilizó como instrumentos un cuestionario. La prueba de hipótesis se realizó con ...

  17. Comparison of the TIP4P-2005, SWM4-DP and BK3 interaction potentials of liquid water with respect to their consistency with neutron and X-ray diffraction data of pure water

    OpenAIRE

    Steinczinger, Z.; Pusztai, L.

    2013-01-01

    Following a fairly comprehensive study on popular interaction potentials of water (Pusztai et al., J. Chem. Phys., 2008, 129, 184103), here two more recent polarizable potential sets, SWM4-DP (Lamoureux et al., Chem. Phys. Lett., 2006, 418, 245) and BK3 (Kiss et al., J. Chem. Phys., 2013, 138, 204507) are compared to the TIP4P-2005 water potential (Abascal et al., J. Chem. Phys., 2005, 123, 234505) that had previously appeared to be most favoravble. The basis of comparison was the compatibili...

  18. Radar channel balancing with commutation

    Energy Technology Data Exchange (ETDEWEB)

    Doerry, Armin Walter

    2014-02-01

    When multiple channels are employed in a pulse-Doppler radar, achieving and maintaining balance between the channels is problematic. In some circumstances the channels may be commutated to achieve adequate balance. Commutation is the switching, trading, toggling, or multiplexing of the channels between signal paths. Commutation allows modulating the imbalance energy away from the balanced energy in Doppler, where it can be mitigated with filtering.

  19. Nuclear reactor coolant channels

    International Nuclear Information System (INIS)

    Macbeth, R.V.

    1978-01-01

    A nuclear reactor coolant channel is described that is suitable for sub-cooled reactors as in pressurised water reactors as well as for bulk boiling, as in boiling water reactors and steam generating nuclear reactors. The arrangement aims to improve heat transfer between the fuel elements and the coolant. Full constructional details are given. See also other similar patents by the author. (U.K.)

  20. Channel box compression device

    International Nuclear Information System (INIS)

    Nakamizo, Hiroshi; Tanaka, Yuki.

    1996-01-01

    The device of the present invention reduces the volume of spent fuel channel boxes of power plant facilities to eliminate secondary wastes, suppress generation of radiation sources and improve storage space efficiency. The device has a box-like shape. A support frame is disposed on the lateral side of the box for supporting spent channel boxes. A horizontal transferring unit and a vertical transferring compression unit driven by a driving mechanism are disposed in the support frame. Further, the compression unit may have a rotational compression roller so as to move freely in the transferring unit. In addition, the transferring unit and the driving mechanism may be disposed outside of pool water. With such a constitution, since spent channel boxes are compressed and bent by horizontal movement of the transferring unit and the vertical movement of the compression unit, no cut pieces or cut powders are generated. Further, if the transferring unit and the driving mechanism are disposed outside of the pool water, it is not necessary to make them waterproof, which facilitates the maintenance. (I.S.)

  1. Ion channeling revisited

    Energy Technology Data Exchange (ETDEWEB)

    Doyle, Barney Lee [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Corona, Aldo [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Nguyen, Anh [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-09-01

    A MS Excel program has been written that calculates accidental, or unintentional, ion channeling in cubic bcc, fcc and diamond lattice crystals or polycrystalline materials. This becomes an important issue when simulating the creation by energetic neutrons of point displacement damage and extended defects using beams of ions. All of the tables and graphs in the three Ion Beam Analysis Handbooks that previously had to be manually looked up and read from were programed into Excel in handy lookup tables, or parameterized, for the case of the graphs, using rather simple exponential functions with different powers of the argument. The program then offers an extremely convenient way to calculate axial and planar half-angles and minimum yield or dechanneling probabilities, effects on half-angles of amorphous overlayers, accidental channeling probabilities for randomly oriented crystals or crystallites, and finally a way to automatically generate stereographic projections of axial and planar channeling half-angles. The program can generate these projections and calculate these probabilities for axes and [hkl] planes up to (555).

  2. TRP channels in kidney disease.

    NARCIS (Netherlands)

    Hsu, Y.J.; Hoenderop, J.G.J.; Bindels, R.J.M.

    2007-01-01

    Mammalian TRP channel proteins form six-transmembrane cation-permeable channels that may be grouped into six subfamilies on the basis of amino acid sequence homology (TRPC, TRPV, TRPM, TRPA, TRPP, and TRPML). Recent studies of TRP channels indicate that they are involved in numerous fundamental cell

  3. Specification of subunit assembly by the hydrophilic amino-terminal domain of the Shaker potassium channel.

    Science.gov (United States)

    Li, M; Jan, Y N; Jan, L Y

    1992-08-28

    The functional heterogeneity of potassium channels in eukaryotic cells arises not only from the multiple potassium channel genes and splice variants but also from the combinatorial mixing of different potassium channel polypeptides to form heteromultimeric channels with distinct properties. One structural element that determines the compatibility of different potassium channel polypeptides in subunit assembly has now been localized to the hydrophilic amino-terminal domain. A Drosophila Shaker B (ShB) potassium channel truncated polypeptide that contains only the hydrophilic amino-terminal domain can form a homomultimer; the minimal requirement for the homophilic interaction has been localized to a fragment of 114 amino acids. Substitution of the amino-terminal domain of a distantly related mammalian potassium channel polypeptide (DRK1) with that of ShB permits the chimeric DRK1 polypeptide to coassemble with ShB.

  4. Channelization of plumes beneath ice shelves

    KAUST Repository

    Dallaston, M. C.

    2015-11-11

    © 2015 Cambridge University Press. We study a simplified model of ice-ocean interaction beneath a floating ice shelf, and investigate the possibility for channels to form in the ice shelf base due to spatial variations in conditions at the grounding line. The model combines an extensional thin-film description of viscous ice flow in the shelf, with melting at its base driven by a turbulent ocean plume. Small transverse perturbations to the one-dimensional steady state are considered, driven either by ice thickness or subglacial discharge variations across the grounding line. Either forcing leads to the growth of channels downstream, with melting driven by locally enhanced ocean velocities, and thus heat transfer. Narrow channels are smoothed out due to turbulent mixing in the ocean plume, leading to a preferred wavelength for channel growth. In the absence of perturbations at the grounding line, linear stability analysis suggests that the one-dimensional state is stable to initial perturbations, chiefly due to the background ice advection.

  5. Alchemy: A Web 2.0 Real-time Quality Assurance Platform for Human Immunodeficiency Virus, Hepatitis C Virus, and BK Virus Quantitation Assays.

    Science.gov (United States)

    Agosto-Arroyo, Emmanuel; Coshatt, Gina M; Winokur, Thomas S; Harada, Shuko; Park, Seung L

    2017-01-01

    The molecular diagnostics laboratory faces the challenge of improving test turnaround time (TAT). Low and consistent TATs are of great clinical and regulatory importance, especially for molecular virology tests. Laboratory information systems (LISs) contain all the data elements necessary to do accurate quality assurance (QA) reporting of TAT and other measures, but these reports are in most cases still performed manually: a time-consuming and error-prone task. The aim of this study was to develop a web-based real-time QA platform that would automate QA reporting in the molecular diagnostics laboratory at our institution, and minimize the time expended in preparing these reports. Using a standard Linux, Nginx, MariaDB, PHP stack virtual machine running atop a Dell Precision 5810, we designed and built a web-based QA platform, code-named Alchemy. Data files pulled periodically from the LIS in comma-separated value format were used to autogenerate QA reports for the human immunodeficiency virus (HIV) quantitation, hepatitis C virus (HCV) quantitation, and BK virus (BKV) quantitation. Alchemy allowed the user to select a specific timeframe to be analyzed and calculated key QA statistics in real-time, including the average TAT in days, tests falling outside the expected TAT ranges, and test result ranges. Before implementing Alchemy, reporting QA for the HIV, HCV, and BKV quantitation assays took 45-60 min of personnel time per test every month. With Alchemy, that time has decreased to 15 min total per month. Alchemy allowed the user to select specific periods of time and analyzed the TAT data in-depth without the need of extensive manual calculations. Alchemy has significantly decreased the time and the human error associated with QA report generation in our molecular diagnostics laboratory. Other tests will be added to this web-based platform in future updates. This effort shows the utility of informatician-supervised resident/fellow programming projects as learning

  6. Early monitoring of the human polyomavirus BK replication and sequencing analysis in a cohort of adult kidney transplant patients treated with basiliximab

    Directory of Open Access Journals (Sweden)

    Mischitelli Monica

    2011-08-01

    Full Text Available Abstract Background Nowadays, better immunosuppressors have decreased the rates of acute rejection in kidney transplantation, but have also led to the emergence of BKV-associated nephropathy (BKVAN. Therefore, we prospectively investigated BKV load in plasma and urine samples in a cohort of kidney transplants, receiving basiliximab combined with a mycophenolate mofetil-based triple immunotherapy, to evaluate the difference between BKV replication during the first 3 months post-transplantation, characterized by the non-depleting action of basiliximab, versus the second 3 months, in which the maintenance therapy acts alone. We also performed sequencing analysis to assess whether a particular BKV subtype/subgroup or transcriptional control region (TCR variants were present. Methods We monitored BK viruria and viremia by quantitative polymerase chain reaction (Q-PCR at 12 hours (Tx, 1 (T1, 3 (T2 and 6 (T3 months post-transplantation among 60 kidney transplant patients. Sequencing analysis was performed by nested-PCR with specific primers for TCR and VP1 regions. Data were statistically analyzed using χ2 test and Student's t-test. Results BKV was detected at Tx in 4/60 urine and in 16/60 plasma, with median viral loads of 3,70 log GEq/mL and 3,79 log GEq/mL, respectively, followed by a significant increase of both BKV-positive transplants (32/60 and median values of viruria (5,78 log GEq/mL and viremia (4,52 log GEq/mL at T2. Conversely, a significantly decrease of patients with viruria and viremia (17/60 was observed at T3, together with a reduction of the median urinary and plasma viral loads (4,09 log GEq/mL and 4,00 log GEq/mL, respectively. BKV TCR sequence analysis always showed the presence of archetypal sequences, with a few single-nucleotide substitutions and one nucleotide insertion that, interestingly, were all representative of the particular subtypes/subgroups we identified by VP1 sequencing analysis: I/b-2 and IV/c-2. Conclusions Our

  7. Alchemy: A web 2.0 real-time quality assurance platform for human immunodeficiency Virus, hepatitis C Virus, and BK Virus quantitation assays

    Directory of Open Access Journals (Sweden)

    Emmanuel Agosto-Arroyo

    2017-01-01

    Full Text Available Background: The molecular diagnostics laboratory faces the challenge of improving test turnaround time (TAT. Low and consistent TATs are of great clinical and regulatory importance, especially for molecular virology tests. Laboratory information systems (LISs contain all the data elements necessary to do accurate quality assurance (QA reporting of TAT and other measures, but these reports are in most cases still performed manually: a time-consuming and error-prone task. The aim of this study was to develop a web-based real-time QA platform that would automate QA reporting in the molecular diagnostics laboratory at our institution, and minimize the time expended in preparing these reports. Methods: Using a standard Linux, Nginx, MariaDB, PHP stack virtual machine running atop a Dell Precision 5810, we designed and built a web-based QA platform, code-named Alchemy. Data files pulled periodically from the LIS in comma-separated value format were used to autogenerate QA reports for the human immunodeficiency virus (HIV quantitation, hepatitis C virus (HCV quantitation, and BK virus (BKV quantitation. Alchemy allowed the user to select a specific timeframe to be analyzed and calculated key QA statistics in real-time, including the average TAT in days, tests falling outside the expected TAT ranges, and test result ranges. Results: Before implementing Alchemy, reporting QA for the HIV, HCV, and BKV quantitation assays took 45–60 min of personnel time per test every month. With Alchemy, that time has decreased to 15 min total per month. Alchemy allowed the user to select specific periods of time and analyzed the TAT data in-depth without the need of extensive manual calculations. Conclusions: Alchemy has significantly decreased the time and the human error associated with QA report generation in our molecular diagnostics laboratory. Other tests will be added to this web-based platform in future updates. This effort shows the utility of informatician

  8. Intracellular ion channels and cancer

    Directory of Open Access Journals (Sweden)

    Luigi eLeanza

    2013-09-01

    Full Text Available Several types of channels play a role in the maintenance of ion homeostasis in subcellular organelles including endoplasmatic reticulum, nucleus, lysosome, endosome and mitochondria. Here we give a brief overview of the contribution of various mitochondrial and other organellar channels to cancer cell proliferation or death. Much attention is focused on channels involved in intracellular calcium signaling and on ion fluxes in the ATP-producing organelle mitochondria. Mitochondrial K+ channels (Ca2+-dependent BKCa and IKCa, ATP-dependent KATP, Kv1.3, two-pore TWIK-related Acid-Sensitive K+ channel-3 (TASK-3, Ca2+ uniporter MCU, Mg2+-permeable Mrs2, anion channels (voltage-dependent chloride channel VDAC, intracellular chloride channel CLIC and the Permeability Transition Pore (MPTP contribute importantly to the regulation of function in this organelle. Since mitochondria play a central role in apoptosis, modulation of their ion channels by pharmacological means may lead to death of cancer cells. The nuclear potassium channel Kv10.1 and the nuclear chloride channel CLIC4 as well as the endoplasmatic reticulum (ER-located inositol 1,4,5-trisphosphate (IP3 receptor, the ER-located Ca2+ depletion sensor STIM1 (stromal interaction molecule 1, a component of the store-operated Ca2+ channel and the ER-resident TRPM8 are also mentioned. Furthermore, pharmacological tools affecting organellar channels and modulating cancer cell survival are discussed. The channels described in this review are summarized on Figure 1. Overall, the view is emerging that intracellular ion channels may represent a promising target for cancer treatment.

  9. 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

  10. Imaging large cohorts of single ion channels and their activity

    Directory of Open Access Journals (Sweden)

    Katia eHiersemenzel

    2013-09-01

    Full Text Available As calcium is the most important signaling molecule in neurons and secretory cells, amongst many other cell types, it follows that an understanding of calcium channels and their regulation of exocytosis is of vital importance. Calcium imaging using calcium dyes such as Fluo3, or FRET-based dyes that have been used widely has provided invaluable information, which combined with modeling has estimated the sub-types of channels responsible for triggering the exocytotic machinery as well as inferences about the relative distances away from vesicle fusion sites these molecules adopt. Importantly, new super-resolution microscopy techniques, combined with novel Ca2+ indicators and imaginative imaging approaches can now define directly the nanoscale locations of very large cohorts of single channel molecules in relation to single vesicles. With combinations of these techniques the activity of individual channels can be visualized and quantified using novel Ca2+ indicators. Fluorescently labeled specific channel toxins can also be used to localize endogenous assembled channel tetramers. Fluorescence lifetime imaging microscopy and other single-photon-resolution spectroscopic approaches offer the possibility to quantify protein-protein interactions between populations of channels and the SNARE protein machinery for the first time. Together with simultaneous electrophysiology, this battery of quantitative imaging techniques has the potential to provide unprecedented detail describing the locations, dynamic behaviours, interactions and conductance activities of many thousands of channel molecules and vesicles in living cells.

  11. River channel patterns: Braided, meandering, and straight

    Science.gov (United States)

    Leopold, Luna Bergere; Wolman, M. Gordon

    1957-01-01

    Channel pattern is used to describe the plan view of a reach of river as seen from an airplane, and includes meandering, braiding, or relatively straight channels.Natural channels characteristically exhibit alternating pools or deep reaches and riffles or shallow reaches, regardless of the type of pattern. The length of the pool or distance between riffles in a straight channel equals the straight line distance between successive points of inflection in the wave pattern of a meandering river of the same width. The points of inflection are also shallow points and correspond to riffles in the straight channel. This distance, which is half the wavelength of the meander, varies approximately as a linear function of channel width. In the data we analysed the meander wavelength, or twice the distance between successive riffles, is from 7 to 12 times the channel width. It is concluded that the mechanics which may lead to meandering operate in straight channels.River braiding is characterized by channel division around alluvial islands. The growth of an island begins as the deposition of a central bar which results from sorting and deposition of the coarser fractions of the load which locally cannot be transported. The bar grows downstream and in height by continued deposition on its surface, forcing the water into the flanking channels, which, to carry the flow, deepen and cut laterally into the original banks. Such deepening locally lowers the water surface and the central bar emerges as an island which becomes stabilized by vegetation. Braiding was observed in a small river in a laboratory. Measurements of the adjustments of velocity, depth, width, and slope associated with island development lead to the conclusion that braiding is one of the many patterns which can maintain quasi-equilibrium among discharge, load, and transporting ability. Braiding does not necessarily indicate an excess of total load.Channel cross section and pattern are ultimately controlled by the

  12. Delivering on a gendered definition of health needs in local ...

    African Journals Online (AJOL)

    Background: Local governments are granted budgetary power in the Local Governments Act of the Republic of Uganda2, which allows for local-level participation and flexibility in the allocation of financial grants channelled annually from central to local governments. The act prescribes a legal mandate to allocate public ...

  13. Local anesthetic-induced inhibition of human neutrophil priming: the influence of structure, lipophilicity, and charge

    NARCIS (Netherlands)

    Picardi, Susanne; Cartellieri, Sibylle; Groves, Danja; Hahnenekamp, Klaus; Gerner, Peter; Durieux, Marcel E.; Stevens, Markus F.; Lirk, Philipp; Hollmann, Markus W.

    2013-01-01

    Local anesthetics (LAs) are widely known for inhibition of voltage-gated sodium channels underlying their antiarrhythmic and antinociceptive effects. However, LAs have significant immunomodulatory properties and were shown to affect human neutrophil functions independent of sodium-channel blockade.

  14. Engineered ion channels as emerging tools for chemical biology.

    Science.gov (United States)

    Mayer, Michael; Yang, Jerry

    2013-12-17

    Over the last 25 years, researchers have developed exogenously expressed, genetically engineered, semi-synthetic, and entirely synthetic ion channels. These structures have sufficient fidelity to serve as unique tools that can reveal information about living organisms. One of the most exciting success stories is optogenetics: the use of light-gated channels to trigger action potentials in specific neurons combined with studies of the response from networks of cells or entire live animals. Despite this breakthrough, the use of molecularly engineered ion channels for studies of biological systems is still in its infancy. Historically, researchers studied ion channels in the context of their own function in single cells or in multicellular signaling and regulation. Only recently have researchers considered ion channels and pore-forming peptides as responsive tools to report on the chemical and physical changes produced by other biochemical processes and reactions. This emerging class of molecular probes has a number of useful characteristics. For instance, these structures can greatly amplify the signal of chemical changes: the binding of one molecule to a ligand-gated ion channel can result in flux of millions of ions across a cell membrane. In addition, gating occurs on sub-microsecond time scales, resulting in fast response times. Moreover, the signal is complementary to existing techniques because the output is ionic current rather than fluorescence or radioactivity. And finally, ion channels are also localized at the membrane of cells where essential processes such as signaling and regulation take place. This Account highlights examples, mostly from our own work, of uses of ion channels and pore-forming peptides such as gramicidin in chemical biology. We discuss various strategies for preparing synthetically tailored ion channels that range from de novo designed synthetic molecules to genetically engineered or simply exogenously expressed or reconstituted wild

  15. Channels in tokamak reactor shields

    International Nuclear Information System (INIS)

    Shchipakin, O.L.

    1981-01-01

    The results of calculations of neutron transport through the channels in the tokamak reactor radiation shields, obtained by the Monte Carlo method and by the method of discrete ordinates, are considered. The given data show that the structural materials of the channel and that of the blanket and shields in the regions close to it are subjected to almost the same irradiation as the first wall and therefore they should satisfy the technical requirements. The radiation energy release in the injector channel wall, caused by neutron shooting, substantially depends on the channel dimensions. At the channel large diameter (0.7-10 m) this dependence noticeably decreases. The investigation of the effect of the injector channel cross section form on the neutron flux density through the channel, testifies to weak dependence of shooting radiation intensity on the form of the channel cross section. It is concluded that measures to decrease unfavourable effect of the channels on the safety of the power tokamak reactor operation and maintenance cause substantial changes in reactor design due to which the channel protection must be developed at first stages. The Monte Carlo method is recommended to be used for variant calculations and when calculating the neutron flux functionals in specific points of the system the discrete ordinate method is preferred [ru

  16. Channel Wall Landslides

    Science.gov (United States)

    2005-01-01

    [figure removed for brevity, see original site] The multiple landslides in this VIS image occur along a steep channel wall. Note the large impact crater in the context image. The formation of the crater may have initially weakened that area of the surface prior to channel formation. Image information: VIS instrument. Latitude -2.7, Longitude 324.8 East (35.2 West). 19 meter/pixel resolution. Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time. NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  17. A Micromechanical RF Channelizer

    Science.gov (United States)

    Akgul, Mehmet

    The power consumption of a radio generally goes as the number and strength of the RF signals it must process. In particular, a radio receiver would consume much less power if the signal presented to its electronics contained only the desired signal in a tiny percent bandwidth frequency channel, rather than the typical mix of signals containing unwanted energy outside the desired channel. Unfortunately, a lack of filters capable of selecting single channel bandwidths at RF forces the front-ends of contemporary receivers to accept unwanted signals, and thus, to operate with sub-optimal efficiency. This dissertation focuses on the degree to which capacitive-gap transduced micromechanical resonators can achieve the aforementioned RF channel-selecting filters. It aims to first show theoretically that with appropriate scaling capacitive-gap transducers are strong enough to meet the needed coupling requirements; and second, to fully detail an architecture and design procedure needed to realize said filters. Finally, this dissertation provides an actual experimentally demonstrated RF channel-select filter designed using the developed procedures and confirming theoretical predictions. Specifically, this dissertation introduces four methods that make possible the design and fabrication of RF channel-select filters. The first of these introduces a small-signal equivalent circuit for parallel-plate capacitive-gap transduced micromechanical resonators that employs negative capacitance to model the dependence of resonance frequency on electrical stiffness in a way that facilitates the analysis of micromechanical circuits loaded with arbitrary electrical impedances. The new circuit model not only correctly predicts the dependence of electrical stiffness on the impedances loading the input and output electrodes of parallel-plate capacitive-gap transduced micromechanical device, but does so in a visually intuitive way that identifies current drive as most appropriate for

  18. Sediment and Vegetation Controls on Delta Channel Networks

    Science.gov (United States)

    Lauzon, R.; Murray, A. B.; Piliouras, A.; Kim, W.

    2016-12-01

    Numerous factors control the patterns of distributary channels formed on a delta, including water and sediment discharge, grain size, sea level rise rates, and vegetation type. In turn, these channel networks influence the shape and evolution of a delta, including what types of plant and animal life - such as humans - it can support. Previous fluvial modeling and flume experiments, outside of the delta context, have addressed how interactions between sediment and vegetation, through their influence on lateral transport of sediment, determine what type of channel networks develops. Similar interactions likely also shape delta flow patterns. Vegetation introduces cohesion, tending to reduce channel migration rates and strengthen existing channel banks, reinforcing existing channels and resulting in localized, relatively stable flow patterns. On the other hand, sediment transport processes can result in lateral migration and frequent switching of active channels, resulting in flow resembling that of a braided stream. While previous studies of deltas have indirectly explored the effects of vegetation through the introduction of cohesive sediment, we directly incorporate key effects of vegetation on flow and sediment transport into the delta-building model DeltaRCM to explore how these effects influence delta channel network formation. Model development is informed by laboratory flume experiments at UT Austin. Here we present initial results of experiments exploring the effects of sea level rise rate, sediment grain size, vegetation type, and vegetation growth rate on delta channel network morphology. These results support the hypothesis that the ability for lateral transport of sediment to occur plays a key role in determining the evolution of delta channel networks and delta morphology.

  19. The Channel Tunnel

    Science.gov (United States)

    2006-01-01

    The Channel Tunnel is a 50.5 km-long rail tunnel beneath the English Channel at the Straits of Dover. It connects Dover, Kent in England with Calais, northern France. The undersea section of the tunnel is unsurpassed in length in the world. A proposal for a Channel tunnel was first put forward by a French engineer in 1802. In 1881, a first attempt was made at boring a tunnel from the English side; the work was halted after 800 m. Again in 1922, English workers started boring a tunnel, and advanced 120 m before it too was halted for political reasons. The most recent attempt was begun in 1987, and the tunnel was officially opened in 1994. At completion it was estimated that the project cost around $18 billion. It has been operating at a significant loss since its opening, despite trips by over 7 million passengers per year on the Eurostar train, and over 3 million vehicles per year. With its 14 spectral bands from the visible to the thermal infrared wavelength region, and its high spatial resolution of 15 to 90 meters (about 50 to 300 feet), ASTER images Earth to map and monitor the changing surface of our planet. ASTER is one of five Earth-observing instruments launched December 18, 1999, on NASA's Terra satellite. The instrument was built by Japan's Ministry of Economy, Trade and Industry. A joint U.S./Japan science team is responsible for validation and calibration of the instrument and the data products. The broad spectral coverage and high spectral resolution of ASTER provides scientists in numerous disciplines with critical information for surface mapping, and monitoring of dynamic conditions and temporal change. Example applications are: monitoring glacial advances and retreats; monitoring potentially active volcanoes; identifying crop stress; determining cloud morphology and physical properties; wetlands evaluation; thermal pollution monitoring; coral reef degradation; surface temperature mapping of soils and geology; and measuring surface heat balance. The

  20. UPSO three channel fast photometer

    Science.gov (United States)

    Gupta, S. K.; Sagar, R.; Joshi, S.; Ashoka, B. N.; Babu, V. C.; Seetha, S.; Girish, V.

    2001-09-01

    The design and performance of a modular portable three channel fast photometer is described. It can be disassembled as single individual channels such that the system can also be used as a single channel photometer. The instrument is put into operation since November 1999 on the 1-m UPSO telescope at Nainital. Since then, it is used extensively for the survey of roAp stars in the northern sky at UPSO. The discoveries made using this new photometer are also mentioned.

  1. Upgrading a marketing channels role

    Directory of Open Access Journals (Sweden)

    Tišma-Borota Ankica

    2002-01-01

    Full Text Available As one of the marketing mix instruments, marketing channels were usually behind other instruments (product, price and promotion. Many companies regarded marketing channels as something that was 'left' after more important strategies of price, product and promotion were created. In recent past, things have changed and marketing channels became more interesting for research. This change came as a result of change in global market functioning especially in competitive advantage, distributors' strength and increasing technology.

  2. Pull Promotions and Channel Coordination

    OpenAIRE

    Eitan Gerstner; James D. Hess

    1995-01-01

    This paper recommends that manufacturers consider a pull price promotion as a coordination device in an independent channel of distribution. Uncoordinated decisions of both manufacturer and retailer to charge high prices can break down the effort to expand the market, resulting in losses to the channel as a whole. We show that manufacturers can enhance channel price coordination by designing pull price discounts that target price-conscious consumers. The increased price coordination improves ...

  3. Cloning, expression in Pichia pastoris, and characterization of a thermostable GH5 mannan endo-1,4-β-mannosidase from Aspergillus niger BK01

    Directory of Open Access Journals (Sweden)

    Sigoillot Jean-Claude

    2009-11-01

    Full Text Available Abstract Background Mannans are key components of lignocellulose present in the hemicellulosic fraction of plant primary cell walls. Mannan endo-1,4-β-mannosidases (1,4-β-D-mannanases catalyze the random hydrolysis of β-1,4-mannosidic linkages in the main chain of β-mannans. Biodegradation of β-mannans by the action of thermostable mannan endo-1,4-β-mannosidase offers significant technical advantages in biotechnological industrial applications, i.e. delignification of kraft pulps or the pretreatment of lignocellulosic biomass rich in mannan for the production of second generation biofuels, as well as for applications in oil and gas well stimulation, extraction of vegetable oils and coffee beans, and the production of value-added products such as prebiotic manno-oligosaccharides (MOS. Results A gene encoding mannan endo-1,4-β-mannosidase or 1,4-β-D-mannan mannanohydrolase (E.C. 3.2.1.78, commonly termed β-mannanase, from Aspergillus niger BK01, which belongs to glycosyl hydrolase family 5 (GH5, was cloned and successfully expressed heterologously (up to 243 μg of active recombinant protein per mL in Pichia pastoris. The enzyme was secreted by P. pastoris and could be collected from the culture supernatant. The purified enzyme appeared glycosylated as a single band on SDS-PAGE with a molecular mass of approximately 53 kDa. The recombinant β-mannanase is highly thermostable with a half-life time of approximately 56 h at 70°C and pH 4.0. The optimal temperature (10-min assay and pH value for activity are 80°C and pH 4.5, respectively. The enzyme is not only active towards structurally different mannans but also exhibits low activity towards birchwood xylan. Apparent Km values of the enzyme for konjac glucomannan (low viscosity, locust bean gum galactomannan, carob galactomannan (low viscosity, and 1,4-β-D-mannan (from carob are 0.6 mg mL-1, 2.0 mg mL-1, 2.2 mg mL-1 and 1.5 mg mL-1, respectively, while the kcat values for these

  4. Quantum communication using a multiqubit entangled channel

    Energy Technology Data Exchange (ETDEWEB)

    Ghose, Shohini, E-mail: sghose@wlu.ca [Department of Physics and Computer Science, Wilfrid Laurier University, Waterloo, Ontario (Canada); Institute for Quantum Computing, University of Waterloo, Ontario (Canada); Hamel, Angele [Department of Physics and Computer Science, Wilfrid Laurier University, Waterloo, Ontario (Canada)

    2015-12-31

    We describe a protocol in which two senders each teleport a qubit to a receiver using a multiqubit entangled state. The multiqubit channel used for teleportation is genuinely 4-qubit entangled and is not equivalent to a product of maximally entangled Bell pairs under local unitary operations. We discuss a scenario in which both senders must participate for the qubits to be successfully teleported. Such an all-or-nothing scheme cannot be implemented with standard two-qubit entangled Bell pairs and can be useful for different communication and computing tasks.

  5. UMTS Common Channel Sensitivity Analysis

    DEFF Research Database (Denmark)

    Pratas, Nuno; Rodrigues, António; Santos, Frederico

    2006-01-01

    and as such it is necessary that both channels be available across the cell radius. This requirement makes the choice of the transmission parameters a fundamental one. This paper presents a sensitivity analysis regarding the transmission parameters of two UMTS common channels: RACH and FACH. Optimization of these channels...... is performed and values for the key transmission parameters in both common channels are obtained. On RACH these parameters are the message to preamble offset, the initial SIR target and the preamble power step while on FACH it is the transmission power offset....

  6. Local food:

    DEFF Research Database (Denmark)

    Sundbo, Donna Isabella Caroline

    2013-01-01

    as expressed by a group of Danish providers and consumers is empirically investigated through interviews, observation and surveys. From this, qualitative and quantitative data are generated, the analysis of which shows how varied perceptions of local food are. The elements of which the perceptions consist......Recently there has been more focus on food in general and local food in particular. But what is local food? And what are the perceptions of this concept according to theory and to providers and consumers of local food? This article first summarises and compares three different theoretical...... frequently mentioned than properties of the production process. Providers emphasise social properties of the product more often than consumers, and consumers emphasise physical properties of the product more often than providers. Inversely, providers emphasise physical properties of production more than...

  7. The batrachotoxin receptor on the voltage-gated sodium channel is guarded by the channel activation gate.

    Science.gov (United States)

    Li, Hong-Ling; Hadid, David; Ragsdale, David S

    2002-04-01

    Batrachotoxin (BTX), from South American frogs of the genus Phyllobates, irreversibly activates voltage-gated sodium channels. Previous work demonstrated that a phenylalanine residue approximately halfway through pore-lining transmembrane segment IVS6 is a critical determinant of channel sensitivity to BTX. In this study, we introduced a series of mutations at this site in the Na(v)1.3 sodium channel, expressed wild-type and mutant channels in Xenopus laevis oocytes, and examined their sensitivity to BTX using voltage clamp recording. We found that substitution of either alanine or isoleucine strongly reduced channel sensitivity to toxin, whereas cysteine, tyrosine, or tryptophan decreased toxin action only modestly. These data suggest an electrostatic ligand-receptor interaction at this site, possibly involving a charged tertiary amine on BTX. We then used a mutant channel (mutant F1710C) with intermediate toxin sensitivity to examine the properties of the toxin-receptor reaction in more detail. In contrast to wild-type channels, which bind BTX almost irreversibly, toxin dissociation from mutant channels was rapid, but only when the channels were open, not when they were closed. These data suggest the closed activation gate trapped bound toxin. Although BTX dissociation required channel activation, it was, paradoxically, slowed by strong membrane depolarization, suggesting additional state-dependent and/or electrostatic influences on the toxin binding reaction. We propose that BTX moves to and from its receptor through the cytoplasmic end of the open ion-conducting pore, in a manner similar to that of quaternary local anesthetics like QX314.

  8. Expected number of quantum channels in quantum networks

    Science.gov (United States)

    Chen, Xi; Wang, He-Ming; Ji, Dan-Tong; Mu, Liang-Zhu; Fan, Heng

    2015-07-01

    Quantum communication between nodes in quantum networks plays an important role in quantum information processing. Here, we proposed the use of the expected number of quantum channels as a measure of the efficiency of quantum communication for quantum networks. This measure quantified the amount of quantum information that can be teleported between nodes in a quantum network, which differs from classical case in that the quantum channels will be consumed if teleportation is performed. We further demonstrated that the expected number of quantum channels represents local correlations depicted by effective circles. Significantly, capacity of quantum communication of quantum networks quantified by ENQC is independent of distance for the communicating nodes, if the effective circles of communication nodes are not overlapped. The expected number of quantum channels can be enhanced through transformations of the lattice configurations of quantum networks via entanglement swapping. Our results can shed lights on the study of quantum communication in quantum networks.

  9. Negative particle planar and axial channeling and channeling collimation

    Energy Technology Data Exchange (ETDEWEB)

    Carrigan, Richard A., Jr.; /Fermilab

    2009-12-01

    While information exists on high energy negative particle channeling there has been little study of the challenges of negative particle bending and channeling collimation. Partly this is because negative dechanneling lengths are relatively much shorter. Electrons are not particularly useful for investigating negative particle channeling effects because their material interactions are dominated by channeling radiation. Another important factor is that the current central challenge in channeling collimation is the proton-proton Large Hadron Collider (LHC) where both beams are positive. On the other hand in the future the collimation question might reemerge for electon-positron or muon colliders. Dechanneling lengths increase at higher energies so that part of the negative particle experimental challenge diminishes. In the article different approaches to determining negative dechanneling lengths are reviewed. The more complicated case for axial channeling is also discussed. Muon channeling as a tool to investigate dechanneling is also discussed. While it is now possible to study muon channeling it will probably not illuminate the study of negative dechanneling.

  10. Soft cooperative spectrum sensing performance under imperfect and non identical reporting channels

    KAUST Repository

    Ben Ghorbel, Mahdi

    2015-02-01

    Cooperation among cognitive radio users improves the spectrum sensing performance by combining local decisions measured over independent sensing channels, allowing reduction of miss-detection and false alarm probabilities. While most of the works in cooperative spectrum sensing techniques assume perfect channels between the cooperating users, this paper studies the effect of imperfect channels when local users report their sensed information to the fusion center. Cooperative detection and false-alarm probabilities are derived for a general scheme of imperfect reporting channels under non necessarily identical sensing and reporting channels. Numerical simulations show that imperfect reporting channels should be considered to optimize the cooperative sensing in terms of consumed energy and probability of error.

  11. Is channel segmentation necessary to reach a multiethnic population with weight-related health promotion? An analysis of use and perception of communication channels.

    Science.gov (United States)

    Hartman, Marieke A; Nierkens, Vera; Cremer, Stephan W; Verhoeff, Arnoud; Stronks, Karien

    2015-01-01

    To explore similarities and differences in the use and perception of communication channels to access weight-related health promotion among women in three ethnic minority groups. The ultimate aim was to determine whether similar channels might reach ethnic minority women in general or whether segmentation to ethnic groups would be required. Eight ethnically homogeneous focus groups were conducted among 48 women of Ghanaian, Antillean/Aruban, or Afro-Surinamese background living in Amsterdam. Our questions concerned which communication channels they usually used to access weight-related health advice or information about programs and whose information they most valued. The content analysis of data was performed. The participants mentioned four channels - regular and traditional health care, general or ethnically specific media, multiethnic and ethnic gatherings, and interpersonal communication with peers in the Netherlands and with people in the home country. Ghanaian women emphasized ethnically specific channels (e.g., traditional health care, Ghanaian churches). They were comfortable with these channels and trusted them. They mentioned fewer general channels - mainly limited to health care - and if discussed, negative perceptions were expressed. Antillean women mentioned the use of ethnically specific channels (e.g., communication with Antilleans in the home country) on balance with general audience-oriented channels (e.g., regular health care). Perceptions were mixed. Surinamese participants discussed, in a positive manner, the use of general audience-oriented channels, while they said they did not use traditional health care or advice from Surinam. Local language proficiency, time resided in the Netherlands, and approaches and messages received seemed to explain channel use and perception. The predominant differences in channel use and perception among the ethnic groups indicate a need for channel segmentation to reach a multiethnic target group with weight

  12. 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

  13. [Role of calcium activated-potassium channels in the injury to rat alveolar macrophages induced by quartz].

    Science.gov (United States)

    Li, Jun; Sun, Jingzhi; Yang, Li; Zhao, Jing; Wang, Zhenglun; Yang, Lei

    2014-01-01

    To investigate the role of calcium activated-potassium channels (KCa) in the injury to rat alveolar macrophages induced by quartz. The experiments were conducted on a rat alveolar macrophage cell line (NR8383) in vitro, where crystal silica (100 üg/ml) and amorphous silica (100 üg/ml) were used as the test substances and the cells without any treatment as negative controls. At first the effects of two kinds of quartz were compared. Then KCa special inhibitors (Paxilline for BK, Tram-34 for IK, Apamin for SK) were added in different doses to the in vitro test system with 100 üg/ml crystal quartz as matrix, to observe the function of such channels. Cell viability, lactate dehydrogenase (LDH), interleukin-1β (IL-1β) and tumor necrosis factor-a (TNF-α) were tested. Comparing to the negative control group, cell viability reduced, LDH leakage, IL-1β and TNF-α release increased significantly in the amorphous quartz group, furthermore, the effects by crystal quartz were much more serious than those by amorphous quartz, with a statistical significance (P quartz group, IK blockers (Tram-34) led to increase in cell viability significantly, with a statistical significance (P quartz in the rat alveolar macrophages cell line in vitro, which might serve as a signal in the early regulation of inflammatory responses by quartz.

  14. One-sided asymptotically mean stationary channels

    OpenAIRE

    Simon, Francois

    2014-01-01

    This paper proposes an analysis of asymptotically mean stationary (AMS) communication channels. A hierarchy based on stability properties (stationarity, quasi-stationarity, recurrence and asymptotically mean stationarity) of channels is identified. Stationary channels are a subclass of quasi-stationary channels which are a subclass of recurrent AMS channels which are a subclass of AMS channels. These classes are proved to be stable under Markovian composition of channels (e.g., the cascade of...

  15. The jellyfish green fluorescent protein: a new tool for studying ion channel expression and function.

    Science.gov (United States)

    Marshall, J; Molloy, R; Moss, G W; Howe, J R; Hughes, T E

    1995-02-01

    Two methods are described for using the jellyfish green fluorescent protein (GFP) as a reporter gene for ion channel expression. GFP fluorescence can be used to identify the transfected cells, and to estimate the relative levels of ion channel expression, in cotransfection experiments. A GFP-NMDAR1 chimera can be constructed that produces a functional, fluorescent receptor subunit. These methods should facilitate studies of ion channel expression, localization, and processing.

  16. Effects of Active Subsidence Vs. Existing Basin Geometry on Fluviodeltaic Channels and Stratal Architecture

    Science.gov (United States)

    Liang, M.; Kim, W.; Passalacqua, P.

    2015-12-01

    Tectonic subsidence and basin topography, both determining the accommodation, are fundamental controls on the basin filling processes. Their effects on the fluvial organization and the resultant subsurface patterns remain difficult to predict due to the lack of understanding about interaction between internal dynamics and external controls. Despite the intensive studies on tectonic steering effects on alluvial architecture, how the self-organization of deltaic channels, especially the distributary channel network, respond to tectonics and basin geometry is mostly unknown. Recently physical experiments and field studies have hinted dramatic differences in fluviodeltaic evolution between ones associated with active differential subsidence and existing basin depth. In this work we designed a series of numerical experiments using a reduced-complexity channel-resolving model for delta formation, and tested over a range of localized subsidence rates and topographic depression in basin geometry. We also used a set of robust delta metrics to analyze: i) shoreline planform asymmetry, ii) channel and lobe geometry, iii) channel network pattern, iv) autogenic timescales, and v) subsurface structure. The modeling results show that given a similar final thickness, active subsidence enhances channel branching with smaller channel sand bodies that are both laterally and vertically connected, whereas existing topographic depression causes more large-scale channel avulsions with larger channel sand bodies. In general, both subsidence and existing basin geometry could steer channels and/or lock channels in place but develop distinct channel patterns and thus stratal architecture.

  17. Ion channels and their molecular environments--glimpses and insights from functional proteomics.

    Science.gov (United States)

    Schulte, Uwe; Müller, Catrin S; Fakler, Bernd

    2011-04-01

    There is emerging evidence from functional analyses and molecular research that the role of ion channels in cell physiology is not only determined by the pore-forming subunits but also depends on their molecular environment. Accordingly, the local and temporal specificity of channel-mediated signal transduction is thought to result from association of these integral membrane proteins with distinct sets of partner proteins or from their assembly into stable macromolecular complexes. As yet, however, the molecular environments of most ion channels have escaped direct investigation, mostly because of technical limitations that precluded their comprehensive molecular analysis. Recent advances in proteomic technologies promoted an experimental workflow that combines affinity purification of readily solubilized protein complexes with quantitative high-resolution mass spectrometry and that offers access to channel-associated protein environments. We will discuss advantages and limitations of this proteomic approach, as well as the results obtained from its application to several types of ion channels including Cav channels, Kv channels, HCN channels, AMPA-type glutamate receptors and GABA(B) receptors. The respective results indicate that the approach provides unbiased and comprehensive information on (i) the subunit composition of channel cores including identification of auxiliary subunits, on (ii) the assembly of channel cores into 'signaling entities' and on (iii) integration of channels into extended protein networks. Thus, quantitative proteomics opens a new window for the investigation of ion channels and their function in the context of various types of cell. Copyright © 2010 Elsevier Ltd. All rights reserved.

  18. Mechanisms underlying stage-1 TRPL channel translocation in Drosophila photoreceptors.

    Directory of Open Access Journals (Sweden)

    Minh-Ha Lieu

    Full Text Available TRP channels function as key mediators of sensory transduction and other cellular signaling pathways. In Drosophila, TRP and TRPL are the light-activated channels in photoreceptors. While TRP is statically localized in the signaling compartment of the cell (the rhabdomere, TRPL localization is regulated by light. TRPL channels translocate out of the rhabdomere in two distinct stages, returning to the rhabdomere with dark-incubation. Translocation of TRPL channels regulates their availability, and thereby the gain of the signal. Little, however, is known about the mechanisms underlying this trafficking of TRPL channels.We first examine the involvement of de novo protein synthesis in TRPL translocation. We feed flies cycloheximide, verify inhibition of protein synthesis, and test for TRPL translocation in photoreceptors. We find that protein synthesis is not involved in either stage of TRPL translocation out of the rhabdomere, but that re-localization to the rhabdomere from stage-1, but not stage-2, depends on protein synthesis. We also characterize an ex vivo eye preparation that is amenable to biochemical and genetic manipulation. We use this preparation to examine mechanisms of stage-1 TRPL translocation. We find that stage-1 translocation is: induced with ATP depletion, unaltered with perturbation of the actin cytoskeleton or inhibition of endocytosis, and slowed with increased membrane sterol content.Our results indicate that translocation of TRPL out of the rhabdomere is likely due to protein transport, and not degradation/re-synthesis. Re-localization from each stage to the rhabdomere likely involves different strategies. Since TRPL channels can translocate to stage-1 in the absence of ATP, with no major requirement of the cytoskeleton, we suggest that stage-1 translocation involves simple diffusion through the apical membrane, which may be regulated by release of a light-dependent anchor in the rhabdomere.

  19. An improved channel assessment scheme

    KAUST Repository

    Bader, Ahmed

    2014-05-01

    A source node in a multihop network determines whether to transmit in a channel based on whether the channel is occupied by a packet transmission with a large number of relays; whether the source node is in the data tones back-off zone; and the source node is in the busy tone back-off zone.

  20. Perceived quality of channel zapping

    NARCIS (Netherlands)

    Kooij, R.E.; Ahmed, K.; Brunnström, K.

    2006-01-01

    The end user experience of service quality is critical to the success of a service provider's IPTV deployment program. A key element involved in validating IPTV quality of experience (QoE) is how quickly and reliably users can change TV channels, often referred to as channel zapping. Currently there