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  1. Pharmacological targeting of native CatSper channels reveals a required role in maintenance of sperm hyperactivation.

    Directory of Open Access Journals (Sweden)

    Anne E Carlson

    2009-08-01

    Full Text Available The four sperm-specific CatSper ion channel proteins are required for hyperactivated motility and male fertility, and for Ca(2+ entry evoked by alkaline depolarization. In the absence of external Ca(2+, Na(+ carries current through CatSper channels in voltage-clamped sperm. Here we show that CatSper channel activity can be monitored optically with the [Na(+](i-reporting probe SBFI in populations of intact sperm. Removal of external Ca(2+ increases SBFI signals in wild-type but not CatSper2-null sperm. The rate of the indicated rise of [Na(+](i is greater for sperm alkalinized with NH(4Cl than for sperm acidified with propionic acid, reflecting the alkaline-promoted signature property of CatSper currents. In contrast, the [Na(+](i rise is slowed by candidate CatSper blocker HC-056456 (IC(50 approximately 3 microM. HC-056456 similarly slows the rise of [Ca(2+](i that is evoked by alkaline depolarization and reported by fura-2. HC-056456 also selectively and reversibly decreased CatSper currents recorded from patch-clamped sperm. HC-056456 does not prevent activation of motility by HCO(3 (- but does prevent the development of hyperactivated motility by capacitating incubations, thus producing a phenocopy of the CatSper-null sperm. When applied to hyperactivated sperm, HC-056456 causes a rapid, reversible loss of flagellar waveform asymmetry, similar to the loss that occurs when Ca(2+ entry through the CatSper channel is terminated by removal of external Ca(2+. Thus, open CatSper channels and entry of external Ca(2+ through them sustains hyperactivated motility. These results indicate that pharmacological targeting of the CatSper channel may impose a selective late-stage block to fertility, and that high-throughput screening with an optical reporter of CatSper channel activity may identify additional selective blockers with potential for male-directed contraception.

  2. CatSper channel, sperm function and male fertility.

    Science.gov (United States)

    Singh, Akhand Pratap; Rajender, Singh

    2015-01-01

    A number of physiological events, such as sperm hyperactivation, chemotaxis towards the egg, capacitation and acrosome reaction, are triggered by activation of sperm ion channels in response to a diverse range of chemical cues. Cation channel of sperm (CatSper), a sperm-specific ion channel, is unique in orchestrating the events for fertilization, and seems to be exclusively evolved for sperm function and male fertility. CatSper acts as a polymodal, chemosensory calcium channel and plays a vital role in the regulation of sperm hyperactivation. CatSper knockout models and application of patch clamp recordings have shown that it is indispensable for male fertility, and mutations and deletions in CatSper gene(s) may lead to infertility. In fact, mutations in CatSper1 and 2 have been identified in infertile individuals; however, CatSper3 and 4 have not been explored. Restricted localization and expression of CatSper in sperm offer an added advantage to developing gamete-based safe non-hormonal contraceptives. This review concisely covers identification, structure, function, and mechanism of action of CatSper channels. The functional importance of this complex ion channel in sperm motility and male fertility is highlighted for further research on male fertility, infertility, and contraception. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  3. CatSper ion channels: Bioinformatics analysis in Homo sapiens

    African Journals Online (AJOL)

    Jane

    2011-08-17

    Aug 17, 2011 ... channels, located in the plasma membrane of sperm tail. It contains a conserved domain of six trans- ... tivated sperm tail motion appears different under different conditions but basically, it changes from ... The CatSper2 is being named as the human autosomal nonsyndromic male infertility gene due to its ...

  4. Disruption of the principal, progesterone-activated sperm Ca2+ channel in a CatSper2-deficient infertile patient

    Science.gov (United States)

    Smith, James F.; Syritsyna, Olga; Fellous, Marc; Serres, Catherine; Mannowetz, Nadja; Kirichok, Yuriy; Lishko, Polina V.

    2013-01-01

    The female steroid hormone progesterone regulates ovulation and supports pregnancy, but also controls human sperm function within the female reproductive tract. Progesterone causes elevation of sperm intracellular Ca2+ leading to sperm hyperactivation, acrosome reaction, and perhaps chemotaxis toward the egg. Although it has been suggested that progesterone-dependent Ca2+ influx into human spermatozoa is primarily mediated by cationic channel of sperm (CatSper), the principal flagellar Ca2+ channel of sperm, conclusive loss-of-function genetic evidence for activation of CatSper by progesterone has yet to be provided. Moreover, it is not clear whether the responsiveness of CatSper to progesterone is an innate property of human spermatozoa or is acquired as the result of exposure to the seminal plasma. Here, by recording ionic currents from spermatozoa of an infertile CatSper-deficient patient, we demonstrate that CatSper is indeed the principal Ca2+ channel of human spermatozoa, and that it is strongly potentiated by progesterone. In addition, by recording CatSper currents from human epididymal and testicular spermatozoa, we show that CatSper sensitivity to progesterone arises early in sperm development and increases gradually to a peak when spermatozoa are ejaculated. These results unambiguously establish an important role of CatSper channel in human sperm nongenomic progesterone signaling and demonstrate that the molecular mechanism responsible for activation of CatSper by progesterone arises early in sperm development concurrently with the CatSper channel itself. PMID:23530196

  5. Down-regulation of CatSper1 channel in epididymal spermatozoa contributes to the pathogenesis of asthenozoospermia, whereas up-regulation of the channel by Sheng-Jing-San treatment improves the sperm motility of asthenozoospermia in rats.

    Science.gov (United States)

    Wang, Ya-Nan; Wang, Bo; Liang, Ming; Han, Cai-Yan; Zhang, Bin; Cai, Jie; Sun, Wei; Xing, Guo-Gang

    2013-02-01

    To determine the expression of CatSper1 channel in epididymal spermatozoa in a rat model of asthenozoospermia, induced by cyclophosphamide (CP), and further examine the effects of soluble granules of Sheng-Jing-San (SJS), a traditional Chinese medicine recipe, on CatSper1 expression and sperm motility in the CP-induced asthenozoospermic rats. Placebo-controlled, randomized trial. Neuroscience Research Institute, Peking University, China. Sexually mature male Sprague-Dawley rats (n = 60). In the CP group, CP at the dose of 35 mg/kg intraperitoneally injected into rats once a day for 7 days; in the normal saline (NS) group, 0.9% saline solution was injected as control. Sperm motility and count were evaluated by computer-assisted sperm assay (CASA); protein and mRNA expression of CatSper1 channel in epididymal spermatozoa was determined by Western blotting and quantitative real-time RT-PCR, respectively. The rats were randomly divided into five groups with 12 rats in each group: CP, normal saline (NS), CP + SJS, CP + NS, and treatment naïve. In the CP + SJS group, after the last injection of CP, SJS at a dose of 30 mg/kg was intragastrically administrated to rats once a day for 14 days; in CP + NS group, saline solution instead of SJS was administrated as control. In the treatment naïve group, rats were normally fed for 21 days as controls. We found a statistically significant reduction of the CatSper1 channel, which is associated with an impairment of sperm motility in the epididymal spermatozoa of CP-induced asthenozoospermic rats. Soluble granules of SJS could dramatically restore the CP-induced down-regulation of CatSper1 in epididymal spermatozoa, which greatly improved the sperm motility in the asthenozoospermic rats. Down-regulation of the CatSper1 channel in epididymal spermatozoa likely contributes to the pathogenesis of asthenozoospermia, whereas up-regulation of the channel by SJS improves sperm motility and thus can be used as an effective therapeutic

  6. Identification of human and mouse CatSper3 and CatSper4 genes: Characterisation of a common interaction domain and evidence for expression in testis

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    Reynolds Lindsey

    2003-08-01

    Full Text Available Abstract Background CatSper1 and CatSper2 are two recently identified channel-like proteins, which show sperm specific expression patterns. Through targeted mutagenesis in the mouse, CatSper1 has been shown to be required for fertility, sperm motility and for cAMP induced Ca2+ current in sperm. Both channels resemble a single pore forming repeat from a four repeat voltage dependent Ca2+ /Na+ channel. However, neither CatSper1 or CatSper2 have been shown to function as cation channels when transfected into cells, singly or in conjunction. As the pore forming units of voltage gated cation channels form a tetramer it has been suggested that the known CatSper proteins require additional subunits and/or interaction partners to function. Results Using in silico gene identification and prediction techniques, we have identified two further members of the CatSper family, CatSper3 and Catsper4. Each carries a single channel-forming domain with the predicted pore-loop containing the consensus sequence T×D×W. Each of the new CatSper genes has evidence for expression in the testis. Furthermore we identified coiled-coil protein-protein interaction domains in the C-terminal tails of each of the CatSper channels, implying that CatSper channels 1,2,3 and 4 may interact directly or indirectly to form a functional tetramer. Conclusions The topological and sequence relationship of CatSper1 and CatSper2 to the four repeat Ca2+ /Na+ channels suggested other members of this family may exist. We have identified a further two novel CatSper genes, conserved in both the human and mouse genomes. Furthermore, all four of the CatSper proteins are predicted to contain a common coiled-coil protein-protein interaction domain in their C-terminal tail. Coupled with expression data this leads to the hypothesis that the CatSper proteins form a functional hetero-tetrameric channel in sperm.

  7. Panax ginseng induces the expression of CatSper genes and sperm hyperactivation

    Science.gov (United States)

    Park, Eun Hwa; Kim, Do Rim; Kim, Ha Young; Park, Seong Kyu; Chang, Mun Seog

    2014-01-01

    The cation channel of sperm (CatSper) protein family plays important roles in male reproduction and infertility. The four members of this family are expressed exclusively in the testis and are localized differently in sperm. To investigate the effects of Panax ginseng treatment on the expression of CatSper genes and sperm hyperactivation in male mice, sperm motility and CatSper gene expression were assessed using a computer-assisted semen analysis system, a Fluoroskan Ascent microplate fluorometer to assess Ca2+ influx, real-time polymerase chain reaction, Western blotting and immunofluorescence. The results suggested that the Ca2+ levels of sperm cells treated with P. ginseng were increased significantly compared with the normal group. The P. ginseng-treated groups showed increased sperm motility parameters, such as the curvilinear velocity and amplitude of lateral head displacement. Taken together, the data suggest that CatSper messenger ribonucleic acid levels were increased significantly in mouse testes in the P. ginseng-treated group, as was the protein level, with the exception of CatSper2. In conclusion, P. ginseng plays an important role in improving sperm hyperactivation via CatSper gene expression. PMID:24969054

  8. Panax ginseng induces the expression of CatSper genes and sperm hyperactivation

    Directory of Open Access Journals (Sweden)

    Eun Hwa Park

    2014-12-01

    Full Text Available The cation channel of sperm (CatSper protein family plays important roles in male reproduction and infertility. The four members of this family are expressed exclusively in the testis and are localized differently in sperm. To investigate the effects of Panax ginseng treatment on the expression of CatSper genes and sperm hyperactivation in male mice, sperm motility and CatSper gene expression were assessed using a computer-assisted semen analysis system, a Fluoroskan Ascent microplate fluorometer to assess Ca 2+ influx, real-time polymerase chain reaction, Western blotting and immunofluorescence. The results suggested that the Ca 2+ levels of sperm cells treated with P. ginseng were increased significantly compared with the normal group. The P. ginseng-treated groups showed increased sperm motility parameters, such as the curvilinear velocity and amplitude of lateral head displacement. Taken together, the data suggest that CatSper messenger ribonucleic acid levels were increased significantly in mouse testes in the P. ginseng-treated group, as was the protein level, with the exception of CatSper2. In conclusion, P. ginseng plays an important role in improving sperm hyperactivation via CatSper gene expression.

  9. Specific loss of CatSper function is sufficient to compromise fertilizing capacity of human spermatozoa.

    Science.gov (United States)

    Williams, Hannah L; Mansell, Steven; Alasmari, Wardah; Brown, Sean G; Wilson, Stuart M; Sutton, Keith A; Miller, Melissa R; Lishko, Polina V; Barratt, Christopher L R; Publicover, Steven J; Martins da Silva, Sarah

    2015-12-01

    Are significant abnormalities of CatSper function present in IVF patients with normal sperm concentration and motility and if so what is their functional significance for fertilization success? Sperm with a near absence of CatSper current failed to respond to activation of CatSper by progesterone and there was fertilization failure at IVF. In human spermatozoa, Ca(2+) influx induced by progesterone is mediated by CatSper, a sperm-specific Ca(2+) channel. A suboptimal Ca(2+) influx is significantly associated with, and more prevalent in, men with abnormal semen parameters, and is associated with reduced fertilizing capacity. However, abnormalities in CatSper current can only be assessed directly using electrophysiology. There is only one report of a CatSper-deficient man who showed no progesterone potentiated CatSper current. A CatSper 2 genetic abnormality was present but there was no information on the [Ca(2+)]i response to CatSper activation by progesterone. Additionally, the semen samples had indicating significant abnormalities (oligoasthenoteratozoospermia) multiple suboptimal functional responses in the spermatozoon. As such it cannot be concluded that impaired CatSper function alone causes infertility or that CatSper blockade is a potential safe target for contraception. Spermatozoa were obtained from donors and subfertile IVF patients attending a hospital assisted reproductive techniques clinic between January 2013 and December 2014. In total 134 IVF patients, 28 normozoospermic donors and 10 patients recalled due to a history of failed/low fertilization at IVF took part in the study. Samples were primarily screened using the Ca(2+) influx induced by progesterone and, if cell number was sufficient, samples were also assessed by hyperactivation and penetration into viscous media. A defective Ca(2+) response to progesterone was defined using the 99% confidence interval from the distribution of response amplitudes in normozoospermic donors. Samples showing a

  10. Exposure to Cadmium Impairs Sperm Functions by Reducing CatSper in Mice

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    Hua-Feng Wang

    2017-05-01

    Full Text Available Background: Cadmium (Cd, a common environmental heavy metal and endocrine disruptor, is known to exert toxic effects on the testes. However, the mechanisms accounting for its toxicity in mature spermatozoa remain unclear. Methods: Adult male C57BL/6 mice were orally administered with CdCl2 for 5 weeks at 3 mg·kg-1·day-1. Additionally, mouse spermatozoa were incubated in vitro with different doses of CdCl2 (0, 10, 50, 250 µM. Several sperm functions including the sperm motility, viability and acrosome reaction (AR ratio were then examined. Furthermore, the current and expression levels of both the sperm-specific Ca2+ channel (CatSper and the sperm-specific K+ channel (KSper were evaluated by patch-clamping and western blotting, respectively. Results: Our data showed that the motility, viability and AR of sperm exposed to cadmium significantly decreased in vivo and in vitro. Interestingly, these changes were correlated with changes in CatSper but not KSper. Conclusion: The findings indicate sperm dysfunction during both chronic and acute cadmium exposure as well as a specific role for CatSper in the reproductive toxicity of cadmium.

  11. Diethylstilbestrol activates CatSper and disturbs progesterone actions in human spermatozoa.

    Science.gov (United States)

    Zou, Qian-Xing; Peng, Zhen; Zhao, Qing; Chen, Hou-Yang; Cheng, Yi-Min; Liu, Qing; He, Yuan-Qiao; Weng, Shi-Qi; Wang, Hua-Feng; Wang, Tao; Zheng, Li-Ping; Luo, Tao

    2017-02-01

    Is diethylstilbestrol (DES), a prototypical endocrine-disrupting chemical (EDC), able to induce physiological changes in human spermatozoa and affect progesterone actions? DES promoted Ca 2+ flux into human spermatozoa by activating the cation channel of sperm (CatSper) and suppressed progesterone-induced Ca 2+ signaling, tyrosine phosphorylation and sperm functions. DES significantly impairs the male reproductive system both in fetal and postnatal exposure. Although various EDCs affect human spermatozoa in a non-genomic manner, the effect of DES on human spermatozoa remains unknown. Sperm samples from normozoospermic donors were exposed in vitro to a range of DES concentrations with or without progesterone at 37°C in a 5% CO 2 incubator to mimic the putative exposure to this toxicant in seminal plasma and the female reproductive tract fluids. The incubation time varied according to the experimental protocols. All experiments were repeated at least five times using different individual sperm samples. Human sperm intracellular calcium concentrations ([Ca 2+ ] i ) were monitored with a multimode plate reader following sperm loading with Ca 2+ indicator Fluo-4 AM, and the whole-cell patch-clamp technique was performed to record CatSper and alkalinization-activated sperm K + channel (KSper) currents. Sperm viability and motility parameters were assessed by an eosin-nigrosin staining kit and a computer-assisted semen analysis system, respectively. The ability of sperm to penetrate into viscous media was examined by penetration into 1% methylcellulose. The sperm acrosome reaction was measured using chlortetracycline staining. The level of tyrosine phosphorylation was determined by western blot assay. DES exposure rapidly increased human sperm [Ca 2+ ] i dose dependently and even at an environmentally relevant concentration (100 pM). The elevation of [Ca 2+ ] i was derived from extracellular Ca 2+ influx and mainly mediated by CatSper. Although DES did not affect sperm

  12. CatSper ion channels: Bioinformatics analysis in Homo sapiens ...

    African Journals Online (AJOL)

    Due to the availability of huge amount of molecular biology data, our main focus was to determine the protein structures, functions and their role in different molecular pathways. The 3-D structure prediction of protein is important in medicine and biotechnology. Molecular docking not only finds the interaction between ...

  13. Morphodynamics of submarine channel inception revealed by new experimental approach.

    Science.gov (United States)

    de Leeuw, Jan; Eggenhuisen, Joris T; Cartigny, Matthieu J B

    2016-03-21

    Submarine channels are ubiquitous on the seafloor and their inception and evolution is a result of dynamic interaction between turbidity currents and the evolving seafloor. However, the morphodynamic links between channel inception and flow dynamics have not yet been monitored in experiments and only in one instance on the modern seafloor. Previous experimental flows did not show channel inception, because flow conditions were not appropriately scaled to sustain suspended sediment transport. Here we introduce and apply new scaling constraints for similarity between natural and experimental turbidity currents. The scaled currents initiate a leveed channel from an initially featureless slope. Channelization commences with deposition of levees in some slope segments and erosion of a conduit in other segments. Channel relief and flow confinement increase progressively during subsequent flows. This morphodynamic evolution determines the architecture of submarine channel deposits in the stratigraphic record and efficiency of sediment bypass to the basin floor.

  14. Morphodynamics of submarine channel inception revealed by new experimental approach

    NARCIS (Netherlands)

    de Leeuw, J.; Eggenhuisen, J.T.; Cartigny, M.J.B.

    2016-01-01

    Submarine channels are ubiquitous on the seafloor and their inception and evolution is a result of dynamic interaction between turbidity currents and the evolving seafloor. However, the morphodynamic links between channel inception and flow dynamics have not yet been monitored in experiments and

  15. Ion channel gene expressions in infertile men: A case-control study

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    Serkan Carkci

    2017-12-01

    Full Text Available Background: Infertility is described as not receiving pregnancy despite unprotected and regular sexual intercourse in a 1 yr period. It is detected by 15% of the couples. Male and female factor in the etiology may be detected in similar rates. Objective: The present study aims to investigate ion channel gene expression in semen samples of infertile male compared with fertile men. Materials and Methods: A total of 150 men who applied to the urology clinic due to infertility were divided into five equal groups: asthenozoospermia, oligozoospermia, oligoasthenoteratozoospermia, teratozoospermia, and normozoospermia (control. All paticipants were evaluated with Cation Channel Spermia (CatSper 1, 2, 3, 4, Proton Voltage Gated Ion Channel1 (Hv1, Potassium Channel Subfamily U1 (KCNU1, and transmembrane protein (TMEM16A gene expression in semen samples. Results: “CatSper1, 4, HV1, KCNU1, and TMEM16A gene expression were detected higher in the oligozoospermia group compared to the controls. CatSper1, 2, 3, 4, KCNU1, and TMEM16A gene expression in the asthenozoospermia group and CatSper1, 2, 3, 4, KCNU1, and TMEM16A gene expression in the teratozoospermia group were detected lower compared to the controls. CatSper1, 4, HV1, and TMEM16A gen expression were higher in the oligoasthenoteratozoospermia men than the controls while CatSper3 gen expression was detected as lower.” Conclusion: It was detected that these ion channels have an effect on sperm progressive motility and morphology. It may be considered that mutations in these ion channels may result in infertility

  16. Parallel Evolution of Sperm Hyper-Activation Ca2+ Channels.

    Science.gov (United States)

    Cooper, Jacob C; Phadnis, Nitin

    2017-07-01

    Sperm hyper-activation is a dramatic change in sperm behavior where mature sperm burst into a final sprint in the race to the egg. The mechanism of sperm hyper-activation in many metazoans, including humans, consists of a jolt of Ca2+ into the sperm flagellum via CatSper ion channels. Surprisingly, all nine CatSper genes have been independently lost in several animal lineages. In Drosophila, sperm hyper-activation is performed through the cooption of the polycystic kidney disease 2 (pkd2) Ca2+ channel. The parallels between CatSpers in primates and pkd2 in Drosophila provide a unique opportunity to examine the molecular evolution of the sperm hyper-activation machinery in two independent, nonhomologous calcium channels separated by > 500 million years of divergence. Here, we use a comprehensive phylogenomic approach to investigate the selective pressures on these sperm hyper-activation channels. First, we find that the entire CatSper complex evolves rapidly under recurrent positive selection in primates. Second, we find that pkd2 has parallel patterns of adaptive evolution in Drosophila. Third, we show that this adaptive evolution of pkd2 is driven by its role in sperm hyper-activation. These patterns of selection suggest that the evolution of the sperm hyper-activation machinery is driven by sexual conflict with antagonistic ligands that modulate channel activity. Together, our results add sperm hyper-activation channels to the class of fast evolving reproductive proteins and provide insights into the mechanisms used by the sexes to manipulate sperm behavior. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  17. Transverse relaxation dispersion of the p7 membrane channel from hepatitis C virus reveals conformational breathing

    International Nuclear Information System (INIS)

    Dev, Jyoti; Brüschweiler, Sven; Ouyang, Bo; Chou, James J.

    2015-01-01

    The p7 membrane protein encoded by hepatitis C virus (HCV) assembles into a homo-hexamer that selectively conducts cations. An earlier solution NMR structure of the hexameric complex revealed a funnel-like architecture and suggests that a ring of conserved asparagines near the narrow end of the funnel are important for cation interaction. NMR based drug-binding experiments also suggest that rimantadine can allosterically inhibit ion conduction via a molecular wedge mechanism. These results suggest the presence of dilation and contraction of the funnel tip that are important for channel activity and that the action of the drug is attenuating this motion. Here, we determined the conformational dynamics and solvent accessibility of the p7 channel. The proton exchange measurements show that the cavity-lining residues are largely water accessible, consistent with the overall funnel shape of the channel. Our relaxation dispersion data show that residues Val7 and Leu8 near the asparagine ring are subject to large chemical exchange, suggesting significant intrinsic channel breathing at the tip of the funnel. Moreover, the hinge regions connecting the narrow and wide regions of the funnel show strong relaxation dispersion and these regions are the binding sites for rimantadine. Presence of rimantadine decreases the conformational dynamics near the asparagine ring and the hinge area. Our data provide direct observation of μs–ms dynamics of the p7 channel and support the molecular wedge mechanism of rimantadine inhibition of the HCV p7 channel

  18. Transverse relaxation dispersion of the p7 membrane channel from hepatitis C virus reveals conformational breathing

    Energy Technology Data Exchange (ETDEWEB)

    Dev, Jyoti; Brüschweiler, Sven [Harvard Medical School, Department of Biological Chemistry and Molecular Pharmacology (United States); Ouyang, Bo [Chinese Academy of Sciences, State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology (China); Chou, James J., E-mail: james-chou@hms.harvard.edu [Harvard Medical School, Department of Biological Chemistry and Molecular Pharmacology (United States)

    2015-04-15

    The p7 membrane protein encoded by hepatitis C virus (HCV) assembles into a homo-hexamer that selectively conducts cations. An earlier solution NMR structure of the hexameric complex revealed a funnel-like architecture and suggests that a ring of conserved asparagines near the narrow end of the funnel are important for cation interaction. NMR based drug-binding experiments also suggest that rimantadine can allosterically inhibit ion conduction via a molecular wedge mechanism. These results suggest the presence of dilation and contraction of the funnel tip that are important for channel activity and that the action of the drug is attenuating this motion. Here, we determined the conformational dynamics and solvent accessibility of the p7 channel. The proton exchange measurements show that the cavity-lining residues are largely water accessible, consistent with the overall funnel shape of the channel. Our relaxation dispersion data show that residues Val7 and Leu8 near the asparagine ring are subject to large chemical exchange, suggesting significant intrinsic channel breathing at the tip of the funnel. Moreover, the hinge regions connecting the narrow and wide regions of the funnel show strong relaxation dispersion and these regions are the binding sites for rimantadine. Presence of rimantadine decreases the conformational dynamics near the asparagine ring and the hinge area. Our data provide direct observation of μs–ms dynamics of the p7 channel and support the molecular wedge mechanism of rimantadine inhibition of the HCV p7 channel.

  19. A proton wire and water channel revealed in the crystal structure of isatin hydrolase

    DEFF Research Database (Denmark)

    Bjerregaard-Andersen, Kaare; Sommer, Theis; Jensen, Jan Kristian

    2014-01-01

    to a novel family of metalloenzymes that include the bacterial kynurenine formamidase. The product state, mimicked by bound thioisatinate, reveals a water molecule that bridges the thioisatinate to a proton wire in an adjacent water channel and thus allows the proton released by the reaction to escape only...... when the product is formed. The functional proton wire present in IH-b represents a unique catalytic feature common to all hydrolases is here trapped and visualized for the first time. The local molecular environment required to coordinate thioisatinate allows stronger and more confident identification...

  20. Use of nonelectrolytes reveals the channel size and oligomeric constitution of the Borrelia burgdorferi P66 porin.

    Directory of Open Access Journals (Sweden)

    Iván Bárcena-Uribarri

    Full Text Available In the Lyme disease spirochete Borrelia burgdorferi, the outer membrane protein P66 is capable of pore formation with an atypical high single-channel conductance of 11 nS in 1 M KCl, which suggested that it could have a larger diameter than 'normal' Gram-negative bacterial porins. We studied the diameter of the P66 channel by analyzing its single-channel conductance in black lipid bilayers in the presence of different nonelectrolytes with known hydrodynamic radii. We calculated the filling of the channel with these nonelectrolytes and the results suggested that nonelectrolytes (NEs with hydrodynamic radii of 0.34 nm or smaller pass through the pore, whereas neutral molecules with greater radii only partially filled the channel or were not able to enter it at all. The diameter of the entrance of the P66 channel was determined to be ≤1.9 nm and the channel has a central constriction of about 0.8 nm. The size of the channel appeared to be symmetrical as judged from one-sidedness of addition of NEs. Furthermore, the P66-induced membrane conductance could be blocked by 80-90% by the addition of the nonelectrolytes PEG 400, PEG 600 and maltohexaose to the aqueous phase in the low millimolar range. The analysis of the power density spectra of ion current through P66 after blockage with these NEs revealed no chemical reaction responsible for channel block. Interestingly, the blockage of the single-channel conductance of P66 by these NEs occurred in about eight subconductance states, indicating that the P66 channel could be an oligomer of about eight individual channels. The organization of P66 as a possible octamer was confirmed by Blue Native PAGE and immunoblot analysis, which both demonstrated that P66 forms a complex with a mass of approximately 460 kDa. Two dimension SDS PAGE revealed that P66 is the only polypeptide in the complex.

  1. Ion channel profile of TRPM8 cold receptors reveals a novel role of TASK-3 potassium channels in thermosensation

    Science.gov (United States)

    Morenilla-Palao, Cruz; Luis, Enoch; Fernández-Peña, Carlos; Quintero, Eva; Weaver, Janelle L.; Bayliss, Douglas A.; Viana, Félix

    2017-01-01

    Summary Animals sense cold ambient temperatures through the activation of peripheral thermoreceptors that express TRPM8, a cold- and menthol-activated ion channel. These receptors can discriminate a very wide range of temperatures from innocuous to noxious. The molecular mechanism responsible for the variable sensitivity of individual cold receptors to temperature is unclear. To address this question, we performed a detailed ion channel expression analysis of cold sensitive neurons, combining BAC transgenesis with a molecular profiling approach in FACS purified TRPM8 neurons. We found that TASK-3 leak potassium channels are highly enriched in a subpopulation of these sensory neurons. The thermal threshold of TRPM8 cold neurons is decreased during TASK-3 blockade and in mice lacking TASK-3 and, most importantly, these mice display hypersensitivity to cold. Our results demonstrate a novel role of TASK-3 channels in thermosensation, showing that a channel-based combinatorial strategy in TRPM8 cold thermoreceptors leads to molecular specialization and functional diversity. PMID:25199828

  2. Contribution of two-pore K+ channels to cardiac ventricular action potential revealed using human iPSC-derived cardiomyocytes.

    Science.gov (United States)

    Chai, Sam; Wan, Xiaoping; Nassal, Drew M; Liu, Haiyan; Moravec, Christine S; Ramirez-Navarro, Angelina; Deschênes, Isabelle

    2017-06-01

    Two-pore K + (K 2p ) channels have been described in modulating background conductance as leak channels in different physiological systems. In the heart, the expression of K 2p channels is heterogeneous with equivocation regarding their functional role. Our objective was to determine the K 2p expression profile and their physiological and pathophysiological contribution to cardiac electrophysiology. Induced pluripotent stem cells (iPSCs) generated from humans were differentiated into cardiomyocytes (iPSC-CMs). mRNA was isolated from these cells, commercial iPSC-CM (iCells), control human heart ventricular tissue (cHVT), and ischemic (iHF) and nonischemic heart failure tissues (niHF). We detected 10 K 2p channels in the heart. Comparing quantitative PCR expression of K 2p channels between human heart tissue and iPSC-CMs revealed K 2p 1.1, K 2p 2.1, K 2p 5.1, and K 2p 17.1 to be higher expressed in cHVT, whereas K 2p 3.1 and K 2p 13.1 were higher in iPSC-CMs. Notably, K 2p 17.1 was significantly lower in niHF tissues compared with cHVT. Action potential recordings in iCells after K 2p small interfering RNA knockdown revealed prolongations in action potential depolarization at 90% repolarization for K 2p 2.1, K 2p 3.1, K 2p 6.1, and K 2p 17.1. Here, we report the expression level of 10 human K 2p channels in iPSC-CMs and how they compared with cHVT. Importantly, our functional electrophysiological data in human iPSC-CMs revealed a prominent role in cardiac ventricular repolarization for four of these channels. Finally, we also identified K 2p 17.1 as significantly reduced in niHF tissues and K 2p 4.1 as reduced in niHF compared with iHF. Thus, we advance the notion that K 2p channels are emerging as novel players in cardiac ventricular electrophysiology that could also be remodeled in cardiac pathology and therefore contribute to arrhythmias. NEW & NOTEWORTHY Two-pore K + (K 2p ) channels are traditionally regarded as merely background leak channels in myriad

  3. Genetic analysis of hyperemesis gravidarum reveals association with intracellular calcium release channel (RYR2).

    Science.gov (United States)

    Fejzo, Marlena Schoenberg; Myhre, Ronny; Colodro-Conde, Lucía; MacGibbon, Kimber W; Sinsheimer, Janet S; Reddy, M V Prasad Linga; Pajukanta, Päivi; Nyholt, Dale R; Wright, Margaret J; Martin, Nicholas G; Engel, Stephanie M; Medland, Sarah E; Magnus, Per; Mullin, Patrick M

    2017-01-05

    Hyperemesis Gravidarum (HG), severe nausea/vomiting in pregnancy (NVP), can cause poor maternal/fetal outcomes. Genetic predisposition suggests the genetic component is essential in discovering an etiology. We performed whole-exome sequencing of 5 families followed by analysis of variants in 584 cases/431 controls. Variants in RYR2 segregated with disease in 2 families. The novel variant L3277R was not found in any case/control. The rare variant, G1886S was more common in cases (p = 0.046) and extreme cases (p = 0.023). Replication of G1886S using Norwegian/Australian data was supportive. Common variants rs790899 and rs1891246 were significantly associated with HG and weight loss. Copy-number analysis revealed a deletion in a patient. RYR2 encodes an intracellular calcium release channel involved in vomiting, cyclic-vomiting syndrome, and is a thyroid hormone target gene. Additionally, RYR2 is a downstream drug target of Inderal, used to treat HG and CVS. Thus, herein we provide genetic evidence for a pathway and therapy for HG. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. A Soluble Fluorescent Binding Assay Reveals PIP2 Antagonism of TREK-1 Channels

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    Cerrone Cabanos

    2017-08-01

    Full Text Available Lipid regulation of ion channels by low-abundance signaling lipids phosphatidylinositol 4,5-bisphosphate (PIP2 and phosphatidic acid (PA has emerged as a central cellular mechanism for controlling ion channels and the excitability of nerves. A lack of robust assays suitable for facile detection of a lipid bound to a channel has hampered the probing of the lipid binding sites and measuring the pharmacology of putative lipid agonists for ion channels. Here, we show a fluorescent PIP2 competition assay for detergent-purified potassium channels, including TWIK-1-related K+-channel (TREK-1. Anionic lipids PA and phosphatidylglycerol (PG bind dose dependently (9.1 and 96 μM, respectively and agonize the channel. Our assay shows PIP2 binds with high affinity (0.87 μM but surprisingly can directly antagonize TREK-1 in liposomes. We propose a model for TREK-1 lipid regulation where PIP2 can compete with PA and PG agonism based on the affinity of the lipid for a site within the channel.

  5. Krebs cycle metabolon: structural evidence of substrate channeling revealed by cross-linking and mass spectrometry.

    Science.gov (United States)

    Wu, Fei; Minteer, Shelley

    2015-02-02

    It has been hypothesized that the high metabolic flux in the mitochondria is due to the self-assembly of enzyme supercomplexes (called metabolons) that channel substrates from one enzyme to another, but there has been no experimental confirmation of this structure or the channeling. A structural investigation of enzyme organization within the Krebs cycle metabolon was accomplished by in vivo cross-linking and mass spectrometry. Eight Krebs cycle enzyme components were isolated upon chemical fixation, and interfacial residues between mitochondrial malate dehydrogenase, citrate synthase, and aconitase were identified. Using constraint protein docking, a low-resolution structure for the three-enzyme complex was achieved, as well as the two-fold symmetric octamer. Surface analysis showed formation of electrostatic channeling upon protein-protein association, which is the first structural evidence of substrate channeling in the Krebs cycle metabolon. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Impedance spectroscopy of micro-Droplets reveals activation of Bacterial Mechanosensitive Channels in Hypotonic Solutions

    Science.gov (United States)

    Ebrahimi, Aida; Alam, Muhammad A.

    Rapid detection of bacterial pathogens is of great importance in healthcare, food safety, environmental monitoring, and homeland security. Most bacterial detection platforms rely on binary fission (i.e. cell growth) to reach a threshold cell population that can be resolved by the sensing method. Since cell division depends on the bacteria type, the detection time of such methods can vary from hours to days. In contrast, in this work, we show that bacteria cells can be detected within minutes by relying on activation of specific protein channels, i.e. mechanosensitive channels (MS channels). When cells are exposed to hypotonic solutions, MS channels allow efflux of solutes to the external solution which leads to release the excessive membrane tension. Release of the cytoplasmic solutes, in turn, results in increase of the electrical conductance measured by droplet-based impedance sensing. The approach can be an effective technique for fast, pre-screening of bacterial contamination at ultra-low concentration.

  7. Optogenetic analysis of a nociceptor neuron and network reveals ion channels acting downstream of primary sensors

    Science.gov (United States)

    Husson, Steven J.; Costa, Wagner Steuer; Wabnig, Sebastian; Stirman, Jeffrey N.; Watson, Joseph D.; Spencer, W. Clay; Akerboom, Jasper; Looger, Loren L.; Treinin, Millet; Miller, David M.; Lu, Hang; Gottschalk, Alexander

    2012-01-01

    Summary Background Nociception generally evokes rapid withdrawal behavior in order to protect the tissue from harmful insults. Most nociceptive neurons responding to mechanical insults display highly branched dendrites, an anatomy shared by Caenorhabditis elegans FLP and PVD neurons, which mediate harsh touch responses. Although several primary molecular nociceptive sensors have been characterized, less is known about modulation and amplification of noxious signals within nociceptor neurons. First, we analyzed the FLP/PVD network by optogenetics and studied integration of signals from these cells in downstream interneurons. Second, we investigated which genes modulate PVD function, based on prior single neuron mRNA profiling of PVD. Results Selectively photoactivating PVD, FLP and downstream interneurons using Channelrhodopsin-2 (ChR2) enabled functionally dissecting this nociceptive network, without interfering signals by other mechanoreceptors. Forward or reverse escape behaviors were determined by PVD and FLP, via integration by command interneurons. To identify mediators of PVD function, acting downstream of primary nocisensor molecules, we knocked down PVD-specific transcripts by RNAi and quantified light-evoked PVD-dependent behavior. Cell-specific disruption of synaptobrevin or voltage-gated Ca2+-channels (VGCCs) showed that PVD signals chemically to command interneurons. Knocking down the DEG/ENaC channel ASIC-1 and the TRPM channel GTL-1 indicated that ASIC-1 may extend PVD’s dynamic range and that GTL-1 may amplify its signals. These channels act cell-autonomously in PVD, downstream of primary mechanosensory molecules. Conclusions Our work implicates TRPM channels in modifying excitability of, and DEG/ENaCs in potentiating signal output from a mechano-nociceptor neuron. ASIC-1 and GTL-1 homologues, if functionally conserved, may denote valid targets for novel analgesics. PMID:22483941

  8. Structure of the Cyanuric Acid Hydrolase TrzD Reveals Product Exit Channel

    Energy Technology Data Exchange (ETDEWEB)

    Bera, Asim K; Aukema, Kelly G.; Elias, Mikael; Wackett, Lawrence P. (UMM)

    2017-03-27

    Cyanuric acid hydrolases are of industrial importance because of their use in aquatic recreational facilities to remove cyanuric acid, a stabilizer for the chlorine. Degradation of excess cyanuric acid is necessary to maintain chlorine disinfection in the waters. Cyanuric acid hydrolase opens the cyanuric acid ring hydrolytically and subsequent decarboxylation produces carbon dioxide and biuret. In the present study, we report the X-ray structure of TrzD, a cyanuric acid hydrolase from Acidovorax citrulli. The crystal structure at 2.19 Å resolution shows a large displacement of the catalytic lysine (Lys163) in domain 2 away from the active site core, whereas the two other active site lysines from the two other domains are not able to move. The lysine displacement is proposed here to open up a channel for product release. Consistent with that, the structure also showed two molecules of the co-product, carbon dioxide, one in the active site and another trapped in the proposed exit channel. Previous data indicated that the domain 2 lysine residue plays a role in activating an adjacent serine residue carrying out nucleophilic attack, opening the cyanuric acid ring, and the mobile lysine guides products through the exit channel.

  9. Structure of the Cyanuric Acid Hydrolase TrzD Reveals Product Exit Channel.

    Science.gov (United States)

    Bera, Asim K; Aukema, Kelly G; Elias, Mikael; Wackett, Lawrence P

    2017-03-27

    Cyanuric acid hydrolases are of industrial importance because of their use in aquatic recreational facilities to remove cyanuric acid, a stabilizer for the chlorine. Degradation of excess cyanuric acid is necessary to maintain chlorine disinfection in the waters. Cyanuric acid hydrolase opens the cyanuric acid ring hydrolytically and subsequent decarboxylation produces carbon dioxide and biuret. In the present study, we report the X-ray structure of TrzD, a cyanuric acid hydrolase from Acidovorax citrulli. The crystal structure at 2.19 Å resolution shows a large displacement of the catalytic lysine (Lys163) in domain 2 away from the active site core, whereas the two other active site lysines from the two other domains are not able to move. The lysine displacement is proposed here to open up a channel for product release. Consistent with that, the structure also showed two molecules of the co-product, carbon dioxide, one in the active site and another trapped in the proposed exit channel. Previous data indicated that the domain 2 lysine residue plays a role in activating an adjacent serine residue carrying out nucleophilic attack, opening the cyanuric acid ring, and the mobile lysine guides products through the exit channel.

  10. 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

  11. Revealing the roles of GORK channels and NADPH oxidase in acclimation to hypoxia in Arabidopsis.

    Science.gov (United States)

    Wang, Feifei; Chen, Zhong-Hua; Liu, Xiaohui; Colmer, Timothy D; Shabala, Lana; Salih, Anya; Zhou, Meixue; Shabala, Sergey

    2017-06-01

    Regulation of root cell K+ is essential for acclimation to low oxygen stress. The potential roles of GORK (depolarization-activated guard cell outward-rectifying potassium) channels and RBOHD (respiratory burst oxidase homologue D) in plant adaptive responses to hypoxia were investigated in the context of tissue specificity (epidermis versus stele; elongation versus mature zone) in roots of Arabidopsis. The expression of GORK and RBOHD was down-regulated by 2- to 3-fold within 1 h and 24 h of hypoxia treatment in Arabidopsis wild-type (WT) roots. Interestingly, a loss of the functional GORK channel resulted in a waterlogging-tolerant phenotype, while rbohD knockout was sensitive to waterlogging. To understand their functions under hypoxia stress, we studied K+, Ca2+, and reactive oxygen species (ROS) distribution in various root cell types. gork1-1 plants had better K+ retention ability in both the elongation and mature zone compared with the WT and rbohD under hypoxia. Hypoxia induced a Ca2+ increase in each cell type after 72 h, and the increase was much less pronounced in rbohD than in the WT. In most tissues except the elongation zone in rbohD, the H2O2 concentration had decreased after 1 h of hypoxia, but then increased significantly after 24 h of hypoxia in each zone and tissue, further suggesting that RBOHD may shape hypoxia-specific Ca2+ signatures via the modulation of apoplastic H2O2 production. Taken together, our data suggest that plants lacking functional GORK channels are more capable of retaining K+ for their better performance under hypoxia, and that RBOHD is crucial in hypoxia-induced Ca2+ signalling for stress sensing and acclimation mechanism. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  12. Differences between main-channel and off-channel food webs in the upper Mississippi River revealed by fatty acid profiles of consumers

    Science.gov (United States)

    Larson, James H.; Bartsch, Michelle; Gutreuter, Steve; Knights, Brent C.; Bartsch, Lynn; Richardson, William B.; Vallazza, Jonathan M.; Arts, Michael T.

    2015-01-01

    Large river systems are often thought to contain a mosaic of patches with different habitat characteristics driven by differences in flow and mixing environments. Off-channel habitats (e.g., backwater areas, secondary channels) can become semi-isolated from main-channel water inputs, leading to the development of distinct biogeochemical environments. Observations of adult bluegill (Lepomis macrochirus) in the main channel of the Mississippi River led to speculation that the main channel offered superior food resources relative to off-channel areas. One important aspect of food quality is the quantity and composition of polyunsaturated fatty acids (PUFA). We sampled consumers from main-channel and backwater habitats to determine whether they differed in PUFA content. Main-channel individuals for relatively immobile species (young-of-year bluegill, zebra mussels [Dreissena polymorpha], and plain pocketbook mussels [Lampsilis cardium]) had significantly greater PUFA content than off-channel individuals. No difference in PUFA was observed for the more mobile gizzard shad (Dorsoma cepedianum), which may move between main-channel and off-channel habitats even at early life-history stages. As off-channel habitats become isolated from main-channel waters, flow and water column nitrogen decrease, potentially improving conditions for nitrogen-fixing cyanobacteria and vascular plants that, in turn, have low PUFA content. We conclude that main-channel food webs of the upper Mississippi River provide higher quality food resources for some riverine consumers as compared to food webs in off-channel habitats.

  13. Adrenaline reveals the torsadogenic effect of combined blockade of potassium channels in anaesthetized guinea pigs.

    Science.gov (United States)

    Michael, G; Kane, K A; Coker, S J

    2008-08-01

    Torsade de pointes (TdP) can be induced in several species by a reduction in cardiac repolarizing capacity. The aim of this study was to assess whether combined I(Kr) and I(Ks) blockade could induce TdP in anaesthetized guinea pigs and whether short-term variability (STV) or triangulation of action potentials could predict TdP. Experiments were performed in open-chest, pentobarbital-anaesthetized, adrenaline-stimulated male Dunkin Hartley guinea pigs, which received three consecutive i.v. infusions of either vehicle, the I(Kr) blocker E-4031 (3, 10 and 30 nmol kg(-1) min(-1)), the I(Ks) blocker HMR1556 (75, 250, 750 nmol kg(-1) min(-1)) or E-4031 and HMR1556 combined. Phenylephrine-stimulated guinea pigs were also treated with the K(+) channel blockers in combination. Arterial blood pressure, ECGs and epicardial monophasic action potential (MAP) were recorded. TdP was observed in 75% of adrenaline-stimulated guinea pigs given the K(+) channel blockers in combination, but was not observed in guinea pigs treated with either I(K) blocker alone, or in phenylephrine-stimulated guinea pigs. Salvos and ventricular tachycardia occurred with adrenaline but not with phenylephrine. No changes in STV or triangulation of the MAP signals were observed before TdP. Combined blockade of both I(Kr) and I(Ks) plus the addition of adrenaline were required to induce TdP in anaesthetized guinea pigs. This suggests that there must be sufficient depletion of repolarization reserve and an appropriate trigger for TdP to occur.

  14. Study results of picking high amplitude reflectors in turbidite channel to reveal detail of methane hydrate concentrated zone

    Energy Technology Data Exchange (ETDEWEB)

    Shimoda, N.; Saeki, T.; Inamori, T.; Kobayashi, T.; Fujii, T. [Japan Oil, Gas and Metals National Corp., Mihama-ku, Chiba (Japan). Technology Research Center

    2008-07-01

    Bottom simulating reflectors are found extensively in the eastern Nankai Trough. BSR is considered as a bottom of methane hydrate bearing sediments. High resolution three-dimensional seismic surveys were conducted in 2002 and a multi-well drilling campaign was executed in 2004. This paper discussed the resource potential of methane hydrate in this area. The paper discussed an evaluation of more than 10 methane hydrate concentrated zones in the Nankai Trough. Methane hydrated concentrated zones in this area are roughly classified into 2 types of turbidite sedimentary facies from the seismic geomorphological point of view known as lobe and channel. This paper attempted to interpret a detailed structure of a channel type methane hydrate concentrated zone. High amplitude reflector patches may indicate sand dominated bodies with high methane hydrate concentration. It was concluded that picked reflector patches demonstrated that the methane hydrate concentrated zone was biforked at a lower current area. Detailed observations also revealed that the methane hydrate concentrated zone was developed in a channel complex of which fluid migration was slowly shifted.

  15. Tryptophan Scanning Reveals Dense Packing of Connexin Transmembrane Domains in Gap Junction Channels Composed of Connexin32*

    Science.gov (United States)

    Brennan, Matthew J.; Karcz, Jennifer; Vaughn, Nicholas R.; Woolwine-Cunningham, Yvonne; DePriest, Adam D.; Escalona, Yerko; Perez-Acle, Tomas; Skerrett, I. Martha

    2015-01-01

    Tryptophan was substituted for residues in all four transmembrane domains of connexin32. Function was assayed using dual cell two-electrode voltage clamp after expression in Xenopus oocytes. Tryptophan substitution was poorly tolerated in all domains, with the greatest impact in TM1 and TM4. For instance, in TM1, 15 substitutions were made, six abolished coupling and five others significantly reduced function. Only TM2 and TM3 included a distinct helical face that lacked sensitivity to tryptophan substitution. Results were visualized on a comparative model of Cx32 hemichannel. In this model, a region midway through the membrane appears highly sensitive to tryptophan substitution and includes residues Arg-32, Ile-33, Met-34, and Val-35. In the modeled channel, pore-facing regions of TM1 and TM2 were highly sensitive to tryptophan substitution, whereas the lipid-facing regions of TM3 and TM4 were variably tolerant. Residues facing a putative intracellular water pocket (the IC pocket) were also highly sensitive to tryptophan substitution. Although future studies will be required to separate trafficking-defective mutants from those that alter channel function, a subset of interactions important for voltage gating was identified. Interactions important for voltage gating occurred mainly in the mid-region of the channel and focused on TM1. To determine whether results could be extrapolated to other connexins, TM1 of Cx43 was scanned revealing similar but not identical sensitivity to TM1 of Cx32. PMID:25969535

  16. Prefrontal activation during two Japanese Stroop tasks revealed with multi-channel near-infrared spectroscopy.

    Science.gov (United States)

    Watanabe, Yukina; Sumitani, Satsuki; Hosokawa, Mai; Ohmori, Tetsuro

    2015-01-01

    The Stroop task is sometimes used in psychiatric research to elicit prefrontal activity, which presumably reflects cognitive functioning. Although there are two Stroop tasks (Kana script and Kanji script) in Japan, it is unclear whether these tasks elicit the same hemoglobin changes. Moreover, it is unclear whether psychological conditions or characteristics influence hemoglobin changes in the Japanese Stroop task. The aim of this study was to clarify whether hemoglobin changes elicited by the two Japanese Stroop tasks accurately reflected cognitive functioning. Hemoglobin changes were measured with multi-channel near-infrared spectroscopy (NIRS) in 100 healthy Japanese participants performing two Japanese Stroop tasks. The Beck-Depression Inventory (BDI), State-Trait-Anxiety Inventory (STAI), and Maudsley Obsessive Compulsive Inventory (MOCI) were administered to participants to identify psychological conditions or personality characteristics. Compared with the Kanji task, the Kana task produced a greater Stroop effect and a larger increase in oxyhemoglobin (oxy-Hb) concentration. Moreover there were no significant correlations between oxy-Hb concentration and BDI, STAI-trait, STAI-state, or MOCI scores. Therefore we found that a participant's psychological conditions or characteristics did not influence the hemodynamic changes during either task. These data suggest the Kana Stroop task is more useful than the Kanji Stroop task for NIRS studies in psychiatric research.

  17. REVEALING THE ACTIVATION PATHWAY FOR TMEM16A CHLORIDE CHANNELS FROM MACROSCOPIC CURRENTS AND KINETIC MODELS

    Science.gov (United States)

    Contreras-Vite, Juan A.; Cruz-Rangel, Silvia; De Jesús-Pérez, José J.; Aréchiga Figueroa, Iván A.; Rodríguez-Menchaca, Aldo A.; Pérez-Cornejo, Patricia; Hartzell, H. Criss; Arreola, Jorge

    2017-01-01

    TMEM16A (ANO1), the pore-forming subunit of calcium-activated chloride channels, regulates several physiological and pathophysiological processes such as smooth muscle contraction, cardiac and neuronal excitability, salivary secretion, tumour growth, and cancer progression. Gating of TMEM16A is complex because it involves the interplay between increases in intracellular calcium concentration ([Ca2+]i), membrane depolarization, extracellular Cl− or permeant anions, and intracellular protons. Our goal here was to understand how these variables regulate TMEM16A gating and to explain four observations. a) TMEM16A is activated by voltage in the absence of intracellular Ca2+. b) The Cl− conductance is decreased after reducing extracellular Cl− concentration ([Cl−]o). c) ICl is regulated by physiological concentrations of [Cl−]o. d) In cells dialyzed with 0.2 µM [Ca2+]i, Cl− has a bimodal effect: at [Cl−]o < 30 mM TMEM16A current activates with a monoexponential time course, but above 30 mM [Cl−]o ICl activation displays fast and slow kinetics. To explain the contribution of Vm, Ca2+ and Cl− to gating, we developed a 12-state Markov chain model. This model explains TMEM16A activation as a sequential, direct, and Vm-dependent binding of two Ca2+ ions coupled to a Vm-dependent binding of an external Cl− ion, with Vm-dependent transitions between states. Our model predicts that extracellular Cl− does not alter the apparent Ca2+ affinity of TMEM16A, which we corroborated experimentally. Rather, extracellular Cl− acts by stabilizing the open configuration induced by Ca2+ and by contributing to the Vm dependence of activation. PMID:27138167

  18. Regional two-dimensional magnetotelluric profile in West Bohemia/Vogtland reveals deep conductive channel into the earthquake swarm region

    Science.gov (United States)

    Muñoz, Gerard; Weckmann, Ute; Pek, Josef; Kováčiková, Světlana; Klanica, Radek

    2018-03-01

    The West Bohemia/Vogtland region, characterized by the intersection of the Eger (Ohře) Rift and the Mariánské Lázně fault, is a geodynamically active area exhibiting repeated occurrence of earthquake swarms, massive CO2 emanations and mid Pleistocene volcanism. The Eger Rift is the only known intra-continental region in Europe where such deep seated, active lithospheric processes currently take place. We present an image of electrical resistivity obtained from two-dimensional inversion of magnetotelluric (MT) data acquired along a regional profile crossing the Eger Rift. At the near surface, the Cheb basin and the aquifer feeding the mofette fields of Bublák and Hartoušov have been imaged as part of a region of very low resistivity. The most striking resistivity feature, however, is a deep reaching conductive channel which extends from the surface into the lower crust spatially correlated with the hypocentres of the seismic events of the Nový Kostel Focal Zone. This channel has been interpreted as imaging a pathway from a possible mid-crustal fluid reservoir to the surface. The resistivity model reinforces the relation between the fluid circulation along deep-reaching faults and the generation of the earthquakes. Additionally, a further conductive channel has been revealed to the south of the profile. This other feature could be associated to fossil hydrothermal alteration related to Mýtina and/or Neualbenreuth Maar structures or alternatively could be the signature of a structure associated to the suture between the Saxo-Thuringian and Teplá-Barrandian zones, whose surface expression is located only a few kilometres away.

  19. Atomic force microscopy imaging reveals the formation of ASIC/ENaC cross-clade ion channels

    Energy Technology Data Exchange (ETDEWEB)

    Jeggle, Pia; Smith, Ewan St. J.; Stewart, Andrew P. [Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD (United Kingdom); Haerteis, Silke; Korbmacher, Christoph [Institut für Zelluläre und Molekulare Physiologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Waldstrasse 6, 91054 Erlangen (Germany); Edwardson, J. Michael, E-mail: jme1000@cam.ac.uk [Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD (United Kingdom)

    2015-08-14

    ASIC and ENaC are co-expressed in various cell types, and there is evidence for a close association between them. Here, we used atomic force microscopy (AFM) to determine whether ASIC1a and ENaC subunits are able to form cross-clade hybrid ion channels. ASIC1a and ENaC could be co-isolated from detergent extracts of tsA 201 cells co-expressing the two subunits. Isolated proteins were incubated with antibodies against ENaC and Fab fragments against ASIC1a. AFM imaging revealed proteins that were decorated by both an antibody and a Fab fragment with an angle of ∼120° between them, indicating the formation of ASIC1a/ENaC heterotrimers. - Highlights: • There is evidence for a close association between ASIC and ENaC. • We used AFM to test whether ASIC1a and ENaC subunits form cross-clade ion channels. • Isolated proteins were incubated with subunit-specific antibodies and Fab fragments. • Some proteins were doubly decorated at ∼120° by an antibody and a Fab fragment. • Our results indicate the formation of ASIC1a/ENaC heterotrimers.

  20. Structural basis for ion selectivity revealed by high-resolution crystal structure of Mg2+ channel MgtE.

    Science.gov (United States)

    Takeda, Hironori; Hattori, Motoyuki; Nishizawa, Tomohiro; Yamashita, Keitaro; Shah, Syed T A; Caffrey, Martin; Maturana, Andrés D; Ishitani, Ryuichiro; Nureki, Osamu

    2014-11-04

    Magnesium is the most abundant divalent cation in living cells and is crucial to several biological processes. MgtE is a Mg(2+) channel distributed in all domains of life that contributes to the maintenance of cellular Mg(2+) homeostasis. Here we report the high-resolution crystal structures of the transmembrane domain of MgtE, bound to Mg(2+), Mn(2+) and Ca(2+). The high-resolution Mg(2+)-bound crystal structure clearly visualized the hydrated Mg(2+) ion within its selectivity filter. Based on those structures and biochemical analyses, we propose a cation selectivity mechanism for MgtE in which the geometry of the hydration shell of the fully hydrated Mg(2+) ion is recognized by the side-chain carboxylate groups in the selectivity filter. This is in contrast to the K(+)-selective filter of KcsA, which recognizes a dehydrated K(+) ion. Our results further revealed a cation-binding site on the periplasmic side, which regulate channel opening and prevents conduction of near-cognate cations.

  1. Adaptable interaction between aquaporin-1 and band 3 reveals a potential role of water channel in blood CO2transport.

    Science.gov (United States)

    Hsu, Kate; Lee, Ting-Ying; Periasamy, Ammasi; Kao, Fu-Jen; Li, Li-Tzu; Lin, Chuang-Yu; Lin, Hui-Ju; Lin, Marie

    2017-10-01

    Human CO 2 respiration requires rapid conversion between CO 2 and HCO 3 - Carbonic anhydrase II facilitates this reversible reaction inside red blood cells, and band 3 [anion exchanger 1 (AE1)] provides a passage for HCO 3 - flux across the cell membrane. These 2 proteins are core components of the CO 2 transport metabolon. Intracellular H 2 O is necessary for CO 2 /HCO 3 - conversion. However, abundantly expressed aquaporin 1 (AQP1) in erythrocytes is thought not to be part of band 3 complexes or the CO 2 transport metabolon. To solve this conundrum, we used Förster resonance energy transfer (FRET) measured by fluorescence lifetime imaging (FLIM-FRET) and identified interaction between aquaporin-1 and band 3 at a distance of 8 nm, within the range of dipole-dipole interaction. Notably, their interaction was adaptable to membrane tonicity changes. This suggests that the function of AQP1 in tonicity response could be coupled or correlated to its function in band 3-mediated CO 2 /HCO 3 - exchange. By demonstrating AQP1 as a mobile component of the CO 2 transport metabolon, our results uncover a potential role of water channel in blood CO 2 transport and respiration.-Hsu, K., Lee, T.-Y., Periasamy, A., Kao, F.-J., Li, L.-T., Lin, C.-Y., Lin, H.-J., Lin, M. Adaptable interaction between aquaporin-1 and band 3 reveals a potential role of water channel in blood CO 2 transport. © FASEB.

  2. Phylogeographic analysis of the red seaweed Palmaria palmata reveals a Pleistocene marine glacial refugium in the English Channel.

    Science.gov (United States)

    Provan, Jim; Wattier, Remi A; Maggs, Christine A

    2005-03-01

    Phylogeography has provided a new approach to the analysis of the postglacial history of a wide range of taxa but, to date, little is known about the effect of glacial periods on the marine biota of Europe. We have utilized a combination of nuclear, plastid and mitochondrial genetic markers to study the biogeographic history of the red seaweed Palmaria palmata in the North Atlantic. Analysis of the nuclear rDNA operon (ITS1-5.8S-ITS2), the plastid 16S-trnI-trnA-23S-5S, rbcL-rbcS and rpl12-rps31-rpl9 regions and the mitochondrial cox2-3 spacer has revealed the existence of a previously unidentified marine refugium in the English Channel, along with possible secondary refugia off the southwest coast of Ireland and in northeast North America and/or Iceland. Coalescent and mismatch analyses date the expansion of European populations from approximately 128,000 BP and suggest a continued period of exponential growth since then. Consequently, we postulate that the penultimate (Saale) glacial maximum was the main event in shaping the biogeographic history of European P. palmata populations which persisted throughout the last (Weichselian) glacial maximum (c. 20,000 BP) in the Hurd Deep, an enigmatic trench in the English Channel.

  3. Structure of the SthK carboxy-terminal region reveals a gating mechanism for cyclic nucleotide-modulated ion channels.

    Directory of Open Access Journals (Sweden)

    Divya Kesters

    Full Text Available Cyclic nucleotide-sensitive ion channels are molecular pores that open in response to cAMP or cGMP, which are universal second messengers. Binding of a cyclic nucleotide to the carboxyterminal cyclic nucleotide binding domain (CNBD of these channels is thought to cause a conformational change that promotes channel opening. The C-linker domain, which connects the channel pore to this CNBD, plays an important role in coupling ligand binding to channel opening. Current structural insight into this mechanism mainly derives from X-ray crystal structures of the C-linker/CNBD from hyperpolarization-activated cyclic nucleotide-modulated (HCN channels. However, these structures reveal little to no conformational changes upon comparison of the ligand-bound and unbound form. In this study, we take advantage of a recently identified prokaryote ion channel, SthK, which has functional properties that strongly resemble cyclic nucleotide-gated (CNG channels and is activated by cAMP, but not by cGMP. We determined X-ray crystal structures of the C-linker/CNBD of SthK in the presence of cAMP or cGMP. We observe that the structure in complex with cGMP, which is an antagonist, is similar to previously determined HCN channel structures. In contrast, the structure in complex with cAMP, which is an agonist, is in a more open conformation. We observe that the CNBD makes an outward swinging movement, which is accompanied by an opening of the C-linker. This conformation mirrors the open gate structures of the Kv1.2 channel or MthK channel, which suggests that the cAMP-bound C-linker/CNBD from SthK represents an activated conformation. These results provide a structural framework for better understanding cyclic nucleotide modulation of ion channels, including HCN and CNG channels.

  4. Atomic force microscopy imaging reveals the formation of ASIC/ENaC cross-clade ion channels.

    Science.gov (United States)

    Jeggle, Pia; Smith, Ewan St J; Stewart, Andrew P; Haerteis, Silke; Korbmacher, Christoph; Edwardson, J Michael

    2015-08-14

    ASIC and ENaC are co-expressed in various cell types, and there is evidence for a close association between them. Here, we used atomic force microscopy (AFM) to determine whether ASIC1a and ENaC subunits are able to form cross-clade hybrid ion channels. ASIC1a and ENaC could be co-isolated from detergent extracts of tsA 201 cells co-expressing the two subunits. Isolated proteins were incubated with antibodies against ENaC and Fab fragments against ASIC1a. AFM imaging revealed proteins that were decorated by both an antibody and a Fab fragment with an angle of ∼120° between them, indicating the formation of ASIC1a/ENaC heterotrimers. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. 2D IR spectroscopy reveals the role of water in the binding of channel-blocking drugs to the influenza M2 channel

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-06-21

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

  6. 2D IR spectroscopy reveals the role of water in the binding of channel-blocking drugs to the influenza M2 channel

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  7. Voltage-dependent conformational changes in human Ca2+- and voltage-activated K+ channel, revealed by voltage-clamp fluorometry

    Science.gov (United States)

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

    2006-01-01

    Large conductance voltage- and Ca2+-activated K+ (BKCa) channels regulate important physiological processes such as neurotransmitter release and vascular tone. BKCa 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. PMID:16895996

  8. 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.

  9. Paracellular barrier and channel functions of TJ claudins in organizing biological systems: advances in the field of barriology revealed in knockout mice.

    Science.gov (United States)

    Tamura, Atsushi; Tsukita, Sachiko

    2014-12-01

    Claudin was first identified as a four-transmembrane protein in the tight junctions (TJs) between epithelial cells. The claudin family has 27 members, which are specifically expressed depending on the epithelial cell type. Accumulating evidence has revealed that claudins are responsible for the paracellular barrier that prevents molecules from passing through epithelial cell sheets. In addition, the extracellular domains of some claudins enable them to act as a permselective paracellular channel for specific molecules, including ions and/or non-ionic solutes. Recent studies using claudin knockout mice revealed that the loss of claudins' specific paracellular barrier and/or channel functions affects specific biological functions and leads to pathological states. In this review, considering recent findings in vivo, we describe how, sometimes in concert with canonical transporters and channels, the paracellular barrier and channel functions of claudins sophisticatedly organize biological systems. Copyright © 2014. Published by Elsevier Ltd.

  10. Fluid escape structures in the Graham Bank region (Sicily Channel, Central Mediterranean) revealing volcanic and neotectonic activity.

    Science.gov (United States)

    Spatola, Daniele; Pennino, Valentina; Basilone, Luca; Interbartolo, Francesco; Micallef, Aaron; Sulli, Attilio; Basilone, Walter

    2016-04-01

    morphometric analysis of these volcanoes has been conducted: they are up to about 115-160 m high and 500-1500 m wide. Most of them show very strongly inclined flanks with 30° of average slope. The SCV2 and SCV3 form the Graham Bank, 3.5X2.8 km wide, elongated in the NW-SE direction. At the top of SCV2 focused seepage plumes were observed in the entire water column, through the CHIRP data, where we calculated that they release, a volume of about 10950 m3 and 43960 m3of gases, respectively. In this work, we present the first results of a data collection that have got as main result the identification and mapping of the fluid escape structures revealing the relationship between the active tectonic with migration of fluids, to be used to assess the Submarine Geo-Hazard in the Sicily Channel. We identified two fluid escape fields whose genesis and evolution appear linked to the neotectonic and volcanic activities respectively, that represent the main controlling factors for the migration of fluid; considering the good correlation between pockmarks and the main identified fault systems. In conclusion, our results suggest that the degassing of fluids in this region is rooted at depth, and is mainly aligned with the NW-SE dip/strike slip fault systems, repeatedly reactivated, and linked to the volcanic activity.

  11. Characterization of the first honeybee Ca²⁺ channel subunit reveals two novel species- and splicing-specific modes of regulation of channel inactivation.

    Science.gov (United States)

    Cens, Thierry; Rousset, Matthieu; Collet, Claude; Raymond, Valérie; Démares, Fabien; Quintavalle, Annabelle; Bellis, Michel; Le Conte, Yves; Chahine, Mohamed; Charnet, Pierre

    2013-07-01

    The honeybee is a model system to study learning and memory, and Ca(2+) signals play a key role in these processes. We have cloned, expressed, and characterized the first honeybee Ca(2+) channel subunit. We identified two splice variants of the Apis CaVβ Ca(2+) channel subunit (Am-CaVβ) and demonstrated expression in muscle and neurons. Although AmCaVβ shares with vertebrate CaVβ subunits the SH3 and GK domains, it beholds a unique N terminus that is alternatively spliced in the first exon to produce a long (a) and short (b) variant. When expressed with the CaV2 channels both, AmCaVβa and AmCaVβb, increase current amplitude, shift the voltage-sensitivity of the channel, and slow channel inactivation as the vertebrate CaVβ2a subunit does. However, as opposed to CaVβ2a, slow inactivation induced by Am-CaVβa was insensitive to palmitoylation but displayed a unique PI3K sensitivity. Inactivation produced by the b variant was PI3K-insensitive but staurosporine/H89-sensitive. Deletion of the first exon suppressed the sensitivity to PI3K inhibitors, staurosporine, or H89. Recording of Ba(2+) currents in Apis neurons or muscle cells evidenced a sensitivity to PI3K inhibitors and H89, suggesting that both AmCaVβ variants may be important to couple cell signaling to Ca(2+) entry in vivo. Functional interactions with phospho-inositide and identification of phosphorylation sites in AmCaVβa and AmCaVβb N termini, respectively, suggest that AmCaVβ splicing promoted two novel and alternative modes of regulation of channel activity with specific signaling pathways. This is the first description of a splicing-dependent kinase switch in the regulation of Ca(2+) channel activity by CaVβ subunit.

  12. Crystal Structure of Inhibitor-Bound P450BM-3 Reveals Open Conformation of Substrate Access Channel

    Energy Technology Data Exchange (ETDEWEB)

    Haines, Donovan C.; Chen, Baozhi; Tomchick, Diana R.; Bondlela, Muralidhar; Hegde, Amita; Machius, Mischa; Peterson, Julian A. (Texas); (UTSMC)

    2008-08-19

    P450BM-3 is an extensively studied P450 cytochrome that is naturally fused to a cytochrome P450 reductase domain. Crystal structures of the heme domain of this enzyme have previously generated many insights into features of P450 structure, substrate binding specificity, and conformational changes that occur on substrate binding. Although many P450s are inhibited by imidazole, this compound does not effectively inhibit P450BM-3. {omega}-Imidazolyl fatty acids have previously been found to be weak inhibitors of the enzyme and show some unusual cooperativity with the substrate lauric acid. We set out to improve the properties of these inhibitors by attaching the {omega}-imidazolyl fatty acid to the nitrogen of an amino acid group, a tactic that we used previously to increase the potency of substrates. The resulting inhibitors were significantly more potent than their parent compounds lacking the amino acid group. A crystal structure of one of the new inhibitors bound to the heme domain of P450BM-3 reveals that the mode of interaction of the amino acid group with the enzyme is different from that previously observed for acyl amino acid substrates. Further, required movements of residues in the active site to accommodate the imidazole group provide an explanation for the low affinity of imidazole itself. Finally, the previously observed cooperativity with lauric acid is explained by a surprisingly open substrate-access channel lined with hydrophobic residues that could potentially accommodate lauric acid in addition to the inhibitor itself.

  13. Pharmacologic inhibition of small-conductance calcium-activated potassium (SK) channels by NS8593 reveals atrial antiarrhythmic potential in horses

    DEFF Research Database (Denmark)

    Haugaard, Maria Mathilde; Hesselkilde, Eva Zander; Pehrson, Steen Michael

    2015-01-01

    . METHODS: Cardiac biopsies were analyzed to investigate the expression level of the most prominent cardiac ion channels, with special focus on SK channels, in the equine heart. Subcellular distribution of SK isoform 2 (SK2) was assessed by immunohistochemistry and confocal microscopy......, and ventricular depolarization and repolarization times. RESULTS: Analysis revealed equivalent mRNA transcript levels of the 3 SK channel isoforms in atria compared to ventricles. Immunohistochemistry and confocal microscopy displayed a widespread distribution of SK2 in both atrial and ventricular cardiomyocytes....... NS8593 terminated all induced AF episodes (duration ≥15 minutes), caused pronounced prolongation of atrial effective refractory period, and reduced AF duration and vulnerability. QRS duration and QTc interval were not affected by treatment. CONCLUSION: SK channels are widely distributed in atrial...

  14. Exome sequencing reveals novel rare variants in the ryanodine receptor and calcium channel genes in malignant hyperthermia families.

    Science.gov (United States)

    Kim, Jerry H; Jarvik, Gail P; Browning, Brian L; Rajagopalan, Ramakrishnan; Gordon, Adam S; Rieder, Mark J; Robertson, Peggy D; Nickerson, Deborah A; Fisher, Nickla A; Hopkins, Philip M

    2013-11-01

    About half of malignant hyperthermia (MH) cases are associated with skeletal muscle ryanodine receptor 1 (RYR1) and calcium channel, voltage-dependent, L type, α1S subunit (CACNA1S) gene mutations, leaving many with an unknown cause. The authors chose to apply a sequencing approach to uncover causal variants in unknown cases. Sequencing the exome, the protein-coding region of the genome, has power at low sample sizes and identified the cause of over a dozen Mendelian disorders. The authors considered four families with multiple MH cases lacking mutations in RYR1 and CACNA1S by Sanger sequencing of complementary DNA. Exome sequencing in two affecteds per family, chosen for maximum genetic distance, were compared. Variants were ranked by allele frequency, protein change, and measures of conservation among mammals to assess likelihood of causation. Finally, putative pathogenic mutations were genotyped in other family members to verify cosegregation with MH. Exome sequencing revealed one rare RYR1 nonsynonymous variant in each of three families (Asp1056His, Val2627Met, Val4234Leu), and one CACNA1S variant (Thr1009Lys) in the fourth family. These were not seen in variant databases or in our control population sample of 5,379 exomes. Follow-up sequencing in other family members verified cosegregation of alleles with MH. The authors found that using both exome sequencing and allele frequency data from large sequencing efforts may aid genetic diagnosis of MH. In a sample selected by the authors, this technique was more sensitive for variant detection in known genes than Sanger sequencing of complementary DNA, and allows for the possibility of novel gene discovery.

  15. A chimeric prokaryotic-eukaryotic pentameric ligand gated ion channel reveals interactions between the extracellular and transmembrane domains shape neurosteroid modulation.

    Science.gov (United States)

    Ghosh, Borna; Tsao, Tzu-Wei; Czajkowski, Cynthia

    2017-10-01

    Pentameric ligand-gated ion channels (pLGICs) are the targets of several clinical and endogenous allosteric modulators including anesthetics and neurosteroids. Molecular mechanisms underlying allosteric drug modulation are poorly understood. Here, we constructed a chimeric pLGIC by fusing the extracellular domain (ECD) of the proton-activated, cation-selective bacterial channel GLIC to the transmembrane domain (TMD) of the human ρ1 chloride-selective GABA A R, and tested the hypothesis that drug actions are regulated locally in the domain that houses its binding site. The chimeric channels were proton-gated and chloride-selective demonstrating the GLIC ECD was functionally coupled to the GABAρ TMD. Channels were blocked by picrotoxin and inhibited by pentobarbital, etomidate and propofol. The point mutation, ρ TMD W328M, conferred positive modulation and direct gating by pentobarbital. The data suggest that the structural machinery mediating general anesthetic modulation resides in the TMD. Proton-activation and neurosteroid modulation of the GLIC-ρ chimeric channels, however, did not simply mimic their respective actions on GLIC and GABAρ revealing that across domain interactions between the ECD and TMD play important roles in determining their actions. Proton-induced current responses were biphasic suggesting that the chimeric channels contain an additional proton sensor. Neurosteroid modulation of the GLIC-ρ chimeric channels by the stereoisomers, 5α-THDOC and 5β-THDOC, were swapped compared to their actions on GABAρ indicating that positive versus negative neurosteroid modulation is not encoded solely in the TMD nor by neurosteroid isomer structure but is dependent on specific interdomain connections between the ECD and TMD. Our data reveal a new mechanism for shaping neurosteroid modulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Regional two-dimensional magnetotelluric profile in West Bohemia/Vogtland reveals deep conductive channel into the earthquake swarm region

    Czech Academy of Sciences Publication Activity Database

    Muňoz, G.; Weckmann, U.; Pek, Josef; Kováčiková, Světlana; Klanica, Radek

    2018-01-01

    Roč. 727, March (2018), s. 1-11 Institutional support: RVO:67985530 Keywords : magnetotellurics * West Bohemia * Fogtland * earthquake swarm * conductive channel * fluids Subject RIV: DC - Siesmology, Volcanology, Earth Structure OBOR OECD: Volcanology

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    Li-Min Yang

    2013-02-01

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

  19. Sar1-GTPase-dependent ER exit of KATP channels revealed by a mutation causing congenital hyperinsulinism

    DEFF Research Database (Denmark)

    Taneja, Tarvinder K; Mankouri, Jamel; Karnik, Rucha

    2009-01-01

    The ATP-sensitive potassium (K(ATP)) channel controls insulin secretion by coupling glucose metabolism to excitability of the pancreatic beta-cell membrane. The channel comprises four subunits each of Kir6.2 and the sulphonylurea receptor (SUR1), encoded by KCNJ11 and ABCC8, respectively. Mutations...... caused by one such mutation in Kir6.2, E282K. The study led to the discovery that Kir6.2 contains a di-acidic ER exit signal, (280)DLE(282), which promotes concentration of the channel into COPII-enriched ER exit sites prior to ER export via a process that requires Sar1-GTPase. The E282K mutation...... abrogates the exit signal, and thereby prevents the ER export and surface expression of the channel. When co-expressed, the mutant subunit was able to associate with the wild-type Kir6.2 and form functional channels. Thus unlike most mutations, the E282K mutation does not cause protein mis-folding. Since...

  20. Fluorescence-tracking of activation gating in human ERG channels reveals rapid S4 movement and slow pore opening.

    Directory of Open Access Journals (Sweden)

    Zeineb Es-Salah-Lamoureux

    2010-05-01

    Full Text Available hERG channels are physiologically important ion channels which mediate cardiac repolarization as a result of their unusual gating properties. These are very slow activation compared with other mammalian voltage-gated potassium channels, and extremely rapid inactivation. The mechanism of slow activation is not well understood and is investigated here using fluorescence as a direct measure of S4 movement and pore opening.Tetramethylrhodamine-5-maleimide (TMRM fluorescence at E519 has been used to track S4 voltage sensor movement, and channel opening and closing in hERG channels. Endogenous cysteines (C445 and C449 in the S1-S2 linker bound TMRM, which caused a 10 mV hyperpolarization of the V((1/2 of activation to -27.5+/-2.0 mV, and showed voltage-dependent fluorescence signals. Substitution of S1-S2 linker cysteines with valines allowed unobstructed recording of S3-S4 linker E519C and L520C emission signals. Depolarization of E519C channels caused rapid initial fluorescence quenching, fit with a double Boltzmann relationship, F-V(ON, with V((1/2 (,1 = -37.8+/-1.7 mV, and V((1/2 (,2 = 43.5+/-7.9 mV. The first phase, V((1/2 (,1, was approximately 20 mV negative to the conductance-voltage relationship measured from ionic tail currents (G-V((1/2 = -18.3+/-1.2 mV, and relatively unchanged in a non-inactivating E519C:S620T mutant (V((1/2 = -34.4+/-1.5 mV, suggesting the fast initial fluorescence quenching tracked S4 voltage sensor movement. The second phase of rapid quenching was absent in the S620T mutant. The E519C fluorescence upon repolarization (V((1/2 = -20.6+/-1.2, k = 11.4 mV and L520C quenching during depolarization (V((1/2 = -26.8+/-1.0, k = 13.3 mV matched the respective voltage dependencies of hERG ionic tails, and deactivation time constants from -40 to -110 mV, suggesting they detected pore-S4 rearrangements related to ionic current flow during pore opening and closing.THE DATA INDICATE: 1 that rapid environmental changes occur at the

  1. Surface circulation patterns in the Sicily Channel and Ionian Sea as revealed by MODIS chlorophyll images from 2003 to 2007

    Science.gov (United States)

    Ciappa, Achille Carlo

    2009-09-01

    The surface circulation in the Sicily Channel and in the Ionian Sea is investigated using MODerate-resolution Infrared Spectro-radiometer (MODIS) chlorophyll-a images collected from 2003 to 2007. The use of chlorophyll as surface tracer in the area is verified by comparison with satellite altimeter measurements available during the same period. The interaction between waters with different concentrations of chlorophyll adds new particulars to the surface circulation of the Atlantic Water (AW) in the study area. In the Sicily Channel, warm anticyclonic structures located in the southern end drive the AW flow along their northern boundary to the south-east, towards the Libyan coast. In winter, the anticyclonic structures contract in a stable nucleus (the Sidra gyre) close to the African coast allowing AW intrusion over the Tunisian shelf (Atlantic Tunisian Current). In summer, the anticyclonic structure expands westwards, limiting the Atlantic Tunisian Current, and northwards, grazing the Atlantic Ionian Stream. It also fragments, allowing occasional AW intrusion into the central part of the Sicily Channel along different pathways. Due to the activity of the Sidra gyre, no evidence of the extension of the Atlantic Tunisian Current along the Libyan coast (east of 15°E) is found in the observation period. AW spreads into the central Ionian for long periods in summer but rarely in winter. It reaches the northern Ionian Sea via anticyclonic eddies (already observed in thermal imagery) departing from the northern and eastern border of the anticyclonic structure, captured by the prevalent clockwise offshore circulation in the northern Ionian (except in summer 2003). The deduced circulation is in agreement with recent studies based on the altimetric Mean Dynamic Topography and trajectories of drifters released in the Sicily Channel in recent years.

  2. Critical role of a K+ channel in Plasmodium berghei transmission revealed by targeted gene disruption

    DEFF Research Database (Denmark)

    Ellekvist, Peter; Maciel, Jorge; Mlambo, Godfree

    2008-01-01

    Regulated K(+) transport across the plasma membrane is of vital importance for the survival of most cells. Two K(+) channels have been identified in the Plasmodium falciparum genome; however, their functional significance during parasite life cycle in the vertebrate host and during transmission...... inhibition of the development of PbKch1-null parasites in Anopheles stephensi mosquitoes. In conclusion, these studies demonstrate that PbKch1 contributes to the transport of K(+) in P. berghei parasites and supports the growth of the parasites, in particular the development of oocysts in the mosquito midgut...

  3. Multiplex multivariate recurrence network from multi-channel signals for revealing oil-water spatial flow behavior.

    Science.gov (United States)

    Gao, Zhong-Ke; Dang, Wei-Dong; Yang, Yu-Xuan; Cai, Qing

    2017-03-01

    The exploration of the spatial dynamical flow behaviors of oil-water flows has attracted increasing interests on account of its challenging complexity and great significance. We first technically design a double-layer distributed-sector conductance sensor and systematically carry out oil-water flow experiments to capture the spatial flow information. Based on the well-established recurrence network theory, we develop a novel multiplex multivariate recurrence network (MMRN) to fully and comprehensively fuse our double-layer multi-channel signals. Then we derive the projection networks from the inferred MMRNs and exploit the average clustering coefficient and the spectral radius to quantitatively characterize the nonlinear recurrent behaviors related to the distinct flow patterns. We find that these two network measures are very sensitive to the change of flow states and the distributions of network measures enable to uncover the spatial dynamical flow behaviors underlying different oil-water flow patterns. Our method paves the way for efficiently analyzing multi-channel signals from multi-layer sensor measurement system.

  4. Functional interaction between S1 and S4 segments in voltage-gated sodium channels revealed by human channelopathies.

    Science.gov (United States)

    Amarouch, Mohamed-Yassine; Kasimova, Marina A; Tarek, Mounir; Abriel, Hugues

    2014-01-01

    The p.I141V mutation of the voltage-gated sodium channel is associated with several clinical hyper-excitability phenotypes. To understand the structural bases of the p.I141V biophysical alterations, molecular dynamics simulations were performed. These simulations predicted that the p.I141V substitution induces the formation of a hydrogen bond between the Y168 residue of the S2 segment and the R225 residue of the S4 segment. We generated a p.I141V-Y168F double mutant for both the Nav1.4 and Nav1.5 channels. The double mutants demonstrated the abolition of the functional effects of the p.I141V mutation, consistent with the formation of a specific interaction between Y168-S2 and R225-S4. The single p.Y168F mutation, however, positively shifted the activation curve, suggesting a compensatory role of these residues on the stability of the voltage-sensing domain.

  5. Cardamonin, a Novel Antagonist of hTRPA1 Cation Channel, Reveals Therapeutic Mechanism of Pathological Pain

    Directory of Open Access Journals (Sweden)

    Shifeng Wang

    2016-08-01

    Full Text Available The increasing demand for safe and effective treatments of chronic pain has promoted the investigation of novel analgesic drugs. Some herbals have been known to be able to relieve pain, while the chemical basis and target involved in this process remained to be clarified. The current study aimed to find anti-nociceptive candidates targeting transient receptor potential ankyrin 1 (TRPA1, a receptor that implicates in hyperalgesia and neurogenic inflammation. In the current study, 156 chemicals were tested for blocking HEK293/TRPA1 ion channel by calcium-influx assay. Docking study was conducted to predict the binding modes of hit compound with TRPA1 using Discovery Studio. Cytotoxicity in HEK293 was conducted by Cell Titer-Glo assay. Additionally, cardiotoxicity was assessed via xCELLigence RTCA system. We uncovered that cardamonin selectively blocked TRPA1 activation while did not interact with TRPV1 nor TRPV4 channel. A concentration-dependent inhibitory effect was observed with IC50 of 454 nM. Docking analysis of cardamonin demonstrated a compatible interaction with A-967079-binding site of TRPA1. Meanwhile, cardamonin did not significantly reduce HEK293 cell viability, nor did it impair cardiomyocyte constriction. Our data suggest that cardamonin is a selective TRPA1 antagonist, providing novel insight into the target of its anti-nociceptive activity.

  6. Honey bee thermal/chemical sensor, AmHsTRPA, reveals neofunctionalization and loss of transient receptor potential channel genes.

    Science.gov (United States)

    Kohno, Keigo; Sokabe, Takaaki; Tominaga, Makoto; Kadowaki, Tatsuhiko

    2010-09-15

    Insects are relatively small heterothermic animals, thus they are highly susceptible to changes in ambient temperature. However, a group of honey bees is able to maintain the brood nest temperature between 32°C and 36°C by either cooling or heating the nest. Nevertheless, how honey bees sense the ambient temperature is not known. We identified a honey bee Hymenoptera-specific transient receptor potential A (HsTRPA) channel (AmHsTRPA), which is activated by heat with an apparent threshold temperature of 34°C and insect antifeedants such as camphor in vitro. AmHsTRPA is expressed in the antennal flagellum, and ablation of the antennal flagella and injection of AmHsTRPA inhibitors impair warmth avoidance of honey bees. Gustatory responses of honey bees to sucrose are suppressed by noxious heat and insect antifeedants, but are relieved in the presence of AmHsTRPA inhibitors. These results suggest that AmHsTRPA may function as a thermal/chemical sensor in vivo. As shown previously, Hymenoptera has lost the ancient chemical sensor TRPA1; however, AmHsTRPA is able to complement the function of Drosophila melanogaster TRPA1. These results demonstrate that HsTRPA, originally arisen by the duplication of Water witch, has acquired thermal- and chemical-responsive properties, which has resulted in the loss of ancient TRPA1. Thus, this is an example of neofunctionalization of the duplicated ion channel gene followed by the loss of the functionally equivalent ancient gene.

  7. Legacies of stream channel modification revealed using General Land Office surveys, with implications for water temperature and aquatic life

    Directory of Open Access Journals (Sweden)

    Seth M. White

    2017-02-01

    Full Text Available Land use legacies can have a discernible influence in present-day watersheds and should be accounted for when designing conservation strategies for riverine aquatic life. We describe the environmental history of three watersheds within the Grande Ronde subbasin of the Columbia River using General Land Office survey field notes from the 19th century. In the two watersheds severely impacted by Euro-American land use, stream channel widths—a metric representing habitat simplification—increased from an average historical width of 16.8 m to an average present width of 20.8 m in large streams; 4.3 m to 5.5 m in small, confined or partly confined streams; and 3.5 m to 6.5 m in small, laterally unconfined steams. Conversely, we did not detect significant change in stream widths in an adjacent, wilderness stream with minimal human impact. Using a mechanistic water temperature model and restoration scenarios based on the historical condition, we predicted that stream restoration in the impacted watersheds could notably decrease average water temperatures—especially when channel narrowing is coupled with riparian restoration—up to a 6.6°C reduction in the upper Grande Ronde River and 3.0°C in Catherine Creek. These reductions in water temperature translated to substantial changes in the percentage of stream network habitable to salmon and steelhead migration (from 29% in the present condition to 79% in the fully restored scenario and to core juvenile rearing (from 13% in the present condition to 36% in the fully restored scenario. We conclude that land use legacies leave an important footprint on the present landscape and are critical for understanding historic habitat-forming processes as a necessary first step towards restoration.

  8. Slo1 is the principal potassium channel of human spermatozoa

    Science.gov (United States)

    Mannowetz, Nadja; Naidoo, Natasha M; Choo, Seung-A Sara; Smith, James F; Lishko, Polina V

    2013-01-01

    Mammalian spermatozoa gain competence to fertilize an oocyte as they travel through the female reproductive tract. This process is accompanied by an elevation of sperm intracellular calcium and a membrane hyperpolarization. The latter is evoked by K+ efflux; however, the molecular identity of the potassium channel of human spermatozoa (hKSper) is unknown. Here, we characterize hKSper, reporting that it is regulated by intracellular calcium but is insensitive to intracellular alkalinization. We also show that human KSper is inhibited by charybdotoxin, iberiotoxin, and paxilline, while mouse KSper is insensitive to these compounds. Such unique properties suggest that the Slo1 ion channel is the molecular determinant for hKSper. We show that Slo1 is localized to the sperm flagellum and is inhibited by progesterone. Inhibition of hKSper by progesterone may depolarize the spermatozoon to open the calcium channel CatSper, thus raising [Ca2+] to produce hyperactivation and allowing sperm to fertilize an oocyte. DOI: http://dx.doi.org/10.7554/eLife.01009.001 PMID:24137539

  9. Metagenome Sequence Analysis of Filamentous Microbial Communities Obtained from Geochemically Distinct Geothermal Channels Reveals Specialization of Three Aquificales Lineages

    Directory of Open Access Journals (Sweden)

    Cristina eTakacs-vesbach

    2013-05-01

    Full Text Available The Aquificales are thermophilic microorganisms that inhabit hydrothermal systems worldwide and are considered one of the earliest lineages of the domain Bacteria. We analyzed metagenome sequence obtained from six thermal ‘filamentous streamer’ communities (~40 Mbp per site, which targeted three different groups of Aquificales found in Yellowstone National Park (YNP. Unassembled metagenome sequence and PCR-amplified 16S rRNA gene libraries revealed that acidic, sulfidic sites were dominated by Hydrogenobaculum (Aquificaceae populations, whereas the circumneutral pH (6.5 - 7.8 sites containing dissolved sulfide were dominated by Sulfurihydrogenibium spp. (Hydrogenothermaceae. Thermocrinis (Aquificaceae populations were found primarily in the circumneutral sites with undetectable sulfide, and to a lesser extent in one sulfidic system at pH 8. Phylogenetic analysis of assembled sequence containing 16S rRNA genes as well as conserved protein-encoding genes revealed that the composition and function of these communities varied across geochemical conditions. Each Aquificales lineage contained genes for CO2 fixation by the reverse TCA cycle, but only the Sulfurihydrogenibium populations perform citrate cleavage using ATP citrate lyase (Acl. The Aquificaceae populations use an alternative pathway catalyzed by two separate enzymes, citryl CoA synthetase (Ccs and citryl CoA lyase (Ccl. All three Aquificales lineages contained evidence of aerobic respiration, albeit due to completely different types of heme Cu oxidases (subunit I involved in oxygen reduction. The distribution of Aquificales populations and differences among functional genes involved in energy generation and electron transport is consistent with the hypothesis that geochemical parameters (e.g., pH, sulfide, H2, O2 have resulted in niche specialization among members of the Aquificales.

  10. Metabolite labelling reveals hierarchies in Clostridium acetobutylicum that selectively channel carbons from sugar mixtures towards biofuel precursors.

    Science.gov (United States)

    Aristilde, Ludmilla

    2017-01-01

    Clostridial fermentation of cellulose and hemicellulose relies on the cellular physiology controlling the metabolism of the cellulosic hexose sugar (glucose) with respect to the hemicellulosic pentose sugars (xylose and arabinose) and the hemicellulosic hexose sugars (galactose and mannose). Here, liquid chromatography-mass spectrometry and stable isotope tracers in Clostridium acetobutylicum were applied to investigate the metabolic hierarchy of glucose relative to the different hemicellulosic sugars towards two important biofuel precursors, acetyl-coenzyme A and butyryl-coenzyme A. The findings revealed constitutive metabolic hierarchies in C. acetobutylicum that facilitate (i) selective investment of hemicellulosic pentoses towards ribonucleotide biosynthesis without substantial investment into biofuel production and (ii) selective contribution of hemicellulosic hexoses through the glycolytic pathway towards biofuel precursors. Long-term isotopic enrichment demonstrated incorporation of both pentose sugars into pentose-phosphates and ribonucleotides in the presence of glucose. Kinetic labelling data, however, showed that xylose was not routed towards the biofuel precursors but there was minor contribution from arabinose. Glucose hierarchy over the hemicellulosic hexoses was substrate-dependent. Kinetic labelling of hexose-phosphates and triose-phosphates indicated that mannose was assimilated but not galactose. Labelling of both biofuel precursors confirmed this metabolic preference. These results highlight important metabolic considerations in the accounting of clostridial mixed-sugar utilization. © 2016 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  11. Neutron diffraction reveals the existence of confined water in triangular and hexagonal channels of modified YPO4 at elevated temperatures

    Science.gov (United States)

    Mishra, S. K.; Ningthoujam, R. S.; Mittal, R.; Vatsa, R. K.; Zbiri, M.; Sharma, K. Shitaljit; Singh, B. P.; Sastry, P. U.; Hansen, T.; Schober, H.; Chaplot, S. L.

    2017-09-01

    We provide experimental evidence for confinement of water molecules in the pores of hexagonal structure of YPO4 at elevated temperatures up to 600 K using powder neutron diffraction. In order to avoid the large incoherent scattering from the hydrogen, deuterated samples of doped YPO4:Ce-Eu were used for diffraction measurements. The presence of water molecules in the triangular and hexagonal pores in the hexagonal structure was established by detailed simulation of the diffraction pattern and Rietveld refinement of the experimental data. It was observed that the presence of water leads specifically to suppression of the intensity of a peak around Q = 1.04 Å-1 while the intensity of peaks around Q = 1.83 Å-1 is enhanced in the neutron-diffraction pattern. We estimate the number of water molecules as 2.36 (6) per formula units at 300 K and the sizes of the hexagonal and triangular pores as 7.2 (1) and 4.5 (1) Å, respectively. With an increase in temperature, the water content in both pores decreases above 450 K and vanishes around 600 K. Analysis of the powder-diffraction data reveals that the hexagonal structure with the pores persist up to 1273 K, and transforms to another structure at 1323 K. The high-temperature phase is not found to have the zircon- or monazite-type structure, but a monoclinic structure (space group P 2 /m ) with lattice parameters am= 6.826 (4 ) Å ,bm= 6.645 (4 ) Å ,cm= 10.435 (9 ) Å , and β = 107.21 (6) ∘ . The monoclinic structure has about 14% smaller volume than the hexagonal structure which essentially reflects the collapse of the pores. The phase transition and the change in the volume are also confirmed by x-ray-diffraction measurements. The hexagonal-to-monoclinic phase transition is found to be irreversible on cooling to room temperature.

  12. Structures of the PutA peripheral membrane flavoenzyme reveal a dynamic substrate-channeling tunnel and the quinone-binding site.

    Science.gov (United States)

    Singh, Harkewal; Arentson, Benjamin W; Becker, Donald F; Tanner, John J

    2014-03-04

    Proline utilization A (PutA) proteins are bifunctional peripheral membrane flavoenzymes that catalyze the oxidation of L-proline to L-glutamate by the sequential activities of proline dehydrogenase and aldehyde dehydrogenase domains. Located at the inner membrane of Gram-negative bacteria, PutAs play a major role in energy metabolism by coupling the oxidation of proline imported from the environment to the reduction of membrane-associated quinones. Here, we report seven crystal structures of the 1,004-residue PutA from Geobacter sulfurreducens, along with determination of the protein oligomeric state by small-angle X-ray scattering and kinetic characterization of substrate channeling and quinone reduction. The structures reveal an elaborate and dynamic tunnel system featuring a 75-Å-long tunnel that links the two active sites and six smaller tunnels that connect the main tunnel to the bulk medium. The locations of these tunnels and their responses to ligand binding and flavin reduction suggest hypotheses about how proline, water, and quinones enter the tunnel system and where L-glutamate exits. Kinetic measurements show that glutamate production from proline occurs without a lag phase, consistent with substrate channeling and implying that the observed tunnel is functionally relevant. Furthermore, the structure of reduced PutA complexed with menadione bisulfite reveals the elusive quinone-binding site. The benzoquinone binds within 4.0 Å of the flavin si face, consistent with direct electron transfer. The location of the quinone site implies that the concave surface of the PutA dimer approaches the membrane. Altogether, these results provide insight into how PutAs couple proline oxidation to quinone reduction.

  13. Ontogenetic Characterization of the Intestinal Microbiota of Channel Catfish through 16S rRNA Gene Sequencing Reveals Insights on Temporal Shifts and the Influence of Environmental Microbes.

    Science.gov (United States)

    Bledsoe, Jacob W; Peterson, Brian C; Swanson, Kelly S; Small, Brian C

    2016-01-01

    Aquaculture recently overtook capture fisheries as the largest producer of food fish, but to continue increasing fish production the industry is in search of better methods of improving fish health and growth. Pre- and probiotic supplementation has gained attention as a means of solving these issues, however, for such approaches to be successful, we must first gain a more holistic understanding of the factors influencing the microbial communities present in the intestines of fish. In this study, we characterize the bacterial communities associated with the digestive tract of a highly valuable U.S. aquaculture species, channel catfish Ictalurus punctatus, over the first 193 days of life to evaluate temporal changes that may occur throughout ontogenetic development of the host. Intestinal microbiota were surveyed with high-throughput DNA sequencing of 16S rRNA V4 gene amplicons derived from fish at 3, 65, 125, and 193 days post hatch (dph), while also characterizing the environmental microbes derived from the water supply and the administered diets. Microbial communities inhabiting the intestines of catfish early in life were dynamic, with significant shifts occurring up to 125 dph when the microbiota somewhat stabilized, as shifts were less apparent between 125 to 193 dph. Bacterial phyla present in the gut of catfish throughout ontogeny include Bacteroidetes, Firmicutes, Fusobacteria, and Proteobacteria; with the species Cetobacterium somerae and Plesiomonas shigelloides showing the highest abundance in the catfish microbiota after 3 dph. Comparisons of the gut microbiota to the environmental microbes reveals that the fish gut is maintained as a niche habitat, separate from the overall microbial communities present in diets and water-supply. Although, there is also evidence that the environmental microbiota serves as an inoculum to the fish gut. Our results have implications for future research related to channel catfish biology and culture, and increase our

  14. Linear and nonlinear analyses of multi-channel mechanomyographic recordings reveal heterogeneous activation of wrist extensors in presence of delayed onset muscle soreness.

    Science.gov (United States)

    Madeleine, Pascal; Hansen, Ernst A; Samani, Afshin

    2014-12-01

    In this study, we applied multi-channel mechanomyographic (MMG) recordings in combination with linear and nonlinear analyses to investigate muscular and musculotendinous effects of high intensity eccentric exercise. Twelve accelerometers arranged in a 3 × 4 matrix over the dominant elbow muscles were used to detect MMG activity in 12 healthy participants. Delayed onset muscle soreness was induced by repetitive high intensity eccentric contractions of the wrist extensor muscles. Average rectified values (ARV) as well as percentage of recurrence (%REC) and percentage of determinism (%DET) extracted from recurrence quantification analysis were computed from data obtained during static-dynamic contractions performed before exercise, immediately after exercise, and in presence of muscle soreness. A linear mixed model was used for the statistical analysis. The ARV, %REC, and %DET maps revealed heterogeneous MMG activity over the wrist extensor muscles before, immediately after, and in presence of muscle soreness (Psoreness compared with before exercise (Psoreness. Recurrence quantification analysis can be suggested as a tool for detection of MMG changes in presence of muscle soreness. Copyright © 2014 IPEM. Published by Elsevier Ltd. All rights reserved.

  15. cAMP control of HCN2 channel Mg2+ block reveals loose coupling between the cyclic nucleotide-gating ring and the pore.

    Directory of Open Access Journals (Sweden)

    Alex K Lyashchenko

    Full Text Available Hyperpolarization-activated cyclic nucleotide-regulated HCN channels underlie the Na+-K+ permeable IH pacemaker current. As with other voltage-gated members of the 6-transmembrane KV channel superfamily, opening of HCN channels involves dilation of a helical bundle formed by the intracellular ends of S6 albeit this is promoted by inward, not outward, displacement of S4. Direct agonist binding to a ring of cyclic nucleotide-binding sites, one of which lies immediately distal to each S6 helix, imparts cAMP sensitivity to HCN channel opening. At depolarized potentials, HCN channels are further modulated by intracellular Mg2+ which blocks the open channel pore and blunts the inhibitory effect of outward K+ flux. Here, we show that cAMP binding to the gating ring enhances not only channel opening but also the kinetics of Mg2+ block. A combination of experimental and simulation studies demonstrates that agonist acceleration of block is mediated via acceleration of the blocking reaction itself rather than as a secondary consequence of the cAMP enhancement of channel opening. These results suggest that the activation status of the gating ring and the open state of the pore are not coupled in an obligate manner (as required by the often invoked Monod-Wyman-Changeux allosteric model but couple more loosely (as envisioned in a modular model of protein activation. Importantly, the emergence of second messenger sensitivity of open channel rectification suggests that loose coupling may have an unexpected consequence: it may endow these erstwhile "slow" channels with an ability to exert voltage and ligand-modulated control over cellular excitability on the fastest of physiologically relevant time scales.

  16. Comparative Proteomics of Ovarian Cancer Aggregate Formation Reveals an Increased Expression of Calcium-activated Chloride Channel Regulator 1 (CLCA1).

    Science.gov (United States)

    Musrap, Natasha; Tuccitto, Alessandra; Karagiannis, George S; Saraon, Punit; Batruch, Ihor; Diamandis, Eleftherios P

    2015-07-10

    Ovarian cancer is a lethal gynecological disease that is characterized by peritoneal metastasis and increased resistance to conventional chemotherapies. This increased resistance and the ability to spread is often attributed to the formation of multicellular aggregates or spheroids in the peritoneal cavity, which seed abdominal surfaces and organs. Given that the presence of metastatic implants is a predictor of poor survival, a better understanding of how spheroids form is critical to improving patient outcome, and may result in the identification of novel therapeutic targets. Thus, we attempted to gain insight into the proteomic changes that occur during anchorage-independent cancer cell aggregation. As such, an ovarian cancer cell line, OV-90, was cultured in adherent and non-adherent conditions using stable isotope labeling with amino acids in cell culture (SILAC). Anchorage-dependent cells (OV-90AD) were grown in tissue culture flasks, whereas anchorage-independent cells (OV-90AI) were grown in suspension using the hanging-drop method. Cellular proteins from both conditions were then identified using LC-MS/MS, which resulted in the quantification of 1533 proteins. Of these, 13 and 6 proteins were up-regulated and down-regulated, respectively, in aggregate-forming cells compared with cells grown as monolayers. Relative gene expression and protein expression of candidates were examined in other cell line models of aggregate formation (TOV-112D and ES-2), which revealed an increased expression of calcium-activated chloride channel regulator 1 (CLCA1). Moreover, inhibitor and siRNA transfection studies demonstrated an apparent effect of CLCA1 on cancer cell aggregation. Further elucidation of the role of CLCA1 in the pathogenesis of ovarian cancer is warranted. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. 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)

  18. A polyether biotoxin binding site on the lipid-exposed face of the pore domain of Kv channels revealed by the marine toxin gambierol

    Science.gov (United States)

    Kopljar, Ivan; Labro, Alain J.; Cuypers, Eva; Johnson, Henry W. B.; Rainier, Jon D.; Tytgat, Jan; Snyders, Dirk J.

    2009-01-01

    Gambierol is a marine polycyclic ether toxin belonging to the group of ciguatera toxins. It does not activate voltage-gated sodium channels (VGSCs) but inhibits Kv1 potassium channels by an unknown mechanism. While testing whether Kv2, Kv3, and Kv4 channels also serve as targets, we found that Kv3.1 was inhibited with an IC50 of 1.2 ± 0.2 nM, whereas Kv2 and Kv4 channels were insensitive to 1 μM gambierol. Onset of block was similar from either side of the membrane, and gambierol did not compete with internal cavity blockers. The inhibition did not require channel opening and could not be reversed by strong depolarization. Using chimeric Kv3.1–Kv2.1 constructs, the toxin sensitivity was traced to S6, in which T427 was identified as a key determinant. In Kv3.1 homology models, T427 and other molecular determinants (L348, F351) reside in a space between S5 and S6 outside the permeation pathway. In conclusion, we propose that gambierol acts as a gating modifier that binds to the lipid-exposed surface of the pore domain, thereby stabilizing the closed state. This site may be the topological equivalent of the neurotoxin site 5 of VGSCs. Further elucidation of this previously undescribed binding site may explain why most ciguatoxins activate VGSCs, whereas others inhibit voltage-dependent potassium (Kv) channels. This previously undescribed Kv neurotoxin site may have wide implications not only for our understanding of channel function at the molecular level but for future development of drugs to alleviate ciguatera poisoning or to modulate electrical excitability in general. PMID:19482941

  19. NOTE: Dielectrophoretic analysis of changes in cytoplasmic ion levels due to ion channel blocker action reveals underlying differences between drug-sensitive and multidrug-resistant leukaemic cells

    Science.gov (United States)

    Duncan, L.; Shelmerdine, H.; Hughes, M. P.; Coley, H. M.; Hübner, Y.; Labeed, F. H.

    2008-01-01

    Dielectrophoresis (DEP)—the motion of particles in non-uniform AC fields—has been used in the investigation of cell electrophysiology. The technique offers the advantages of rapid determination of the conductance and capacitance of membrane and cytoplasm. However, it is unable to directly determine the ionic strengths of individual cytoplasmic ions, which has potentially limited its application in assessing cell composition. In this paper, we demonstrate how dielectrophoresis can be used to investigate the cytoplasmic ion composition by using ion channel blocking agents. By blocking key ion transporters individually, it is possible to determine their overall contribution to the free ions in the cytoplasm. We use this technique to evaluate the relative contributions of chloride, potassium and calcium ions to the cytoplasmic conductivities of drug sensitive and resistant myelogenous leukaemic (K562) cells in order to determine the contributions of individual ion channel activity in mediating multi-drug resistance in cancer. Results indicate that whilst K+ and Ca2+ levels were extremely similar between sensitive and resistant lines, levels of Cl- were elevated by three times to that in the resistant line, implying increased chloride channel activity. This result is in line with current theories of MDR, and validates the use of ion channel blockers with DEP to investigate ion channel function.

  20. Dielectrophoretic analysis of changes in cytoplasmic ion levels due to ion channel blocker action reveals underlying differences between drug-sensitive and multidrug-resistant leukaemic cells

    International Nuclear Information System (INIS)

    Duncan, L; Shelmerdine, H; Hughes, M P; Coley, H M; Huebner, Y; Labeed, F H

    2008-01-01

    Dielectrophoresis (DEP)-the motion of particles in non-uniform AC fields-has been used in the investigation of cell electrophysiology. The technique offers the advantages of rapid determination of the conductance and capacitance of membrane and cytoplasm. However, it is unable to directly determine the ionic strengths of individual cytoplasmic ions, which has potentially limited its application in assessing cell composition. In this paper, we demonstrate how dielectrophoresis can be used to investigate the cytoplasmic ion composition by using ion channel blocking agents. By blocking key ion transporters individually, it is possible to determine their overall contribution to the free ions in the cytoplasm. We use this technique to evaluate the relative contributions of chloride, potassium and calcium ions to the cytoplasmic conductivities of drug sensitive and resistant myelogenous leukaemic (K562) cells in order to determine the contributions of individual ion channel activity in mediating multi-drug resistance in cancer. Results indicate that whilst K + and Ca 2+ levels were extremely similar between sensitive and resistant lines, levels of Cl - were elevated by three times to that in the resistant line, implying increased chloride channel activity. This result is in line with current theories of MDR, and validates the use of ion channel blockers with DEP to investigate ion channel function. (note)

  1. The comprehensive analysis of DEG/ENaC subunits in Hydra reveals a large variety of peptide-gated channels, potentially involved in neuromuscular transmission.

    Science.gov (United States)

    Assmann, Marc; Kuhn, Anne; Dürrnagel, Stefan; Holstein, Thomas W; Gründer, Stefan

    2014-10-14

    It is generally the case that fast transmission at neural synapses is mediated by small molecule neurotransmitters. The simple nervous system of the cnidarian Hydra, however, contains a large repertoire of neuropeptides and it has been suggested that neuropeptides are the principal transmitters of Hydra. An ion channel directly gated by Hydra-RFamide neuropeptides has indeed been identified in Hydra - the Hydra Na+ channel (HyNaC) 2/3/5, which is expressed at the oral side of the tentacle base. Hydra-RFamides are more widely expressed, however, being found in neurons of the head and peduncle region. Here, we explore whether further peptide-gated HyNaCs exist, where in the animal they are expressed, and whether they are all gated by Hydra-RFamides. We report molecular cloning of seven new HyNaC subunits - HyNaC6 to HyNaC12, all of which are members of the DEG/ENaC gene family. In Xenopus oocytes, these subunits assemble together with the four already known subunits into thirteen different ion channels that are directly gated by Hydra-RFamide neuropeptides with high affinity (up to 40 nM). In situ hybridization suggests that HyNaCs are expressed in epitheliomuscular cells at the oral and the aboral side of the tentacle base and at the peduncle. Moreover, diminazene, an inhibitor of HyNaCs, delayed tentacle movement in live Hydra. Our results show that Hydra has a large variety of peptide-gated ion channels that are activated by a restricted number of related neuropeptides. The existence and expression pattern of these channels, and behavioral effects induced by channel blockers, suggests that Hydra co-opted neuropeptides for fast neuromuscular transmission.

  2. Interaction between the Cardiac Rapidly (IKr) and Slowly (IKs) Activating Delayed Rectifier Potassium Channels Revealed by Low K+-induced hERG Endocytic Degradation*

    Science.gov (United States)

    Guo, Jun; Wang, Tingzhong; Yang, Tonghua; Xu, Jianmin; Li, Wentao; Fridman, Michael D.; Fisher, John T.; Zhang, Shetuan

    2011-01-01

    Cardiac repolarization is controlled by the rapidly (IKr) and slowly (IKs) activating delayed rectifier potassium channels. The human ether-a-go-go-related gene (hERG) encodes IKr, whereas KCNQ1 and KCNE1 together encode IKs. Decreases in IKr or IKs cause long QT syndrome (LQTS), a cardiac disorder with a high risk of sudden death. A reduction in extracellular K+ concentration ([K+]o) induces LQTS and selectively causes endocytic degradation of mature hERG channels from the plasma membrane. In the present study, we investigated whether IKs compensates for the reduced IKr under low K+ conditions. Our data show that when hERG and KCNQ1 were expressed separately in human embryonic kidney (HEK) cells, exposure to 0 mm K+ for 6 h completely eliminated the mature hERG channel expression but had no effect on KCNQ1. When hERG and KCNQ1 were co-expressed, KCNQ1 significantly delayed 0 mm K+-induced hERG reduction. Also, hERG degradation led to a significant reduction in KCNQ1 in 0 mm K+ conditions. An interaction between hERG and KCNQ1 was identified in hERG+KCNQ1-expressing HEK cells. Furthermore, KCNQ1 preferentially co-immunoprecipitated with mature hERG channels that are localized in the plasma membrane. Biophysical and pharmacological analyses indicate that although hERG and KCNQ1 closely interact with each other, they form distinct hERG and KCNQ1 channels. These data extend our understanding of delayed rectifier potassium channel trafficking and regulation, as well as the pathology of LQTS. PMID:21844197

  3. The cytochrome P450 genes of channel catfish: their involvement in disease defense responses as revealed by meta-analysis of RNA-Seq datasets

    Science.gov (United States)

    Cytochrome P450s (CYPs) encode one of the most diverse enzyme superfamily in nature. They catalyze oxidative reactions of endogenous molecules and exogenous chemicals. Methods: We identifiedCYPs genes through in silico analysis using EST, RNA-Seq and genome databases of channel catfish.Phylogenetic ...

  4. Microscopic mechanisms for long QT syndrome type 1 revealed by single-channel analysis of I(Ks) with S3 domain mutations in KCNQ1.

    Science.gov (United States)

    Eldstrom, Jodene; Wang, Zhuren; Werry, Daniel; Wong, Nathan; Fedida, David

    2015-02-01

    The slowly activating delayed rectifier current IKs participates in cardiac repolarization, particularly at high heart rates, and mutations in this K(+) channel complex underlie long QT syndrome (LQTS) types 1 and 5. The purpose of this study was to determine biophysical mechanisms of LQT1 through single-channel kinetic analysis of IKs carrying LQT1 mutations in the S3 transmembrane region of the pore-forming subunit KCNQ1. We analyzed cell-attached recordings from mammalian cells in which a single active KCNQ1 (wild type or mutant) and KCNE1 complex could be detected. The S3 mutants of KCNQ1 studied (D202H, I204F, V205M, and S209F), with the exception of S209F, all led to a reduction in channel activity through distinct kinetic mechanisms. D202H, I204F, and V205M showed decreased open probability (Po) compared with wild type (0.07, 0.04, and 0.12 vs 0.2); increased first latency from 1.66 to >2 seconds at +60 mV (I204F, V205M); variable-to-severe reductions in open dwell times (≥50% in V205M); stabilization of closed states (D202H); and an inability of channels to reach full conductance levels (V205M, I204F). S209F is a kinetic gain-of-function mutation with a high Po (0.40) and long open-state dwell times. S3 mutations in KCNQ1 cause diverse kinetic defects in I(Ks), affecting opening and closing properties, and can account for LQT1 phenotypes. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  5. The Prevention Disaster Program of Flood in 2013 for the 4th Grade Students of Kawatanaka Primary School, Tokushima Prefecture, Japan and Underflow Channels Revealed in 2016

    Science.gov (United States)

    Kawamata, Sanae; Murata, Mamoru

    2017-12-01

    The Typhoon No. 18 caused flood on September 15, 2013 in the Kawata River basin, Yoshinogawa City, Tokushima Prefecture. The Kawata River is a raised river bed of 36.7 m with banks to 40.5 m above sea level. The heavy rain did not destroy the banks but made the river level 39.4 m high and then pressed the underflow channel. As the Kawatanaka primary school is located at 36.2 m height, it was not submerged although the underflow channel overbanked the adjacent playground. An educational program on the prevention and reduction for natural disaster, which consists of science, social studies and presentation, was conducted to 18 students of the 4th grade in the period of integrated study in the Kawatanaka primary school from September 17, 2013. On the first day, flow current markings from 625 holes, 30 cm to 1 mm in diameter, on the playground were observed. The flow currents showed direction from SE to NW. On the basis of their observations on the flow currents that water runs from high to low, the students considered the phenomena as a result of tilting of the ground. They conducted activity as their homework to confirm their hypothesis to know if there is any tilt in the ground. They took plastic bottle filled with water and reviled that the ground had 1 to 2 degrees’ tilt to the NW during the experiment. On the bases of the difference between E to W flow of the Kawata River and their SE to NW estimated current flow on the playground and the fact that the bank of the river was not destroyed, the students suggested that the heavy rain had pressed the underflow channels. The suggested channels were found on the playground, where new school buildings were constructed in 2016, by one of the students who studied the program in 2013.

  6. Long-term fluid expulsion revealed by carbonate crusts and pockmarks connected to subsurface gas anomalies and palaeo-channels in the central North Sea

    Science.gov (United States)

    Chand, Shyam; Crémière, Antoine; Lepland, Aivo; Thorsnes, Terje; Brunstad, Harald; Stoddart, Daniel

    2017-06-01

    Gas seepage through the seafloor into the water column is inferred based on acoustic mapping, video observations and geochemical analyses at multiple locations in the Viking Graben and Utsira High areas of the central North Sea. Flares in the Viking Graben occur both inside and along the periphery of a submarine melt water channel where pockmarks (up to 500 m in diameter) and methane-derived carbonate crusts are found on the seafloor, indicating focussing of fluid flow in the vicinity of the channel. The flares can be related to gas accumulations close to the seafloor as well as in Quaternary and deeper strata, observed as high-amplitude reflections on seismic data. Many palaeo-channels, which act as accumulation zones, are observed in the subsurface of both the Viking Graben and Utsira High areas. The deeper origin of gas is partially supported by results of isotope analyses of headspace gas collected from sediment samples of the Viking Graben, which show a mixed microbial/thermogenic origin whereas isotope data on free seeping gas in the Viking Graben indicate a predominantly microbial origin. Based on these lines of evidence, a structure-controlled fluid flow model is proposed whereby hydrocarbons migrate in limited amount from deep thermogenic reservoirs along faults, and these deep fluids are strongly diluted by microbial methane. Moreover, the existence of subsurface pockmarks at several stratigraphic levels indicates long-term fluid flow, interpreted to be caused by gas hydrate destabilisation and stress-related high overpressures.

  7. Geomorphology, denudation rates, and stream channel profiles reveal patterns of mountain building adjacent to the San Andreas fault in northern California, USA

    Science.gov (United States)

    DeLong, Stephen B.; Hilley, George E.; Prentice, Carol S.; Crosby, Christopher J.; Yokelson, Intan N.

    2017-01-01

    Relative horizontal motion along strike-slip faults can build mountains when motion is oblique to the trend of the strike-slip boundary. The resulting contraction and uplift pose off-fault seismic hazards, which are often difficult to detect because of the poor vertical resolution of satellite geodesy and difficulty of locating offset datable landforms in active mountain ranges. Sparse geomorphic markers, topographic analyses, and measurement of denudation allow us to map spatiotemporal patterns of uplift along the northern San Andreas fault. Between Jenner and Mendocino, California, emergent marine terraces found southwest of the San Andreas fault record late Pleistocene uplift rates between 0.20 and 0.45 mm yr–1 along much of the coast. However, on the northeast side of the San Andreas fault, a zone of rapid uplift (0.6–1.0 mm yr–1) exists adjacent to the San Andreas fault, but rates decay northeastward as the coast becomes more distant from the San Andreas fault. A newly dated 4.5 Ma shallow-marine deposit located at ∼500 m above sea level (masl) adjacent to the San Andreas fault is warped down to just 150 masl 15 km northeast of the San Andreas fault, and it is exposed at just 60–110 masl to the west of the fault. Landscape denudation rates calculated from abundance of cosmogenic radionuclides in fluvial sediment northeast of, and adjacent to, the San Andreas fault are 0.16–0.29 mm yr–1, but they are only 0.03–0.07 mm yr–1 west of the fault. Basin-average channel steepness and the denudation rates can be used to infer the erosive properties of the underlying bedrock. Calibrated erosion rates can then be estimated across the entire landscape using the spatial distribution of channel steepness with these erosive properties. The lower-elevation areas of this landscape that show high channel steepness (and hence calibrated erosion rate) are distinct from higher-elevation areas with systematically lower channel steepness and denudation rates

  8. Evolutionary analyses of KCNQ1 and HERG voltage-gated potassium channel sequences reveal location-specific susceptibility and augmented chemical severities of arrhythmogenic mutations

    Directory of Open Access Journals (Sweden)

    Accili Eric A

    2008-06-01

    Full Text Available Abstract Background Mutations in HERG and KCNQ1 potassium channels have been associated with Long QT syndrome and atrial fibrillation, and more recently with sudden infant death syndrome and sudden unexplained death. In other proteins, disease-associated amino acid mutations have been analyzed according to the chemical severity of the changes and the locations of the altered amino acids according to their conservation over metazoan evolution. Here, we present the first such analysis of arrhythmia-associated mutations (AAMs in the HERG and KCNQ1 potassium channels. Results Using evolutionary analyses, AAMs in HERG and KCNQ1 were preferentially found at evolutionarily conserved sites and unevenly distributed among functionally conserved domains. Non-synonymous single nucleotide polymorphisms (nsSNPs are under-represented at evolutionarily conserved sites in HERG, but distribute randomly in KCNQ1. AAMs are chemically more severe, according to Grantham's Scale, than changes observed in evolution and their severity correlates with the expected chemical severity of the involved codon. Expected chemical severity of a given amino acid also correlates with its relative contribution to arrhythmias. At evolutionarily variable sites, the chemical severity of the changes is also correlated with the expected chemical severity of the involved codon. Conclusion Unlike nsSNPs, AAMs preferentially locate to evolutionarily conserved, and functionally important, sites and regions within HERG and KCNQ1, and are chemically more severe than changes which occur in evolution. Expected chemical severity may contribute to the overrepresentation of certain residues in AAMs, as well as to evolutionary change.

  9. 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.

  10. Identification of the main processes underlying ecosystem functioning in the Eastern English Channel, with a focus on flatfish species, as revealed through the application of the Atlantis end-to-end model

    Science.gov (United States)

    Girardin, Raphaël; Fulton, Elizabeth A.; Lehuta, Sigrid; Rolland, Marie; Thébaud, Olivier; Travers-Trolet, Morgane; Vermard, Youen; Marchal, Paul

    2018-02-01

    The ecosystem model Atlantis was used to investigate the key dynamics and processes that structure the Eastern English Channel ecosystem, with a particular focus on two commercial flatfish species, sole (Solea solea) and plaice (Pleuronectes platessa). This complex model was parameterized with data collected from diverse sources (a literature review, survey data, as well as landings and stock assessment information) and tuned so both simulated biomass and catch fit 2002-2011 observations. Here, the outputs are mainly presented for the two focus species and for some other vertebrates found to be important in the trophic network. The calibration process revealed the importance of coastal areas in the Eastern English Channel and of nutrient inputs from estuaries: a lack of river nutrients decreases the productivity of nursery grounds and adversely affects the production of sole and plaice. The role of discards in the trophic network is also highlighted. While sole and plaice did not have a strong influence on the trophic network of vertebrates, they are important predators for benthic invertebrates and compete for food with crustaceans, whiting (Merlangius merlangus) and other demersal fish. We also found that two key species, cod (Gadus morhua) and whiting, thoroughly structured the Eastern English Channel trophic network.

  11. 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)

  12. Insect sodium channels and insecticide resistance

    OpenAIRE

    Dong, Ke

    2007-01-01

    Voltage-gated sodium channels are essential for the generation and propagation of action potentials (i.e., electrical impulses) in excitable cells. Although most of our knowledge about sodium channels is derived from decades of studies of mammalian isoforms, research on insect sodium channels is revealing both common and unique aspects of sodium channel biology. In particular, our understanding of the molecular dynamics and pharmacology of insect sodium channels has advanced greatly in recent...

  13. 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.

  14. 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

  15. 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.

  16. Single-channel kinetics of BK (Slo1 channels

    Directory of Open Access Journals (Sweden)

    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.

  17. Voltage-gated Proton Channels

    Science.gov (United States)

    DeCoursey, Thomas E.

    2014-01-01

    Voltage-gated proton channels, HV1, have vaulted from the realm of the esoteric into the forefront of a central question facing ion channel biophysicists, namely the mechanism by which voltage-dependent gating occurs. This transformation is the result of several factors. Identification of the gene in 2006 revealed that proton channels are homologues of the voltage-sensing domain of most other voltage-gated ion channels. Unique, or at least eccentric, properties of proton channels include dimeric architecture with dual conduction pathways, perfect proton selectivity, a single-channel conductance ~103 smaller than most ion channels, voltage-dependent gating that is strongly modulated by the pH gradient, ΔpH, and potent inhibition by Zn2+ (in many species) but an absence of other potent inhibitors. The recent identification of HV1 in three unicellular marine plankton species has dramatically expanded the phylogenetic family tree. Interest in proton channels in their own right has increased as important physiological roles have been identified in many cells. Proton channels trigger the bioluminescent flash of dinoflagellates, facilitate calcification by coccolithophores, regulate pH-dependent processes in eggs and sperm during fertilization, secrete acid to control the pH of airway fluids, facilitate histamine secretion by basophils, and play a signaling role in facilitating B-cell receptor mediated responses in B lymphocytes. The most elaborate and best-established functions occur in phagocytes, where proton channels optimize the activity of NADPH oxidase, an important producer of reactive oxygen species. Proton efflux mediated by HV1 balances the charge translocated across the membrane by electrons through NADPH oxidase, minimizes changes in cytoplasmic and phagosomal pH, limits osmotic swelling of the phagosome, and provides substrate H+ for the production of H2O2 and HOCl, reactive oxygen species crucial to killing pathogens. PMID:23798303

  18. 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

  19. Hydraulic characteristics of flood waves passing compound channels

    OpenAIRE

    冨永, 晃宏; 長尾, 正志; 三尾, 憲史; 劉, 建

    1994-01-01

    Hydraulic characteristics of unsteady flows were investigated experimentally when flood waves were passing through compound open channels. Some noticeable features of unsteady flow structure in compound channels were revealed which were significantly different from those in single rectangular channels. The unsteadiness of velocity appears very large in main channels and the peak of velocity appears very earlier than in rectangular channels. Lateral shear stress increases in a rising stage at ...

  20. 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....

  1. 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...

  2. 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.

  3. 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 ...

  4. 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...

  5. 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)

  6. 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,...

  7. Outward-Rectifying K^+ Channels in Stomatal Guard Cell Protoplasts

    OpenAIRE

    Shigeru, Hosoi; Moritoshi, Iino; Ken-ichiro, Shimazaki; Tsukuba Research Laboratory, Hamamatsu Photonics; Department of Biology, Tokyo Metropolitan University; Division of Environmental Biology, National Institute for Environmental Studies

    1988-01-01

    Ion channels in stomatal guard cell protoplasts from Vicia faba were examined using the patch-clamp technique. Most ion channels having unit conductance ranging between 10 and 30 pS showed clear outward-rectification in symmetrical 50 mM KCl. The large inside-out membranes contained these outward-rectifiers as the major and relatively stable channels. The channels were K^+ ion-selective. Kinetic analysis revealed that the channels have three conductance states: open, closed and inactivated. T...

  8. Mathematics revealed

    CERN Document Server

    Berman, Elizabeth

    1979-01-01

    Mathematics Revealed focuses on the principles, processes, operations, and exercises in mathematics.The book first offers information on whole numbers, fractions, and decimals and percents. Discussions focus on measuring length, percent, decimals, numbers as products, addition and subtraction of fractions, mixed numbers and ratios, division of fractions, addition, subtraction, multiplication, and division. The text then examines positive and negative numbers and powers and computation. Topics include division and averages, multiplication, ratios, and measurements, scientific notation and estim

  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. 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

  11. 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.)

  12. Direct action of endocrine disrupting chemicals on human sperm

    DEFF Research Database (Denmark)

    Schiffer, Christian; Müller, Astrid; Egeberg, Dorte L

    2014-01-01

    sperm. We show that structurally diverse EDCs activate the sperm-specific CatSper channel and, thereby, evoke an intracellular Ca(2+) increase, a motility response, and acrosomal exocytosis. Moreover, EDCs desensitize sperm for physiological CatSper ligands and cooperate in low-dose mixtures to elevate...... Ca(2+) levels in sperm. We conclude that EDCs interfere with various sperm functions and, thereby, might impair human fertilization....

  13. 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.

  14. 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. 

  15. 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 ...

  16. 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...

  17. 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.

  18. 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...

  19. 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 ...

  20. NSAIDs acutely inhibit TRPC channels in freshly isolated rat glomeruli

    Energy Technology Data Exchange (ETDEWEB)

    Ilatovskaya, Daria V. [Department of Physiology, Medical College of Wisconsin, Milwaukee, WI (United States); Institute of Cytology RAS, St. Petersburg (Russian Federation); Levchenko, Vladislav; Ryan, Robert P.; Cowley, Allen W. [Department of Physiology, Medical College of Wisconsin, Milwaukee, WI (United States); Staruschenko, Alexander, E-mail: Staruschenko@mcw.edu [Department of Physiology, Medical College of Wisconsin, Milwaukee, WI (United States)

    2011-05-06

    Highlights: {yields} We have established a unique approach to search for physiologically relevant mechanisms of TRPC channels in podocytes. {yields} This study describes endogenous TRPC channels in the isolated decapsulated glomeruli preparation. {yields} We report for the first time that NSAIDs inhibit TRPC channels in podocytes. -- Abstract: Using a novel approach for analysis of TRPC channel activity, we report here that NSAIDs are involved into regulation of TRPC channels in the podocytes of the freshly isolated decapsulated glomeruli. Fluorescence and electron microscopy techniques confirmed the integrity of podocytes in the glomeruli. Western blotting showed that TRPC1, 3 and 6 are highly expressed in the glomeruli. Single-channel patch clamp analysis revealed cation currents with distinct TRPC properties. This is the first report describing single TRPC-like currents in glomerular podocytes. Furthermore, our data provide a novel mechanism of NSAIDs regulation of TRPC channels, which might be implicated in maintaining the glomerular filtration barrier.

  1. Unsupervised Idealization of Ion Channel Recordings by Minimum Description Length: Application to Human PIEZO1-Channels

    Directory of Open Access Journals (Sweden)

    Jakob K. Dreyer

    2017-04-01

    Full Text Available Researchers can investigate the mechanistic and molecular basis of many physiological phenomena in cells by analyzing the fundamental properties of single ion channels. These analyses entail recording single channel currents and measuring current amplitudes and transition rates between conductance states. Since most electrophysiological recordings contain noise, the data analysis can proceed by idealizing the recordings to isolate the true currents from the noise. This de-noising can be accomplished with threshold crossing algorithms and Hidden Markov Models, but such procedures generally depend on inputs and supervision by the user, thus requiring some prior knowledge of underlying processes. Channels with unknown gating and/or functional sub-states and the presence in the recording of currents from uncorrelated background channels present substantial challenges to such analyses. Here we describe and characterize an idealization algorithm based on Rissanen's Minimum Description Length (MDL Principle. This method uses minimal assumptions and idealizes ion channel recordings without requiring a detailed user input or a priori assumptions about channel conductance and kinetics. Furthermore, we demonstrate that correlation analysis of conductance steps can resolve properties of single ion channels in recordings contaminated by signals from multiple channels. We first validated our methods on simulated data defined with a range of different signal-to-noise levels, and then showed that our algorithm can recover channel currents and their substates from recordings with multiple channels, even under conditions of high noise. We then tested the MDL algorithm on real experimental data from human PIEZO1 channels and found that our method revealed the presence of substates with alternate conductances.

  2. Unsupervised Idealization of Ion Channel Recordings by Minimum Description Length: Application to Human PIEZO1-Channels

    Science.gov (United States)

    Gnanasambandam, Radhakrishnan; Nielsen, Morten S.; Nicolai, Christopher; Sachs, Frederick; Hofgaard, Johannes P.; Dreyer, Jakob K.

    2017-01-01

    Researchers can investigate the mechanistic and molecular basis of many physiological phenomena in cells by analyzing the fundamental properties of single ion channels. These analyses entail recording single channel currents and measuring current amplitudes and transition rates between conductance states. Since most electrophysiological recordings contain noise, the data analysis can proceed by idealizing the recordings to isolate the true currents from the noise. This de-noising can be accomplished with threshold crossing algorithms and Hidden Markov Models, but such procedures generally depend on inputs and supervision by the user, thus requiring some prior knowledge of underlying processes. Channels with unknown gating and/or functional sub-states and the presence in the recording of currents from uncorrelated background channels present substantial challenges to such analyses. Here we describe and characterize an idealization algorithm based on Rissanen's Minimum Description Length (MDL) Principle. This method uses minimal assumptions and idealizes ion channel recordings without requiring a detailed user input or a priori assumptions about channel conductance and kinetics. Furthermore, we demonstrate that correlation analysis of conductance steps can resolve properties of single ion channels in recordings contaminated by signals from multiple channels. We first validated our methods on simulated data defined with a range of different signal-to-noise levels, and then showed that our algorithm can recover channel currents and their substates from recordings with multiple channels, even under conditions of high noise. We then tested the MDL algorithm on real experimental data from human PIEZO1 channels and found that our method revealed the presence of substates with alternate conductances. PMID:28496407

  3. 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.

  4. 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

  5. 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.

  6. 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...

  7. 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

  8. A model for the distribution channels planning process

    NARCIS (Netherlands)

    Neves, M.F.; Zuurbier, P.; Campomar, M.C.

    2001-01-01

    Research of existing literature reveals some models (sequence of steps) for companies that want to plan distribution channels. None of these models uses strong contributions from transaction cost economics, bringing a possibility to elaborate on a "distribution channels planning model", with these

  9. 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....

  10. 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...

  11. 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.

  12. 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.

  13. 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.

  14. A novel potassium channel in photosynthetic cyanobacteria.

    Directory of Open Access Journals (Sweden)

    Manuela Zanetti

    Full Text Available Elucidation of the structure-function relationship of a small number of prokaryotic ion channels characterized so far greatly contributed to our knowledge on basic mechanisms of ion conduction. We identified a new potassium channel (SynK in the genome of the cyanobacterium Synechocystis sp. PCC6803, a photosynthetic model organism. SynK, when expressed in a K(+-uptake-system deficient E. coli strain, was able to recover growth of these organisms. The protein functions as a potassium selective ion channel when expressed in Chinese hamster ovary cells. The location of SynK in cyanobacteria in both thylakoid and plasmamembranes was revealed by immunogold electron microscopy and Western blotting of isolated membrane fractions. SynK seems to be conserved during evolution, giving rise to a TPK (two-pore K(+ channel family member which is shown here to be located in the thylakoid membrane of Arabidopsis. Our work characterizes a novel cyanobacterial potassium channel and indicates the molecular nature of the first higher plant thylakoid cation channel, opening the way to functional studies.

  15. Evaporative Lithography in Open Microfluidic Channel Networks

    KAUST Repository

    Lone, Saifullah

    2017-02-24

    We demonstrate a direct capillary-driven method based on wetting and evaporation of various suspensions to fabricate regular two-dimensional wires in an open microfluidic channel through continuous deposition of micro- or nanoparticles under evaporative lithography, akin to the coffee-ring effect. The suspension is gently placed in a loading reservoir connected to the main open microchannel groove on a PDMS substrate. Hydrophilic conditions ensure rapid spreading of the suspension from the loading reservoir to fill the entire channel length. Evaporation during the spreading and after the channel is full increases the particle concentration toward the end of the channel. This evaporation-induced convective transport brings particles from the loading reservoir toward the channel end where this flow deposits a continuous multilayered particle structure. The particle deposition front propagates backward over the entire channel length. The final dry deposit of the particles is thereby much thicker than the initial volume fraction of the suspension. The deposition depth is characterized using a 3D imaging profiler, whereas the deposition topography is revealed using a scanning electron microscope. The patterning technology described here is robust and passive and hence operates without an external field. This work may well become a launching pad to construct low-cost and large-scale thin optoelectronic films with variable thicknesses and interspacing distances.

  16. 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

  17. 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....

  18. A Simulator of Periodically Switching Channels for Power Line Communications

    Science.gov (United States)

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

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

  19. 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...

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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)

  9. Role of TRP channels in the cardiovascular system.

    Science.gov (United States)

    Yue, Zhichao; Xie, Jia; Yu, Albert S; Stock, Jonathan; Du, Jianyang; Yue, Lixia

    2015-02-01

    The transient receptor potential (TRP) superfamily consists of a large number of nonselective cation channels with variable degree of Ca(2+)-permeability. The 28 mammalian TRP channel proteins can be grouped into six subfamilies: canonical, vanilloid, melastatin, ankyrin, polycystic, and mucolipin TRPs. The majority of these TRP channels are expressed in different cell types including both excitable and nonexcitable cells of the cardiovascular system. Unlike voltage-gated ion channels, TRP channels do not have a typical voltage sensor, but instead can sense a variety of other stimuli including pressure, shear stress, mechanical stretch, oxidative stress, lipid environment alterations, hypertrophic signals, and inflammation products. By integrating multiple stimuli and transducing their activity to downstream cellular signal pathways via Ca(2+) entry and/or membrane depolarization, TRP channels play an essential role in regulating fundamental cell functions such as contraction, relaxation, proliferation, differentiation, and cell death. With the use of targeted deletion and transgenic mouse models, recent studies have revealed that TRP channels are involved in numerous cellular functions and play an important role in the pathophysiology of many diseases in the cardiovascular system. Moreover, several TRP channels are involved in inherited diseases of the cardiovascular system. This review presents an overview of current knowledge concerning the physiological functions of TRP channels in the cardiovascular system and their contributions to cardiovascular diseases. Ultimately, TRP channels may become potential therapeutic targets for cardiovascular diseases. Copyright © 2015 the American Physiological Society.

  10. Channel properties of Nax expressed in neurons.

    Directory of Open Access Journals (Sweden)

    Masahito Matsumoto

    Full Text Available Nax is a sodium-concentration ([Na+]-sensitive Na channel with a gating threshold of ~150 mM for extracellular [Na+] ([Na+]o in vitro. We previously reported that Nax was preferentially expressed in the glial cells of sensory circumventricular organs including the subfornical organ, and was involved in [Na+] sensing for the control of salt-intake behavior. Although Nax was also suggested to be expressed in the neurons of some brain regions including the amygdala and cerebral cortex, the channel properties of Nax have not yet been adequately characterized in neurons. We herein verified that Nax was expressed in neurons in the lateral amygdala of mice using an antibody that was newly generated against mouse Nax. To investigate the channel properties of Nax expressed in neurons, we established an inducible cell line of Nax using the mouse neuroblastoma cell line, Neuro-2a, which is endogenously devoid of the expression of Nax. Functional analyses of this cell line revealed that the [Na+]-sensitivity of Nax in neuronal cells was similar to that expressed in glial cells. The cation selectivity sequence of the Nax channel in cations was revealed to be Na+ ≈ Li+ > Rb+ > Cs+ for the first time. Furthermore, we demonstrated that Nax bound to postsynaptic density protein 95 (PSD95 through its PSD95/Disc-large/ZO-1 (PDZ-binding motif at the C-terminus in neurons. The interaction between Nax and PSD95 may be involved in promoting the surface expression of Nax channels because the depletion of endogenous PSD95 resulted in a decrease in Nax at the plasma membrane. These results indicated, for the first time, that Nax functions as a [Na+]-sensitive Na channel in neurons as well as in glial cells.

  11. Screen-based identification and validation of four novel ion channels as regulators of renal ciliogenesis

    NARCIS (Netherlands)

    Slaats, Gisela G|info:eu-repo/dai/nl/413981452; Wheway, Gabrielle; Foletto, Veronica; Szymanska, Katarzyna; van Balkom, Bas W M|info:eu-repo/dai/nl/256594783; Logister, Ive; Den Ouden, Krista; Keijzer-Veen, Mandy G|info:eu-repo/dai/nl/292371950; Lilien, Marc R|info:eu-repo/dai/nl/271538899; Knoers, Nine V|info:eu-repo/dai/nl/298974460; Johnson, Colin A; Giles, Rachel H|info:eu-repo/dai/nl/173658725

    2015-01-01

    To investigate the contribution of ion channels to ciliogenesis we carried out an siRNA-based reverse genetics screen of all ion channels in the mouse genome in murine inner medullary collecting duct kidney cells. This screen revealed four candidate ion channel genes: Kcnq1, Kcnj10, Kcnf1 and Clcn4.

  12. KCa2 and KCa3 channels in learning and memory processes, and neurodegeneration

    Directory of Open Access Journals (Sweden)

    Els F. E. Kuiper

    2012-06-01

    Full Text Available Calcium-activated potassium (KCa channels are present throughout the central nervous system as well as many peripheral tissues. Activation of KCa channels is essential for maintenance of the neuronal membrane potential and was shown to underlie the afterhyperpolarization (AHP that regulates action potential firing and limits the firing frequency of repetitive action potentials. Different subtypes of KCa channels were anticipated on the basis of their physiological and pharmacological profiles, and cloning revealed two well defined but phylogenetic distantly related groups of channels. The group subject of this review includes both the small-conductance KCa2 channels (KCa2.1, KCa2.2, and KCa2.3 and the intermediate-conductance (KCa3.1 channel. These channels are activated by submicromolar intracellular Ca2+ concentrations and are voltage independent. Of all KCa channels only the KCa2 channels can be potently but differentially blocked by the bee-venom apamin. In the past few years modulation of KCa channel activation revealed new roles for KCa2 channels in controlling dendritic excitability, synaptic functioning and synaptic plasticity. Furthermore, KCa2 channels appeared to be involved in neurodegeneration, and learning and memory processes. In this review, we focus on the role of KCa2 and KCa3 channels in these latter mechanisms with emphasis on learning and memory, Alzheimer’s disease and on the interplay between neuroinflammation and different neurotransmitters/neuromodulators, their signalling components and KCa channel activation.

  13. 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.

  14. 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…

  15. 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…

  16. 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

  17. Anomalous passage of ultrarelativistic electrons in thick single crystals in axial channeling

    Energy Technology Data Exchange (ETDEWEB)

    Khokonov, M.K. (Moskovskij Gosudarstvennyj Univ. (USSR). Nauchno-Issledovatel' skij Inst. Yadernoj Fiziki); Telegin, V.I. (Gosudarstvennyj Komitet po Ispol' zovaniyu Atomnoj Ehnergii SSSR, Moscow. Inst. Atomnoj Ehnergii)

    1983-07-01

    The dynamics of ultrarelativistic axially channeled electrons in thick crystals is studied. It is revealed that a certain fraction of initial electrons have anomalously large dechanneling depths. It is shown also that the dechanneling depth in heavy and light crystals are comparable. In some cases, the number of channeled electrons can strongly increase at the expense of quasi-channeled electrons. The problem of quasi-channeling is also considered.

  18. 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.

  19. Sedimentary processes of the lower Monterey Fan channel and channel-mouth lobe

    Science.gov (United States)

    Klaucke, I.; Masson, D.G.; Kenyon, Neil H.; Gardner, J.V.

    2004-01-01

    The distribution of deposits, sediment transport pathways and processes on the lower Monterey Fan channel and channel-mouth lobe (CML) are studied through the integration of GLORIA and TOBI sidescan sonar data with 7-kHz subbottom profiler records and sediment cores for ground-truthing. The lower Monterey channel is characterised by an up to 30-m-deep channel with poorly developed levees and alternating muddy and silty muddy overbank deposits. The channel is discontinuous, disappearing where gradients are less than about 1:350. Ground-truthing of the large CML shows that the entire CML is characterised by widespread deposits of generally fine sand, with coarser sand at the base of turbidites. Sand is particularly concentrated in finger-like areas of low-backscatter intensity and is interpreted as the result of non-turbulent sediment-gravity flows depositing metres thick massive, fine sand. TOBI sidescan sonar data reveal recent erosional features in the form of scours, secondary channels, large flow slides, and trains of blocks at the distal end of the CML. Erosion is probably related to increasing gradient as the CML approaches Murray Fracture zone and to differential loading of sandy submarine fan deposits onto pelagic clays. Reworking of older flow slides by sediment transport processes on the lobe produces trains of blocks that are several metres in diameter and aligned parallel to the flow direction. ?? 2004 Elsevier B.V. All rights reserved.

  20. Strategies for sustainable channel relations in mobile telecom sector

    Directory of Open Access Journals (Sweden)

    Githa Heggde

    2011-01-01

    Full Text Available The telecom sector in India largely comprises of wireless connections for phones. As of today, there are approximately 21 network providers in the country with about 7 per each circle, each offering competitive pricing to the consumers. The main objective of the study is to provide an accurate role for the company executive in developing channel relations. Further to this, the study explores the strategies which can sustain a good working relationship between the company and its channel members in the mobile telecom sector. The constructs identified for developing sustainable relationships were Setting distribution objectives, Channel design, Logistics, Image Building, Inventory management, Channel management, Payment & credit, Promotional assistance, Setting targets, Coverage frequency , Motivating channel members to perform. The sample selected contained distributors from the Mobile telecom sector and company executives/channel managers of leading telecom companies. Factor analysis and Friedman’s test was applied. The findings revealed a correlation in attitude between distributors and the executives. Motivating distributors was rated as the most important strategy by the company. The distributors felt that all channel partners needed to have positive attitude towards the channel while company executives felt that aggression made channel members perform effectively. Such findings will be of use to mobile telecom companies who are new entrants to the Indian market and to existing companies who plan to expand their coverage.

  1. 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.

  2. 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.

  3. ``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.

  4. 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.

  5. Gabapentin Modulates HCN4 Channel Voltage-Dependence

    Directory of Open Access Journals (Sweden)

    Han-Shen Tae

    2017-08-01

    Full Text Available Gabapentin (GBP is widely used to treat epilepsy and neuropathic pain. There is evidence that GBP can act on hyperpolarization-activated cation (HCN channel-mediated Ih in brain slice experiments. However, evidence showing that GBP directly modulates HCN channels is lacking. The effect of GBP was tested using two-electrode voltage clamp recordings from human HCN1, HCN2, and HCN4 channels expressed in Xenopus oocytes. Whole-cell recordings were also made from mouse spinal cord slices targeting either parvalbumin positive (PV+ or calretinin positive (CR+ inhibitory neurons. The effect of GBP on Ih was measured in each inhibitory neuron population. HCN4 expression was assessed in the spinal cord using immunohistochemistry. When applied to HCN4 channels, GBP (100 μM caused a hyperpolarizing shift in the voltage of half activation (V1/2 thereby reducing the currents. Gabapentin had no impact on the V1/2 of HCN1 or HCN2 channels. There was a robust increase in the time to half activation for HCN4 channels with only a small increase noted for HCN1 channels. Gabapentin also caused a hyperpolarizing shift in the V1/2 of Ih measured from HCN4-expressing PV+ inhibitory neurons in the spinal dorsal horn. Gabapentin had minimal effect on Ih recorded from CR+ neurons. Consistent with this, immunohistochemical analysis revealed that the majority of CR+ inhibitory neurons do not express somatic HCN4 channels. In conclusion, GBP reduces HCN4 channel-mediated currents through a hyperpolarized shift in the V1/2. The HCN channel subtype selectivity of GBP provides a unique tool for investigating HCN4 channel function in the central nervous system. The HCN4 channel is a candidate molecular target for the acute analgesic and anticonvulsant actions of GBP.

  6. 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.

  7. 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.)

  8. Amiloride-insensitive sodium channels are directly regulated by actin cytoskeleton dynamics in human lymphoma cells.

    Science.gov (United States)

    Sudarikova, Anastasia V; Tsaplina, Olga A; Chubinskiy-Nadezhdin, Vladislav I; Morachevskaya, Elena A; Negulyaev, Yuri A

    2015-05-22

    Sodium influx mediated by ion channels of plasma membrane underlies fundamental physiological processes in cells of blood origin. However, little is known about the single channel activity and regulatory mechanisms of sodium-specific channels in native cells. In the present work, we used different modes of patch clamp technique to examine ion channels involved in Na-transporting pathway in U937 human lymphoma cells. The activity of native non-voltage-gated sodium (NVGS) channels with unitary conductance of 10 pS was revealed in cell-attached, inside-out and whole-cell configurations. NVGS channel activity is directly controlled by submembranous actin cytoskeleton. Specifically, an activation of sodium channels in U937 cells in response to microfilament disassembly was demonstrated on single-channel and integral current level. Inside-out experiments showed that filament assembly on cytoplasmic membrane surface caused fast inactivation of the channels. Biophysical characteristics of NVGS channels in U937 cells were similar to that of epithelial sodium channels (ENaCs). However, we found that amiloride, a known inhibitor of DEG/ENaC, did not block NVGS channels in U937 cells. Whole-cell current measurements revealed no amiloride-sensitive component of membrane current. Our data show that cortical actin structures represent the main factor that controls the activity of amiloride-insensitive ENaC-like channels in human lymphoma cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. 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.)

  10. 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).

  11. 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

  12. Kv7 channels can function without constitutive calmodulin tethering.

    Directory of Open Access Journals (Sweden)

    Juan Camilo Gómez-Posada

    Full Text Available M-channels are voltage-gated potassium channels composed of Kv7.2-7.5 subunits that serve as important regulators of neuronal excitability. Calmodulin binding is required for Kv7 channel function and mutations in Kv7.2 that disrupt calmodulin binding cause Benign Familial Neonatal Convulsions (BFNC, a dominantly inherited human epilepsy. On the basis that Kv7.2 mutants deficient in calmodulin binding are not functional, calmodulin has been defined as an auxiliary subunit of Kv7 channels. However, we have identified a presumably phosphomimetic mutation S511D that permits calmodulin-independent function. Thus, our data reveal that constitutive tethering of calmodulin is not required for Kv7 channel function.

  13. Gating the Selectivity Filter in ClC Chloride Channels

    Science.gov (United States)

    Dutzler, Raimund; Campbell, Ernest B.; MacKinnon, Roderick

    2003-04-01

    ClC channels conduct chloride (Cl-) ions across cell membranes and thereby govern the electrical activity of muscle cells and certain neurons, the transport of fluid and electrolytes across epithelia, and the acidification of intracellular vesicles. The structural basis of ClC channel gating was studied. Crystal structures of wild-type and mutant Escherichia coli ClC channels bound to a monoclonal Fab fragment reveal three Cl- binding sites within the 15-angstrom neck of an hourglass-shaped pore. The Cl- binding site nearest the extracellular solution can be occupied either by a Cl- ion or by a glutamate carboxyl group. Mutations of this glutamate residue in Torpedo ray ClC channels alter gating in electrophysiological assays. These findings reveal a form of gating in which the glutamate carboxyl group closes the pore by mimicking a Cl- ion.

  14. 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.

  15. 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

  16. Computational Fluid Dynamics Study of Channel Geometric Effect for Fischer-Tropsch Microchannel Reactor

    International Nuclear Information System (INIS)

    Na, Jonggeol; Jung, Ikhwan; Kshetrimayum, Krishnadash S.; Park, Seongho; Park, Chansaem; Han, Chonghun

    2014-01-01

    Driven by both environmental and economic reasons, the development of small to medium scale GTL(gas-to-liquid) process for offshore applications and for utilizing other stranded or associated gas has recently been studied increasingly. Microchannel GTL reactors have been preferred over the conventional GTL reactors for such applications, due to its compactness, and additional advantages of small heat and mass transfer distance desired for high heat transfer performance and reactor conversion. In this work, multi-microchannel reactor was simulated by using commercial CFD code, ANSYS FLUENT, to study the geometric effect of the microchannels on the heat transfer phenomena. A heat generation curve was first calculated by modeling a Fischer-Tropsch reaction in a single-microchannel reactor model using Matlab-ASPEN integration platform. The calculated heat generation curve was implemented to the CFD model. Four design variables based on the microchannel geometry namely coolant channel width, coolant channel height, coolant channel to process channel distance, and coolant channel to coolant channel distance, were selected for calculating three dependent variables namely, heat flux, maximum temperature of coolant channel, and maximum temperature of process channel. The simulation results were visualized to understand the effects of the design variables on the dependent variables. Heat flux and maximum temperature of cooling channel and process channel were found to be increasing when coolant channel width and height were decreased. Coolant channel to process channel distance was found to have no effect on the heat transfer phenomena. Finally, total heat flux was found to be increasing and maximum coolant channel temperature to be decreasing when coolant channel to coolant channel distance was decreased. Using the qualitative trend revealed from the present study, an appropriate process channel and coolant channel geometry along with the distance between the adjacent

  17. 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.

  18. The elusive character of discontinuous deep-water channels: New insights from Lucia Chica channel system, offshore California

    Science.gov (United States)

    Maier, K.L.; Fildani, A.; Paull, C.K.; Graham, S.A.; McHargue, T.R.; Caress, D.W.; McGann, M.

    2011-01-01

    New high-resolution autonomous underwater vehicle (AUV) seafloor images, with 1 m lateral resolution and 0.3 m vertical resolution, reveal unexpected seafloor rugosity and low-relief (architecture of the depositional area. Flowstripped turbidity currents separated into and reactivated multiple channels to create a distributary pattern and developed discontinuous trains of cyclic scours and megaflutes, which may be erosional precursors to continuous channels. The diverse features now imaged in the Lucia Chica channel system (offshore California) are likely common in modern and ancient systems with similar overall morphologies, but have not been previously mapped with lower-resolution detection methods in any of these systems. ?? 2011 Geological Society of America.

  19. The Extended-Window Channel Estimator for Iterative Channel-and-Symbol Estimation

    Directory of Open Access Journals (Sweden)

    Barry John R

    2005-01-01

    Full Text Available The application of the expectation-maximization (EM algorithm to channel estimation results in a well-known iterative channel-and-symbol estimator (ICSE. The EM-ICSE iterates between a symbol estimator based on the forward-backward recursion (BCJR equalizer and a channel estimator, and may provide approximate maximum-likelihood blind or semiblind channel estimates. Nevertheless, the EM-ICSE has high complexity, and it is prone to misconvergence. In this paper, we propose the extended-window (EW estimator, a novel channel estimator for ICSE that can be used with any soft-output symbol estimator. Therefore, the symbol estimator may be chosen according to performance or complexity specifications. We show that the EW-ICSE, an ICSE that uses the EW estimator and the BCJR equalizer, is less complex and less susceptible to misconvergence than the EM-ICSE. Simulation results reveal that the EW-ICSE may converge faster than the EM-ICSE.

  20. A novel mixing mechanism in sinuous seafloor channels: Implications for submarine channel evolution

    Science.gov (United States)

    Dorrell, R. M.; Peakall, J.; Burns, C.; Keevil, G. M.

    2018-02-01

    Previous experimental studies of density currents in sinuous seafloor channels have almost exclusively studied hydrodynamics either by considering time independent, instantaneous, flow measurements or by compiling time-averaged flow measurements. Here we present a novel study of the time dependent dynamics of a density driven flow in a sinuous channel fed by a source of constant discharge. The experiments show that whilst source conditions may be temporally steady, flow conditions are temporally unsteady with timescales of flow variation driven by flow interaction with channel topography. Temporal variations reveal that both downstream and cross-stream flows vary significantly from time average observations and predictions, across scales larger than those predicted for turbulence in equivalent straight channels. Large-scale variations are shown to increase the average production of turbulence across the height of the flow, providing a new mechanism for enhanced mixing of sediment within gravity currents. Further such large-scale variations in flow conditions are recorded in the change in orientation of near-bed secondary flow, providing a plausible mechanism to reduce the cross-stream transport of bedload material and explain the ultimate stabilisation of sinuous seafloor channel systems.

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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

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

    Science.gov (United States)

    Kajma, Anna; Szewczyk, Adam

    2012-10-01

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

  7. 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.

  8. 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.

  9. 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 ...

  10. 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....

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Modes of Operation of the BKCa Channel β2 Subunit

    Science.gov (United States)

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

    2007-01-01

    The β2 subunit of the large conductance Ca2+- and voltage-activated K+ channel (BKCa) modulates a number of channel functions, such as the apparent Ca2+/voltage sensitivity, pharmacological and kinetic properties of the channel. In addition, the N terminus of the β2 subunit acts as an inactivating particle that produces a relatively fast inactivation of the ionic conductance. Applying voltage clamp fluorometry to fluorescently labeled human BKCa channels (hSlo), we have investigated the mechanisms of operation of the β2 subunit. We found that the leftward shift on the voltage axis of channel activation curves (G(V)) produced by coexpression with β2 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 β2 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 BKCa channels coexpressed with the β2 subunit. The experimental observations are consistent with the view that the β2 subunit of BKCa channels facilitates channel activation by changing the voltage sensor equilibrium and that the β2-induced inactivation process does not follow a typical N-type mechanism. PMID:17591990

  13. 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.

  14. 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.

  15. 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

  16. Differential effect of brief electrical stimulation on voltage-gated potassium channels.

    Science.gov (United States)

    Cameron, Morven A; Al Abed, Amr; Buskila, Yossi; Dokos, Socrates; Lovell, Nigel H; Morley, John W

    2017-05-01

    Electrical stimulation of neuronal tissue is a promising strategy to treat a variety of neurological disorders. The mechanism of neuronal activation by external electrical stimulation is governed by voltage-gated ion channels. This stimulus, typically brief in nature, leads to membrane potential depolarization, which increases ion flow across the membrane by increasing the open probability of these voltage-gated channels. In spiking neurons, it is activation of voltage-gated sodium channels (Na V channels) that leads to action potential generation. However, several other types of voltage-gated channels are expressed that also respond to electrical stimulation. In this study, we examine the response of voltage-gated potassium channels (K V channels) to brief electrical stimulation by whole cell patch-clamp electrophysiology and computational modeling. We show that nonspiking amacrine neurons of the retina exhibit a large variety of responses to stimulation, driven by different K V -channel subtypes. Computational modeling reveals substantial differences in the response of specific K V -channel subtypes that is dependent on channel kinetics. This suggests that the expression levels of different K V -channel subtypes in retinal neurons are a crucial predictor of the response that can be obtained. These data expand our knowledge of the mechanisms of neuronal activation and suggest that K V -channel expression is an important determinant of the sensitivity of neurons to electrical stimulation. NEW & NOTEWORTHY This paper describes the response of various voltage-gated potassium channels (K V channels) to brief electrical stimulation, such as is applied during prosthetic electrical stimulation. We show that the pattern of response greatly varies between K V channel subtypes depending on activation and inactivation kinetics of each channel. Our data suggest that problems encountered when artificially stimulating neurons such as cessation in firing at high frequencies, or

  17. Targeting the Small- and Intermediate-Conductance Ca2+-Activated Potassium Channels: The Drug-Binding Pocket at the Channel/Calmodulin Interface

    Directory of Open Access Journals (Sweden)

    Meng Cui

    2014-10-01

    Full Text Available The small- and intermediate-conductance Ca2+-activated potassium (SK/IK channels play important roles in the regulation of excitable cells in both the central nervous and cardiovascular systems. Evidence from animal models has implicated SK/IK channels in neurological conditions such as ataxia and alcohol use disorders. Further, genome-wide association studies have suggested that cardiovascular abnormalities such as arrhythmias and hypertension are associated with single nucleotide polymorphisms that occur within the genes encoding the SK/IK channels. The Ca2+ sensitivity of the SK/IK channels stems from a constitutively bound Ca2+-binding protein: calmodulin. Small-molecule positive modulators of SK/IK channels have been developed over the past decade, and recent structural studies have revealed that the binding pocket of these positive modulators is located at the interface between the channel and calmodulin. SK/IK channel positive modulators can potentiate channel activity by enhancing the coupling between Ca2+ sensing via calmodulin and mechanical opening of the channel. Here, we review binding pocket studies that have provided structural insight into the mechanism of action for SK/IK channel positive modulators. These studies lay the foundation for structure-based drug discovery efforts that can identify novel SK/IK channel positive modulators. © 2014 S. Karger AG, Basel

  18. 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.

  19. 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...

  20. Crystal structures of the TRIC trimeric intracellular cation channel orthologues.

    Science.gov (United States)

    Kasuya, Go; Hiraizumi, Masahiro; Maturana, Andrés D; Kumazaki, Kaoru; Fujiwara, Yuichiro; Liu, Keihong; Nakada-Nakura, Yoshiko; Iwata, So; Tsukada, Keisuke; Komori, Tomotaka; Uemura, Sotaro; Goto, Yuhei; Nakane, Takanori; Takemoto, Mizuki; Kato, Hideaki E; Yamashita, Keitaro; Wada, Miki; Ito, Koichi; Ishitani, Ryuichiro; Hattori, Motoyuki; Nureki, Osamu

    2016-12-01

    Ca 2+ release from the sarcoplasmic reticulum (SR) and endoplasmic reticulum (ER) is crucial for muscle contraction, cell growth, apoptosis, learning and memory. The trimeric intracellular cation (TRIC) channels were recently identified as cation channels balancing the SR and ER membrane potentials, and are implicated in Ca 2+ signaling and homeostasis. Here we present the crystal structures of prokaryotic TRIC channels in the closed state and structure-based functional analyses of prokaryotic and eukaryotic TRIC channels. Each trimer subunit consists of seven transmembrane (TM) helices with two inverted repeated regions. The electrophysiological, biochemical and biophysical analyses revealed that TRIC channels possess an ion-conducting pore within each subunit, and that the trimer formation contributes to the stability of the protein. The symmetrically related TM2 and TM5 helices are kinked at the conserved glycine clusters, and these kinks are important for the channel activity. Furthermore, the kinks of the TM2 and TM5 helices generate lateral fenestrations at each subunit interface. Unexpectedly, these lateral fenestrations are occupied with lipid molecules. This study provides the structural and functional framework for the molecular mechanism of this ion channel superfamily.

  1. TRP channels: sensors and transducers of gasotransmitter signals

    Directory of Open Access Journals (Sweden)

    Nobuaki eTakahashi

    2012-08-01

    Full Text Available The transient receptor potential (trp gene superfamily encodes cation channels that act as multimodal sensors for a wide variety of stimuli from outside and inside the cell. Upon sensing, they transduce electrical and Ca2+ signals via their cation channel activities. These functional features of TRP channels allow the body to react and adapt to different forms of environmental changes. Indeed, members of one class of TRP channels have emerged as sensors of gaseous messenger molecules that control various cellular processes. Nitric oxide (NO, a vasoactive gaseous molecule, regulates TRP channels directly via cysteine S-nitrosylation or indirectly via cGMP/PKG-dependent phosphorylation. Recent studies have revealed that changes in the availability of molecular oxygen (O2 also control the activation of TRP channels. Anoxia induced by O2-glucose deprivation and severe hypoxia (1% O2 activates TRPM7 and TRPC6, respectively, whereas TRPA1 has recently been identified as a novel sensor of hyperoxia and mild hypoxia (15% O2 in vagal and sensory neurons. TRPA1 also detects other gaseous molecules such as hydrogen sulfide (H2S and carbon dioxide (CO2. In this review, we focus on how signaling by gaseous molecules is sensed and integrated by TRP channels.

  2. Effective capacity of multiple antenna channels: Correlation and keyhole

    KAUST Repository

    Zhong, Caijun

    2012-01-01

    In this study, the authors derive the effective capacity limits for multiple antenna channels which quantify the maximum achievable rate with consideration of link-layer delay-bound violation probability. Both correlated multiple-input single-output and multiple-input multiple-output keyhole channels are studied. Based on the closed-form exact expressions for the effective capacity of both channels, the authors look into the asymptotic high and low signal-to-noise ratio regimes, and derive simple expressions to gain more insights. The impact of spatial correlation on effective capacity is also characterised with the aid of a majorisation theory result. It is revealed that antenna correlation reduces the effective capacity of the channels and a stringent quality-of-service requirement causes a severe reduction in the effective capacity but can be alleviated by increasing the number of antennas. © 2012 The Institution of Engineering and Technology.

  3. 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.

  4. 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

  5. Channel Communication and Reconfigurable Hardware

    NARCIS (Netherlands)

    Bos, M.; Havinga, Paul J.M.; Smit, Gerardus Johannes Maria; Karelse, F.

    2000-01-01

    Many applications can be structured as a set of processes or threads that communicate via channels. These threads can be executed on various platforms (e.g. general purpose CPU, DSP, FPGA, etc). In our research we apply channels as a basic communication mechanism between threads in a reconfigurable

  6. Hydraulic jumps in a channel

    DEFF Research Database (Denmark)

    Bonn, D.; Andersen, Anders Peter; Bohr, Tomas

    2009-01-01

    We present a study of hydraulic jumps with flow predominantly in one direction, created either by confining the flow to a narrow channel with parallel walls or by providing an inflow in the form of a narrow sheet. In the channel flow, we find a linear height profile upstream of the jump as expected...

  7. Defect Distributions in Channeling Experiments

    DEFF Research Database (Denmark)

    Andersen, Hans Henrik; Sigmund, P.

    1965-01-01

    A simple collision model allows to calculate energy losses of perfectly channeled particles. The maximum energy loss is related in a simple way to the displacement energy of lattice atoms perpendicular to the channel. From that, one obtains rather definite predictions on the possibility...

  8. Compressive Sensing Based Bayesian Sparse Channel Estimation for OFDM Communication Systems: High Performance and Low Complexity

    Science.gov (United States)

    Xu, Li; Shan, Lin; Adachi, Fumiyuki

    2014-01-01

    In orthogonal frequency division modulation (OFDM) communication systems, channel state information (CSI) is required at receiver due to the fact that frequency-selective fading channel leads to disgusting intersymbol interference (ISI) over data transmission. Broadband channel model is often described by very few dominant channel taps and they can be probed by compressive sensing based sparse channel estimation (SCE) methods, for example, orthogonal matching pursuit algorithm, which can take the advantage of sparse structure effectively in the channel as for prior information. However, these developed methods are vulnerable to both noise interference and column coherence of training signal matrix. In other words, the primary objective of these conventional methods is to catch the dominant channel taps without a report of posterior channel uncertainty. To improve the estimation performance, we proposed a compressive sensing based Bayesian sparse channel estimation (BSCE) method which cannot only exploit the channel sparsity but also mitigate the unexpected channel uncertainty without scarifying any computational complexity. The proposed method can reveal potential ambiguity among multiple channel estimators that are ambiguous due to observation noise or correlation interference among columns in the training matrix. Computer simulations show that proposed method can improve the estimation performance when comparing with conventional SCE methods. PMID:24983012

  9. Amazon floodplain channels regulate channel-floodplain water exchange

    Science.gov (United States)

    Bates, P. D.; Baugh, C.; Trigg, M.

    2017-12-01

    We examine the role of floodplain channels in regulating the exchange of water between the Amazon main stem and its extensive floodplains using a combination of field survey, remote sensing and numerical modelling for a 30,000 km2 area around the confluence of the Solimões and Purus rivers. From Landsat imagery we identified 1762 individual floodplain channel reaches with total length of nearly 9300 line km that range in width from 900m to 20m. Using a boat survey we measured width and depth along 509 line km of floodplain channels in 45 separate reaches and used these data to develop geomorphic relationships between width and depth. This enabled reconstruction of the depth of all other channels in the Landsat survey to an RMSE of 2.5m. We then constructed a 2D hydraulic model of this site which included all 9300km of floodplain channels as sub-grid scale features using a recently developed version of the LISFLOOD-FP code. The DEM for the model was derived from a version of the SRTM Digital Elevation Model that was processed to remove vegetation artefacts. The model was run at 270m resolution over the entire 30,000 km2 domain for the period from 2002-2009. Simulations were run with and without floodplain channels to examine the impact of these features on floodplain flow dynamics and storage. Simulated floodplain channel hydraulics were validated against a combination of in-situ and remotely sensed data. Our results show that approximately 100 km3 of water is exchanged between the channel and the floodplain during a typical annual cycle, and 8.5±2.1% of mainstem flows is routed through the floodplain. The overall effect of floodplains channels was to increase the duration of connections between the Amazon River and the floodplain. Inclusion of floodplain channels in the model increased inundation volume by 7.3% - 11.3% at high water, and decreased it at low water by 4.0% - 16.6%, with the range in these estimates due to potential errors in floodplain channel

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

    Directory of Open Access Journals (Sweden)

    Abdolrazagh MADAHI

    2014-12-01

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

  11. Role of calcium activated potassium channels in atrial fibrillation pathophysiology and therapy

    DEFF Research Database (Denmark)

    Diness, Jonas G.; Bentzen, Bo H.; S. Sørensen, Ulrik

    2015-01-01

    Small-conductance Ca2+-activated potassium (SK) channels are relative newcomers within the field of cardiac electrophysiology. In recent years, an increased focus has been given to these channels since they might constitute a relatively atrial selective target. The present review will give...... a general introduction to SK channels followed by their proposed function in the heart under normal and pathophysiological conditions. It is revealed how anti-arrhythmic effects can be obtained by SK channel inhibition in a number of species in situations of atrial fibrillation. On the contrary......, the beneficial effects of SK channel inhibition in situations of heart failure are questionable and still needs investigation. The understanding of cardiac SK channels is rapidly increasing these years, and hopefully this will clarify whether SK channel inhibition has potential as a new anti-atrial fibrillation...

  12. NALCN ion channels have alternative selectivity filters resembling calcium channels or sodium channels

    NARCIS (Netherlands)

    Senatore, A.; Monteil, A.; van Minnen, J.; Smit, A.B.; Spafford, J.D.

    2013-01-01

    NALCN is a member of the family of ion channels with four homologous, repeat domains that include voltage-gated calcium and sodium channels. NALCN is a highly conserved gene from simple, extant multicellular organisms without nervous systems such as sponges and placozoans and mostly remains a single

  13. Anomalous passage of ultrarelativistic electrons in thick single crystals in axial channeling

    International Nuclear Information System (INIS)

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

    1983-01-01

    The dynamics of ultrarelativistic axially channeled electrons in thick crystals is studied. It is revealed that a certain fraction of initial electrons have anomalously large dechanneling depths. It is shown also that the dechanneling depth in heavy and light crystals are comparable. In some cases, the number of channeled electrons can strongly increase at the expense of quasi-channeled electrons. The problem of quasichanneling is also considered. (author)

  14. Nonadditivity of quantum capacities of quantum multiple-access channels and the butterfly network

    International Nuclear Information System (INIS)

    Huang Peng; He Guangqiang; Zhu Jun; Zeng Guihua

    2011-01-01

    Multipartite quantum information transmission without additional classical resources is investigated. We show purely quantum superadditivity of quantum capacity regions of quantum memoryless multiple-access (MA) channels, which are not entanglement breaking. Also, we find that the superadditivity holds when the MA channel extends to the quantum butterfly network, which can achieve quantum network coding. The present widespread effects for the channels which enable entanglement distribution have not been revealed for multipartite scenarios.

  15. A novel mitochondrial KATP channel assay

    Science.gov (United States)

    Wojtovich, Andrew P.; Williams, David M; Karcz, Marcin K.; Lopes, Coeli M. B.; Gray, Daniel A; Nehrke, Keith W.; Brookes, Paul S.

    2010-01-01

    Rationale The mitochondrial ATP sensitive potassium channel (mKATP) is implicated in cardioprotection by ischemic preconditioning (IPC), but the molecular identity of the channel remains controversial. The validity of current methods to assay mKATP activity is disputed. Objective We sought to develop novel methods to assay mKATP activity and its regulation. Methods & Results Using a thallium (Tl+) sensitive fluorophore, we developed a novel Tl+ flux based assay for mKATP activity, and used this assay probe several aspects of mKATP function. The following key observations were made: (i) Time-dependent run-down of mKATP activity was reversed by phosphatidylinositol-4,5-bisphosphate (PIP2). (ii) Dose responses of mKATP to nucleotides revealed a UDP EC50 of ~20 μmol/L and an ATP IC50 of ~5 μmol/L. (iii) The antidepressant fluoxetine (Prozac™) inhibited mKATP (IC50 2.4 μmol/L). Fluoxetine also blocked cardioprotection triggered by IPC, but did not block protection triggered by a mKATP independent stimulus. The related antidepressant zimelidine was without effect on either mKATP or IPC. Conclusions The Tl+ flux mKATP assay was validated by correlation with a classical mKATP channel osmotic swelling assay (R2 0.855). The pharmacologic profile of mKATP (response to ATP, UDP, PIP2, and fluoxetine) is consistent with that of an inward rectifying K+ channel (KIR) and is somewhat closer to that of the KIR6.2 than the KIR6.1 isoform. The effect of fluoxetine on mKATP-dependent cardioprotection has implications for the growing use of antidepressants in patients who may benefit from preconditioning. PMID:20185796

  16. Substrate channeling in proline metabolism

    Science.gov (United States)

    Arentson, Benjamin W.; Sanyal, Nikhilesh; Becker, Donald F.

    2012-01-01

    Proline metabolism is an important pathway that has relevance in several cellular functions such as redox balance, apoptosis, and cell survival. Results from different groups have indicated that substrate channeling of proline metabolic intermediates may be a critical mechanism. One intermediate is pyrroline-5-carboxylate (P5C), which upon hydrolysis opens to glutamic semialdehyde (GSA). Recent structural and kinetic evidence indicate substrate channeling of P5C/GSA occurs in the proline catabolic pathway between the proline dehydrogenase and P5C dehydrogenase active sites of bifunctional proline utilization A (PutA). Substrate channeling in PutA is proposed to facilitate the hydrolysis of P5C to GSA which is unfavorable at physiological pH. The second intermediate, gamma-glutamyl phosphate, is part of the proline biosynthetic pathway and is extremely labile. Substrate channeling of gamma-glutamyl phosphate is thought to be necessary to protect it from bulk solvent. Because of the unfavorable equilibrium of P5C/GSA and the reactivity of gamma-glutamyl phosphate, substrate channeling likely improves the efficiency of proline metabolism. Here, we outline general strategies for testing substrate channeling and review the evidence for channeling in proline metabolism. PMID:22201749

  17. Melt Channel Formation in Paraffin With Applications to Lava Channels

    Science.gov (United States)

    Whitehead, J. A.; Mills, C. J.

    2005-12-01

    We present the results from laboratory experiments designed to explore channel formation caused by instabilities in fluid flow, and to provide a simple experimental basis to facilitate the extension of lava channel theory. Kelemen et. al. [1995] reported on a series of experiments that explored channel formation resulting from fluid instabilities caused by the ``reactive infiltration instability'' (RII). However, the material used in portions of their experiments was undesirable because of a poorly suited rheology. Therefore, our experiments were initiated as an extension of those earlier experiments, using instead a material with more robust rheological properties. The material chosen for this series of experiments is a paraffin with a freezing temperature of 4°C, which is transparent when liquid and opaque-white when frozen. The paraffin is pumped at a constant and controlled rate into a narrow gap between two circular plates, both with a diameter of ~51cm. The gap is open along the circumference of the plates, allowing the paraffin to flow out of the gap once it reaches the edge of the plate. The upper plate is constructed of Plexiglas to allow observation of the wax below, and it has a hole in the center through which the paraffin is pumped. The lower plate is constructed of aluminum, painted black, and kept at -5°C by circulating coolant through a reservoir below the it. As the paraffin, which is kept at 20°C before being pumped into the gap, flows over the cold lower plate, it begins to freeze and eventually fills up the gap between the plates. A single channel then forms, surrounded by solid paraffin, and the liquid being pumped in is transported via this channel to the edge of the plate. This is a stable state for all but the lowest flow rates attempted and verifies the results from the earlier work exploring the RII. We conducted experiments at different flows rates from 270mL/min to <30mL/min, and recorded the dimensions of the steady state channel

  18. ACE Strategy with Virtual Channels

    Directory of Open Access Journals (Sweden)

    T. Tichy

    2008-12-01

    Full Text Available Cochlear implant is an electronic device, which can mediate hearing sensations to profoundly deaf people. Contemporary cochlear implants are sophisticated electronic devices; however, their performance could still be improved. This paper describes an experiment we made in that direction: additional 21 virtual channels were implemented by sequential stimulation of adjacent intracochlear electrodes, and the ACE strategy with virtual channels (ACEv, Advanced Combination Encoder strategy with virtual channels for the Nucleus® 24 Cochlear Implant System was created and verified in a clinical test with four patients.

  19. Molecular Cloning and Sequencing of Hemoglobin-Beta Gene of Channel Catfish, Ictalurus Punctatus Rafinesque

    Science.gov (United States)

    : Hemoglobin-y gene of channel catfish , lctalurus punctatus, was cloned and sequenced . Total RNA from head kidneys was isolated, reverse transcribed and amplified . The sequence of the channel catfish hemoglobin-y gene consists of 600 nucleotides . Analysis of the nucleotide sequence reveals one o...

  20. Exponential decay and exponential recovery of modal gains in high count rate channel electron multipliers

    International Nuclear Information System (INIS)

    Hahn, S.F.; Burch, J.L.

    1980-01-01

    A series of data on high count rate channel electron multipliers revealed an initial drop and subsequent recovery of gains in exponential fashion. The FWHM of the pulse height distribution at the initial stage of testing can be used as a good criterion for the selection of operating bias voltage of the channel electron multiplier

  1. Sodium channels in planar lipid bilayers. Channel gating kinetics of purified sodium channels modified by batrachotoxin

    Science.gov (United States)

    1986-01-01

    Single channel currents of sodium channels purified from rat brain and reconstituted into planar lipid bilayers were recorded. The kinetics of channel gating were investigated in the presence of batrachotoxin to eliminate inactivation and an analysis was conducted on membranes with a single active channel at any given time. Channel opening is favored by depolarization and is strongly voltage dependent. Probability density analysis of dwell times in the closed and open states of the channel indicates the occurrence of one open state and several distinct closed states in the voltage (V) range-120 mV less than or equal to V less than or equal to +120 mV. For V less than or equal to 0, the transition rates between stages are exponentially dependent on the applied voltage, as described in mouse neuroblastoma cells (Huang, L. M., N. Moran, and G. Ehrenstein. 1984. Biophysical Journal. 45:313- 322). In contrast, for V greater than or equal to 0, the transition rates are virtually voltage independent. Autocorrelation analysis (Labarca, P., J. Rice, D. Fredkin, and M. Montal. 1985. Biophysical Journal. 47:469-478) shows that there is no correlation in the durations of successive open or closing events. Several kinetic schemes that are consistent with the experimental data are considered. This approach may provide information about the mechanism underlying the voltage dependence of channel activation. PMID:2426388

  2. The importance of channel non-uniformity in riverine ecosystems

    Science.gov (United States)

    Pasternack, G. B.

    2007-12-01

    A key aspect of the hierarchical controls on riverine ecosystems that has been undervalued in both river science and restoration is the role of channel non-uniformity. As the water depth to bed grain size ratio decreases, channel non-uniformity takes over as a dominant control on hydraulic, geomorphic, and ecologic processes in rivers. As a case in point, the degree of channel degradation and habitat loss that ensues after dams are built may be directly related to maintenance of channel non-uniformity. The study reported here evaluated channel change at different spatial (submeter to km) and temporal (seasonal to interdecadal) scales in a regulated, but still dynamic, gravel-cobble river. The objectives were to (1) determine the cause of the persistence of riffles and pools even as the channel incised more than 10 m over 70 years and (2) evaluate the linkage between channel change and anadromous fish habitat in such a dynamic setting. The study area was the top 10.5 km of the Yuba River below Englebright Dam. Although this dam has blocked bedload transport into the reach for 65 years causing significant channel incision, a residual of 17.7 million m3 of sediment remains in the study reach due to historical hydraulic mining for gold. The approach used was to combine the knowledge gained at multiple scales using different methods, including historical aerial photo analysis, channel DEM analysis and differencing, 2D hydrodynamic modeling, hydraulic geometry analysis, fish observations, process-based hydrogeomorphic monitoring, and sediment transport experiments. These diverse methods revealed an array of mechanisms contributing to channel change and habitat rejuvenation, most notable including flow-convergence routing responsible for maintaining riffles and pools over a range of flows. Anadromous fish were observed to shift their pattern of habitat utilization in response to channel change in predictable ways. The primary lesson for river management is that more

  3. Multi-channel Kondo necklace

    International Nuclear Information System (INIS)

    Fazekas, P.; Kee Haeyoung.

    1993-06-01

    A multi-channel generalization of Doniach's Kondo necklace model is formulated, and its phase diagram studied in the mean-field approximation. Our intention is to introduce the possible simplest model which displays some of the features expected from the overscreened Kondo lattice. The N conduction electron channels are represented by N sets of pseudospins τ J , j = 1 1,..., N which are all antiferromagnetically coupled to a periodic array of modul S = 1/2 spins. Exploiting permutation symmetry in the channel index j allows us to write down the self-consistency equation for general N. For N > 2, we find that the critical temperature is rising with increasing Kondo interaction; we interpret this effect by pointing out that the Kondo coupling creates the composite pseudospin objects which undergo an ordering transition. The relevance of our findings to the underlying fermionic multi-channel problem is discussed. (author). 33 refs, 1 fig

  4. FMCG companies specific distribution channels

    Directory of Open Access Journals (Sweden)

    Ioana Barin

    2009-12-01

    Full Text Available Distribution includes all activities undertaken by the producer, alone or in cooperation, since the end of the final finished products or services until they are in possession of consumers. The distribution consists of the following major components: distribution channels or marketing channels, which together form a distribution network; logistics o rphysical distribution. In order to effective achieve, distribution of goods requires an amount of activities and operational processes related to transit of goods from producer to consumer, the best conditions, using existing distribution channels and logistics system. One of the essential functions of a distribution is performing acts of sale, through which, with the actual movement of goods, their change of ownership takes place, that the successive transfer of ownership from producer to consumer. This is an itinerary in the economic cycle of goods, called the distribution channel.

  5. Potassium Channels in Neurofbromatosis-1

    National Research Council Canada - National Science Library

    Chen, Mingkui

    2006-01-01

    .... We were the first to investigate potential mechanisms of cognitive impairment in NF-1 at the molecular level involving potassium channels, and demonstrated a possible mechanism for the learning deficits seen in NF1...

  6. Prediction of concentrated flow width in ephemeral gully channels

    Science.gov (United States)

    Nachtergaele, J.; Poesen, J.; Sidorchuk, A.; Torri, D.

    2002-07-01

    Empirical prediction equations of the form W = aQb have been reported for rills and rivers, but not for ephemeral gullies. In this study six experimental data sets are used to establish a relationship between channel width (W, m) and flow discharge (Q, m3 s-1) for ephemeral gullies formed on cropland. The resulting regression equation (W = 2·51 Q0·412; R2 = 0·72; n = 67) predicts observed channel width reasonably well. Owing to logistic limitations related to the respective experimental set ups, only relatively small runoff discharges (i.e. Q channel width was attributed to a calculated peak runoff discharge on sealed cropland, the application field of the regression equation was extended towards larger discharges (i.e. 5 × 10channels revealed that the discharge exponent (distribution over the wetted perimeter between rills, gullies and rivers, (ii) a decrease in probability of a channel formed in soil material with uniform erosion resistance from rills over gullies to rivers and (iii) a decrease in average surface slope from rills over gullies to rivers.channel width equation for concentrated flow on cropland. For the frozen soils the equation

  7. Heteromeric Anopheline odorant receptors exhibit distinct channel properties.

    Directory of Open Access Journals (Sweden)

    Gregory M Pask

    Full Text Available Insect odorant receptors (ORs function as odorant-gated ion channels consisting of a conventional, odorant-binding OR and the Orco coreceptor. While Orco can function as a homomeric ion channel, the role(s of the conventional OR in heteromeric OR complexes has largely focused only on odorant recognition.To investigate other roles of odorant-binding ORs, we have employed patch clamp electrophysiology to investigate the properties of the channel pore of several OR complexes formed by a range of different odorant-specific Anopheles gambiae ORs (AgOrs each paired with AgOrco. These studies reveal significant differences in cation permeability and ruthenium red susceptibility among different AgOr complexes.With observable differences in channel function, the data support a model in which the odorant-binding OR also affects the channel pore. The variable effect contributed by the conventional OR on the conductive properties of odorant-gated sensory channels adds additional complexity to insect olfactory signaling, with differences in odor coding beginning with ORs on the periphery of the olfactory system.

  8. Marketing channel behaviour and performance

    OpenAIRE

    Duarte, Margarida

    2000-01-01

    Thesis submitted to University of Manchester for the degree of Doctor of Philosophy in the Faculty of Business Administration. A major aim of this study is to offer a relatively comprehensive picture of marketing channel behaviour and performance. Given the statistical difficulties in testing a very large, comprehensive model to achieve this aim, two separate but overlapping models are proposed. One model specifically addresses behaviour in marketing channels, while the other integrates k...

  9. Learning the MMSE Channel Estimator

    OpenAIRE

    Neumann, David; Wiese, Thomas; Utschick, Wolfgang

    2017-01-01

    We present a method for estimating conditionally Gaussian random vectors with random covariance matrices, which uses techniques from the field of machine learning. Such models are typical in communication systems, where the covariance matrix of the channel vector depends on random parameters, e.g., angles of propagation paths. If the covariance matrices exhibit certain Toeplitz and shift-invariance structures, the complexity of the MMSE channel estimator can be reduced to O(M log M) floating ...

  10. Eight channel telephone telemetry system

    Science.gov (United States)

    Smith, R. E.

    1973-01-01

    A portable, indirectly coupled telephone system is reported which transmits/to a central receiving site eight channels of EEG data of sufficient fidelity for screening and/or limited diagnostic use. The system requires no electrical connection to the telephone at the transmitter or at the receiver and is compatible with common EEG recording practice for real-time recording. It accepts 8 input channels simultaneously with one telephone transmitter and one telephone receiver operates from standard power sources.

  11. Buried late Pleistocene fluvial channels on the inner continental shelf off Vengurla, west coast of India

    Digital Repository Service at National Institute of Oceanography (India)

    SubbaRaju, L.V.; Krishna, K.S.; Chaubey, A.K.

    Analysis of echosounding, side-scan sonar and shallow seismic data collected west of Burnt islands off Vengurla, west coast of India, revealed a featureless seabed, thicknesses of subsurface layers, and presence of buried channels filled...

  12. 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

  13. Modelling debris flows down general channels

    Directory of Open Access Journals (Sweden)

    S. P. Pudasaini

    2005-01-01

    Full Text Available This paper is an extension of the single-phase cohesionless dry granular avalanche model over curved and twisted channels proposed by Pudasaini and Hutter (2003. It is a generalisation of the Savage and Hutter (1989, 1991 equations based on simple channel topography to a two-phase fluid-solid mixture of debris material. Important terms emerging from the correct treatment of the kinematic and dynamic boundary condition, and the variable basal topography are systematically taken into account. For vanishing fluid contribution and torsion-free channel topography our new model equations exactly degenerate to the previous Savage-Hutter model equations while such a degeneration was not possible by the Iverson and Denlinger (2001 model, which, in fact, also aimed to extend the Savage and Hutter model. The model equations of this paper have been rigorously derived; they include the effects of the curvature and torsion of the topography, generally for arbitrarily curved and twisted channels of variable channel width. The equations are put into a standard conservative form of partial differential equations. From these one can easily infer the importance and influence of the pore-fluid-pressure distribution in debris flow dynamics. The solid-phase is modelled by applying a Coulomb dry friction law whereas the fluid phase is assumed to be an incompressible Newtonian fluid. Input parameters of the equations are the internal and bed friction angles of the solid particles, the viscosity and volume fraction of the fluid, the total mixture density and the pore pressure distribution of the fluid at the bed. Given the bed topography and initial geometry and the initial velocity profile of the debris mixture, the model equations are able to describe the dynamics of the depth profile and bed parallel depth-averaged velocity distribution from the initial position to the final deposit. A shock capturing, total variation diminishing numerical scheme is implemented to

  14. Electrophysiological characterisation of KCNQ channel modulators

    DEFF Research Database (Denmark)

    Schrøder, R.L

    Potassium (K+) ion channels are ubiquitously expressed in mammalian cells, and each channel serves a precise physiological role due to its specific biophysical characteristics and expression pattern. A few K+ channels are targets for certain drugs, and in this thesis it is suggested that the KCNQ K......+ channels may be targets for neuroprotective, anti-epileptic and anti-nociceptive compounds. The importance of these channels is underscored by the fact that four out of five KCNQ channel subtypes are involved in severe human diseases. However, the pharmacology of the KCNQ channels is yet poorly understood...... as these channels were identified only recently. Therefore, there is a need for understanding the biophysical behavior and pharmacology of these ion channels. KCNQ channels belong to the group of voltage-activated K+ channels. The subfamily consists of KCNQ1-5, which is primarily expressed in the CNS, heart, ear...

  15. NALCN ion channels have alternative selectivity filters resembling calcium channels or sodium channels.

    Directory of Open Access Journals (Sweden)

    Adriano Senatore

    Full Text Available NALCN is a member of the family of ion channels with four homologous, repeat domains that include voltage-gated calcium and sodium channels. NALCN is a highly conserved gene from simple, extant multicellular organisms without nervous systems such as sponges and placozoans and mostly remains a single gene compared to the calcium and sodium channels which diversified into twenty genes in humans. The single NALCN gene has alternatively-spliced exons at exons 15 or exon 31 that splices in novel selectivity filter residues that resemble calcium channels (EEEE or sodium channels (EKEE or EEKE. NALCN channels with alternative calcium, (EEEE and sodium, (EKEE or EEKE -selective pores are conserved in simple bilaterally symmetrical animals like flatworms to non-chordate deuterostomes. The single NALCN gene is limited as a sodium channel with a lysine (K-containing pore in vertebrates, but originally NALCN was a calcium-like channel, and evolved to operate as both a calcium channel and sodium channel for different roles in many invertebrates. Expression patterns of NALCN-EKEE in pond snail, Lymnaea stagnalis suggest roles for NALCN in secretion, with an abundant expression in brain, and an up-regulation in secretory organs of sexually-mature adults such as albumen gland and prostate. NALCN-EEEE is equally abundant as NALCN-EKEE in snails, but is greater expressed in heart and other muscle tissue, and 50% less expressed in the brain than NALCN-EKEE. Transfected snail NALCN-EEEE and NALCN-EKEE channel isoforms express in HEK-293T cells. We were not able to distinguish potential NALCN currents from background, non-selective leak conductances in HEK293T cells. Native leak currents without expressing NALCN genes in HEK-293T cells are NMDG(+ impermeant and blockable with 10 µM Gd(3+ ions and are indistinguishable from the hallmark currents ascribed to mammalian NALCN currents expressed in vitro by Lu et al. in Cell. 2007 Apr 20;129(2:371-83.

  16. Planar channeling in superlattices: Theory

    International Nuclear Information System (INIS)

    Ellison, J.A.; Picraux, S.T.; Allen, W.R.; Chu, W.K.

    1988-01-01

    The well-known continuum model theory for planar channeled energetic particles in perfect crystals is extended to layered crystalline structures and applied to superlattices. In a strained-layer structure, the planar channels with normals which are not perpendicular to the growth direction change their direction at each interface, and this dramatically influences the channeling behavior. The governing equation of motion for a planar channeled ion in a strained-layer superlattice with equal layer thicknesses is a one degree of freedom nonlinear oscillator which is periodically forced with a sequence of δ functions. These δ functions, which are of equal spacing and amplitude with alternating sign, represent the tilts at each of the interfaces. Thus upon matching an effective channeled particle wavelength, corresponding to a natural period of the nonlinear oscillator, to the period of the strained-layer superlattice, corresponding to the periodic forcing, strong resonance effects are expected. The condition of one effective wavelength per period corresponds to a rapid dechanneling at a well-defined depth (catastrophic dechanneling), whereas two wavelengths per period corresponds to no enhanced dechanneling after the first one or two layers (resonance channeling). A phase plane analysis is used to characterize the channeled particle motion. Detailed calculations using the Moliere continuum potential are compared with our previously described modified harmonic model, and new results are presented for the phase plane evolution, as well as the dechanneling as a function of depth, incident angle, energy, and layer thickness. General scaling laws are developed and nearly universal curves are obtained for the dechanneling versus depth under catastrophic dechanneling

  17. Historic Rio Grande Channel Change: Relating Channel Adjustments Measured from Aerial Photography to Human and Climate Induced Changes in Hydrology

    Science.gov (United States)

    Meyer, G. A.; Swanson, B. J.; Coonrod, J.

    2008-12-01

    Over the last century, flow regulation, changes in land and water use, and climate change, including severe droughts, have altered geomorphic processes along the Middle Rio Grande. In association with the USACE Urban Flood Demonstration Program, we investigated changes in channel and island widths and areas as measured on 1972-2006 aerial photographs in relation to average and peak flows in the Rio Grande through Bernalillo County, NM (Albuquerque). We employed all recent (1992-2006) photographs, which were often taken annually or biannually. Digitized and georeferenced photographs were analyzed using a GIS, with particular attention paid to quantifying potential measurement error and its propagation through estimates of channel areas and bank erosion rates. Average total channel widths decreased from 169 m in 1972 to 130 m in 2006. Narrowing was concentrated in the upper and lower sections of the study reach where tributary sediment inputs and degradation related to dam operations constrict the active channel. Decreases in channel width and area coincide with periods of low flows, although the area changes are associated with large errors. Vegetated island areas have greatly increased since 1972, although islands per se were also lost during the later study period by bank attachment. Bank erosion estimates also have large associated errors. Nonetheless, erosion rates appear to be generally decreasing over time, but accelerated during the 2005 high flows. Additional research will compare geomorphic change along the Rio Grande study reach to channel adjustments along the Rio Chama, both below and above El Vado Dam, to better understand regional channel responses to dam operations and drought cycles. Initial investigations reveal that channel responses to these perturbations along the Rio Chama, a major Rio Grande tributary, are similar to the adjustments observed along the Rio Grande through Albuquerque, but the magnitude of the change is not as dramatic.

  18. Volume of the space of qubit-qubit channels and state transformations under random quantum channels

    OpenAIRE

    Lovas, Attila; Andai, Attila

    2017-01-01

    The simplest building blocks for quantum computations are the qubit-qubit quantum channels. In this paper, we analyze the structure of these channels via their Choi representation. The restriction of a quantum channel to the space of classical states (i.e. probability distributions) is called the underlying classical channel. The structure of quantum channels over a fixed classical channel is studied, the volume of general and unital qubit channels with respect to the Lebesgue measure is comp...

  19. 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...

  20. Lithofacies characterization and channel development in the ...

    African Journals Online (AJOL)

    ... and multistory channel complex. The different stages of channel development can be considered in terms of low efficiency and high efficiency flows, which are related to slope equilibrium. Keywords: Outcrop, slope, channel development, channel architecture, process model, lowstand. Journal of Mining and Geology Vol.

  1. Information transfer through quantum channels

    International Nuclear Information System (INIS)

    Kretschmann, D.

    2007-01-01

    This PhD thesis represents work done between Aug. 2003 and Dec. 2006 in Reinhard F. Werner's quantum information theory group at Technische Universitaet Braunschweig, and Artur Ekert's Centre for Quantum Computation at the University of Cambridge. My thesis falls into the field of abstract quantum information theory. This work investigates both fundamental properties of quantum channels and their asymptotic capacities for classical as well as quantum information transfer. Stinespring's theorem is the basic structure theorem for quantum channels. It implies that every quantum channel can be represented as a unitary evolution on an enlarged system. In Ch. 3 we present a continuity theorem for Stinespring's representation: two quantum channels are similar if and only if it is possible to find unitary implementations that are likewise similar, with dimension-independent norm bounds. The continuity theorem allows to derive a formulation of the information-disturbance tradeoff in terms of quantum channels, and a continuity estimate for the no-broadcasting principle. In Ch. 4 we then apply the continuity theorem to give a strengthened no-go proof for quantum bit commitment, an important cryptographic primitive. This result also provides a natural characterization of those protocols that fall outside the standard setting of unconditional security, and thus may allow secure bit commitment. We present a new such protocol whose security relies on decoherence in the receiver's lab. Ch. 5 reviews the capacities of quantum channels for the transfer of both classical and quantum information, and investigates several variations in the notion of channel capacity. Memory effects are then investigated in detail in Ch. 6. We advertise a model which is sufficiently general to encompass all causal automata: every quantum process in which the outputs up to any given time t do not depend on the inputs at times t'>t can be represented as a concatenated memory channel. We then explain how

  2. Information transfer through quantum channels

    Energy Technology Data Exchange (ETDEWEB)

    Kretschmann, D.

    2007-03-12

    This PhD thesis represents work done between Aug. 2003 and Dec. 2006 in Reinhard F. Werner's quantum information theory group at Technische Universitaet Braunschweig, and Artur Ekert's Centre for Quantum Computation at the University of Cambridge. My thesis falls into the field of abstract quantum information theory. This work investigates both fundamental properties of quantum channels and their asymptotic capacities for classical as well as quantum information transfer. Stinespring's theorem is the basic structure theorem for quantum channels. It implies that every quantum channel can be represented as a unitary evolution on an enlarged system. In Ch. 3 we present a continuity theorem for Stinespring's representation: two quantum channels are similar if and only if it is possible to find unitary implementations that are likewise similar, with dimension-independent norm bounds. The continuity theorem allows to derive a formulation of the information-disturbance tradeoff in terms of quantum channels, and a continuity estimate for the no-broadcasting principle. In Ch. 4 we then apply the continuity theorem to give a strengthened no-go proof for quantum bit commitment, an important cryptographic primitive. This result also provides a natural characterization of those protocols that fall outside the standard setting of unconditional security, and thus may allow secure bit commitment. We present a new such protocol whose security relies on decoherence in the receiver's lab. Ch. 5 reviews the capacities of quantum channels for the transfer of both classical and quantum information, and investigates several variations in the notion of channel capacity. Memory effects are then investigated in detail in Ch. 6. We advertise a model which is sufficiently general to encompass all causal automata: every quantum process in which the outputs up to any given time t do not depend on the inputs at times t'>t can be represented as a concatenated memory

  3. Differential subcellular distribution of ion channels and the diversity of neuronal function.

    Science.gov (United States)

    Nusser, Zoltan

    2012-06-01

    Following the astonishing molecular diversity of voltage-gated ion channels that was revealed in the past few decades, the ion channel repertoire expressed by neurons has been implicated as the major factor governing their functional heterogeneity. Although the molecular structure of ion channels is a key determinant of their biophysical properties, their subcellular distribution and densities on the surface of nerve cells are just as important for fulfilling functional requirements. Recent results obtained with high resolution quantitative localization techniques revealed complex, subcellular compartment-specific distribution patterns of distinct ion channels. Here I suggest that within a given neuron type every ion channel has a unique cell surface distribution pattern, with the functional consequence that this dramatically increases the computational power of nerve cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Optimality of private quantum channels

    International Nuclear Information System (INIS)

    Bouda, Jan; Ziman, Mario

    2007-01-01

    We addressed the question of optimality of private quantum channels. We have shown that the Shannon entropy of the classical key necessary to securely transfer the quantum information is lower bounded by the entropy exchange of the private quantum channel E and the von Neumann entropy of the ciphertext state ρ (0) . Based on these bounds we have shown that decomposition of private quantum channels into orthogonal unitaries (if they exist) optimizes the entropy. For non-ancillary single-qubit PQC we have derived the optimal entropy for the arbitrary set of plaintexts. In particular, we have shown that except when the (closure of the) set of plaintexts contains all states, one bit key is sufficient. We characterized and analysed all the possible single-qubit private quantum channels for an arbitrary set of plaintexts. For the set of plaintexts consisting of all qubit states we have characterized all possible approximate private quantum channels and we have derived the relation between the security parameter and the corresponding minimal entropy

  5. EDC IMPACT: Chemical UV filters can affect human sperm function in a progesterone-like manner

    OpenAIRE

    Rehfeld, A; Egeberg, D L; Almstrup, K; Petersen, J H; Dissing, S; Skakkebæk, N E

    2017-01-01

    Human sperm cell function must be precisely regulated to achieve natural fertilization. Progesterone released by the cumulus cells surrounding the egg induces a Ca2+ influx into human sperm cells via the CatSper Ca2+-channel and thereby controls sperm function. Multiple chemical UV filters have been shown to induce a Ca2+ influx through CatSper, thus mimicking the effect of progesterone on Ca2+ signaling. We hypothesized that these UV filters could also mimic the effect of progesterone on spe...

  6. The minimum yield in channeling

    International Nuclear Information System (INIS)

    Uguzzoni, A.; Gaertner, K.; Lulli, G.; Andersen, J.U.

    2000-01-01

    A first estimate of the minimum yield was obtained from Lindhard's theory, with the assumption of a statistical equilibrium in the transverse phase-space of channeled particles guided by a continuum axial potential. However, computer simulations have shown that this estimate should be corrected by a fairly large factor, C (approximately equal to 2.5), called the Barrett factor. We have shown earlier that the concept of a statistical equilibrium can be applied to understand this result, with the introduction of a constraint in phase-space due to planar channeling of axially channeled particles. Here we present an extended test of these ideas on the basis of computer simulation of the trajectories of 2 MeV α particles in Si. In particular, the gradual trend towards a full statistical equilibrium is studied. We also discuss the introduction of this modification of standard channeling theory into descriptions of the multiple scattering of channeled particles (dechanneling) by a master equation and show that the calculated minimum yields are in very good agreement with the results of a full computer simulation

  7. KCNE4 is an inhibitory subunit to the KCNQ1 channel

    DEFF Research Database (Denmark)

    Grunnet, Morten; Jespersen, Thomas; Rasmussen, Hanne Borger

    2002-01-01

    subunit to KCNQ1 channels. Co-expression of KCNQ1 and KCNE4 in Xenopus oocytes completely inhibited the KCNQ1 current. This was reproduced in mammalian CHO-K1 cells. Experiments with delayed expression of mRNA coding for KCNE4 in KCNQ1-expressing oocytes suggested that KCNE4 exerts its effect on KCNQ1...... channels already expressed in the plasma membrane. This notion was supported by immunocytochemical studies and Western blotting, showing no significant difference in plasma membrane expression of KCNQ1 channels in the presence or absence of KCNE4. The impact of KCNE4 on KCNQ1 was specific since no effect...... of KCNE4 could be detected if co-expressed with KCNQ2-5 channels or hERG1 channels. RT-PCR studies revealed high KCNE4 expression in embryos and adult uterus, where significant expression of KCNQ1 channels has also been demonstrated....

  8. Charged and Neutral Particles Channeling Phenomena Channeling 2008

    Science.gov (United States)

    Dabagov, Sultan B.; Palumbo, Luigi

    2010-04-01

    On the discovery of coherent Bremsstrahlung in a single crystal at the Frascati National Laboratories / C. Barbiellini, G. P. Murtas and S. B. Dabagov -- Advances in coherent Bremsstrahlung and LPM-effect studies (to the lOOth anniversary from the birth of L. D. Landau) / N. F. Shul'ga -- Spectra of radiation and created particles at intermediate energy in oriented crystal taking into account energy loss / V. N. Baier and V. M. Katkov -- The coherent Bremsstrahlung beam at MAX-lab facility / K. Fissum ... [et al.] -- Radiation from thin, structured targets (CERN NA63) / A. Dizdar -- Hard incoherent radiation in thick crystals / N. F. Shul'ga, V. V. Syshchenko and A. I. Tarnovsky -- Coherent Bremsstrahlung in periodically deformed crystals with a complex base / A. R. Mkrtchyan, A. A. Saharian and V. V. Parazian -- Induction of coherent x-ray Bremsstrahlung in crystals under the influence of acoustic waves / A. R. Mkrtchyan and V. V. Parazian -- Coherent processes in bent single crystals / V. A. Maisheev -- Experimental and theoretical investigation of complete transfer phenomenon for media with various heat exchange coefficients / A. R. Mkrtchyan, A. E. Movsisyan and V. R. Kocharyan -- Coherent pair production in crystals / A. R. Mkrtchyan, A. A. Saharian and V. V. Parazian -- Negative particle planar and axial channeling and channeling collimation / R. A. Carrigan, Jr. -- CERN crystal-based collimation in modern hadron colliders / W. Scandale -- Studies and application of bent crystals for beam steering at 70 GeV IHEP accelerator / A. G. Afonin ... [et al.] -- Crystal collimation studies at the Tevatron (T-980) / N. V. Mokhov ... [et al.] -- Fabrication of crystals for channeling of particles in accellerators / A. Mazzolari ... [et al.] -- New possibilities to facilitate collimation of both positively and negatively charged particle beams by crystals / V. Guidi, A. Mazzolari and V. V. Tikhomirov -- Increase of probability of particle capture into the channeling

  9. Building Atomic Models of the Ion Channels Based on Low Resolution Electron Microscopy Maps and Homology Modeling.

    Science.gov (United States)

    Novoseletsky, Valery; Malak, Olfat A; Loussouarn, Gildas; Sokolova, Olga S

    2018-01-01

    Voltage-gated potassium channels play pivotal roles in excitable and non-excitable cells. For many decades, structural properties and molecular mechanisms of these channels were inferred from functional observations. At the turn of the twenty-first century, structural biology revealed major aspects in the structural basis of ion channel organization, permeation, and gating. Among the available tools, homology modeling associated with low resolution microscopy helps in delineating the different structural elements of voltage-gated channels. Here, we describe in detail the methodology of homology modeling, using the 3D structure of the Kv2.1ΔCTA ion channel as a reference.

  10. Numerical modelling of channel processes and analysis of possible channel improvement measures on the Lena River near city Yakutsk

    Science.gov (United States)

    Krylenko, Inna; Belikov, Vitaly; Zavadskii, Aleksander; Borisova, Natalya; Golovlyov, Pavel; Rumyantsev, Alexey

    2017-04-01

    variants of channel improvement measures, including different dam constructions, river bed dredging, closing of some river branches were considered and included into modelling scenarios. Analyses of results of modelling has allowed to reveal, that more expensive big dams which are partitioning off a part the main channel are not so effective, because their construction lead to significant increasing of flow velocities and corresponding increasing in sediment transport. Local channel regulations measures (small dam at Ponomarev island near Yakutsk and bed dredging) can give some effect in a few years due to formation of the new line of the depths maximum near water intake structure and Yakutsk port. For improving of the navigation conditions near Ghatay port closing of the small channel branch Ghataiskaya can be effective.

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

    Science.gov (United States)

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

    2012-12-01

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

  12. Structure and Mechanism of a Pentameric Formate Channel

    Energy Technology Data Exchange (ETDEWEB)

    Waight, A.; Love, J; Wang, D

    2010-01-01

    Formate transport across the inner membrane is a critical step in anaerobic bacterial respiration. Members of the formate/nitrite transport protein family function to shuttle substrate across the cytoplasmic membrane. In bacterial pathogens, the nitrite transport protein is involved in protecting bacteria from peroxynitrite released by host macrophages. We have determined the 2.13-{angstrom} structure of the formate channel FocA from Vibrio cholerae, which reveals a pentamer in which each monomer possesses its own substrate translocation pore. Unexpectedly, the fold of the FocA monomer resembles that found in water and glycerol channels. The selectivity filter in FocA consists of a cytoplasmic slit and a central constriction ring. A 2.5-{angstrom} high-formate structure shows two formate ions bound to the cytoplasmic slit via both hydrogen bonding and van der Waals interactions, providing a structural basis for the substrate selectivity of the channel.

  13. TAURINE REGULATION OF VOLTAGE-GATED CHANNELS IN RETINAL NEURONS

    Science.gov (United States)

    Rowan, Matthew JM; Bulley, Simon; Purpura, Lauren; Ripps, Harris; Shen, Wen

    2017-01-01

    Taurine activates not only Cl−-permeable ionotropic receptors, but also receptors that mediate metabotropic responses. The metabotropic property of taurine was revealed in electrophysiological recordings obtained after fully blocking Cl−-permeable receptors with an inhibitory “cocktail” consisting of picrotoxin, SR95531, and strychnine. We found that taurine’s metabotropic effects regulate voltage-gated channels in retinal neurons. After applying the inhibitory cocktail, taurine enhanced delayed outward rectifier K+ channels preferentially in Off-bipolar cells, and the effect was completely blocked by the specific PKC inhibitor, GF109203X. Additionally, taurine also acted through a metabotropic pathway to suppress both L- and N-type Ca2+ channels in retinal neurons, which were insensitive to the potent GABAB receptor inhibitor, CGP55845. This study reinforces our previous finding that taurine in physiological concentrations produces a multiplicity of metabotropic effects that precisely govern the integration of signals being transmitted from the retina to the brain. PMID:23392926

  14. Channels of Monetary Transmission in the CIS

    OpenAIRE

    Jamilov, Rustam

    2012-01-01

    Twenty years have passed since the breakdown of the Soviet Union, and it is time to draw a concluding line for monetary policy efficiency in the Commonwealth of Independent States (CIS). We propose a comprehensive treatment of the subject for nine members of the CIS for the period of 2000-2009. Four transmission channels are investigated: interest rate channel, exchange rate channel, bank lending channel, and monetary channel. First, we design a VAR framework for each CIS member-state and inv...

  15. Modification of single Na+ channels by batrachotoxin.

    OpenAIRE

    Quandt, F N; Narahashi, T

    1982-01-01

    The modifications in the properties of voltage-gated Na+ channels caused by batrachotoxin were studied by using the patch clamp method for measuring single channel currents from excised membranes of N1E-115 neuroblastoma cells. The toxin-modified open state of the Na+ channel has a decreased conductance in comparison to that of normal Na+ channels. The lifetime of the modified open state is drastically prolonged, and channels now continue to open during a maintained depolarization so that the...

  16. Pharmacological modulation of SK3 channels

    DEFF Research Database (Denmark)

    Grunnet, M; Jespersen, Thomas; Angelo, K

    2001-01-01

    Small-conductance, calcium-activated K+ channels (SK channels) are voltage-insensitive channels that have been identified molecularly within the last few years. As SK channels play a fundamental role in most excitable cells and participate in afterhyperpolarization (AHP) and spike-frequency adapt...... at concentrations of 3 microM and above. Amitriptyline, a tricyclic antidepressive widely used clinically, inhibits SK3 channels with an IC50 of 39.1 +/- 10 microM (n=6)....

  17. Axial channeling of uttrarelativistic electrons

    Energy Technology Data Exchange (ETDEWEB)

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

    1982-07-01

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

  18. Axial channeling of uttrarelativistic electrons

    International Nuclear Information System (INIS)

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

    1982-01-01

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

  19. Evaluate interference in digital channels

    Science.gov (United States)

    Davarian, F.; Sumida, J.

    1985-01-01

    Any future mobile satellite service (MSS) which is to provide simultaneous mobile communications for a large number of users will have to make very efficient use of the spectrum. As the spectrum available for an MSS is limited, the system's channels should be packed as closely together as possible, with minimum-width guard bands. In addition the employment of frequency reuse schemes is an important factor. Difficulties regarding these solutions are related to the introduction of interference in the link. A balance must be achieved between the competing aims of spectrum conservation and low interference. While the interference phenomenon in narrowband FM voice channels is reasonably well understood, very little effort, however, has been devoted to the problem in digital radios. Attention is given to work, which illuminates the effects of cochannel and adjacent channel interference on digital FM (FSK) radios.

  20. Pannexin-1 channels in epilepsy.

    Science.gov (United States)

    Aquilino, Mark S; Whyte-Fagundes, Paige; Zoidl, Georg; Carlen, Peter L

    2017-09-05

    Pannexin-1 (Panx1) expression is raised in several animal seizure models and in resected human epileptic brain tissue, suggesting relevance to epilepsy. Multiple factors that are characteristic of seizures are thought to regulate Panx1 channel opening, including elevated levels of extracellular K + . Panx1, when open, 1) releases ATP, glutamate, and other metabolites into the extracellular medium, and 2) may depolarize the membrane due to a channel reversal potential around 0mV. Resultant ATP release from stimulated Panx1 can activate purinergic receptors, including P2X7 receptors. Glutamate and other signaling molecules released by Panx1 opening may have both excitatory and inhibitory actions on seizure generation. This review examines the critical and complex roles of Panx1 channels in epilepsy, which could provide a basis for future therapeutics. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Sanshool on The Fingertip Interferes with Vibration Detection in a Rapidly-Adapting (RA Tactile Channel.

    Directory of Open Access Journals (Sweden)

    Scinob Kuroki

    Full Text Available An Asian spice, Szechuan pepper (sanshool, is well known for the tingling sensation it induces on the mouth and on the lips. Electrophysiological studies have revealed that its active ingredient can induce firing of mechanoreceptor fibres that typically respond to mechanical vibration. Moreover, a human behavioral study has reported that the perceived frequency of sanshool-induced tingling matches with the preferred frequency range of the tactile rapidly adapting (RA channel, suggesting the contribution of sanshool-induced RA channel firing to its unique perceptual experience. However, since the RA channel may not be the only channel activated by sanshool, there could be a possibility that the sanshool tingling percept may be caused in whole or in part by other sensory channels. Here, by using a perceptual interference paradigm, we show that the sanshool-induced RA input indeed contributes to the human tactile processing. The absolute detection thresholds for vibrotactile input were measured with and without sanshool application on the fingertip. Sanshool significantly impaired detection of vibrations at 30 Hz (RA channel dominant frequency, but did not impair detection of higher frequency vibrations at 240 Hz (Pacinian-corpuscle (PC channel dominant frequency or lower frequency vibrations at 1 Hz (slowly adapting 1 (SA1 channel dominant frequency. These results show that the sanshool induces a peripheral RA channel activation that is relevant for tactile perception. This anomalous activation of RA channels may contribute to the unique tingling experience of sanshool.

  2. Novel Sodium Channel Inhibitor From Leeches

    Directory of Open Access Journals (Sweden)

    Gan Wang

    2018-03-01

    Full Text Available Considering blood-sucking habits of leeches from surviving strategy of view, it can be hypothesized that leech saliva has analgesia or anesthesia functions for leeches to stay undetected by the host. However, no specific substance with analgesic function has been reported from leech saliva although clinical applications strongly indicated that leech therapy produces a strong and long lasting pain-reducing effect. Herein, a novel family of small peptides (HSTXs including 11 members which show low similarity with known peptides was identified from salivary glands of the leech Haemadipsa sylvestris. A typical HSTX is composed of 22–25 amino acid residues including four half-cysteines, forming two intra-molecular disulfide bridges, and an amidated C-terminus. HSTX-I exerts significant analgesic function by specifically inhibiting voltage-gated sodium (NaV channels (NaV1.8 and NaV1.9 which contribute to action potential electrogenesis in neurons and potential targets to develop analgesics. This study reveals that sodium channel inhibitors are analgesic substances in the leech. HSTXs are excellent candidates or templates for development of analgesics.

  3. Antenna for Ultrawideband Channel Sounding

    DEFF Research Database (Denmark)

    Zhekov, Stanislav Stefanov; Tatomirescu, Alexandru; Pedersen, Gert F.

    2016-01-01

    A novel compact antenna for ultrawideband channel sounding is presented. The antenna is composed of a symmetrical biconical antenna modified by adding a cylinder and a ring to each cone. A feeding coaxial cable is employed during the simulations in order to evaluate and reduce its impact on the a......A novel compact antenna for ultrawideband channel sounding is presented. The antenna is composed of a symmetrical biconical antenna modified by adding a cylinder and a ring to each cone. A feeding coaxial cable is employed during the simulations in order to evaluate and reduce its impact...

  4. The Orange Juice Distribution Channels

    African Journals Online (AJOL)

    the agents in the European marketing channels of the FCOJ, focusing on the final juice consumers, retailing, food ... Marketing channels are defined as “a set of interdependent organisations involved in the process of making a .... Mexico - 8.0 8.0 8.3 8.0 8.0 - -. Venezuela - 7.9 8.0 7.5 7.3 7.1 - -. Taiwan - 4.4 4.9 6.2 6.6 7.0 - -.

  5. Fast water transport in graphene nanofluidic channels.

    Science.gov (United States)

    Xie, Quan; Alibakhshi, Mohammad Amin; Jiao, Shuping; Xu, Zhiping; Hempel, Marek; Kong, Jing; Park, Hyung Gyu; Duan, Chuanhua

    2018-03-01

    Superfast water transport discovered in graphitic nanoconduits, including carbon nanotubes and graphene nanochannels, implicates crucial applications in separation processes and energy conversion. Yet lack of complete understanding at the single-conduit level limits development of new carbon nanofluidic structures and devices with desired transport properties for practical applications. Here, we show that the hydraulic resistance and slippage of single graphene nanochannels can be accurately determined using capillary flow and a novel hybrid nanochannel design without estimating the capillary pressure. Our results reveal that the slip length of graphene in the graphene nanochannels is around 16 nm, albeit with a large variation from 0 to 200 nm regardless of the channel height. We corroborate this finding with molecular dynamics simulation results, which indicate that this wide distribution of the slip length is due to the surface charge of graphene as well as the interaction between graphene and its silica substrate.

  6. Surfing Peer-to-Peer IPTV: Distributed Channel Switching

    Science.gov (United States)

    Kermarrec, A.-M.; Le Merrer, E.; Liu, Y.; Simon, G.

    It is now common for IPTV systems attracting millions of users to be based on a peer-to-peer (P2P) architecture. In such systems, each channel is typically associated with one P2P overlay network connecting the users. This significantly enhances the user experience by relieving the source from dealing with all connections. Yet, the joining process resulting in a peer to be integrated in channel overlay usually requires a significant amount of time. As a consequence, switching from one channel to another is far to be as fast as in IPTV solutions provided by telco operators. In this paper, we tackle the issue of efficient channel switching in P2P IPTV system. This is to the best of our knowledge the first study on this topic. First, we conducted and analyzed a set of measurements of one of the most popular P2P systems (PPlive). These measurements reveal that the set of contacts that a joining peer receives from the central server are of the utmost importance in the start-up process. On those neigbors, depends the speed to acquire the first video frames to play. We then formulate the switching problem, and propose a simple distributed algorithm, as an illustration of the concept, which aims at leveraging the presence of peers in the network to fasten the switch process. The principle is that each peer maintains as neighbors peers involved in other channels, providing peers with good contacts upon channel switching. Finally, simulations show that our approach leads to substantial improvements on the channel switching time. As our algorithmic solution does not have any prerequisite on the overlays, it appears to be an appealing add-on for existing P2P IPTV systems.

  7. A New Sensors-Based Covert Channel on Android

    Directory of Open Access Journals (Sweden)

    Ahmed Al-Haiqi

    2014-01-01

    Full Text Available Covert channels are not new in computing systems, and have been studied since their first definition four decades ago. New platforms invoke thorough investigations to assess their security. Now is the time for Android platform to analyze its security model, in particular the two key principles: process-isolation and the permissions system. Aside from all sorts of malware, one threat proved intractable by current protection solutions, that is, collusion attacks involving two applications communicating over covert channels. Still no universal solution can countermeasure this sort of attack unless the covert channels are known. This paper is an attempt to reveal a new covert channel, not only being specific to smartphones, but also exploiting an unusual resource as a vehicle to carry covert information: sensors data. Accelerometers generate signals that reflect user motions, and malware applications can apparently only read their data. However, if the vibration motor on the device is used properly, programmatically produced vibration patterns can encode stolen data and hence an application can cause discernible effects on acceleration data to be received and decoded by another application. Our evaluations confirmed a real threat where strings of tens of characters could be transmitted errorless if the throughput is reduced to around 2.5–5 bps. The proposed covert channel is very stealthy as no unusual permissions are required and there is no explicit communication between the colluding applications.

  8. A new sensors-based covert channel on android.

    Science.gov (United States)

    Al-Haiqi, Ahmed; Ismail, Mahamod; Nordin, Rosdiadee

    2014-01-01

    Covert channels are not new in computing systems, and have been studied since their first definition four decades ago. New platforms invoke thorough investigations to assess their security. Now is the time for Android platform to analyze its security model, in particular the two key principles: process-isolation and the permissions system. Aside from all sorts of malware, one threat proved intractable by current protection solutions, that is, collusion attacks involving two applications communicating over covert channels. Still no universal solution can countermeasure this sort of attack unless the covert channels are known. This paper is an attempt to reveal a new covert channel, not only being specific to smartphones, but also exploiting an unusual resource as a vehicle to carry covert information: sensors data. Accelerometers generate signals that reflect user motions, and malware applications can apparently only read their data. However, if the vibration motor on the device is used properly, programmatically produced vibration patterns can encode stolen data and hence an application can cause discernible effects on acceleration data to be received and decoded by another application. Our evaluations confirmed a real threat where strings of tens of characters could be transmitted errorless if the throughput is reduced to around 2.5-5 bps. The proposed covert channel is very stealthy as no unusual permissions are required and there is no explicit communication between the colluding applications.

  9. Does Erythropoietin Regulate TRPC Channels in Red Blood Cells?

    Directory of Open Access Journals (Sweden)

    Jens Danielczok

    2017-03-01

    Full Text Available Background: Cation channels play an essential role in red blood cells (RBCs ion homeostasis. One set of ion channels are the transient receptor potential channels of canonical type (TRPC channels. The abundance of these channels in primary erythroblasts, erythroid cell lines and RBCs was associated with an increase in intracellular Ca2+ upon stimulation with Erythropoietin (Epo. In contrast two independent studies on Epo-treated patients revealed diminished basal Ca2+ concentration or reduced phosphatidylserine exposure to the outer membrane leaflet. Methods: To resolve the seemingly conflicting reports we challenged mature human and mouse RBCs of several genotypes with Epo and Prostaglandin E2 (PGE2 and recorded the intracellular Ca2+ content. Next Generation Sequencing was utilised to approach a molecular analysis of reticulocytes. Results/Conclusions: Our results allow concluding that Epo and PGE2 regulation of the Ca2+ homeostasis is distinctly different between murine and human RBCs and that changes in intracellular Ca2+ upon Epo treatment is a primary rather than a compensatory effect. In human RBCs, Epo itself has no effect on Ca2+ fluxes but inhibits the PGE2-induced Ca2+ entry. In murine mature RBCs functional evidence indicates TRPC4/C5 mediated Ca2+ entry activated by Epo whereas PGE2 leads to a TRPC independent Ca2+ entry.

  10. Zinc as Allosteric Ion Channel Modulator: Ionotropic Receptors as Metalloproteins

    Science.gov (United States)

    Peralta, Francisco Andrés; Huidobro-Toro, Juan Pablo

    2016-01-01

    Zinc is an essential metal to life. This transition metal is a structural component of many proteins and is actively involved in the catalytic activity of cell enzymes. In either case, these zinc-containing proteins are metalloproteins. However, the amino acid residues that serve as ligands for metal coordination are not necessarily the same in structural proteins compared to enzymes. While crystals of structural proteins that bind zinc reveal a higher preference for cysteine sulfhydryls rather than histidine imidazole rings, catalytic enzymes reveal the opposite, i.e., a greater preference for the histidines over cysteines for catalysis, plus the influence of carboxylic acids. Based on this paradigm, we reviewed the putative ligands of zinc in ionotropic receptors, where zinc has been described as an allosteric modulator of channel receptors. Although these receptors do not strictly qualify as metalloproteins since they do not normally bind zinc in structural domains, they do transitorily bind zinc at allosteric sites, modifying transiently the receptor channel’s ion permeability. The present contribution summarizes current information showing that zinc allosteric modulation of receptor channels occurs by the preferential metal coordination to imidazole rings as well as to the sulfhydryl groups of cysteine in addition to the carboxyl group of acid residues, as with enzymes and catalysis. It is remarkable that most channels, either voltage-sensitive or transmitter-gated receptor channels, are susceptible to zinc modulation either as positive or negative regulators. PMID:27384555

  11. Visualizing multi-channel networks

    DEFF Research Database (Denmark)

    Antemijczuk, Paweł; Magiera, Marta; Jørgensen, Sune Lehmann

    2014-01-01

    In this paper, we propose a visualization to illustrate social interactions, built from multiple distinct channels of communication. The visualization displays a summary of dense personal information in a compact graphical notation. The starting point is an abstract drawing of a spider’s web. Below...

  12. Sorting out river channel patterns

    NARCIS (Netherlands)

    Kleinhans, M.G.

    2010-01-01

    Rivers self-organize their pattern/planform through feedbacks between bars, channels, floodplain and vegetation, which emerge as a result of the basic spatial sorting process of wash load sediment and bed sediment. The balance between floodplain formation and destruction determines the width and

  13. Sales promotion and channel coordination

    NARCIS (Netherlands)

    Wierenga, B.; Soethoudt, J.M.

    2010-01-01

    Consumer sales promotions are usually the result of the decisions of two marketing channel parties, the manufacturer and the retailer. In making these decisions, each party normally follows its own interest: i.e. maximizes its own profit. Unfortunately, this results in a suboptimal outcome for the

  14. Single top t-channel

    CERN Document Server

    Faltermann, Nils

    2017-01-01

    The production of single top quarks allows to study the interplay of top quark physics and the electroweak sector of the standard model. Deviations from predictions can be a hint for physics beyond the standard model. The t-channel is the dominant production mode for single top quarks at the LHC. This talk presents the latest measurements from the ATLAS and CMS collaborations.

  15. Improved Ion-Channel Biosensors

    Science.gov (United States)

    Nadeau, Jay; White, Victor; Dougherty, Dennis; Maurer, Joshua

    2004-01-01

    An effort is underway to develop improved biosensors of a type based on ion channels in biomimetic membranes. These sensors are microfabricated from silicon and other materials compatible with silicon. As described, these sensors offer a number of advantages over prior sensors of this type.

  16. CONDUCTIVE CHANNEL FOR ENERGY TRANSMISSION

    Directory of Open Access Journals (Sweden)

    V. V. Apollonov

    2014-01-01

    Full Text Available Laser spark obtained by using a conical optics is much more appropriate to form conducting channels in atmosphere. Only two types of lasers are actively considered to be used in forming high-conductivity channels in atmosphere, controlled by laser spark: pulsed sub-microsecond gas and chemical lasers (CO2, DF and short pulse solid-state and UV lasers. Main advantage of short pulse lasers is their ability in forming of super long ionized channels with a characteristic diameter of ~100  µ  in atmosphere along the  beam propagation direction. At estimated electron densities below  10 ⋅ 16 cm–3 in these filaments and laser wavelengths in the range of 0,5–1,0 mm, the plasma barely absorbs laser radiation.  In this case, the length of the track composed of many filaments is determined by the laser intensity and may reach many kilometers at a femtosecond pulse energy of ~100 mJ. However, these lasers could not be used to form high-conductivity long channels in atmosphere. The ohmic resistance of this type a conducting channels turned out to be very high, and the gas in the channels could not be strongly heated (< 1 J. An electric breakdown controlled by radiation of femtosecond solid-state laser was implemented in only at a length of 3 m with a voltage of 2 MV across the discharge gap (670 kV/m.Not so long ago scientific group from P. N. Lebedev has improved that result, the discharge gap – 1 m had been broken under KrF laser irradiation when switching high-voltage (up to 390 kV/m electric discharge by 100-ns UV pulses. Our previous result  –  16 m long conducting channel controlled by a  laser spark at the voltage  –  3 MV  – was obtained more than 20 years ago in Russia and Japan by using pulsed CO2  laser with energy  –  0,5 kJ. An average electric field strength  was < 190 kV/m. It is still too much for efficient applications.

  17. Architecture and quantitative assessment of channeled clastic deposits, Shihezi sandstone (Lower Permian, Ordos Basin, China

    Directory of Open Access Journals (Sweden)

    Chengye Jia

    2017-02-01

    Full Text Available Lower Permian Shihezi sandstone in Ordos Basin is the largest gas reservoir in China. Architecture elements of channel, overbank and floodplain facies of braided channel deposits were identified through an outcrops survey, and their proportion of channel facies have been quantitatively estimated from well logging. Characteristics of architecture elements, such as sand thickness, bounding surfaces and lithofacies were investigated through outcrops and core. Petrology of Shihezi sandstone has also been studied in detail. Analysis on sandstone components shows that monocrystalline quartz with approximately 76% bulk volume, and lithic up to 5%–45% bulk volume, are the two main components. Litharenite and lithic quartz sandstone are the main rock types. Compaction is concluded by former researchers as the control factor of low permeability. Examination through thin section reveals that secondary pores developed well in coarse sand. Inter-granular dissolution is included as the positive effect to increasing porosity, and is concluded as the control factor to the generation of net pay. Scale of coarse grained channel fills and channel bar sandstone bodies are quantitatively estimated. Strike-oriented, dip-oriented, and vertical distribution of channel fills and channel bar sandstone bodies have been investigated. The geometry of sand bodies can be depicted as an elongated lens. Subsurface mapping reveals that channel sandstone bodies distribute widely from both lateral and longitudinal cross section profiles, and are poorly connected.

  18. Interior point decoding for linear vector channels

    International Nuclear Information System (INIS)

    Wadayama, T

    2008-01-01

    In this paper, a novel decoding algorithm for low-density parity-check (LDPC) codes based on convex optimization is presented. The decoding algorithm, called interior point decoding, is designed for linear vector channels. The linear vector channels include many practically important channels such as inter-symbol interference channels and partial response channels. It is shown that the maximum likelihood decoding (MLD) rule for a linear vector channel can be relaxed to a convex optimization problem, which is called a relaxed MLD problem

  19. An Effective Channel Allocation Scheme to Reduce Co-Channel and Adjacent Channel Interference for WMN Backhaul

    International Nuclear Information System (INIS)

    Abbasi, S.; Ismaili, I.A.; Khuhawar, F.Y.

    2016-01-01

    Two folded work presents channel allocation scheme sustaining channel orthogonality and channel spacing to reduce CCI (Co-Channel Interference) and ACI (Adjacent Channel Interference) for inter flow of an intra-flow link. Proposed scheme as a part of radio resource allocation is applied on infrastructure based backhaul of wireless mesh network using directional antennas. The proposed approach is applied separately on 2.4 and 5GHz bands. Interference of connectivity graph is modelled by strongly connected directed graph and greedy algorithms are used for channel allocation. We have used OPNET Modeller suite to simulate network models for this research. The proposed arrangement reduces the channel interference and increases system throughput. In this research, the influence of channel is computed in terms of network throughput and delay. (author)

  20. The MISO wiretap channel with channel uncertainty: Asymptotic perspectives

    KAUST Repository

    Chaaban, Anas

    2017-05-12

    The N-antenna MISO Gaussian wiretap channel with imperfect channel-state information at the transmitter (CSIT) is studied in terms of secrecy rate scaling versus the signal-to-noise ratio (SNR) and N. Two schemes are considered, beamforming (BF) and artificial noise injection (AN). It is shown that if the CSIT error is independent of SNR, then both schemes do not achieve scaling versus SNR. However, if this error vanishes as SNR increases, then AN achieves the optimal scaling versus SNR, contrary to BF. Scaling can be achieved in BF by increasing N. In fact, BF achieves the optimal scaling versus N. In the AN scheme however, injecting noise in multiple direction deteriorates its scaling versus N. Nevertheless, AN can achieve the optimal scaling if noise is sent in only one direction. This leads to better performance than BF if the CSIT error is smaller than a threshold which is also derived.

  1. 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.

  2. Information Sharing and Channel Construction of Supply Chain under Asymmetric Demand Information

    Directory of Open Access Journals (Sweden)

    Guangdong Wu

    2014-01-01

    Full Text Available Information sharing and marketing channel building have become an important problem of supply chain management theory and practice. The research of information sharing focused on traditional channel of supply chain between upstream and downstream enterprises; however, the research ignores the behavior of information sharing with potential entrants and composite structure characteristics about traditional marketing channel with the direct channel. This paper uses the model to research the effects brought about sharing demand information with potential entrants and building marketing channel, which reveals information sharing and channel building mechanism in the supply chain. The study found that the five-force model of Porter regards potential entrants only as a threat that is one-sided. When the channel competitiveness meets certain conditions, manufacturer and retailer will share demand information with potential entrants. Building composite marketing channel is the manufacturer's absolute dominant strategy. Channel construction will increase the entry barriers for potential entrants and weaken the effect of double marginalization; meanwhile, the performance of supply chain will be augmented.

  3. 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.

  4. The KATP channel in migraine pathophysiology

    DEFF Research Database (Denmark)

    Al-Karagholi, Mohammad Al-Mahdi; Hansen, Jakob Møller; Severinsen, Johanne

    2017-01-01

    BACKGROUND: To review the distribution and function of KATP channels, describe the use of KATP channels openers in clinical trials and make the case that these channels may play a role in headache and migraine. DISCUSSION: KATP channels are widely present in the trigeminovascular system and play...... an important role in the regulation of tone in cerebral and meningeal arteries. Clinical trials using synthetic KATP channel openers report headache as a prevalent-side effect in non-migraine sufferers, indicating that KATP channel opening may cause headache, possibly due to vascular mechanisms. Whether KATP...... channel openers can provoke migraine in migraine sufferers is not known. CONCLUSION: We suggest that KATP channels may play an important role in migraine pathogenesis and could be a potential novel therapeutic anti-migraine target....

  5. Channel Estimation in DCT-Based OFDM

    Science.gov (United States)

    Wang, Yulin; Zhang, Gengxin; Xie, Zhidong; Hu, Jing

    2014-01-01

    This paper derives the channel estimation of a discrete cosine transform- (DCT-) based orthogonal frequency-division multiplexing (OFDM) system over a frequency-selective multipath fading channel. Channel estimation has been proved to improve system throughput and performance by allowing for coherent demodulation. Pilot-aided methods are traditionally used to learn the channel response. Least square (LS) and mean square error estimators (MMSE) are investigated. We also study a compressed sensing (CS) based channel estimation, which takes the sparse property of wireless channel into account. Simulation results have shown that the CS based channel estimation is expected to have better performance than LS. However MMSE can achieve optimal performance because of prior knowledge of the channel statistic. PMID:24757439

  6. Matagorda Ship Channel, Texas: Jetty Stability Study

    National Research Council Canada - National Science Library

    Kraus, Nicholas C; Lin, Lihwa; Batten, Brian K; Brown, Gary L

    2006-01-01

    .... The current has produced a large area of scour on the bay side of the inlet adjacent to the west jetty, and vessels encountering a strong along-channel and cross-channel current at the entrance...

  7. Coastal Maintained Channels in US waters

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This layer shows coastal channels and waterways that are maintained and surveyed by the U.S. Army Corps of Engineers (USACE). These channels are necessary...

  8. Modification of single Na+ channels by batrachotoxin.

    Science.gov (United States)

    Quandt, F N; Narahashi, T

    1982-11-01

    The modifications in the properties of voltage-gated Na+ channels caused by batrachotoxin were studied by using the patch clamp method for measuring single channel currents from excised membranes of N1E-115 neuroblastoma cells. The toxin-modified open state of the Na+ channel has a decreased conductance in comparison to that of normal Na+ channels. The lifetime of the modified open state is drastically prolonged, and channels now continue to open during a maintained depolarization so that the probability of a channel being open becomes constant. Modified and normal open states of Na+ channels coexist in batrachotoxin-exposed membrane patches. Unlike the normal condition, Na+ channels exposed to batrachotoxin open spontaneously at large negative potentials. These spontaneous openings apparently cause the toxin-induced increase in Na+ permeability which, in turn, causes membrane depolarization.

  9. Targeting sodium channels in cardiac arrhythmia

    NARCIS (Netherlands)

    Remme, Carol Ann; Wilde, Arthur A. M.

    2014-01-01

    Cardiac voltage-gated sodium channels are responsible for proper electrical conduction in the heart. During acquired pathological conditions and inherited sodium channelopathies, altered sodium channel function causes conduction disturbances and ventricular arrhythmias. Although the clinical,

  10. Quantum Correlations Evolution Asymmetry in Quantum Channels

    International Nuclear Information System (INIS)

    Li Meng; Huang Yun-Feng; Guo Guang-Can

    2017-01-01

    It was demonstrated that the entanglement evolution of a specially designed quantum state in the bistochastic channel is asymmetric. In this work, we generalize the study of the quantum correlations, including entanglement and quantum discord, evolution asymmetry to various quantum channels. We found that the asymmetry of entanglement and quantum discord only occurs in some special quantum channels, and the behavior of the entanglement evolution may be quite different from the behavior of the quantum discord evolution. To quantum entanglement, in some channels it decreases monotonously with the increase of the quantum channel intensity. In some other channels, when we increase the intensity of the quantum channel, it decreases at first, then keeps zero for some time, and then rises up. To quantum discord, the evolution becomes more complex and you may find that it evolutes unsmoothly at some points. These results illustrate the strong dependence of the quantum correlations evolution on the property of the quantum channels. (paper)

  11. Channel CAT: A Tactical Link Analysis Tool

    National Research Council Canada - National Science Library

    Coleman, Michael

    1997-01-01

    .... This thesis produced an analysis tool, the Channel Capacity Analysis Tool (Channel CAT), designed to provide an automated tool for the analysis of design decisions in developing client-server software...

  12. 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...

  13. Thermoelectricity in Heterogeneous Nanofluidic Channels.

    Science.gov (United States)

    Li, Long; Wang, Qinggong

    2018-04-19

    Ionic fluids are essential to energy conversion, water desalination, drug delivery, and lab-on-a-chip devices. Ionic transport in nanoscale confinements and complex physical fields still remain elusive. Here, a nanofluidic system is developed using nanochannels of heterogeneous surface properties to investigate transport properties of ions under different temperatures. Steady ionic currents are observed under symmetric temperature gradients, which is equivalent to generating electricity using waste heat (e.g., electronic chips and solar panels). The currents increase linearly with temperature gradient and nonlinearly with channel size. Contributions to ion motion from temperatures and channel properties are evaluated for this phenomenon. The findings provide insights into the study of confined ionic fluids in multiphysical fields, and suggest applications in thermal energy conversion, temperature sensors, and chip-level thermal management. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Radio propagation measurement and channel modelling

    CERN Document Server

    Salous, Sana

    2013-01-01

    While there are numerous books describing modern wireless communication systems that contain overviews of radio propagation and radio channel modelling, there are none that contain detailed information on the design, implementation and calibration of radio channel measurement equipment, the planning of experiments and the in depth analysis of measured data. The book would begin with an explanation of the fundamentals of radio wave propagation and progress through a series of topics, including the measurement of radio channel characteristics, radio channel sounders, measurement strategies

  15. Degenerate RFID Channel Modeling for Positioning Applications

    Directory of Open Access Journals (Sweden)

    A. Povalac

    2012-12-01

    Full Text Available This paper introduces the theory of channel modeling for positioning applications in UHF RFID. It explains basic parameters for channel characterization from both the narrowband and wideband point of view. More details are given about ranging and direction finding. Finally, several positioning scenarios are analyzed with developed channel models. All the described models use a degenerate channel, i.e. combined signal propagation from the transmitter to the tag and from the tag to the receiver.

  16. Improving Channel Coordination Through Franchising

    OpenAIRE

    Rajiv Lal

    1990-01-01

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

  17. Digital Multi Channel Analyzer Enhancement

    International Nuclear Information System (INIS)

    Gonen, E.; Marcus, E.; Wengrowicz, U.; Beck, A.; Nir, J.; Sheinfeld, M.; Broide, A.; Tirosh, D.

    2002-01-01

    A cement analyzing system based on radiation spectroscopy had been developed [1], using novel digital approach for real-time, high-throughput and low-cost Multi Channel Analyzer. The performance of the developed system had a severe problem: the resulted spectrum suffered from lack of smoothness, it was very noisy and full of spikes and surges, therefore it was impossible to use this spectrum for analyzing the cement substance. This paper describes the work carried out to improve the system performance

  18. Trafficking of neuronal calcium channels

    Czech Academy of Sciences Publication Activity Database

    Weiss, Norbert; Zamponi, G. W.

    2017-01-01

    Roč. 1, č. 1 (2017), č. článku NS20160003. ISSN 2059-6553 R&D Projects: GA ČR GA15-13556S; GA MŠk 7AMB15FR015 Institutional support: RVO:61388963 Keywords : calcium channel * neuron * trafficing Subject RIV: ED - Physiology OBOR OECD: Physiology (including cytology) http://www. neuron alsignaling.org/content/1/1/NS20160003

  19. Muon decay channeling in silicon

    International Nuclear Information System (INIS)

    Bosshard, A.; Patterson, B.D.; Straumann, U.; Truoel, P.; Wichert, Th.

    1984-01-01

    This experiment employs the channeling effect of the host lattice on the trajectories of decay positrons in order to determine the position of positive muons implanted into silicon crystals. Low-momentum ( 0 ). In order to achieve sufficient angular resolution, the Si wafer is bent to a spherical shape, thereby focussing a particular crystal axis to a point at the center of the MWPC (located 3.4 m from the wafer). (Auth.)

  20. 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.

  1. Decreased expression of Kv7 channels in Hirchsprung's disease.

    Science.gov (United States)

    O'Donnell, Anne-Marie; Coyle, David; Puri, Prem

    2017-07-01

    Voltage-dependent K + channels (Kv channels) participate in electrical rhythmicity and smooth muscle responses and are regulated by excitatory and inhibitory neurotransmitters. Kv channels also participate in the interstitial cell of Cajal (ICC) and smooth muscle cell (SMC) responses to neural inputs. The Kv family consists of 12 subfamilies, Kv1-Kv12, with five members of the Kv7 family identified to date: Kv7.1-Kv7.5. A recent study identified the potassium channel Kv7.5 as having a role in the excitability of ICC-IM in the mouse colon. We therefore designed this study to test the hypothesis that Kv7 channels are present in the normal human colon and are reduced in Hirschprung's disease (HSCR). HSCR tissue specimens were collected at the time of pull-through surgery (n=10), while normal control tissue specimens were obtained at the time of colostomy closure in patients with imperforate anus (n=10). Kv7.3-Kv7.5 immunohistochemistry was performed and visualized using confocal microscopy to assess their distribution. Western blot analysis was undertaken to determine Kv7.3-Kv7.5 protein quantification. Kv7.3 and Kv7.4-immunoreactivity was co-localized with neuron and ICC markers, while Kv7.5 was found to be expressed on both ICCs and SMCs. Western blot analysis revealed similar levels of Kv7.3 and Kv7.5 expression in the normal colon and HSCR colon, while Kv7.4 proteins were found to be markedly decreased in ganglionic specimens and decreased further in aganglionic specimens. A deficiency of Kv7.4 channels in the ganglionic and aganglionic bowel may place a role in colonic dysmotility in HSCR. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Long-pore Electrostatics in Inward-rectifier Potassium Channels

    Science.gov (United States)

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

    2008-01-01

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

  3. 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.

  4. 47 CFR 95.29 - Channels available.

    Science.gov (United States)

    2010-10-01

    ... no more than 5 watts ERP. (g) Fixed stations in GMRS systems authorized before March 18, 1968... transmission of another GMRS station on a different channel or channels), the licensee of the GMRS system must... GMRS system from the following 462 MHz channels: 462.5500, 462.5750, 462.6000, 462.6250, 462.6500, 462...

  5. Modulation of ERG channels by XE991

    DEFF Research Database (Denmark)

    Elmedyb, Pernille; Calloe, Kirstine; Schmitt, Nicole

    2007-01-01

    In neuronal tissue, KCNQ2-5 channels conduct the physiologically important M-current. In some neurones, the M-current may in addition be conducted partly by ERG potassium channels, which have widely overlapping expression with the KCNQ channel subunits. XE991 and linopiridine are known to be stan...

  6. Electronic Commerce and Retail Channel Substitution

    NARCIS (Netherlands)

    M.C.W. Janssen (Maarten); R. van der Noll

    2002-01-01

    textabstractWe analyze a market where firms compete in a conventional and an electronic retail channel. Consumers easily compare prices online, but some incur purchase uncertainties on the online channel. We investigate the market shares of the two retail channels and the prices that are charged. We

  7. Molecular determinants in TRPV5 channel assembly.

    NARCIS (Netherlands)

    Chang, Q.; Gyftogianni, E.; Graaf, K.F.J. van de; Hoefs, S.J.G.; Weidema, A.F.; Bindels, R.J.M.; Hoenderop, J.G.J.

    2004-01-01

    The epithelial Ca(2+) channels TRPV5 and TRPV6 mediate the Ca(2+) influx in 1,25-dihydroxyvitamin D(3)-responsive epithelia and are therefore essential in the maintenance of the body Ca(2+) balance. These Ca(2+) channels assemble in (hetero)tetrameric channel complexes with different functional

  8. Molecular determinants in TRPV5 channel assembly

    NARCIS (Netherlands)

    Chang, Qing; Gyftogianni, Emmanouela; van de Graaf, Stan F. J.; Hoefs, Susan; Weidema, Freek A.; Bindels, René J. M.; Hoenderop, Joost G. J.

    2004-01-01

    The epithelial Ca(2+) channels TRPV5 and TRPV6 mediate the Ca(2+) influx in 1,25-dihydroxyvitamin D(3)-responsive epithelia and are therefore essential in the maintenance of the body Ca(2+) balance. These Ca(2+) channels assemble in (hetero)tetrameric channel complexes with different functional

  9. Effect of wall compliance on peristaltic transport of a Newtonian fluid in an asymmetric channel

    Directory of Open Access Journals (Sweden)

    Mohamed H. Haroun

    2006-01-01

    Full Text Available Peristaltic transport of an incompressible viscous fluid in an asymmetric compliant channel is studied. The channel asymmetry is produced by choosing the peristaltic wave train on the walls to have different amplitudes and phases. The fluid-solid interaction problem is investigated by considering equations of motion of both the fluid and the deformable boundaries. The driving mechanism of the muscle is represented by assuming the channel walls to be compliant. The phenomenon of the “mean flow reversal” is discussed. The effect of wave amplitude ratio, width of the channel, phase difference, wall elastance, wall tension, and wall damping on mean-velocity and reversal flow has been investigated. The results reveal that the reversal flow occurs near the boundaries which is not possible in the elastic symmetric channel case.

  10. The use of service channels by citizens in the Netherlands: implications for multi-channel management

    NARCIS (Netherlands)

    Pieterson, Willem Jan; Ebbers, Wolfgang E.

    2008-01-01

    Many governmental organizations are changing their service channel management strategies to multi-channel management. However, very few empirical studies exist that explore how these multi-channel strategies should be shaped. In this article we test a number of hypotheses on citizens' channel use

  11. Behavioral characterization of mice lacking Trek channels

    Directory of Open Access Journals (Sweden)

    Kelsey eMirkovic

    2012-09-01

    Full Text Available Two-pore domain K+ (K2P channels are thought to underlie background K+ conductance in many cell types. The Trek subfamily of K2P channels consists of three members, Trek1/Kcnk2, Trek2/Kcnk10, and Traak/Kcnk4, all three of which are expressed in the rodent CNS. Constitutive ablation of the Trek1 gene in mice correlates with enhanced sensitivity to ischemia and epilepsy, decreased sensitivity to the effects of inhaled anesthetics, increased sensitivity to thermal and mechanical pain, and resistance to depression. While the distribution of Trek2 mRNA in the CNS is broad, little is known about the relevance of this Trek family member to neurobiology and behavior. Here, we probed the effect of constitutive Trek2 ablation, as well as the simultaneous constitutive ablation of all three Trek family genes, in paradigms that assess motor activity, coordination, anxiety-related behavior, learning and memory, and drug-induced reward-related behavior. No differences were observed between Trek2–/– and Trek1/2/Traak–/– mice in coordination or total distance traveled in an open-field. A gender-dependent impact of Trek ablation on open-field anxiety-related behavior was observed, as female but not male Trek2–/– and Trek1/2/Traak–/– mice spent more time in, and made a greater number of entries into, the center of the open-field than wild-type counterparts. Further evaluation of anxiety-related behavior in the elevated plus maze and light/dark box, however, did not reveal a significant influence of genotype on performance for either gender. Furthermore, Trek–/– mice behaved normally in tests of learning and memory, including contextual fear conditioning and novel object recognition, and with respect to opioid-induced motor stimulation and conditioned place preference. Collectively, these data argue that despite their broad distribution in the CNS, Trek channels exert a minimal influence on a wide-range of behaviors.

  12. Channel discrimination power of bipartite quantum states

    Science.gov (United States)

    Caiaffa, Matteo; Piani, Marco

    2018-03-01

    We quantify the usefulness of a bipartite quantum state in the ancilla-assisted channel discrimination of arbitrary quantum channels, formally defining a worst-case-scenario channel discrimination power for bipartite quantum states. We show that such a quantifier is deeply connected with the operator Schmidt decomposition of the state. We compute the channel discrimination power exactly for pure states, and provide upper and lower bounds for general mixed states. We show that highly entangled states can outperform any state that passes the realignment criterion for separability and that the channel discrimination power of a state is bounded by its quantum discord.

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

    Directory of Open Access Journals (Sweden)

    Panpan Hou

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

  14. Beaconing Performance in IEEE 802.11p Vehicular Networks: the Effect of Radio Channel Congestion

    OpenAIRE

    Librino, Francesco; Renda, Maria Elena; Santi, Paolo

    2013-01-01

    In this paper, we study the performance of the beaconing mechanism underlying active safety vehicular applications in presence of different levels of channel congestion. The importance of this study lies in the fact that channel congestion is considered a major factor influencing communication performance in vehicular networks, and that ours is the first investigation of the effects of congestion based on extensive, real-world measurements. The results of our study reveal that congestion has ...

  15. Omni-Channel Retailing Research – State of the art and intellectual foundation

    OpenAIRE

    Galipoglu, E; Kotzab, H; Teller, Christoph; Yumurtacı Hüseyinoğlu, IO; Pöppelbuß, J

    2017-01-01

    Purpose: The aims of this paper are to (1) identify, evaluate and structure the research that focuses on omni-channel retailing from the perspective of logistics and supply chain management, and (2) to reveal the intellectual foundation of omni-channel retailing research. Methodology: The paper applies a multi-method approach by conducting a content-analysis-based literature review of 70 academic papers. Based on the reference lists of these papers, we performed a citation and co-citation ...

  16. Analysis and Transceiver Design for the MIMO Broadcast Channel

    CERN Document Server

    Hunger, Raphael

    2013-01-01

    This book deals with the optimization-based joint design of the transmit and receive filters in   MIMO broadcast channel in which the user terminals may be equipped with several antenna elements. Furthermore, the maximum performance of the system in the high power regime as well as the set of all feasible quality-of-service requirements is analyzed. First, a fundamental duality is derived that holds between the MIMO broadcast channel and virtual MIMO multiple access channel. This duality construct allows for the efficient solution of problems originally posed in the broadcast channel in the dual domain where a possibly hidden convexity can often be revealed. On the basis of the established duality result, the gradient-projection algorithm is introduced as a tool to solve constrained optimization problems to global optimality under certain conditions. The gradient-projection tool is then applied to solving the weighted sum rate maximization problem which is a central optimization that arises in any network u...

  17. Defective channels lead to an impaired skin barrier.

    Science.gov (United States)

    Blaydon, Diana C; Kelsell, David P

    2014-10-15

    Channels are integral membrane proteins that form a pore, allowing the passive movement of ions or molecules across a membrane (along a gradient), either between compartments within a cell, between intracellular and extracellular environments or between adjacent cells. The ability of cells to communicate with one another and with their environment is a crucial part of the normal physiology of a tissue that allows it to carry out its function. Cell communication is particularly important during keratinocyte differentiation and formation of the skin barrier. Keratinocytes in the skin epidermis undergo a programme of apoptosis-driven terminal differentiation, whereby proliferating keratinocytes in the basal (deepest) layer of the epidermis stop proliferating, exit the basal layer and move up through the spinous and granular layers of the epidermis to form the stratum corneum, the external barrier. Genes encoding different families of channel proteins have been found to harbour mutations linked to a variety of rare inherited monogenic skin diseases. In this Commentary, we discuss how human genetic findings in aquaporin (AQP) and transient receptor potential (TRP) channels reveal different mechanisms by which these channel proteins function to ensure the proper formation and maintenance of the skin barrier. © 2014. Published by The Company of Biologists Ltd.

  18. Channeling of protons through radial deformed carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Borka Jovanović, V., E-mail: vborka@vinca.rs [Atomic Physics Laboratory (040), Vinča Institute of Nuclear Sciences, University of Belgrade, P.O. Box 522, 11001 Belgrade (Serbia); Borka, D. [Atomic Physics Laboratory (040), Vinča Institute of Nuclear Sciences, University of Belgrade, P.O. Box 522, 11001 Belgrade (Serbia); Galijaš, S.M.D. [Faculty of Physics, University of Belgrade, P.O. Box 368, 11001 Belgrade (Serbia)

    2017-05-18

    Highlights: • For the first time we presented theoretically obtained distributions of channeled protons with radially deformed SWNT. • Our findings indicate that influence of the radial deformation is very strong and it should not be omitted in simulations. • We show that the spatial and angular distributions depend strongly of level of radial deformation of nanotube. • Our obtained results can be compared with measured distributions to reveal the presence of various types of defects in SWNT. - Abstract: In this paper we have presented a theoretical investigation of the channeling of 1 GeV protons with the radial deformed (10, 0) single-wall carbon nanotubes (SWNTs). We have calculated channeling potential within the deformed nanotubes. For the first time we presented theoretically obtained spatial and angular distributions of channeled protons with radially deformed SWNT. We used a Monte Carlo (MC) simulation technique. We show that the spatial and angular distributions depend strongly of level of radial deformation of nanotube. These results may be useful for nanotube characterization and production and guiding of nanosized ion beams.

  19. Sculpting ion channel functional expression with engineered ubiquitin ligases

    Science.gov (United States)

    Kanner, Scott A; Morgenstern, Travis

    2017-01-01

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

  20. Modeling of Doppler frequency shift in multipath radio channels

    Directory of Open Access Journals (Sweden)

    Penzin M.S.

    2016-06-01

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

  1. BKCa-Channel Structure and Function

    Science.gov (United States)

    Cox, Daniel H.

    Among ion channels, the large-conductance Ca2+-activated K+ channel (BKCa channel) is in many ways unique. It has a very large single-channel conductance—ten times that of most vertebrate K+ channels—and yet it maintains strict K+ selectivity. It senses as little as 200 nM Ca2+, but it contains no consensus Ca2+-binding motifs, and it is the only channel to be activated by both intracellular Ca2+ and membrane voltage. In fact, there is a synergy between these stimuli such that the higher the internal Ca2+ concentration ([Ca2+]), the smaller the depolarization needed to activate the channel. Furthermore, the BKCa channel has its own brand of auxiliary subunits that profoundly affect gating. In this chapter, I will discuss what is understood about the origins of these properties in terms of allosteric models and channel structure. At the outset, however, I should say that there is not yet a crystal structure of the BKCa channel or any of its components, so much of the current thinking about BKCa-channel structure relies on analogy to other channels.

  2. Performance Analysis of Iterative Channel Estimation and Multiuser Detection in Multipath DS-CDMA Channels

    OpenAIRE

    Li, Husheng; Betz, Sharon M.; Poor, H. Vincent

    2006-01-01

    This paper examines the performance of decision feedback based iterative channel estimation and multiuser detection in channel coded aperiodic DS-CDMA systems operating over multipath fading channels. First, explicit expressions describing the performance of channel estimation and parallel interference cancellation based multiuser detection are developed. These results are then combined to characterize the evolution of the performance of a system that iterates among channel estimation, multiu...

  3. Relativistic Channeling of a Picosecond Laser Pulse in a Near-Critical Preformed Plasma

    International Nuclear Information System (INIS)

    Borghesi, M.; MacKinnon, A.J.; Barringer, L.; Gaillard, R.; Gizzi, L.; Meyer, C.; Willi, O.; Pukhov, A.; Meyer-ter-Vehn, J.

    1997-01-01

    Relativistic self-channeling of a picosecond laser pulse in a preformed plasma near critical density has been observed both experimentally and in 3D particle-in-cell simulations. Optical probing measurements indicate the formation of a single pulsating propagation channel, typically of about 5μm in diameter. The computational results reveal the importance in the channel formation of relativistic electrons traveling with the light pulse and of the corresponding self-generated magnetic field. copyright 1997 The American Physical Society

  4. Direct visualization of the trimeric structure of the ASIC1a channel, using AFM imaging

    International Nuclear Information System (INIS)

    Carnally, Stewart M.; Dev, Harveer S.; Stewart, Andrew P.; Barrera, Nelson P.; Van Bemmelen, Miguel X.; Schild, Laurent; Henderson, Robert M.; Edwardson, J.Michael

    2008-01-01

    There has been confusion about the subunit stoichiometry of the degenerin family of ion channels. Recently, a crystal structure of acid-sensing ion channel (ASIC) 1a revealed that it assembles as a trimer. Here, we used atomic force microscopy (AFM) to image unprocessed ASIC1a bound to mica. We detected a mixture of subunit monomers, dimers and trimers. In some cases, triple-subunit clusters were clearly visible, confirming the trimeric structure of the channel, and indicating that the trimer sometimes disaggregated after adhesion to the mica surface. This AFM-based technique will now enable us to determine the subunit arrangement within heteromeric ASICs

  5. Common-Message Broadcast Channels with Feedback in the Nonasymptotic Regime: Full Feedback

    DEFF Research Database (Denmark)

    Trillingsgaard, Kasper Fløe; Yang, Wei; Durisi, Giuseppe

    2018-01-01

    We investigate the maximum coding rate achievable on a two-user broadcast channel for the case where a common message is transmitted with feedback using either fixed-blocklength codes or variable-length codes. For the fixed-blocklength-code setup, we establish nonasymptotic converse...... and achievability bounds. An asymptotic analysis of these bounds reveals that feedback improves the second-order term compared to the no-feedback case. In particular, for a certain class of anti-symmetric broadcast channels, we show that the dispersion is halved. For the variable-length-code setup, we demonstrate...... that the channel dispersion is zero....

  6. Feedback Halves the Dispersion for Some Two-User Broadcast Channels with Common Message

    DEFF Research Database (Denmark)

    Trillingsgaard, Kasper Fløe; Yang, Wei; Durisi, Giuseppe

    2017-01-01

    We investigate the maximum coding rate achievable on a two-user broadcast channel for the case where a common- message is transmitted using fixed-blocklength codes with feed- back. Specifically, we focus on a family of broadcast channels com- posed of two antisymmetric Z-channels. For this setup......, we obtain matching upper and lower bounds on the dispersion term in the asymptotic expansion of the maximum coding rate. These bounds reveal that the dispersion is halved compared to the no-feedback case...

  7. On luminescence bleaching of tidal channel sediments

    DEFF Research Database (Denmark)

    Fruergaard, Mikkel; Pejrup, Morten; Murray, Andrew S.

    2015-01-01

    We investigate the processes responsible for bleaching of the quartz OSL signal from tidal channel sediment. Tidal dynamics are expected to play an important role for complete bleaching of tidal sediments. However, no studies have examined the amount of reworking occurring in tidal channels...... and on tidal flats due to the mixing caused by currents and waves. We apply bed level data to evaluate the amount of vertical sediment reworking in modern tidal channels and at a tidal flat. Cycles of deposition and erosion are measured with a bed level sensor, and the results show that gross sedimentation...... was several times higher than net sedimentation. We propose that tidal channel sediment is bleached either on the tidal flat before it is transported to the tidal channels and incorporated in channel-fill successions or, alternatively, on the shallow intertidal part of the channel banks. Based...

  8. Post-Translational Modifications of TRP Channels

    Directory of Open Access Journals (Sweden)

    Olaf Voolstra

    2014-04-01

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

  9. Clay mineral variations near Pennsylvanian sandstone channels

    International Nuclear Information System (INIS)

    Shaffer, N.R.; Indiana Univ., Bloomington, IN; Murray, H.H.

    1993-01-01

    Large linear sandstone bodies in the Illinois Basin have been interpreted as representing fresh water river channels that flowed through generally marine to brackish Pennsylvanian deltaic environments; fresh water from such channels could have affected deposition of adjacent coal-bearing rocks. Low-sulfur coals are commonly associated with the sandstone bodies, which may also host petroleum, uranium, fresh water, or other resources. Thus techniques to locate such channels would be economically useful. Previous studies have shown that clay mineral distributions and bulk chemistries of clay-rich sediments are affected when fresh waters mix with sea water. Such changes associated laterally with freshwater channels might have caused distinctive clay mineral or chemical patterns to develop around the channels. Mineralogies and chemical compositions of more than 500 mudrock samples taken immediately above the springfield Coal Member of the Petersburg Formation from 52 sections located from channel margins to 63 miles distant were determined to discern patterns that could aid in finding channels

  10. A BWR fuel channel tracking system

    International Nuclear Information System (INIS)

    Reynolds, R.S.

    1987-01-01

    A relational database management system with a query language, Reference 1, has been used to develop a Boiling Water Reactor (BWR) fuel channel tracking system on a microcomputer. The software system developed implements channel vendor and Nuclear Regulatory Commission recommendations for in-core channel movements between reactor operating cycles. A BWR Fuel channel encloses the fuel bundle and is typically fabricated using Ziracoly-4. The channel serves three functions: (1) it provides a barrier to separate two parallel flow paths, one inside the fuel assembly and the other in the bypass region outside the fuel assembly and between channels; (2) it guides the control rod as it moves between fuel assemblies and provides a bearing surface for the blades; and (3) it provides rigidity for the fuel bundle. All of these functions are necessary in typical BWR core designs. Fuel channels are not part of typical Pressurized Water Reactor (PWR) core designs

  11. 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...

  12. Multicarrier chaotic communications in multipath fading channels without channel estimation

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Shilian, E-mail: wangsl@nudt.edu.cn; Zhang, Zhili [College of Electrical Science and Engineering, National University of Defense Technology, Changsha, 410073, P R China (China)

    2015-01-15

    A multi-carrier chaotic shift keying(MC-CSK) communication scheme with low probability of interception(LPI) is proposed in this article. We apply chaotic spreading sequences in the frequency domain, mapping a different chip of a chaotic sequence to an individual orthogonal frequency division multiplexing(OFDM) subcarrier. In each block size of $M$ OFDM symbols, we use one pilot OFDM symbol inserted time-spaced in all-frequency to transmit the reference chaotic signal and use the other M-1 OFDM symbols to transmit the information-bearing signals each spreaded by the reference chaotic signal. At the receiver, we construct a differential detector after DFT and recover the information bits from the correlations between the pilot OFDM symbol and the other M-1 OFDM symbols in each block size of M. Performance analysis and computer simulations show that the MC-CSK outperforms differential chaos shift keying(DCSK) in AWGN channels with high bandwidth efficiency for the block size of M=2 and that the MC-CSK exploits effectively the frequent diversity of the multipath channel.

  13. Multicarrier chaotic communications in multipath fading channels without channel estimation

    International Nuclear Information System (INIS)

    Wang, Shilian; Zhang, Zhili

    2015-01-01

    A multi-carrier chaotic shift keying(MC-CSK) communication scheme with low probability of interception(LPI) is proposed in this article. We apply chaotic spreading sequences in the frequency domain, mapping a different chip of a chaotic sequence to an individual orthogonal frequency division multiplexing(OFDM) subcarrier. In each block size of $M$ OFDM symbols, we use one pilot OFDM symbol inserted time-spaced in all-frequency to transmit the reference chaotic signal and use the other M-1 OFDM symbols to transmit the information-bearing signals each spreaded by the reference chaotic signal. At the receiver, we construct a differential detector after DFT and recover the information bits from the correlations between the pilot OFDM symbol and the other M-1 OFDM symbols in each block size of M. Performance analysis and computer simulations show that the MC-CSK outperforms differential chaos shift keying(DCSK) in AWGN channels with high bandwidth efficiency for the block size of M=2 and that the MC-CSK exploits effectively the frequent diversity of the multipath channel

  14. Conductive Channel for Energy Transmission

    Science.gov (United States)

    Apollonov, Victor V.

    2011-11-01

    For many years the attempts to create conductive channels of big length were taken in order to study the upper atmosphere and to settle special tasks, related to energy transmission. There upon the program of creation of "Impulsar" represents a great interest, as this program in a combination with high-voltage high repetition rate electrical source can be useful to solve the above mentioned problems (N. Tesla ideas for the days of high power lasers). The principle of conductive channel production can be shortly described as follows. The "Impulsar"—laser jet engine vehicle—propulsion take place under the influence of powerful high repetition rate pulse-periodic laser radiation. In the experiments the CO2—laser and solid state Nd:YAG laser systems had been used. Active impulse appears thanks to air breakdown (30 km), placed in the vicinity of the focusing mirror-acceptor of the breakdown waves. With each pulse of powerful laser the device rises up, leaving a bright and dense trace of products with high degree of ionization and metallization by conductive nano-particles due to ablation. Conductive dust plasma properties investigation in our experiments was produced by two very effective approaches: high power laser controlled ablation and by explosion of wire. Experimental and theoretical results of conductive canal modeling will be presented. The estimations show that with already experimentally demonstrated figures of specific thrust impulse the lower layers of the Ionosphere can be reached in several ten seconds that is enough to keep the high level of channel conductivity and stability with the help of high repetition rate high voltage generator. Some possible applications for new technology are highlighted.

  15. Precipitation patterns during channel flow

    Science.gov (United States)

    Jamtveit, B.; Hawkins, C.; Benning, L. G.; Meier, D.; Hammer, O.; Angheluta, L.

    2013-12-01

    Mineral precipitation during channelized fluid flow is widespread in a wide variety of geological systems. It is also a common and costly phenomenon in many industrial processes that involve fluid flow in pipelines. It is often referred to as scale formation and encountered in a large number of industries, including paper production, chemical manufacturing, cement operations, food processing, as well as non-renewable (i.e. oil and gas) and renewable (i.e. geothermal) energy production. We have studied the incipient stages of growth of amorphous silica on steel plates emplaced into the central areas of the ca. 1 meter in diameter sized pipelines used at the hydrothermal power plant at Hellisheidi, Iceland (with a capacity of ca 300 MW electricity and 100 MW hot water). Silica precipitation takes place over a period of ca. 2 months at approximately 120°C and a flow rate around 1 m/s. The growth produces asymmetric ca. 1mm high dendritic structures ';leaning' towards the incoming fluid flow. A novel phase-field model combined with the lattice Boltzmann method is introduced to study how the growth morphologies vary under different hydrodynamic conditions, including non-laminar systems with turbulent mixing. The model accurately predicts the observed morphologies and is directly relevant for understanding the more general problem of precipitation influenced by turbulent mixing during flow in channels with rough walls and even for porous flow. Reference: Hawkins, C., Angheluta, L., Hammer, Ø., and Jamtveit, B., Precipitation dendrites in channel flow. Europhysics Letters, 102, 54001

  16. Propagation Characterization and MIMO Channel-Modelling for 3G

    DEFF Research Database (Denmark)

    Schumacher, Laurent; Berger, Lars Torsten; Ramiro-Moreno, Juan

    2004-01-01

    This paper presents a survey of MIMO channel models, distinguishing between determinsistic and stochastic channel models.......This paper presents a survey of MIMO channel models, distinguishing between determinsistic and stochastic channel models....

  17. Identification of the molecular site of ivabradine binding to HCN4 channels.

    Science.gov (United States)

    Bucchi, Annalisa; Baruscotti, Mirko; Nardini, Marco; Barbuti, Andrea; Micheloni, Stefano; Bolognesi, Martino; DiFrancesco, Dario

    2013-01-01

    Ivabradine is a specific heart rate-reducing agent approved as a treatment of chronic stable angina. Its mode of action involves a selective and specific block of HCN channels, the molecular components of sinoatrial "funny" (f)-channels. Different studies suggest that the binding site of ivabradine is located in the inner vestibule of HCN channels, but the molecular details of ivabradine binding are unknown. We thus sought to investigate by mutagenesis and in silico analysis which residues of the HCN4 channel, the HCN isoform expressed in the sinoatrial node, are involved in the binding of ivabradine. Using homology modeling, we verified the presence of an inner cavity below the channel pore and identified residues lining the cavity; these residues were replaced with alanine (or valine) either alone or in combination, and WT and mutant channels were expressed in HEK293 cells. Comparison of the block efficiency of mutant vs WT channels, measured by patch-clamp, revealed that residues Y506, F509 and I510 are involved in ivabradine binding. For each mutant channel, docking simulations correctly explain the reduced block efficiency in terms of proportionally reduced affinity for ivabradine binding. In summary our study shows that ivabradine occupies a cavity below the channel pore, and identifies specific residues facing this cavity that interact and stabilize the ivabradine molecule. This study provides an interpretation of known properties of f/HCN4 channel block by ivabradine such as the "open channel block", the current-dependence of block and the property of "trapping" of drug molecules in the closed configuration.

  18. Flexible linings for drainage channels

    Energy Technology Data Exchange (ETDEWEB)

    Crowhurst, A.D.

    1984-12-01

    Watercourses formed in fill areas present special problems. Since soils may not be fully compacted erosion may occur to a greater degree than would otherwise be the case. Rigid structures built under these conditions may well fail due to settlement or to scour from flows passing under the structure. Concrete may well also be more obtrusive in rural landscapes. An alternative exists in the form of thin layers of wire enclosed rip-rap which have several advantages when used for channel linings. This method gives both strength and economy coupled with a natural appearance.

  19. Mechanosensitive gating of Kv channels.

    Directory of Open Access Journals (Sweden)

    Catherine E Morris

    Full Text Available K-selective voltage-gated channels (Kv are multi-conformation bilayer-embedded proteins whose mechanosensitive (MS Popen(V implies that at least one conformational transition requires the restructuring of the channel-bilayer interface. Unlike Morris and colleagues, who attributed MS-Kv responses to a cooperative V-dependent closed-closed expansion↔compaction transition near the open state, Mackinnon and colleagues invoke expansion during a V-independent closed↔open transition. With increasing membrane tension, they suggest, the closed↔open equilibrium constant, L, can increase >100-fold, thereby taking steady-state Popen from 0→1; "exquisite sensitivity to small…mechanical perturbations", they state, makes a Kv "as much a mechanosensitive…as…a voltage-dependent channel". Devised to explain successive gK(V curves in excised patches where tension spontaneously increased until lysis, their L-based model falters in part because of an overlooked IK feature; with recovery from slow inactivation factored in, their g(V datasets are fully explained by the earlier model (a MS V-dependent closed-closed transition, invariant L≥4. An L-based MS-Kv predicts neither known Kv time courses nor the distinctive MS responses of Kv-ILT. It predicts Kv densities (hence gating charge per V-sensor several-fold different from established values. If opening depended on elevated tension (L-based model, standard gK(V operation would be compromised by animal cells' membrane flaccidity. A MS V-dependent transition is, by contrast, unproblematic on all counts. Since these issues bear directly on recent findings that mechanically-modulated Kv channels subtly tune pain-related excitability in peripheral mechanoreceptor neurons we undertook excitability modeling (evoked action potentials. Kvs with MS V-dependent closed-closed transitions produce nuanced mechanically-modulated excitability whereas an L-based MS-Kv yields extreme, possibly excessive

  20. Suppression of ion conductance by electro-osmotic flow in nano-channels with weakly overlapping electrical double layers

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2016-08-01

    Full Text Available This theoretical study investigates the nonlinear ionic current-voltage characteristics of nano-channels that have weakly overlapping electrical double layers. Numerical simulations as well as a 1-D mathematical model are developed to reveal that the electro-osmotic flow (EOF interplays with the concentration-polarization process and depletes the ion concentration inside the channels, thus significantly suppressing the channel conductance. The conductance may be restored at high electrical biases in the presence of recirculating vortices within the channels. As a result of the EOF-driven ion depletion, a limiting-conductance behavior is identified, which is intrinsically different from the classical limiting-current behavior.

  1. Novel asymptotic results on the high-order statistics of the channel capacity over generalized fading channels

    KAUST Repository

    Yilmaz, Ferkan

    2012-06-01

    The exact analysis of the higher-order statistics of the channel capacity (i.e., higher-order ergodic capacity) often leads to complicated expressions involving advanced special functions. In this paper, we provide a generic framework for the computation of the higher-order statistics of the channel capacity over generalized fading channels. As such, this novel framework for the higher-order statistics results in simple, closed-form expressions which are shown to be asymptotically tight bounds in the high signal-to-noise ratio (SNR) regime of a variety of fading environment. In addition, it reveals the existence of differences (i.e., constant capacity gaps in log-domain) among different fading environments. By asymptotically tight bound we mean that the high SNR limit of the difference between the actual higher-order statistics of the channel capacity and its asymptotic bound (i.e., lower bound) tends to zero. The mathematical formalism is illustrated with some selected numerical examples that validate the correctness of our newly derived results. © 2012 IEEE.

  2. 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.

  3. Two-dimensional kinetic analysis suggests nonsequential gating of mechanosensitive channels in Xenopus oocytes.

    Science.gov (United States)

    Gil, Z; Magleby, K L; Silberberg, S D

    2001-10-01

    Xenopus oocytes express mechanosensitive (MS(XO)) channels that can be studied in excised patches of membrane with the patch-clamp technique. This study examines the steady-state kinetic gating properties of MS(XO) channels using detailed single-channel analysis. The open and closed one-dimensional dwell-time distributions were described by the sums of 2-3 open and 5-7 closed exponential components, respectively, indicating that the channels enter at least 2-3 open and 5-7 closed kinetic states during gating. Dependency plots revealed that the durations of adjacent open and closed intervals were correlated, indicating two or more gateway states in the gating mechanism for MS channels. Maximum likelihood fitting of two-dimensional dwell-time distributions to both generic and specific models was used to examine gating mechanism and rank models. A kinetic scheme with five closed and five open states, in which each closed state could make a direct transition to an open state (two-tiered model) could account for the major features of the single-channel data. Two-tiered models that allowed direct transitions to subconductance open states in addition to the fully open state were also consistent with multiple gateway states. Thus, the gating mechanism of MS(XO) channels differs from the sequential (linear) gating mechanisms considered for MS channels in bacteria, chick skeletal muscle, and Necturus proximal tubule.

  4. Structure resonances due to space charge in periodic focusing channels

    Science.gov (United States)

    Li, Chao; Jameson, R. A.

    2018-02-01

    The Vlasov-Poisson model is one of the most effective methods to study the space charge dominated beam evolution self-consistently in a periodic focusing channel. Since the approach to get the solution with this model is not trivial, previous studies are limited in degenerated conditions, either in smoothed channel (constant focusing) [I. Hofmann, Phys. Rev. E 57, 4713 (1998)] or in alternating gradient focusing channel with equal initial beam emittance condition in the degrees of freedom [I. Hofmann et al., Part. Accel. 13, 145 (1983); Chao Li et al., THOBA02, IPAC2016]. To establish a basis, we intentionally limit this article to the study of the pure transverse periodic focusing lattice with arbitrary initial beam condition, and the same lattice structure in both degrees of freedom, but with possibility of different focusing strengths. This will show the extension of the existing work. The full Hamiltonian is invoked for a pure transverse focusing lattice in various initial beam conditions, revealing different mode structure and additional modes beyond those of the degenerated cases. Application of the extended method to realistic lattices (including longitudinal accelerating elements) and further details will then reveal many new insights, and will be presented in later work.

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

    Directory of Open Access Journals (Sweden)

    Darryl W Hondorp

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

  6. TypeScript revealed

    CERN Document Server

    Maharry, Dan

    2013-01-01

    TypeScript Revealed is a quick 100-page guide to Anders Hejlsberg's new take on JavaScript. With this brief, fast-paced introduction to TypeScript, .NET, Web and Windows 8 application developers who are already familiar with JavaScript will easily get up to speed with TypeScript and decide whether or not to start incorporating it into their own development. TypeScript is 'JavaScript for Application-scale development'; a superset of JavaScript that brings to it an additional object-oriented-like syntax familiar to .NET programmers that compiles down into simple, clean JavaScript that any browse

  7. Revealing the programming process

    DEFF Research Database (Denmark)

    Bennedsen, Jens; Caspersen, Michael Edelgaard

    2005-01-01

    One of the most important goals of an introductory programming course is that the students learn a systematic approach to the development of computer programs. Revealing the programming process is an important part of this; however, textbooks do not address the issue -- probably because...... the textbook medium is static and therefore ill-suited to expose the process of programming. We have found that process recordings in the form of captured narrated programming sessions are a simple, cheap, and efficient way of providing the revelation.We identify seven different elements of the programming...

  8. Pauli diagonal channels constant on axes

    Energy Technology Data Exchange (ETDEWEB)

    Nathanson, Michael [Department of Mathematics and Computer Science, St. Mary' s College of California, Moraga, CA 94575 (United States); Ruskai, Mary Beth [Department of Mathematics, Tufts University, Medford, MA 02155 (United States)

    2007-07-13

    We define and study the properties of channels which are analogous to unital qubit channels in several ways. A full treatment can be given only when the dimension d = p{sup m} a prime power, in which case each of the d + 1 mutually unbiased bases (MUB) defines an axis. Along each axis the channel looks like a depolarizing channel, but the degree of depolarization depends on the axis. When d is not a prime power, some of our results still hold, particularly in the case of channels with one symmetry axis. We describe the convex structure of this class of channels and the subclass of entanglement breaking channels. We find new bound entangled states for d = 3. For these channels, we show that the multiplicativity conjecture for maximal output p-norm holds for p = 2. We also find channels with behaviour not exhibited by unital qubit channels, including two pairs of orthogonal bases with equal output entropy in the absence of symmetry. This provides new numerical evidence for the additivity of minimal output entropy.

  9. 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.

  10. A Perspective on the MIMO Wiretap Channel

    KAUST Repository

    Oggier, Frederique

    2015-10-01

    A wiretap channel is a communication channel between a transmitter Alice and a legitimate receiver Bob, in the presence of an eavesdropper Eve. The goal of communication is to achieve reliability between Alice and Bob, but also confidentiality despite Eve’s presence. Wiretap channels are declined in all kinds of flavors, depending on the underlying channels used by the three players: discrete memoryless channels, additive Gaussian noise channels, or fading channels, to name a few. In this survey, we focus on the case where the three players use multiple-antenna channels with Gaussian noise to communicate. After summarizing known results for multiple-input–multiple-output (MIMO) channels, both in terms of achievable reliable data rate (capacity) and code design, we introduce the MIMO wiretap channel. We then state the MIMO wiretap capacity, summarize the idea of the proof(s) behind this result, and comment on the insights given by the proofs on the physical meaning of the secrecy capacity. We finally discuss design criteria for MIMO wiretap codes.

  11. Quantum circuits for quantum channels

    Science.gov (United States)

    Iten, Raban; Colbeck, Roger; Christandl, Matthias

    2017-05-01

    We study the implementation of quantum channels with quantum computers while minimizing the experimental cost, measured in terms of the number of controlled-not (cnot) gates required (single-qubit gates are free). We consider three different models. In the first, the quantum circuit model (QCM), we consider sequences of single-qubit and cnot gates and allow qubits to be traced out at the end of the gate sequence. In the second (RandomQCM), we also allow external classical randomness. In the third (MeasuredQCM) we also allow measurements followed by operations that are classically controlled on the outcomes. We prove lower bounds on the number of cnot gates required and give near-optimal decompositions in almost all cases. Our main result is a MeasuredQCM circuit for any channel from m qubits to n qubits that uses at most one ancilla and has a low cnot count. We give explicit examples for small numbers of qubits that provide the lowest known cnot counts.

  12. Stable channel of reclaimed tidal lowland

    Science.gov (United States)

    Syarifudin, Achmad; Imanuddin, Momon S.; Moerwanto, Arie S.; Suryadi, F. X.

    2017-11-01

    This study aimed to develop models of the Operation and Maintenance in the reclaimed tidal marsh area to get a stable channel. The research location is reclaimed tidal delta area Telang I Primary 8 representing land typology A/B and a survey conducted in 13 South Secondary Schemes following existing tertiary Telang I. MIKE - 11 computer models used used to analyze the movement of sediment in the channel in both the Primary channel 8, SPD, SDU and tertiary channels in block 13 South. Calibration model with multiple channels in the field of physical parameters has been performed to obtain results close to the results of measurement modeling sediment movement in the channel. The integration models of MIKE - 11 models with various scenarios are used to model the operation and maintenance of the channel in the tidal marsh area to get a stable channel. According to the scheme P8 - 13S, OM models obtained 75 percent, in which the secondary channel (SPD/SDU) and built flap gate in tertiary channel, get a well prototype model of the stable channel (equilibriums), where the average erosion on P8 at a distance of 3,200 m in the amount of 4,472,049 m3 and the mean sedimentation in the SPD of 963,836 m3 and mean of sedimentation in the tertiary channel of 3,508,213 m3. Similarly, on average erosion P8 by 4,135,649 m3 and the mean sedimentation in the SDU of 681,304 m3 and the mean sedimentation in the tertiary channel of 3,454,345 m3.

  13. Fractional quantum conductance in edge channels of silicon quantum wells

    Energy Technology Data Exchange (ETDEWEB)

    Bagraev, Nikolay; Klyachkin, Leonid; Kudryavtsev, Andrey; Malyarenko, Anna [Ioffe Physical Technical Institute, Polytekhnicheskaya 26, 194021 St. Petersburg (Russian Federation)

    2013-12-04

    We present the findings for the fractional quantum conductance of holes that is caused by the edge channels in the silicon nanosandwich prepared within frameworks of the Hall geometry. This nanosandwich represents the ultra-narrow p-type silicon quantum well (Si-QW), 2 nm, confined by the δ-barriers heavily doped with boron on the n-type Si (100) surface. The edge channels in the Si-QW plane are revealed by measuring the longitudinal quantum conductance staircase, G{sub xx}, as a function of the voltage applied to the Hall contacts, V{sub xy}, to a maximum of 4e{sup 2}/h. In addition to the standard plateau, 2e{sup 2}/h, the variations of the V{sub xy} voltage appear to exhibit the fractional form of the quantum conductance staircase with the plateaus and steps that bring into correlation respectively with the odd and even fractions.

  14. Swell activated chloride channel function in human neutrophils

    Energy Technology Data Exchange (ETDEWEB)

    Salmon, Michael D. [Leukocyte and Ion Channel Research Laboratory, School of Health and Biosciences, University of East London, Stratford Campus, London E15 4LZ (United Kingdom); Ahluwalia, Jatinder, E-mail: j.ahluwalia@uel.ac.uk [Leukocyte and Ion Channel Research Laboratory, School of Health and Biosciences, University of East London, Stratford Campus, London E15 4LZ (United Kingdom)

    2009-04-17

    Non-excitable cells such as neutrophil granulocytes are the archetypal inflammatory immune cell involved in critical functions of the innate immune system. The electron current generated (I{sub e}) by the neutrophil NADPH oxidase is electrogenic and rapidly depolarises the membrane potential. For continuous function of the NADPH oxidase, I{sub e} has to be balanced to preserve electroneutrality, if not; sufficient depolarisation would prevent electrons from leaving the cell and neutrophil function would be abrogated. Subsequently, the depolarisation generated by the neutrophil NADPH oxidase I{sub e} must be counteracted by ion transport. The finding that depolarisation required counter-ions to compensate electron transport was followed by the observation that chloride channels activated by swell can counteract the NADPH oxidase membrane depolarisation. In this mini review, we discuss the research findings that revealed the essential role of swell activated chloride channels in human neutrophil function.

  15. MarkoLAB: A simulator to study ionic channel's stochastic behavior.

    Science.gov (United States)

    da Silva, Robson Rodrigues; Goroso, Daniel Gustavo; Bers, Donald M; Puglisi, José Luis

    2017-08-01

    Mathematical models of the cardiac cell have started to include markovian representations of the ionic channels instead of the traditional Hodgkin & Huxley formulations. There are many reasons for this: Markov models are not restricted to the idea of independent gates defining the channel, they allow more complex description with specific transitions between open, closed or inactivated states, and more importantly those states can be closely related to the underlying channel structure and conformational changes. We used the LabVIEW ® and MATLAB ® programs to implement the simulator MarkoLAB that allow a dynamical 3D representation of the markovian model of the channel. The Monte Carlo simulation was used to implement the stochastic transitions among states. The user can specify the voltage protocol by setting the holding potential, the step-to voltage and the duration of the stimuli. The most studied feature of a channel is the current flowing through it. This happens when the channel stays in the open state, but most of the time, as revealed by the low open probability values, the channel remains on the inactive or closed states. By focusing only when the channel enters or leaves the open state we are missing most of its activity. MarkoLAB proved to be quite useful to visualize the whole behavior of the channel and not only when the channel produces a current. Such dynamic representation provides more complete information about channel kinetics and will be a powerful tool to demonstrate the effect of gene mutations or drugs on the channel function. MarkoLAB provides an original way of visualizing the stochastic behavior of a channel. It clarifies concepts, such as recovery from inactivation, calcium- versus voltage-dependent inactivation, and tail currents. It is not restricted to ionic channels only but it can be extended to other transporters, such as exchangers and pumps. This program is intended as a didactical tool to illustrate the dynamical behavior of a

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    elements that control the kinetics of ATP-dependent regulation of KATP (Kir6.2 + SUR1) channels using rapid concentration jumps. WT Kir6.2 channels re-open after rapid washout of ATP with a time constant of approximately 60 ms. Extending similar kinetic measurements to numerous mutants revealed fairly...... modest effects on gating kinetics despite significant changes in ATP sensitivity and open probability. However, we identified a pair of highly conserved neighboring amino acids (Trp68, Lys170) that control the rate of channel opening and inhibition in response to ATP. Paradoxically, mutations of Trp68...... or Lys170 markedly slow the kinetics of channel opening (500 ms and 700 ms for Trp68Leu and Lys170Asn, respectively), while increasing channel open probability. Examining the functional effects of these residues using phi-value analysis revealed a steep negative slope. This finding implies...

  17. Sediment supply controls equilibrium channel geometry in gravel rivers.

    Science.gov (United States)

    Pfeiffer, Allison M; Finnegan, Noah J; Willenbring, Jane K

    2017-03-28

    In many gravel-bedded rivers, floods that fill the channel banks create just enough shear stress to move the median-sized gravel particles on the bed surface ( D 50 ). Because this observation is common and is supported by theory, the coincidence of bankfull flow and the incipient motion of D 50 has become a commonly used assumption. However, not all natural gravel channels actually conform to this simple relationship; some channels maintain bankfull stresses far in excess of the critical stress required to initiate sediment transport. We use a database of >300 gravel-bedded rivers and >600 10 Be-derived erosion rates from across North America to explore the hypothesis that sediment supply drives the magnitude of bankfull shear stress relative to the critical stress required to mobilize the median bed surface grain size ([Formula: see text]). We find that [Formula: see text] is significantly higher in West Coast river reaches (2.35, n = 96) than in river reaches elsewhere on the continent (1.03, n = 245). This pattern parallels patterns in erosion rates (and hence sediment supplies). Supporting our hypothesis, we find a significant correlation between upstream erosion rate and local [Formula: see text] at sites where this comparison is possible. Our analysis reveals a decrease in bed surface armoring with increasing [Formula: see text], suggesting channels accommodate changes in sediment supply through adjustments in bed surface grain size, as also shown through numerical modeling. Our findings demonstrate that sediment supply is encoded in the bankfull hydraulic geometry of gravel bedded channels through its control on bed surface grain size.

  18. Docking Studies of Phthalimide Pharmacophore as a Sodium Channel Blocker

    Directory of Open Access Journals (Sweden)

    Maryam Iman

    2013-09-01

    Full Text Available   Objective(s: Recently, phthalimide derivatives were designed based on ameltolide and thalidomide as they possess a similar degree of anticonvulsant potency due to their phenytoin-like profile. The ability of phthalimide pharmacophore to interact with neuronal voltage-dependent sodium channels was studied in the batrachotoxin affinity assay. Therefore, in the present study, a series of 19 compounds of phthalimide pharmacophore possessing a variety of substituents (NO2, NH2 , Me, Cl, COOH, MeO at 2-, 3-, and 4- position of the N-phenyl ring and N-(3-amino-2-methylphenyl succinimide, were subjected to docking studies in order to inhibit voltage-gated sodium channels.   Materials and Methods : Chemical structures of all compounds were designed using HYPERCHEM program and Conformational studies were performed through semi-empirical molecular orbital calculations method followed by PM3 force field. Total energy gradient calculated as a root mean square (RMS value, until the RMS gradient was 0.01 kcal mol-1. Among all energy minima conformers, the global minimum of compounds was used in docking calculations. Using a model of the open pore of Na channels, docking study was performed by AUTODOCK4.2 program. Results : Docking studies have revealed that these types of ligands interacted mainly with II-S6 residues of NaV1.2 through making hydrogen bonds and have additional hydrophobic interactions with domain I, II, III and IV in the channel's inner pore. Conclusion   : These computational studies have displayed that these compounds are capable of inhibiting Na channel, efficiently.

  19. Functional Importance of L- and P/Q-Type Voltage-Gated Calcium Channels in Human Renal Vasculature

    DEFF Research Database (Denmark)

    Hansen, Pernille B; Poulsen, Christian B; Walter, Steen

    2011-01-01

    Calcium channel blockers are widely used for treatment of hypertension, because they decrease peripheral vascular resistance through inhibition of voltage-gated calcium channels. Animal studies of renal vasculature have shown expression of several types of calcium channels that are involved......-type subtype (Ca(v) 3.1 and Ca(v) 3.2) voltage-gated calcium channels (Ca(v)s), and quantitative PCR showed highest expression of L-type channels in renal arteries and variable expression between patients of subtypes of calcium channels in intrarenal vessels. Immunohistochemical labeling of kidney sections...... revealed signals for Ca(v) 2.1 and Ca(v) 3.1 associated with smooth muscle cells of preglomerular and postglomerular vessels. In human intrarenal arteries, depolarization with potassium induced a contraction inhibited by the L-type antagonist nifedipine, EC(50) 1.2×10(-8) mol/L. The T-type antagonist...

  20. 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

  1. Distribution and function of HCN channels in the apical dendritic tuft of neocortical pyramidal neurons.

    Science.gov (United States)

    Harnett, Mark T; Magee, Jeffrey C; Williams, Stephen R

    2015-01-21

    The apical tuft is the most remote area of the dendritic tree of neocortical pyramidal neurons. Despite its distal location, the apical dendritic tuft of layer 5 pyramidal neurons receives substantial excitatory synaptic drive and actively processes corticocortical input during behavior. The properties of the voltage-activated ion channels that regulate synaptic integration in tuft dendrites have, however, not been thoroughly investigated. Here, we use electrophysiological and optical approaches to examine the subcellular distribution and function of hyperpolarization-activated cyclic nucleotide-gated nonselective cation (HCN) channels in rat layer 5B pyramidal neurons. Outside-out patch recordings demonstrated that the amplitude and properties of ensemble HCN channel activity were uniform in patches excised from distal apical dendritic trunk and tuft sites. Simultaneous apical dendritic tuft and trunk whole-cell current-clamp recordings revealed that the pharmacological blockade of HCN channels decreased voltage compartmentalization and enhanced the generation and spread of apical dendritic tuft and trunk regenerative activity. Furthermore, multisite two-photon glutamate uncaging demonstrated that HCN channels control the amplitude and duration of synaptically evoked regenerative activity in the distal apical dendritic tuft. In contrast, at proximal apical dendritic trunk and somatic recording sites, the blockade of HCN channels decreased excitability. Dynamic-clamp experiments revealed that these compartment-specific actions of HCN channels were heavily influenced by the local and distributed impact of the high density of HCN channels in the distal apical dendritic arbor. The properties and subcellular distribution pattern of HCN channels are therefore tuned to regulate the interaction between integration compartments in layer 5B pyramidal neurons. Copyright © 2015 the authors 0270-6474/15/351024-14$15.00/0.

  2. Glycosylation stabilizes hERG channels on the plasma membrane by decreasing proteolytic susceptibility.

    Science.gov (United States)

    Lamothe, Shawn M; Hulbert, Maggie; Guo, Jun; Li, Wentao; Yang, Tonghua; Zhang, Shetuan

    2018-01-05

    The human ether-a-go-go related gene ( hERG)-encoded channel hERG undergoes N-linked glycosylation at position 598, which is located in the unusually long S5-pore linker of the channel. In other work we have demonstrated that hERG is uniquely susceptible to proteolytic cleavage at the S5-pore linker by proteinase K (PK) and calpain (CAPN). The scorpion toxin BeKm-1, which binds to the S5-pore linker of hERG, protects hERG from such cleavage. In the present study, our data revealed that, compared with normal glycosylated hERG channels, nonglycosylated hERG channels were significantly more susceptible to cleavage by extracellular PK. Furthermore, the protective effect of BeKm-1 on hERG from PK-cleavage was lost when glycosylation of hERG was inhibited. The inactivation-deficient mutant hERG channels S620T and S631A were resistant to PK cleavage, and inhibition of glycosylation rendered both mutants susceptible to PK cleavage. Compared with normal glycosylated channels, nonglycosylated hERG channels were also more susceptible to cleavage mediated by CAPN, which was present in the medium of human embryonic kidney cells under normal culture conditions. Inhibition of CAPN resulted in an increase of nonglycosylated hERG current. In summary, our results revealed that N-linked glycosylation protects hERG against protease-mediated degradation and thus contributes to hERG channel stability on the plasma membrane.-Lamothe, S. M., Hulbert, M., Guo, J., Li, W., Yang, T., Zhang, S. Glycosylation stabilizes hERG channels on the plasma membrane by decreasing proteolytic susceptibility.

  3. Android Emotions Revealed

    DEFF Research Database (Denmark)

    Vlachos, Evgenios; Schärfe, Henrik

    2012-01-01

    This work presents a method for designing facial interfaces for sociable android robots with respect to the fundamental rules of human affect expression. Extending the work of Paul Ekman towards a robotic direction, we follow the judgment-based approach for evaluating facial expressions to test...... in which case an android robot like the Geminoid|DK –a duplicate of an Original person- reveals emotions convincingly; when following an empirical perspective, or when following a theoretical one. The methodology includes the processes of acquiring the empirical data, and gathering feedback on them. Our...... findings are based on the results derived from a number of judgments, and suggest that before programming the facial expressions of a Geminoid, the Original should pass through the proposed procedure. According to our recommendations, the facial expressions of an android should be tested by judges, even...

  4. Chemistry of plutonium revealed

    International Nuclear Information System (INIS)

    Connick, R.E.

    1992-01-01

    In 1941 one goal of the Manhattan Project was to unravel the chemistry of the synthetic element plutonium as rapidly as possible. In this paper the work carried out at Berkeley from the spring of 1942 to the summer of 1945 is described briefly. The aqueous chemistry of plutonium is quite remarkable. Important insights were obtained from tracer experiments, but the full complexity was not revealed until macroscopic amounts (milligrams) became available. Because processes for separation from fission products were based on aqueous solutions, such solution chemistry was emphasized, particularly precipitation and oxidation-reduction behavior. The latter turned out to be unusually intricate when it was discovered that two more oxidation states existed in aqueous solution than had previously been suspected. Further, an equilibrium was rapidly established among the four aqueous oxidation states, while at the same time any three were not in equilibrium. These and other observations made while doing a crash study of a previously unknown element are reported

  5. Pore size matters for potassium channel conductance

    Science.gov (United States)

    Moldenhauer, Hans; Pincuntureo, Matías

    2016-01-01

    Ion channels are membrane proteins that mediate efficient ion transport across the hydrophobic core of cell membranes, an unlikely process in their absence. K+ channels discriminate K+ over cations with similar radii with extraordinary selectivity and display a wide diversity of ion transport rates, covering differences of two orders of magnitude in unitary conductance. The pore domains of large- and small-conductance K+ channels share a general architectural design comprising a conserved narrow selectivity filter, which forms intimate interactions with permeant ions, flanked by two wider vestibules toward the internal and external openings. In large-conductance K+ channels, the inner vestibule is wide, whereas in small-conductance channels it is narrow. Here we raise the idea that the physical dimensions of the hydrophobic internal vestibule limit ion transport in K+ channels, accounting for their diversity in unitary conductance. PMID:27619418

  6. Roughness coefficients for stream channels in Arizona

    Science.gov (United States)

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

    1973-01-01

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

  7. US U-25 channel performance analysis

    Energy Technology Data Exchange (ETDEWEB)

    Doss, E.; Pan, Y. C.

    1980-07-01

    The results of an ANL computational analysis of the performance of the US U-25 MHD channel are presented. This channel has gone through several revisions. The major revision occurred after it had been decided by the DOE Office of MHD to operate the channel with platinum-clad copper electrodes (cold), rather than with ceramic electrodes (hot), as originally planned. This work has been performed at the request of the DOE Office of MHD and the US U-25 generator design Review Committee. The channel specifications and operating conditions are presented. The combustor temperature and thermodynamic and electrical properties of the plasma are computed, and the results are discussed. The MHD channel performance has been predicted for different operating conditions. Sensitivity studies have also been performed on the effects of mass flow rate, surface roughness, combustor temperatures, and loading on the channel performance.

  8. Analytical Prediction Of Meandering Channel Evolution

    Science.gov (United States)

    Chen, D.; Duan, J. G.

    2003-12-01

    The evolution of meandering channels, as a complex phenomenon, has been the research subject challenging river engineers for decades. The evolution of meandering channels is a complex morph-dynamic process resulted from the interaction among flow, sediment, and bank material. The rate of bank erosion was conventionally assumed to be proportional to the magnitude of near-bank excessive velocity or shear stress. A number of laboratory experiments on mild curved channels of flat beds indicated that the high velocity zone crosses the channel centerline at the neighborhood of the downstream inflection point instead of immediately downstream of the apex. If bank erosion only occurs at the places of high shear stress, the erosion of convex banks should be observed in these laboratory flumes, and the bends tend to subside. However, numerous experiments proved that a moderately or highly sinuous channel was initiated from a straight or mildly curved channel of no transverse slope by eroding the concave banks. Obviously

  9. KATP Channels in the Cardiovascular System.

    Science.gov (United States)

    Foster, Monique N; Coetzee, William A

    2016-01-01

    KATP channels are integral to the functions of many cells and tissues. The use of electrophysiological methods has allowed for a detailed characterization of KATP channels in terms of their biophysical properties, nucleotide sensitivities, and modification by pharmacological compounds. However, even though they were first described almost 25 years ago (Noma 1983, Trube and Hescheler 1984), the physiological and pathophysiological roles of these channels, and their regulation by complex biological systems, are only now emerging for many tissues. Even in tissues where their roles have been best defined, there are still many unanswered questions. This review aims to summarize the properties, molecular composition, and pharmacology of KATP channels in various cardiovascular components (atria, specialized conduction system, ventricles, smooth muscle, endothelium, and mitochondria). We will summarize the lessons learned from available genetic mouse models and address the known roles of KATP channels in cardiovascular pathologies and how genetic variation in KATP channel genes contribute to human disease. Copyright © 2016 the American Physiological Society.

  10. Pharmaceutical Distribution Market Channels in Poland

    OpenAIRE

    Agnieszka Woś

    2009-01-01

    Distribution on the pharmaceutical market in Poland is interesting and the most difficult sphere to manage. Numerous varied and specialized companies operating on the market cause that the processes of choosing middlemen in distribution channels are very complex. The hereby article presents the role and location of the companies operating within distribution channels on the pharmaceutical market. It draws attention to the development of non-pharmacy and non-wholesale sales channels.

  11. Monetary Policy and the Redistribution Channel

    OpenAIRE

    Adrien Auclert

    2015-01-01

    This paper evaluates the role of redistribution in the transmission mechanism of monetary policy to consumption. Using consumer theory, I show that redistribution has aggregate effects whenever marginal propensities to consume (MPCs) covary, across households, with balance-sheet exposures to aggregate shocks. Unexpected inflation gives rise to a Fisher channel and real interest rate shocks to an interest rate exposure channel; both channels are likely to contribute to the expansionary effects...

  12. Quantum privacy and Schur product channels

    Science.gov (United States)

    Levick, Jeremy; Kribs, David W.; Pereira, Rajesh

    2017-12-01

    We investigate the quantum privacy properties of an important class of quantum channels, by making use of a connection with Schur product matrix operations and associated correlation matrix structures. For channels implemented by mutually commuting unitaries, which cannot privatise qubits encoded directly into subspaces, we nevertheless identify private algebras and subsystems that can be privatised by the channels. We also obtain further results by combining our analysis with tools from the theory of quasi-orthogonal operator algebras and graph theory.

  13. Stability analysis for downflow in heated channels

    International Nuclear Information System (INIS)

    Sampaio, P.A.B. de.

    1985-01-01

    Stability and flow distribution are analysed for downflow in heated channels. It is shown that at low flow rates instabilities associated with the buoyancy forces may appear. A computer code in FORTRAN language to determine downflow distribution among n heated channels is presented. The model used to calculate downflow distribution and the onset of instability is compared with experiments performed in a test section with two parallel channels. (Author) [pt

  14. Multi-Channel Capacitive Sensor Arrays

    OpenAIRE

    Wang, Bingnan; Long, Jiang; Teo, Koon Hoo

    2016-01-01

    In this paper, multi-channel capacitive sensor arrays based on microstrip band-stop filters are studied. The sensor arrays can be used to detect the proximity of objects at different positions and directions. Each capacitive sensing structure in the array is connected to an inductive element to form resonance at different frequencies. The resonances are designed to be isolated in the frequency spectrum, such that the change in one channel does not affect resonances at other channels. The indu...

  15. Universal communication part II: channels with memory

    OpenAIRE

    Lomnitz, Yuval; Feder, Meir

    2012-01-01

    Consider communication over a channel whose probabilistic model is completely unknown vector-wise and is not assumed to be stationary. Communication over such channels is challenging because knowing the past does not indicate anything about the future. The existence of reliable feedback and common randomness is assumed. In a previous paper it was shown that the Shannon capacity cannot be attained, in general, if the channel is not known. An alternative notion of "capacity" was defined, as the...

  16. Dynamic Phenylalanine Clamp Interactions Define Single-Channel Polypeptide Translocation through the Anthrax Toxin Protective Antigen Channel.

    Science.gov (United States)

    Ghosal, Koyel; Colby, Jennifer M; Das, Debasis; Joy, Stephen T; Arora, Paramjit S; Krantz, Bryan A

    2017-03-24

    Anthrax toxin is an intracellularly acting toxin where sufficient detail is known about the structure of its channel, allowing for molecular investigations of translocation. The toxin is composed of three proteins, protective antigen (PA), lethal factor (LF), and edema factor (EF). The toxin's translocon, PA, translocates the large enzymes, LF and EF, across the endosomal membrane into the host cell's cytosol. Polypeptide clamps located throughout the PA channel catalyze the translocation of LF and EF. Here, we show that the central peptide clamp, the ϕ clamp, is a dynamic site that governs the overall peptide translocation pathway. Single-channel translocations of a 10-residue, guest-host peptide revealed that there were four states when peptide interacted with the channel. Two of the states had intermediate conductances of 10% and 50% of full conductance. With aromatic guest-host peptides, the 50% conducting intermediate oscillated with the fully blocked state. A Trp guest-host peptide was studied by manipulating its stereochemistry and prenucleating helix formation with a covalent linkage in the place of a hydrogen bond or hydrogen-bond surrogate (HBS). The Trp peptide synthesized with ʟ-amino acids translocated more efficiently than peptides synthesized with D- or alternating D,ʟ-amino acids. HBS stapled Trp peptide exhibited signs of steric hindrance and difficulty translocating. However, when mutant ϕ clamp (F427A) channels were tested, the HBS peptide translocated normally. Overall, peptide translocation is defined by dynamic interactions between the peptide and ϕ clamp. These dynamics require conformational flexibility, such that the peptide productively forms both extended-chain and helical states during translocation. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    Chang, Xi-Lang

    2008-10-01

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

  18. Channel Restoration Design for Meandering Rivers

    National Research Council Canada - National Science Library

    Soar, Philip

    2001-01-01

    A framework for channel restoration design is presented that attempts to bridge the divide between reconnaissance level geomorphological designs at one extreme and numerical modeling of hydrodynamics...

  19. Achromatic Cooling Channel with Li Lenses

    Energy Technology Data Exchange (ETDEWEB)

    Balbekov, V. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States)

    2002-04-29

    A linear cooling channel with Li lenses, solenoids, and 201 MHz RF cavities is considered. A special lattice design is used to minimize chromatic aberrations by suppression of several betatron resonances. Transverse emittance of muon beam decreases from 2 mm to 0.5 mm at the channel of about 110 m length. Longitudinal heating is modest, therefore transmission of the channel is rather high: 96% without decay and 90% with decay. Minimal beam emittance achievable by similar channel estimated as about 0.25 mm at surface field of Li lenses 10 T.

  20. Flow and sediment transport across oblique channels

    DEFF Research Database (Denmark)

    Hjelmager Jensen, Jacob; Madsen, Erik Østergaard; Fredsøe, Jørgen

    1998-01-01

    A 3D numerical investigation of flow across channels aligned obliquely to the main flow direction has been conducted. The applied numerical model solves the Reynolds-averaged Navier-Stokes equations using the k-ε model for turbulence closure on a curvilinear grid. Three momentum equations...... are solved, but the computational domain is 2D due to a uniformity along the channel alignment. Two important flow features arise when the flow crosses the channel: (i) the flow will be refracted in the direction of the channel alignment. This may be described by a depth-averaged model. (ii) due to shear...

  1. Calcium channel blockers and prostate cancer.

    Science.gov (United States)

    Loughlin, Kevin R

    2014-07-01

    The relationship between calcium channel blockers and prostate cancer has been an area of increased interest to investigators. Calcium channel blockers have been shown to influence cell proliferation, differentiation, and apoptosis. Clinically, the association between calcium channel blockers and the development of prostate cancer has been controversial. However, on a basic science level, there is evidence that calcium channel blockers induce cytotoxicity in androgen receptor positive cell lines and may offer an innovative strategy for the treatment of castration-resistant prostate cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Measuring Balance Across Multiple Radar Receiver Channels.

    Energy Technology Data Exchange (ETDEWEB)

    Doerry, Armin W.; Bickel, Douglas L.

    2018-03-01

    When radar receivers employ multiple channels, the general intent is for the receive channels to be as alike as possible, if not as ideal as possible. This is usually done via prudent hardware design, supplemented by system calibration. Towards this end, we require a quality metric for ascertaining the goodness of a radar channel, and the degree of match to sibling channels. We propose a relevant and useable metric to do just that. Acknowledgements This report was the result of an unfunded research and development activity.

  3. The Origins of Transmembrane Ion Channels

    Science.gov (United States)

    Pohorille, Andrew; Wilson, Michael A.

    2012-01-01

    Even though membrane proteins that mediate transport of ions and small molecules across cell walls are among the largest and least understood biopolymers in contemporary cells, it is still possible to shed light on their origins and early evolution. The central observation is that transmembrane portions of most ion channels are simply bundles of -helices. By combining results of experimental and computer simulation studies on synthetic models and natural channels, mostly of non-genomic origin, we show that the emergence of -helical channels was protobiologically plausible, and did not require highly specific amino acid sequences. Despite their simple structure, such channels could possess properties that, at the first sight, appear to require markedly larger complexity. Specifically, we explain how the antiamoebin channels, which are made of identical helices, 16 amino acids in length, achieve efficiency comparable to that of highly evolved channels. We further show that antiamoebin channels are extremely flexible, compared to modern, genetically coded channels. On the basis of our results, we propose that channels evolved further towards high structural complexity because they needed to acquire stable rigid structures and mechanisms for precise regulation rather than improve efficiency. In general, even though architectures of membrane proteins are not nearly as diverse as those of water-soluble proteins, they are sufficiently flexible to adapt readily to the functional demands arising during evolution.

  4. Customer Engagement Tool (Multi Channel Communication)

    Data.gov (United States)

    Social Security Administration — Add new infrastructure within SSA's Enterprise Architecture to allow interactions over multiple, yet to be defined, channels. Possibilities include: Provide a portal...

  5. Fuel channel closure and adapter

    International Nuclear Information System (INIS)

    Cashen, W.S.

    1985-01-01

    This invention provides a mechanical closure/actuating ram combination particularly suited for use in sealing the ends of the pressure tubes when a CANDU-type reactor is refueled. It provides a cluster that may be inserted into a fuel channel end fitting to provide at least partial closing off of a pressure tube while permitting the disengagement of the fueling machine and its withdrawal from the closure for other purposes. The invention also provides a ram/closure combination wherein the application of loading force to a deformable sealing disk is regulated by a massive load bar component forming part of the fueling machine and being therefore accessible for maintenance or replacement

  6. Channeling and related crystal effects

    International Nuclear Information System (INIS)

    Uggerhoj, Erik

    1995-01-01

    Channeling, the interaction of particles with oriented crystals, has been applied in a wide variety of scientific and technological areas. A workshop at Aarhus, Denmark, this summer highlighted progress and future directions. Radiation emission has been explored and linked to coherent bremsstrahlung and other oriented crystal radiations. Dramatic effects have been found for ultra-relativistic electrons with Lorentz factors of 105 6. Single crystals are unique for investigations of quantum electrodynamics in strong external fields because probabilities for processes in axial/ planar fields are determined by the magnitude of these fields in the particle rest frame. Erik Uggerhoj of Aarhus reported on an extensive series of experiments concerning radiation emission, pair production, and shower formation carried out at CERN by the NA43 collaboration. As Vladimir Baier of Novosibirsk and Yuri Kononets of Kurchatov noted, theoretical treatment of these interconnected radiation distributions is challenging and much work needs to be done. In general, the agreement with the CERN experiments is good, but many areas like polarization phenomena and particle production need investigation. Prominent among high energy applications is extraction from accelerators. At the workshop, Alexei Asseev reported on beam extraction using a bent crystal at Serpukhov. Konrad Elsener and Jukka Klem reviewed recent CERN SPS studies driven by the possibility of using crystals for extraction of LHC beams. Thornton Murphy of Fermilab announced a step in that direction, with a demonstration this summer of extraction from the Tevatron at 900 GeV. Bent crystal channeling is also used for handling extracted high energy beams. Niels Doble presented a beautiful example of a beam for the CERN NA48 CP-violation experiment. Yuri Chesnokov reported that beams had been deflected through angles up to 150 milliradians at Serpukhov

  7. EPICS channel access using websocket

    International Nuclear Information System (INIS)

    Uchiyama, A.; Furukawa, K.; Higurashi, Y.

    2012-01-01

    Web technology is useful as a means of widely disseminating accelerator and beam status information. For this purpose, WebOPI was implemented by SNS as a web-based system using Ajax (asynchronous JavaScript and XML) with EPICS. On the other hand, it is often necessary to control the accelerator from different locations as well as the central control room during beam operation and maintenance. However, it is not realistic to replace the GUI-based operator interface (OPI) with a Web-based system using Ajax technology because of interactive performance issue. Therefore, as a next generation OPI over the web using EPICS Channel Access (CA), we developed a client system based on WebSocket, which is a new protocol provided by the Internet Engineering Task Force (IETF) for Web-based systems. WebSocket is a web technology that provides bidirectional, full-duplex communication channels over a single TCP connection. By utilizing Node.js and the WebSocket access library called Socket.IO, a WebSocket server was implemented. Node.js is a server-side JavaScript language built on the Google V8 JavaScript Engine. In order to construct the WebSocket server as an EPICS CA client, an add-on for Node.js was developed in C/C++ using the EPICS CA library, which is included in the EPICS base. As a result, for accelerator operation, Web-based client systems became available not only in the central control room but also with various types of equipment. (author)

  8. n-Channel semiconductor materials design for organic complementary circuits.

    Science.gov (United States)

    Usta, Hakan; Facchetti, Antonio; Marks, Tobin J

    2011-07-19

    Organic semiconductors have unique properties compared to traditional inorganic materials such as amorphous or crystalline silicon. Some important advantages include their adaptability to low-temperature processing on flexible substrates, low cost, amenability to high-speed fabrication, and tunable electronic properties. These features are essential for a variety of next-generation electronic products, including low-power flexible displays, inexpensive radio frequency identification (RFID) tags, and printable sensors, among many other applications. Accordingly, the preparation of new materials based on π-conjugated organic molecules or polymers has been a central scientific and technological research focus over the past decade. Currently, p-channel (hole-transporting) materials are the leading class of organic semiconductors. In contrast, high-performance n-channel (electron-transporting) semiconductors are relatively rare, but they are of great significance for the development of plastic electronic devices such as organic field-effect transistors (OFETs). In this Account, we highlight the advances our team has made toward realizing moderately and highly electron-deficient n-channel oligomers and polymers based on oligothiophene, arylenediimide, and (bis)indenofluorene skeletons. We have synthesized and characterized a "library" of structurally related semiconductors, and we have investigated detailed structure-property relationships through optical, electrochemical, thermal, microstructural (both single-crystal and thin-film), and electrical measurements. Our results reveal highly informative correlations between structural parameters at various length scales and charge transport properties. We first discuss oligothiophenes functionalized with perfluoroalkyl and perfluoroarene substituents, which represent the initial examples of high-performance n-channel semiconductors developed in this project. The OFET characteristics of these compounds are presented with an

  9. Molecular and functional characterization of Bemisia tabaci aquaporins reveals the water channel diversity of hemipteran insects

    Science.gov (United States)

    The Middle East-Asia Minor 1 (MEAM1) whitefly, Bemisia tabaci (Gennadius) is an economically important pest of food, fiber, and ornamental crops. This pest has evolved a number of adaptations to overcome physiological challenges, including 1) the ability to regulate osmotic stress between gut lumen ...

  10. An information-guided channel-hopping scheme for block-fading channels with estimation errors

    KAUST Repository

    Yang, Yuli

    2010-12-01

    Information-guided channel-hopping technique employing multiple transmit antennas was previously proposed for supporting high data rate transmission over fading channels. This scheme achieves higher data rates than some mature schemes, such as the well-known cyclic transmit antenna selection and space-time block coding, by exploiting the independence character of multiple channels, which effectively results in having an additional information transmitting channel. Moreover, maximum likelihood decoding may be performed by simply decoupling the signals conveyed by the different mapping methods. In this paper, we investigate the achievable spectral efficiency of this scheme in the case of having channel estimation errors, with optimum pilot overhead for minimum meansquare error channel estimation, when transmitting over blockfading channels. Our numerical results further substantiate the robustness of the presented scheme, even with imperfect channel state information. ©2010 IEEE.

  11. Differential Effects of TRPA and TRPV Channels on Behaviors of

    Directory of Open Access Journals (Sweden)

    Jennifer Thies

    2016-01-01

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

  12. Experimental study on the effects of channel gap size on mixed convection heat transfer characteristics in vertical rectangular channels heated from both sides

    International Nuclear Information System (INIS)

    Sudo, Y.; Kaminaga, M.

    1990-01-01

    The effects of channel gap size on mixed forced and free convective heat transfer characteristics were experimentally investigated for water flowing near atmospheric pressure in a 750 mm long and 50 mm wide channel heated from both sides. The channel gap sizes investigated were 2.5, 6, 18 and 50 mm. Experiments were carried out for both aiding and opposing forced convective flows with a Reynolds number Re x of 4x10 to 6x10 6 and a Grashof number Gr x of 2x10 4 to 6x10 11 , where the distance x from the inlet of the channel is adopted as the characteristic length in Re x and Gr x . As for the results, the following were revealed for the parameters ranges investigated in this study. (1) When the dimensionless parameter, Gr x /Re x 21/8 Pr 1/2 is less than 10 -4 , the flow shows the nature of forced convective heat transfer for a channel with any channel gap size in both aiding and opposing flows. (2) When Gr x /Re x 21/8 Pr 1/2 is larger than 10 -2 , the flow shows the nature of free convective heat transfer for a channel with any channel gap size in both aiding and opposing flows. (3) When Gr x /Re x 21/8 Pr 1/2 is between 10 -4 and 10 -2 for the channel with a channel gap size equal to or larger than 6 mm, the heat transfer coefficients in both aiding and opposing flows become, on the average, higher than those predicted by the previous correlations for either the pure turbulent forced convection or the pure free convection, and can be expressed in simple forms with a combination of Gr x /Re x 21/8 Pr 1/2 and the previous correlation for either the pure turbulent forced convection or the free convection along a flat plate. (4) When Gr x /Re x 21/8 Pr 1/2 is between 10 -4 and 10 -2 for the channel with a channel gap size of 2.5 mm, the heat transfer coefficients in both aiding and opposing flows also become, on the average, higher than those predicted by the previous correlations for either the pure turbulent forced convection or the pure free convection. (orig./GL)

  13. The hydraulic geometry of narrow and deep channels; evidence for flow optimisation and controlled peatland growth

    Science.gov (United States)

    Nanson, Rachel A.; Nanson, Gerald C.; Huang, He Qing

    2010-04-01

    At-a-station and bankfull hydraulic geometry analyses of peatland channels at Barrington Tops, New South Wales, Australia, reveal adjustments in self-forming channels in the absence of sediment load. Using Rhodes ternary diagram, comparisons are made with hydraulic geometry data from self-forming channels carrying bedload in alluvial settings elsewhere. Despite constraints on channel depths caused at some locations by the restricted thickness of peat, most stations have cohesive, near-vertical, well-vegetated banks, and width/depth (w/d) ratios of ∼ 2 that are optimal for sediment-free flow. Because banks are strong, resist erosion and can stand nearly vertical, and depth is sometimes constrained, adjustments to discharge are accommodated largely by changes in velocity. These findings are consistent with the model of maximum flow efficiency and the overarching least action principle in open channels. The bankfull depth of freely adjusting laterally active channels in clastic alluvium is well known to be related to the thickness of floodplain alluvium and a similar condition appears to apply to these swamps that grow in situ and are formed almost entirely of organic matter. The thickness of peat in these swamps rarely exceeds that required to form a bankfull channel of optimum w/d ratio for the transport of sediment-free water. Swamp vegetation is highly dependent on proximity to the water table. To maintain a swamp-channel and associated floodplain system, the channels must flow with sufficient water much of the time; they not only offer an efficient morphology for flow but do so in a way that enables bankfull conditions to occur many times a year. They also prevent the swamp from growing above a level linked to the depth of the channel. Once the channel attains the most efficient cross section, further growth of the swamp vertically is restricted by enhanced flow velocities and limited flow depths. This means that the volume of peat in such swamps is determined

  14. The Geomorphically Effective Hydrograph: An Emerging Concept For Interpreting Channel Morphology And Evolution

    Science.gov (United States)

    Grant, G.; Hempel, L. A.; Marwan, H.; Eaton, B. C.; Lewis, S.

    2017-12-01

    of magnitude. Flume studies reveal how channel organization, defined as the tendency to form regularly-spaced pools, riffles, and bars, is related to the flashiness of the hydrograph. Drawing on these and other studies, we develop a conceptual model that accounts for hydrograph shape as an overarching control on channel development and evolution.

  15. Four-mode gating model of fast inactivation of sodium channel Nav1.2a.

    Science.gov (United States)

    Huth, Tobias; Schmidtmayer, Johann; Alzheimer, Christian; Hansen, Ulf-Peter

    2008-10-01

    Basic principles of the gating mechanisms of neuronal sodium channels, especially the fast inactivation process, were revealed by a quantitative analysis of the effects of the chemically irreversible modifying agent chloramine T. The compound is known to enhance the open probability of sodium channels by interfering with the inactivation process. The key for the deduction of structure-function relationships was obtained from the analysis of single-channel patch-clamp data, especially the finding that chloramine T-induced modification of inactivation occurred in four steps. These steps were termed modes 1-4 (four-mode gating model), and their temporal sequence was always the same. The kinetic analysis of single-channel traces with an improved two-dimensional dwell-time fit revealed the possible mechanism related to each mode. Similarities to the kinetics of the sodium channel mutant F1489Q led to the assignment of modes 1 and 2 to transient defects in the locking of the inactivation particle (hinged lid). In the third mode, the hinged lid was unable to lock permanently. Finally, in mode 4, the apparent single-channel current was reduced, which could be explained by fast gating, presumably related to the selectivity filter.

  16. XPM-induced degradation of multilevel phase modulated channel caused by neighboring NRZ modulated channels

    DEFF Research Database (Denmark)

    Jensen, Jesper Bevensee; Schiellerup, G.; Peucheret, Christophe

    2008-01-01

    The impact of XPM from NRZ modulated channels on an 8-level phase modulated channel in a WDM system was investigated. Requirements on launch power are found. 400 km transmission was achieved with negligible penalty.......The impact of XPM from NRZ modulated channels on an 8-level phase modulated channel in a WDM system was investigated. Requirements on launch power are found. 400 km transmission was achieved with negligible penalty....

  17. 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)

  18. Performance Evaluation of Closed-Loop Spatial Multiplexing Codebook Based on Indoor MIMO Channel Measurement

    Directory of Open Access Journals (Sweden)

    Junjun Gao

    2012-01-01

    Full Text Available Closed-loop MIMO technique standardized in LTE can support different layer transmissions through precoding operation to match the channel multiplexing capability. However, the performance of the limited size codebook still needs to be evaluated in real channel environment for further insights. Based on the wideband MIMO channel measurement in a typical indoor scenario, capacity loss (CL of the limited size codebook relative to perfect precoding is studied first in two extreme channel conditions. The results show that current codebook design for single layer transmission is nearly capacity lossless, and the CL will increase with the number of transmitted layers. Furthermore, the capacity improvement of better codebook selection criterions is very limited compared to CL. Then we define the maximum capacity boost achieved by frequency domain layer adaption (FDLA and investigate its sensitivity to SNR and channel condition. To survey the effect of frequency domain channel variation on MIMO-OFDM system, we define a function to measure the fluctuation levels of the key channel metrics within a subband and reveal the inherent relationship between them. Finally, a capacity floor resulted as the feedback interval increases in frequency domain.

  19. Flow structure and channel morphology at a natural confluent meander bend

    Science.gov (United States)

    Riley, James D.; Rhoads, Bruce L.

    2012-08-01

    Previous experimental, field, and modeling studies of confluence dynamics have focused mainly on junctions formed by straight channels. In contrast, natural rivers often meander and tributaries can enter meandering rivers on the outside of bends to form a junction planform known as a confluent meander bend. In this study, field measurements of three-dimensional velocity components and bed topography at a confluent meander bend reveal a complex hydrodynamic environment that responds to changes in momentum-flux ratio, while channel morphology remains relatively stable. Flow from the tributary deflects high-velocity flow and helical motion in the curving main river toward the inside of the bend, inducing bed scour and inhibiting point-bar development. The high junction angle forces the tributary flow to abruptly realign to the orientation of the downstream channel, initiating a counter-rotating helical cell over the outer portion of the bend. Two surface-convergent helical cells persist through the downstream channel, where the combined flows accelerate as the channel cross-sectional area is constricted by a bar along the downstream junction corner, precluding flow separation. Long-term stability of its planform suggests that this confluent meander bend represents a quasi-stable channel configuration. Overall, patterns of flow and channel morphology are quite different from typical patterns in most meander bends, but are generally consistent with a conceptual model of confluent meander bends derived from previous laboratory experiments and numerical modeling.

  20. Phase distribution of nitrogen-water two-phase flow in parallel micro channels

    Science.gov (United States)

    Zhou, Mi; Wang, Shuangfeng; Zhou, You

    2017-04-01

    The present work experimentally investigated the phase splitting characteristics of gas-liquid two-phase flow passing through a horizontal-oriented micro-channel device with three parallel micro-channels. The hydraulic diameters of the header and the branch channels were 0.6 and 0.4 mm, respectively. Five different liquids, including de-ionized water and sodium dodecyl sulfate (SDS) solution with different concentration were employed. Different from water, the surface tension of SDS solution applied in this work decreased with the increment of mass concentration. Through series of visual experiments, it was found that the added SDS surfactant could obviously facilitate the two-phase flow through the parallel micro channels while SDS solution with low concentration would lead to an inevitable blockage of partial outlet branches. Experimental results revealed that the two phase distribution characteristics depended highly on the inlet flow patterns and the outlet branch numbers. To be specific, at the inlet of slug flow, a large amount of gas preferred flowing into the middle branch channel while the first branch was filled with liquid. However, when the inlet flow pattern was shifted to annular flow, all of the gas passed through the second and the last branches, with a little proportion of liquid flowing into the first channel. By comparison with the experimental results obtained from a microchannel device with five parallel micro-T channels, uneven distribution of the two phase can be markedly noticed in our present work.

  1. 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.

  2. 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.

  3. Slick (Kcnt2 Sodium-Activated Potassium Channels Limit Peptidergic Nociceptor Excitability and Hyperalgesia

    Directory of Open Access Journals (Sweden)

    Danielle L Tomasello

    2017-09-01

    Full Text Available The Slick (Kcnt2 sodium-activated potassium (K Na channel is a rapidly gating and weakly voltage-dependent and sodium-dependent potassium channel with no clearly defined physiological function. Within the dorsal root ganglia (DRGs, we show Slick channels are exclusively expressed in small-sized and medium-sized calcitonin gene–related peptide (CGRP-containing DRG neurons, and a pool of channels are localized to large dense-core vesicles (LDCV-containing CGRP. We stimulated DRG neurons for CGRP release and found Slick channels contained within CGRP-positive LDCV translocated to the neuronal membrane. Behavioral studies in Slick knockout (KO mice indicated increased basal heat detection and exacerbated thermal hyperalgesia compared with wild-type littermate controls during neuropathic and chronic inflammatory pain. Electrophysiologic recordings of DRG neurons from Slick KO mice revealed that Slick channels contribute to outward current, propensity to fire action potentials (APs, and to AP properties. Our data suggest that Slick channels restrain the excitability of CGRP-containing neurons, diminishing pain behavior after inflammation and injury.

  4. Maximum-Likelihood Semiblind Equalization of Doubly Selective Channels Using the EM Algorithm

    Directory of Open Access Journals (Sweden)

    Gideon Kutz

    2010-01-01

    Full Text Available Maximum-likelihood semi-blind joint channel estimation and equalization for doubly selective channels and single-carrier systems is proposed. We model the doubly selective channel as an FIR filter where each filter tap is modeled as a linear combination of basis functions. This channel description is then integrated in an iterative scheme based on the expectation-maximization (EM principle that converges to the channel description vector estimation. We discuss the selection of the basis functions and compare various functions sets. To alleviate the problem of convergence to a local maximum, we propose an initialization scheme to the EM iterations based on a small number of pilot symbols. We further derive a pilot positioning scheme targeted to reduce the probability of convergence to a local maximum. Our pilot positioning analysis reveals that for high Doppler rates it is better to spread the pilots evenly throughout the data block (and not to group them even for frequency-selective channels. The resulting equalization algorithm is shown to be superior over previously proposed equalization schemes and to perform in many cases close to the maximum-likelihood equalizer with perfect channel knowledge. Our proposed method is also suitable for coded systems and as a building block for Turbo equalization algorithms.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Molecular mechanism of ATP binding and ion channel activation in P2X receptors

    Energy Technology Data Exchange (ETDEWEB)

    Hattori, Motoyuki; Gouaux, Eric (Oregon HSU)

    2012-10-24

    P2X receptors are trimeric ATP-activated ion channels permeable to Na{sup +}, K{sup +} and Ca{sup 2+}. The seven P2X receptor subtypes are implicated in physiological processes that include modulation of synaptic transmission, contraction of smooth muscle, secretion of chemical transmitters and regulation of immune responses. Despite the importance of P2X receptors in cellular physiology, the three-dimensional composition of the ATP-binding site, the structural mechanism of ATP-dependent ion channel gating and the architecture of the open ion channel pore are unknown. Here we report the crystal structure of the zebrafish P2X4 receptor in complex with ATP and a new structure of the apo receptor. The agonist-bound structure reveals a previously unseen ATP-binding motif and an open ion channel pore. ATP binding induces cleft closure of the nucleotide-binding pocket, flexing of the lower body {beta}-sheet and a radial expansion of the extracellular vestibule. The structural widening of the extracellular vestibule is directly coupled to the opening of the ion channel pore by way of an iris-like expansion of the transmembrane helices. The structural delineation of the ATP-binding site and the ion channel pore, together with the conformational changes associated with ion channel gating, will stimulate development of new pharmacological agents.

  7. The origin of Venusian channels: Modelling of thermal erosion by lava

    Science.gov (United States)

    Bussey, D. B. J.; Sorensen, S-A.; Guest, J. E.

    1993-01-01

    Magellan imagery has revealed that channels, apparently volcanic in origin, are abundant on the surface of Venus. There has been much debate about the origin of these channels. Are they the result of erosional (either thermal or mechanical) or constructional processes? A common characteristic of the simple sinuous channels is that they show evidence of erosion near their source and then become purely constructional, forming levees and in some cases roofing over completely. One method of showing that thermal erosion is capable of producing the type of channels seen is to use computer modeling incorporating the physical conditions on Venus and the physical characteristics of the different types of lava that may have been erupted. It is possible to calculate, relatively easily, two channel parameters. The first is the erosion rate, which combined with eruption duration, gives depth. The second is for how long after leaving the source the erupted lava will continue to be capable of thermal erosion before constructional processes dominate. Making assumptions about the rheology of the lava (e.g., assume it behaves as a Bingham plastic) along with the slope angle yields a flow velocity and therefore a distance over which thermal erosion will take place. Due to the resolution (both vertical and horizontal) of the Magellan altimetric data, the distance from the source that the channel is erosional can be much more accurately measured than the depth of the channel. This will remain the case until stereo imagery becomes available for large areas of the planet.

  8. The formate channel FocA exports the products of mixed-acid fermentation.

    Science.gov (United States)

    Lü, Wei; Du, Juan; Schwarzer, Nikola J; Gerbig-Smentek, Elke; Einsle, Oliver; Andrade, Susana L A

    2012-08-14

    Formate is a major metabolite in the anaerobic fermentation of glucose by many enterobacteria. It is translocated across cellular membranes by the pentameric ion channel/transporter FocA that, together with the nitrite channel NirC, forms the formate/nitrite transporter (FNT) family of membrane transport proteins. Here we have carried out an electrophysiological analysis of FocA from Salmonella typhimurium to characterize the channel properties and assess its specificity toward formate and other possible permeating ions. Single-channel currents for formate, hypophosphite and nitrite revealed two mechanistically distinct modes of gating that reflect different types of structural rearrangements in the transport channel of each FocA protomer. Moreover, FocA did not conduct cations or divalent anions, but the chloride anion was identified as further transported species, along with acetate, lactate and pyruvate. Formate, acetate and lactate are major end products of anaerobic mixed-acid fermentation, the pathway where FocA is predominantly required, so that this channel is ideally adapted to act as a multifunctional export protein to prevent their intracellular accumulation. Because of the high degree of conservation in the residues forming the transport channel among FNT family members, the flexibility in conducting multiple molecules is most likely a general feature of these proteins.

  9. Innate immune response of channel catfish (Ictalurus punctatus) mannose-binding lectin to channel catfish virus

    Science.gov (United States)

    The channel catfish virus (CCV) is a pathogenic herpesvirus that infects channel catfish (Ictalurus punctatus) in pond aquaculture in the Southeast USA. The innate immune protein mannose-binding lectin (MBL) could play an important role in the innate response of channel catfish by binding to the CC...

  10. Highlights for the 6th International Ion Channel Conference: ion channel structure, function, disease and therapeutics

    Directory of Open Access Journals (Sweden)

    Limei Wang

    2017-11-01

    Full Text Available To foster communication and interactions amongst international scholars and scientists in the field of ion channel research, the 6th International Ion Channel Conference (IICC-2017 was held between June 23–27, 2017 in the eastern coastal city of Qingdao, China. The meeting consisted of 450 attendees and 130 speakers and poster presenters. The program consisted of research progress, new findings and ongoing studies that were focused on (1 Ion channel structure and function; (2 Ion channel physiology and human diseases; (3 Ion channels as targets for drug discovery; (4 Technological advances in ion channel research. An insightful overview was presented on the structure and function of the mechanotransduction channel Drosophila NOMPC (No mechanoreceptor potential C, a member of the transient receptor potential (TRP channel family. Recent studies on Transmembrane protein 16 or Anoctamin-1 (TMEM16A, a member of the calcium-activated chloride channel [CaCC] family were summarized as well. In addition, topics for ion channel regulation, homeostatic feedback and brain disorders were thoroughly discussed. The presentations at the IICC-2017 offer new insights into our understanding of ion channel structures and functions, and ion channels as targets for drug discovery.

  11. Multi-reaction-channel fitting calculations in a coupled-channel ...

    Indian Academy of Sciences (India)

    Gx; 13.75.Jz; 14.20.Gk; 25.80.-e. 1. Introduction. To describe channel coupling effects we adopt the K-matrix formalism. ... Also for some of the strangeness production channels the effect of including the ρ-channel clearly affects the .... The range multiplier for the values is given on top, the name of the parameter below. 220.

  12. Optimising the Quality of Experience during Channel Zapping : The Impact of Advertisements during Channel Zapping

    NARCIS (Netherlands)

    Kooij, R.E.; Klos, V.B.; Godana, B.E.; Nicolai, F.P.; Ahmed, O.K.

    2009-01-01

    Nowadays various digital television services are available. However, the user of these services experiences longer delays than the traditional analog TV while switching from channel to channel. The digital TV operator usually displays a black screen with the channel number during zapping. However,

  13. Calcium channelopathies in inherited neurological disorders: relevance to drug screening for acquired channel disorders.

    Science.gov (United States)

    Lory, Philippe; Mezghrani, Alexandre

    2010-07-01

    Mutations located in the human genes encoding voltage-gated calcium channels are responsible for a variety of diseases referred to as calcium channelopathies, including familial hemiplegic migraine, episodic ataxia type 2, spinocerebellar ataxia type 6, childhood absence epilepsy and autism spectrum disorder, all of which are rare inherited forms of common neurological disorders. The genetic basis of these calcium channelopathies provides a unique opportunity to investigate their underlying mechanisms from the molecular to whole-organism levels. Studies of channelopathies provide insight on the relationships between channel structure and function, and reveal diverse and unexpected physiological roles for the channels. Importantly, these studies may also lead to the identification of drugs for the treatment of genetically acquired channel disorders, as well as to novel therapeutic practices. In this feature review, recent findings regarding neurological calcium channelopathies are discussed.

  14. Effect of Multimodal Pore Channels on Cargo Release from Mesoporous Silica Nanoparticles

    Directory of Open Access Journals (Sweden)

    Sushilkumar A. Jadhav

    2016-01-01

    Full Text Available Mesoporous silica nanoparticles (MSNs with multimodal pore channels were fully characterized by TEM, nitrogen adsorption-desorption, and DLS analyses. MSNs with average diameter of 200 nm with dual pore channel zones with pore diameters of 1.3–2.6 and 4 nm were tested for their use in drug delivery application. Important role of the multimodal pore systems present on MSNs on the quantitative release of model drug ibuprofen was investigated. The results obtained revealed that the release profile for ibuprofen clearly shows distinct zones which can be attributed to the respective porous channel zones present on the particles. The fluctuations in the concentration of ibuprofen during the prolonged release from MSNs were caused by the multimodal pore channel systems.

  15. Theoretical postulation of PLC channel model

    Directory of Open Access Journals (Sweden)

    Alexandru Ionuţ Chiuţă

    2009-05-01

    Full Text Available The objective of this document is to supply atheoretical basis for modelling the communicationlinks over powerlines. A comprehensive summary oftransmission properties and the noise scenario onpublic mains supply when used for data transmissionare given.Different PLC models - PLC channel, noise inPLC channel, coupling units, filters and conditioningdevices – will be created and they will be used tosimulate the PLC channel.PLC applications will have to work at veryunusual channels, solely designed for optimalelectrical power transportation, completelydisregarding signal transmission at high frequencies.It is shown that the typical properties aredescribed by transfer functions and noise scenariostypical for access and inhouse networks. The generaltransfer function for different channel types is derivedand, since an emulation system should reproducetypical classes of channels rather than singlemeasurements, the transfer function is concretisedwith reference channels. These are later serving asbasis for development of channel simulators andchannel emulators. Special attention is paid tomodelling of aperiodic impulsive noise since PLCsystems are reacting very sensitive to them and thisclass of noise has been insufficiently considered so far.

  16. Channel One Online: Advertising Not Educating.

    Science.gov (United States)

    Pasnik, Shelley

    Rather than viewing Channel One's World Wide Web site as an authentic news bureau, as the organization claims, it is better understood as an advertising delivery system. The web site is an attempt to expand Channel One's reach into schools, taking advantage of unsuspecting teachers and students who might fall prey to spurious claims. This paper…

  17. Energy detector performance in Rician fading channel

    Directory of Open Access Journals (Sweden)

    Brkić Srđan S.

    2013-01-01

    Full Text Available In this paper we analyzed the problem of detection of unknown signals in the Rician fading channel. A closed-form expression for the probability of detection is derived, followed by the numerical results. The analysis was extended to the case of cooperative sensor network in which the environment can be modelled by independent Rician fading channels.

  18. The sedimentary record of submarine channel morphodynamics

    NARCIS (Netherlands)

    de Leeuw, J.

    2017-01-01

    Submarine channels are ubiquitous on the ocean floor and are considered to be the equivalent of rivers on land. These channels are created by turbidity currents, which originate from the continental margins and which can transport sediment for thousands of kilometres into the oceans. The aim of this

  19. Polyps in continent catheterizable bladder channels.

    Science.gov (United States)

    Groth, Travis W; Mitchell, Michael E; Balcom, Anthony H

    2013-02-01

    We describe our experience with polyps encountered in bladder continent catheterizable channels. An IRB-approved retrospective study was conducted on all patients at Children's Hospital of Wisconsin with continent catheterizable channels managed by a single physician over a 16-year time period. Fifty-five patients were identified with bladder channels. During a median follow-up of 7 years (range 3-16 years), 20% (11/55) of bladder channels developed polyps. The time to diagnosis of a polyp in bladder channels from initial surgery ranged from 3 months to 8 years (median of 29 months). Fifty-five percent (6/11) of patients who developed bladder polyps were symptomatic. All patients' symptoms resolved after treatment by endoscopic resection. Forty-five percent (5/11) of polyps recurred after resection. The time of recurrence ranged from 4 months to 7 years (median of 19 months). Polyps were universally benign inflammatory granulomatous tissue. This is the first series reporting the incidence of polyps in bladder catheterizable channels. Patients with continent catheterizable bladder channels can develop symptomatic polyps in their channels, of unknown long-term significance and risk. Copyright © 2011 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

  20. Measuring vibrations in fuel channels CNE

    International Nuclear Information System (INIS)

    Martín Ghiselli, A.; Fiori, J.; Sacchi, M.; Villabrille, G.

    2013-01-01

    This paper present a description of implementation and execution of vibration measurements made at the request of NUCLEOELECTRICA ARGENTINA S.A. on the ends of the reactor fuel channels of Embalse Nuclear Power Plant to explore possible differences between the dynamic behavior of empty fuel channel and with full charge of fuel elements inside. (author)

  1. Hydrodynamic blood plasma separation in microfluidic channels

    DEFF Research Database (Denmark)

    Jouvet, Lionel

    2010-01-01

    The separation of red blood cells from plasma flowing in microchannels is possible by biophysical effects such as the Zweifach–Fung bifurcation law. In the present study, daughter channels are placed alongside a main channel such that cells and plasma are collected separately. The device is aimed...

  2. Steady turbulent flow in curved rectangular channels

    NARCIS (Netherlands)

    De Vriend, H.J.

    1979-01-01

    After the study of fully developed and developing steady laminar flow in curved channels of shallow rectangular wet cross-section (see earlier reports in this series), steady turbulent flow in such channels is investigated as a next step towards a mathematical model of the flow in shallow river

  3. Developing laminar flow in curved rectangular channels

    NARCIS (Netherlands)

    De Vriend, H.J.

    1978-01-01

    As an intermediate step between earlier investigations on fully developed laminar flow in curved channels of shallow rectancular wet cross-section and the mathematical modeling of turbulent flow in river bends, a mathematical model of developing laminar flow in such channels is investigated. The

  4. 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.

  5. Forbidden Channels and SIMP Dark Matter

    OpenAIRE

    Choi Soo-Min; Kang Yoo-Jin; Lee Hyun Min

    2018-01-01

    In this review, we focus on dark matter production from thermal freeze-out with forbidden channels and SIMP processes. We show that forbidden channels can be dominant to produce dark matter depending on the dark photon and / or dark Higgs mass compared to SIMP.

  6. Laboratory Experiments on Meandering Meltwater Channels

    Science.gov (United States)

    Fernandez, R.; Berens, J.; Parker, G.; Stark, C. P.

    2017-12-01

    Meandering channels of all scales and flowing over a wide variety of media have common planform patterns. Although the analogy in planform suggests there is a common underlying framework, the constitutive relations driving planform evolution through vertical incision/deposition and lateral migration differ from medium to medium. The driving processes in alluvial and mixed bedrock-alluvial meandering channels have been studied substantially over the last decades. However, this is not the case for meandering channels in other media such as ice or soluble rock. Here we present results from experiments conducted at the Ven Te Chow Hydrosystems Laboratory of the University of Illinois at Urbana-Champaign on meltwater meandering channels. A rivulet is carved into an ice block and water is allowed to flow at a constant discharge. Planform evolution is analyzed with time lapse imaging and complemented with rubber molds of the channel once the experiment is over. These molds give us the full 3D structure of the meandering, including incisional overhang. Vertical incision rates are measured throughout the run by taking elevations along the channel, and these measurements are complemented with analysis from the molds. We show examples of meandering of intense amplitude with deep overhangs. Features resembling scroll bars document cyclically punctuated melting. We report on lateral migration rates, incision rates, sinuosity, channel depths, channel widths, reach averaged velocities, bend wavelengths and amplitudes and compare them to values reported in the literature for alluvial rivers.

  7. Adaptive RAC codes employing statistical channel evaluation ...

    African Journals Online (AJOL)

    An adaptive encoding technique using row and column array (RAC) codes employing a different number of parity columns that depends on the channel state is proposed in this paper. The trellises of the proposed adaptive codes and a statistical channel evaluation technique employing these trellises are designed and ...

  8. Mixed convection in a baffled grooved channel

    Indian Academy of Sciences (India)

    In the present numerical work, flow structure and heat transfer characteristics are investigated in a baffled grooved channel, differentially heated from the sides. The baffle is placed vertically downward from the top wall of grooved channel geometry, with the motive of diverting outside forced flow towards the inside of the ...

  9. Pharmacological modulation of SK3 channels

    DEFF Research Database (Denmark)

    Grunnet, M; Jespersen, Thomas; Angelo, K

    2001-01-01

    -frequency adaptation, pharmacological modulation of SK channels may be of significant clinical importance. Here we report the functional expression of SK3 in HEK293 and demonstrate a broad pharmacological profile for these channels. Brain slice studies commonly employ 4-aminopyridine (4-AP) to block voltage...

  10. Ion channel model development and validation

    Science.gov (United States)

    Nelson, Peter Hugo

    2010-03-01

    The structure of the KcsA ion channel selectivity filter is used to develop three simple models of ion channel permeation. The quantitative predictions of the knock-on model are tested by comparison with experimental data from single-channel recordings of the KcsA channel. By comparison with experiment, students discover that the knock-on model can't explain saturation of ion channel current as the concentrations of the bathing solutions are increased. By inverting the energy diagram, students derive the association-dissociation model of ion channel permeation. This model predicts non-linear Michaelis-Menten saturating behavior that requires students to perform non-linear least-squares fits to the experimental data. This is done using Excel's solver feature. Students discover that this simple model does an excellent job of explaining the qualitative features of ion channel permeation but cannot account for changes in voltage sensitivity. The model is then extended to include an electrical dissociation distance. This rapid translocation model is then compared with experimental data from a wide variety of ion channels and students discover that this model also has its limitations. Support from NSF DUE 0836833 is gratefully acknowledged.

  11. Hydraulics of free overfall in -shaped channels

    Indian Academy of Sciences (India)

    R. Narasimhan (Krishtel eMaging) 1461 1996 Oct 15 13:05:22

    MS received 15 October 2001; revised 13 February 2002. Abstract. In this paper, two methods are presented to analyse the free overfall in. -shaped (equilateral triangle-shaped) channels. First, the flow upstream of a free overfall from smooth horizontal or mildly sloping -shaped channels is analysed theoretically to ...

  12. Channel selection for automatic seizure detection

    DEFF Research Database (Denmark)

    Duun-Henriksen, Jonas; Kjaer, Troels Wesenberg; Madsen, Rasmus Elsborg

    2012-01-01

    Objective: To investigate the performance of epileptic seizure detection using only a few of the recorded EEG channels and the ability of software to select these channels compared with a neurophysiologist. Methods: Fifty-nine seizures and 1419 h of interictal EEG are used for training and testing...

  13. Functional architecture of the CFTR chloride channel.

    Science.gov (United States)

    Linsdell, Paul

    2014-02-01

    Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), a member of the ATP-binding cassette (ABC) family of membrane transport proteins. CFTR is unique among ABC proteins in that it functions not as an active transporter but as an ATP-gated Cl(-) channel. As an ion channel, the function of the CFTR transmembrane channel pore that mediates Cl(-) movement has been studied in great detail. On the other hand, only low resolution structural data is available on the transmembrane parts of the protein. The structure of the channel pore has, however, been modeled on the known structure of active transporter ABC proteins. Currently, significant barriers exist to building a unified view of CFTR pore structure and function. Reconciling functional data on the channel with indirect structural data based on other proteins with very different transport functions and substrates has proven problematic. This review summarizes current structural and functional models of the CFTR Cl(-) channel pore, including a comprehensive review of previous electrophysiological investigations of channel structure and function. In addition, functional data on the three-dimensional arrangement of pore-lining helices, as well as contemporary hypotheses concerning conformational changes in the pore that occur during channel opening and closing, are discussed. Important similarities and differences between different models of the pore highlight current gaps in our knowledge of CFTR structure and function. In order to fill these gaps, structural and functional models of the membrane-spanning pore need to become better integrated.

  14. REVIEW OF WIRELESS MIMO CHANNEL MODELS | Anioke ...

    African Journals Online (AJOL)

    The need to increase spectral efficiency has led to the design of multiple antenna systems for both transmit and receive sides otherwise known as MIMO. Channel modeling forms an integral part of this design. Therefore it is very important to investigate and understand existing MIMO channel models. This paper provides a ...

  15. Voltage-gated lipid ion channels

    DEFF Research Database (Denmark)

    Blicher, Andreas; Heimburg, Thomas Rainer

    2013-01-01

    probability as a function of voltage. The voltage-dependence of the lipid pores is found comparable to that of protein channels. Lifetime distributions of open and closed events indicate that the channel open distribution does not follow exponential statistics but rather power law behavior for long open times...

  16. REVIEW OF WIRELESS MIMO CHANNEL MODELS

    African Journals Online (AJOL)

    user

    The need to increase spectral efficiency has led to the design of multiple antenna systems for both transmit and receive sides otherwise known as MIMO. Channel modeling forms an integral part of this design. Therefore it is very important to investigate and understand existing MIMO channel models. This paper provides a ...

  17. Privacy of a lossy bosonic memory channel

    International Nuclear Information System (INIS)

    Ruggeri, Giovanna; Mancini, Stefano

    2007-01-01

    We study the security of the information transmission between two honest parties realized through a lossy bosonic memory channel when losses are captured by a dishonest party. We then show that entangled inputs can enhance the private information of such a channel, which however does never overcome that of unentangled inputs in absence of memory

  18. Radio Channel Modeling in Body Area Networks

    NARCIS (Netherlands)

    An, L.; Bentum, Marinus Jan; Meijerink, Arjan; Scanlon, W.G.

    2009-01-01

    A body area network (BAN) is a network of bodyworn or implanted electronic devices, including wireless sensors which can monitor body parameters or to de- tect movements. One of the big challenges in BANs is the propagation channel modeling. Channel models can be used to understand wave propagation

  19. Radio channel modeling in body area networks

    NARCIS (Netherlands)

    An, L.; Bentum, Marinus Jan; Meijerink, Arjan; Scanlon, W.G.

    2010-01-01

    A body area network (BAN) is a network of bodyworn or implanted electronic devices, including wireless sensors which can monitor body parameters or to detect movements. One of the big challenges in BANs is the propagation channel modeling. Channel models can be used to understand wave propagation in

  20. Micromachining of buried micro channels in silicon

    NARCIS (Netherlands)

    de Boer, Meint J.; Tjerkstra, R.W.; Berenschot, Johan W.; Jansen, Henricus V.; Burger, G.J.; Burger, G.J.; Gardeniers, Johannes G.E.; Elwenspoek, Michael Curt; van den Berg, Albert

    A new method for the fabrication of micro structures for fluidic applications, such as channels, cavities, and connector holes in the bulk of silicon wafers, called buried channel technology (BCT), is presented in this paper. The micro structures are constructed by trench etching, coating of the

  1. Channel agnostic healthcare for resource constrained environments

    CSIR Research Space (South Africa)

    Alberts, Ronell

    2015-01-01

    Full Text Available . In order to reach as many end users as possible through the devices that they already own and are comfortable with, channel agnostic access is needed that would support the different mobile access channels using a variety of communications protocols...

  2. Atlantic water flow through the Faroese Channels

    Directory of Open Access Journals (Sweden)

    B. Hansen

    2017-11-01

    Full Text Available Through the Faroese Channels – the collective name for a system of channels linking the Faroe–Shetland Channel, Wyville Thomson Basin, and Faroe Bank Channel – there is a deep flow of cold waters from Arctic regions that exit the system as overflow through the Faroe Bank Channel and across the Wyville Thomson Ridge. The upper layers, in contrast, are dominated by warm, saline water masses from the southwest, termed Atlantic water. In spite of intensive research over more than a century, there are still open questions on the passage of these waters through the system with conflicting views in recent literature. Of special note is the suggestion that there is a flow of Atlantic water from the Faroe–Shetland Channel through the Faroe Bank Channel, which circles the Faroes over the slope region in a clockwise direction. Here, we combine the observational evidence from ship-borne hydrography, moored current measurements, surface drifter tracks, and satellite altimetry to address these questions and propose a general scheme for the Atlantic water flow through this channel system. We find no evidence for a continuous flow of Atlantic water from the Faroe–Shetland Channel to the Faroe Bank Channel over the Faroese slope. Rather, the southwestward-flowing water over the Faroese slope of the Faroe–Shetland Channel is totally recirculated within the combined area of the Faroe–Shetland Channel and Wyville Thomson Basin, except possibly for a small release in the form of eddies. This does not exclude a possible westward flow over the southern tip of the Faroe Shelf, but even including that, we estimate that the average volume transport of a Circum-Faroe Current does not exceed 0.5 Sv (1 Sv  =  106 m3 s−1. Also, there seems to be a persistent flow of Atlantic water from the western part of the Faroe Bank Channel into the Faroe–Shetland Channel that joins the Slope Current over the Scottish slope. These conclusions will affect

  3. Atlantic water flow through the Faroese Channels

    Science.gov (United States)

    Hansen, Bogi; Poulsen, Turið; Margretha Húsgarð Larsen, Karin; Hátún, Hjálmar; Østerhus, Svein; Darelius, Elin; Berx, Barbara; Quadfasel, Detlef; Jochumsen, Kerstin

    2017-11-01

    Through the Faroese Channels - the collective name for a system of channels linking the Faroe-Shetland Channel, Wyville Thomson Basin, and Faroe Bank Channel - there is a deep flow of cold waters from Arctic regions that exit the system as overflow through the Faroe Bank Channel and across the Wyville Thomson Ridge. The upper layers, in contrast, are dominated by warm, saline water masses from the southwest, termed Atlantic water. In spite of intensive research over more than a century, there are still open questions on the passage of these waters through the system with conflicting views in recent literature. Of special note is the suggestion that there is a flow of Atlantic water from the Faroe-Shetland Channel through the Faroe Bank Channel, which circles the Faroes over the slope region in a clockwise direction. Here, we combine the observational evidence from ship-borne hydrography, moored current measurements, surface drifter tracks, and satellite altimetry to address these questions and propose a general scheme for the Atlantic water flow through this channel system. We find no evidence for a continuous flow of Atlantic water from the Faroe-Shetland Channel to the Faroe Bank Channel over the Faroese slope. Rather, the southwestward-flowing water over the Faroese slope of the Faroe-Shetland Channel is totally recirculated within the combined area of the Faroe-Shetland Channel and Wyville Thomson Basin, except possibly for a small release in the form of eddies. This does not exclude a possible westward flow over the southern tip of the Faroe Shelf, but even including that, we estimate that the average volume transport of a Circum-Faroe Current does not exceed 0.5 Sv (1 Sv = 106 m3 s-1). Also, there seems to be a persistent flow of Atlantic water from the western part of the Faroe Bank Channel into the Faroe-Shetland Channel that joins the Slope Current over the Scottish slope. These conclusions will affect potential impacts from offshore activities in the

  4. An intermediate-conductance Ca2+-activated K+ channel is important for secretion in pancreatic duct cells

    DEFF Research Database (Denmark)

    Hayashi, Mikio; Wang, Jing; Hede, Susanne Edeling

    2012-01-01

    the molecular basis of functional K(+) channels in rodent and human pancreatic ducts (Capan-1, PANC-1, and CFPAC-1) using molecular and electrophysiological techniques. RT-PCR analysis revealed mRNAs for KCNQ1, KCNH2, KCNH5, KCNT1, and KCNT2, as well as KCNN4 coding for the following channels: KVLQT1; HERG; EAG......2; Slack; Slick; and an intermediate-conductance Ca(2+)-activated K(+) (IK) channel (K(Ca)3.1). The following functional studies were focused on the IK channel. 5,6-Dichloro-1-ethyl-1,3-dihydro-2H-benzimidazole-2-one (DC-EBIO), an activator of IK channel, increased equivalent short-circuit current...... revealed IK channels with an average conductance of 80 pS in freshly isolated rodent duct cells. These results indicated that the IK channels may, at least in part, be involved in setting the resting membrane potential. Furthermore, the IK channels are involved in anion and potassium transport...

  5. Complex Simulation Model of Mobile Fading Channel

    Directory of Open Access Journals (Sweden)

    Tomas Marek

    2005-01-01

    Full Text Available In the mobile communication environment the mobile channel is the main limiting obstacle to reach the best performance of wireless system. Modeling of the radio channel consists of two basic fading mechanisms - Long-term fading and Short-term fading. The contribution deals with simulation of complex mobile radio channel, which is the channel with all fading components. Simulation model is based on Clarke-Gans theoretical model for fading channel and is developed in MATLAB environment. Simulation results have shown very good coincidence with theory. This model was developed for hybrid adaptation 3G uplink simulator (described in this issue during the research project VEGA - 1/0140/03.

  6. Indoor MIMO Channel Measurement and Modeling

    DEFF Research Database (Denmark)

    Nielsen, Jesper Ødum; Andersen, Jørgen Bach

    2005-01-01

    Forming accurate models of the multiple input multiple output (MIMO) channel is essential both for simulation as well as understanding of the basic properties of the channel. This paper investigates different known models using measurements obtained with a 16x32 MIMO channel sounder for the 5.8GHz...... band. The measurements were carried out in various indoor scenarios including both temporal and spatial aspects of channel changes. The models considered include the so-called Kronecker model, a model proposed by Weichselberger et. al., and a model involving the full covariance matrix, the most...... accurate model for Gaussian channels. For each of the environments different sizes of both the transmitter and receiver antenna arrays are investigated, 2x2 up to 16x32. Generally it was found that in terms of capacity cumulative distribution functions (CDFs) all models fit well for small array sizes...

  7. Customers’ Perception regarding Assurance of Bancassurance Channel

    Directory of Open Access Journals (Sweden)

    Choudhury Mousumi

    2016-12-01

    Full Text Available Bancassurance has evolved as a strong distribution channel in India. Bancassurance means that the insurance company and the bank come together to offer insurance products from the counter of the banks to the bank’s customer. The present study attempts to analyse customers’ perception regarding assurance of bancassurance channel in providing insurance-related services. The study also tries to find out the impact of various demographic variables on customers’ perception regarding assurance of bancassurance channel. The study finds that customers consider bancassurance channel having high assurance in providing insurance services. It is also found in the study that there is no significant association between the demographic variables considered in the study and customers’ perception regarding assurance of bancassurance channel.

  8. An intracellular anion channel critical for pigmentation.

    Science.gov (United States)

    Bellono, Nicholas W; Escobar, Iliana E; Lefkovith, Ariel J; Marks, Michael S; Oancea, Elena

    2014-12-16

    Intracellular ion channels are essential regulators of organellar and cellular function, yet the molecular identity and physiological role of many of these channels remains elusive. In particular, no ion channel has been characterized in melanosomes, organelles that produce and store the major mammalian pigment melanin. Defects in melanosome function cause albinism, characterized by vision and pigmentation deficits, impaired retinal development, and increased susceptibility to skin and eye cancers. The most common form of albinism is caused by mutations in oculocutaneous albinism II (OCA2), a melanosome-specific transmembrane protein with unknown function. Here we used direct patch-clamp of skin and eye melanosomes to identify a novel chloride-selective anion conductance mediated by OCA2 and required for melanin production. Expression of OCA2 increases organelle pH, suggesting that the chloride channel might regulate melanin synthesis by modulating melanosome pH. Thus, a melanosomal anion channel that requires OCA2 is essential for skin and eye pigmentation.

  9. Simplifying Electron Beam Channeling in Scanning Transmission Electron Microscopy (STEM).

    Science.gov (United States)

    Wu, Ryan J; Mittal, Anudha; Odlyzko, Michael L; Mkhoyan, K Andre

    2017-08-01

    Sub-angstrom scanning transmission electron microscopy (STEM) allows quantitative column-by-column analysis of crystalline specimens via annular dark-field images. The intensity of electrons scattered from a particular location in an atomic column depends on the intensity of the electron probe at that location. Electron beam channeling causes oscillations in the STEM probe intensity during specimen propagation, which leads to differences in the beam intensity incident at different depths. Understanding the parameters that control this complex behavior is critical for interpreting experimental STEM results. In this work, theoretical analysis of the STEM probe intensity reveals that intensity oscillations during specimen propagation are regulated by changes in the beam's angular distribution. Three distinct regimes of channeling behavior are observed: the high-atomic-number (Z) regime, in which atomic scattering leads to significant angular redistribution of the beam; the low-Z regime, in which the probe's initial angular distribution controls intensity oscillations; and the intermediate-Z regime, in which the behavior is mixed. These contrasting regimes are shown to exist for a wide range of probe parameters. These results provide a new understanding of the occurrence and consequences of channeling phenomena and conditions under which their influence is strengthened or weakened by characteristics of the electron probe and sample.

  10. Stretch-activated cation channel from larval bullfrog skin

    DEFF Research Database (Denmark)

    Hillyard, Stanley D; Willumsen, Niels J; Marrero, Mario B

    2010-01-01

    Cell-attached patches from isolated epithelial cells from larval bullfrog skin revealed a cation channel that was activated by applying suction (-1 kPa to -4.5 kPa) to the pipette. Activation was characterized by an initial large current spike that rapidly attenuated to a stable value and showed...... was markedly reduced with N-methyl-D-glucamide (NMDG)-Cl Ringer's solution in the pipette. Neither amiloride nor ATP, which are known to stimulate an apical cation channel in Ussing chamber preparations of larval frog skin, produced channel activation nor did these compounds affect the response to suction....... Stretch activation was not affected by varying the pipette concentrations of Ca(2+) between 0 mmol l(-1) and 4 mmol l(-1) or by varying pH between 6.8 and 8.0. However, conductance was reduced with 4 mmol l(-1) Ca(2+). Western blot analysis of membrane homogenates from larval bullfrog and larval toad skin...

  11. Channel-Mediated Lactate Release by K+-Stimulated Astrocytes

    KAUST Repository

    Sotelo-Hitschfeld, T.

    2015-03-11

    Excitatory synaptic transmission is accompanied by a local surge in interstitial lactate that occurs despite adequate oxygen availability, a puzzling phenomenon termed aerobic glycolysis. In addition to its role as an energy substrate, recent studies have shown that lactate modulates neuronal excitability acting through various targets, including NMDA receptors and G-protein-coupled receptors specific for lactate, but little is known about the cellular and molecular mechanisms responsible for the increase in interstitial lactate. Using a panel of genetically encoded fluorescence nanosensors for energy metabolites, we show here that mouse astrocytes in culture, in cortical slices, and in vivo maintain a steady-state reservoir of lactate. The reservoir was released to the extracellular space immediately after exposure of astrocytes to a physiological rise in extracellular K+ or cell depolarization. Cell-attached patch-clamp analysis of cultured astrocytes revealed a 37 pS lactate-permeable ion channel activated by cell depolarization. The channel was modulated by lactate itself, resulting in a positive feedback loop for lactate release. A rapid fall in intracellular lactate levels was also observed in cortical astrocytes of anesthetized mice in response to local field stimulation. The existence of an astrocytic lactate reservoir and its quick mobilization via an ion channel in response to a neuronal cue provides fresh support to lactate roles in neuronal fueling and in gliotransmission.

  12. Benzocyclobutene (BCB) based neural implants with microfluidic channel.

    Science.gov (United States)

    Lee, K; He, J; Wang, L

    2004-01-01

    Benzocyclobutene (BCB) based intracortical neural implants for basic neuroscience research in animal models was fabricated, in which microfluidic channel was embedded to deliver chemical reagents. BCB presents several attractive features for chronic applications: flexibility, biocompatibility, desirable chemical and electrical properties, and can be easily manufactured using existing batch microfabrication technology; The fabricated implants have single shank with three recording sites (20 x 20 microm) and two reservoirs (inlet and outlet). The channel had large volume (40 microm width and 10 microm height), and hydrophobic surface to provide a high degree of chemical inertness. All the recording sites were positioned near the end of the shank in order to increase the probability of recording neural signals from a target volume of tissue. In vitro biocompatibility tests of fabricated implants revealed no adverse toxic effects on cultured cells. The implant with a 5 microm silicon backbone layer penetrated rat's pia without buckling, a major drawback of polymer alone. The averaged impedance value at 1 kHz was approximately 1.2 MOmega. Water flowing through the channel was observed. Depending on the amount of the driving pressure from the syringes, the delivery speed of the water was totally controlled.

  13. A computer program for analyzing channel geometry

    Science.gov (United States)

    Regan, R.S.; Schaffranek, R.W.

    1985-01-01

    The Channel Geometry Analysis Program (CGAP) provides the capability to process, analyze, and format cross-sectional data for input to flow/transport simulation models or other computational programs. CGAP allows for a variety of cross-sectional data input formats through use of variable format specification. The program accepts data from various computer media and provides for modification of machine-stored parameter values. CGAP has been devised to provide a rapid and efficient means of computing and analyzing the physical properties of an open-channel reach defined by a sequence of cross sections. CGAP 's 16 options provide a wide range of methods by which to analyze and depict a channel reach and its individual cross-sectional properties. The primary function of the program is to compute the area, width, wetted perimeter, and hydraulic radius of cross sections at successive increments of water surface elevation (stage) from data that consist of coordinate pairs of cross-channel distances and land surface or channel bottom elevations. Longitudinal rates-of-change of cross-sectional properties are also computed, as are the mean properties of a channel reach. Output products include tabular lists of cross-sectional area, channel width, wetted perimeter, hydraulic radius, average depth, and cross-sectional symmetry computed as functions of stage; plots of cross sections; plots of cross-sectional area and (or) channel width as functions of stage; tabular lists of cross-sectional area and channel width computed as functions of stage for subdivisions of a cross section; plots of cross sections in isometric projection; and plots of cross-sectional area at a fixed stage as a function of longitudinal distance along an open-channel reach. A Command Procedure Language program and Job Control Language procedure exist to facilitate program execution on the U.S. Geological Survey Prime and Amdahl computer systems respectively. (Lantz-PTT)

  14. The Challenge of Interpreting Glutamate-Receptor Ion-Channel Structures.

    Science.gov (United States)

    Mayer, Mark L

    2017-11-21

    Ion channels activated by glutamate mediate excitatory synaptic transmission in the central nervous system. Similar to other ligand-gated ion channels, their gating cycle begins with transitions from a ligand-free closed state to glutamate-bound active and desensitized states. In an attempt to reveal the molecular mechanisms underlying gating, numerous structures for glutamate receptors have been solved in complexes with agonists, antagonists, allosteric modulators, and auxiliary proteins. The embarrassingly rich library of structures emerging from this work reveals very dynamic molecules with a more complex conformational spectrum than anticipated from functional studies. Unanticipated conformations solved for complexes with competitive antagonists and a lack of understanding of the structural basis for ion channel subconductance states further highlight challenges that have yet to be addressed. Published by Elsevier Inc.

  15. Identification and characterization of Ca2+-activated K+ channels in granulosa cells of the human ovary

    Directory of Open Access Journals (Sweden)

    Berg Ulrike

    2009-04-01

    Full Text Available Abstract Background Granulosa cells (GCs represent a major endocrine compartment of the ovary producing sex steroid hormones. Recently, we identified in human GCs a Ca2+-activated K+ channel (KCa of big conductance (BKCa, which is involved in steroidogenesis. This channel is activated by intraovarian signalling molecules (e.g. acetylcholine via raised intracellular Ca2+ levels. In this study, we aimed at characterizing 1. expression and functions of KCa channels (including BKCa beta-subunits, and 2. biophysical properties of BKCa channels. Methods GCs were obtained from in vitro-fertilization patients and cultured. Expression of mRNA was determined by standard RT-PCR and protein expression in human ovarian slices was detected by immunohistochemistry. Progesterone production was measured in cell culture supernatants using ELISAs. Single channels were recorded in the inside-out configuration of the patch-clamp technique. Results We identified two KCa types in human GCs, the intermediate- (IK and the small-conductance KCa (SK. Their functionality was concluded from attenuation of human chorionic gonadotropin-stimulated progesterone production by KCa blockers (TRAM-34, apamin. Functional IK channels were also demonstrated by electrophysiological recording of single KCa channels with distinctive features. Both, IK and BKCa channels were found to be simultaneously active in individual GCs. In agreement with functional data, we identified mRNAs encoding IK, SK1, SK2 and SK3 in human GCs and proteins of IK and SK2 in corresponding human ovarian cells. Molecular characterization of the BKCa channel revealed the presence of mRNAs encoding several BKCa beta-subunits (beta2, beta3, beta4 in human GCs. The multitude of beta-subunits detected might contribute to variations in Ca2+ dependence of individual BKCa channels which we observed in electrophysiological recordings. Conclusion Functional and molecular studies indicate the presence of active IK and SK

  16. The Zambezi Channel: A new perspective on submarine channel evolution at low latitudes

    Science.gov (United States)

    Wiles, E.; Green, A.; Watkeys, M.; Jokat, W.

    2017-06-01

    Submarine channels are not stand-alone systems. They are long-lived systems modified by imperceptibly slow processes and rapid gravity flows, in some part controlled by hinterland dynamics. The submarine Zambezi Channel, within the Mozambique Channel, receives sediment from the Zambezi River catchment which has a dynamic tectonic and morphological history. Using recently collected multibeam bathymetry and PARASOUND data we discuss the geomorphology of the Zambezi Channel. Results show this system to be distinct in geomorphologic character when compared to other low-latitude submarine channels, sharing similarities with high-latitude systems. We propose a new, source-to-sink, hypothesis for the evolution of the Zambezi Channel, taking in to consideration hinterland tectonics, palaeo-lake development, river capture and rapid gravity flows. This hypothesis accounts for the unique present-day anatomy of the Zambezi Channel within the dynamic framework of the systems regional setting.

  17. PSIONplus: Accurate Sequence-Based Predictor of Ion Channels and Their Types.

    Science.gov (United States)

    Gao, Jianzhao; Cui, Wei; Sheng, Yajun; Ruan, Jishou; Kurgan, Lukasz

    2016-01-01

    Ion channels are a class of membrane proteins that attracts a significant amount of basic research, also being potential drug targets. High-throughput identification of these channels is hampered by the low levels of availability of their structures and an observation that use of sequence similarity offers limited predictive quality. Consequently, several machine learning predictors of ion channels from protein sequences that do not rely on high sequence similarity were developed. However, only one of these methods offers a wide scope by predicting ion channels, their types and four major subtypes of the voltage-gated channels. Moreover, this and other existing predictors utilize relatively simple predictive models that limit their accuracy. We propose a novel and accurate predictor of ion channels, their types and the four subtypes of the voltage-gated channels called PSIONplus. Our method combines a support vector machine model and a sequence similarity search with BLAST. The originality of PSIONplus stems from the use of a more sophisticated machine learning model that for the first time in this area utilizes evolutionary profiles and predicted secondary structure, solvent accessibility and intrinsic disorder. We empirically demonstrate that the evolutionary profiles provide the strongest predictive input among new and previously used input types. We also show that all new types of inputs contribute to the prediction. Results on an independent test dataset reveal that PSIONplus obtains relatively good predictive performance and outperforms existing methods. It secures accuracies of 85.4% and 68.3% for the prediction of ion channels and their types, respectively, and the average accuracy of 96.4% for the discrimination of the four ion channel subtypes. Standalone version of PSIONplus is freely available from https://sourceforge.net/projects/psion/.

  18. Differential distribution of the sodium-activated potassium channels slick and slack in mouse brain.

    Science.gov (United States)

    Rizzi, Sandra; Knaus, Hans-Günther; Schwarzer, Christoph

    2016-07-01

    The sodium-activated potassium channels Slick (Slo2.1, KCNT2) and Slack (Slo2.2, KCNT1) are high-conductance potassium channels of the Slo family. In neurons, Slick and Slack channels are involved in the generation of slow afterhyperpolarization, in the regulation of firing patterns, and in setting and stabilizing the resting membrane potential. The distribution and subcellular localization of Slick and Slack channels in the mouse brain have not yet been established in detail. The present study addresses this issue through in situ hybridization and immunohistochemistry. Both channels were widely distributed and exhibited distinct distribution patterns. However, in some brain regions, their expression overlapped. Intense Slick channel immunoreactivity was observed in processes, varicosities, and neuronal cell bodies of the olfactory bulb, granular zones of cortical regions, hippocampus, amygdala, lateral septal nuclei, certain hypothalamic and midbrain nuclei, and several regions of the brainstem. The Slack channel showed primarily a diffuse immunostaining pattern, and labeling of cell somata and processes was observed only occasionally. The highest Slack channel expression was detected in the olfactory bulb, lateral septal nuclei, basal ganglia, and distinct areas of the midbrain, brainstem, and cerebellar cortex. In addition, comparing our data obtained from mouse brain with a previously published study on rat brain revealed some differences in the expression and distribution of Slick and Slack channels in these species. J. Comp. Neurol. 524:2093-2116, 2016. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

  19. Structural insights into the voltage and phospholipid activation of the mammalian TPC1 channel.

    Science.gov (United States)

    She, Ji; Guo, Jiangtao; Chen, Qingfeng; Zeng, Weizhong; Jiang, Youxing; Bai, Xiao-Chen

    2018-03-21

    The organellar two-pore channel (TPC) functions as a homodimer, in which each subunit contains two homologous Shaker-like six-transmembrane (6-TM)-domain repeats. TPCs belong to the voltage-gated ion channel superfamily and are ubiquitously expressed in animals and plants. Mammalian TPC1 and TPC2 are localized at the endolysosomal membrane, and have critical roles in regulating the physiological functions of these acidic organelles. Here we present electron cryo-microscopy structures of mouse TPC1 (MmTPC1)-a voltage-dependent, phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P 2 )-activated Na + -selective channel-in both the apo closed state and ligand-bound open state. Combined with functional analysis, these structures provide comprehensive structural insights into the selectivity and gating mechanisms of mammalian TPC channels. The channel has a coin-slot-shaped ion pathway in the filter that defines the selectivity of mammalian TPCs. Only the voltage-sensing domain from the second 6-TM domain confers voltage dependence on MmTPC1. Endolysosome-specific PtdIns(3,5)P 2 binds to the first 6-TM domain and activates the channel under conditions of depolarizing membrane potential. Structural comparisons between the apo and PtdIns(3,5)P 2 -bound structures show the interplay between voltage and ligand in channel activation. These MmTPC1 structures reveal lipid binding and regulation in a 6-TM voltage-gated channel, which is of interest in light of the emerging recognition of the importance of phosphoinositide regulation of ion channels.

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

    Directory of Open Access Journals (Sweden)

    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

  1. A novel mitochondrial K(ATP) channel assay.

    Science.gov (United States)

    Wojtovich, Andrew P; Williams, David M; Karcz, Marcin K; Lopes, Coeli M B; Gray, Daniel A; Nehrke, Keith W; Brookes, Paul S

    2010-04-16

    The mitochondrial ATP sensitive potassium channel (mK(ATP)) is implicated in cardioprotection by ischemic preconditioning (IPC), but the molecular identity of the channel remains controversial. The validity of current methods to assay mK(ATP) activity is disputed. We sought to develop novel methods to assay mK(ATP) activity and its regulation. Using a thallium (Tl(+))-sensitive fluorophore, we developed a novel Tl(+) flux based assay for mK(ATP) activity, and used this assay probe several aspects of mK(ATP) function. The following key observations were made. (1) Time-dependent run down of mK(ATP) activity was reversed by phosphatidylinositol-4,5-bisphosphate (PIP(2)). (2) Dose responses of mK(ATP) to nucleotides revealed a UDP EC(50) of approximately 20 micromol/L and an ATP IC(50) of approximately 5 micromol/L. (3) The antidepressant fluoxetine (Prozac) inhibited mK(ATP) (IC(50)=2.4 micromol/L). Fluoxetine also blocked cardioprotection triggered by IPC, but did not block protection triggered by a mK(ATP)-independent stimulus. The related antidepressant zimelidine was without effect on either mK(ATP) or IPC. The Tl(+) flux mK(ATP) assay was validated by correlation with a classical mK(ATP) channel osmotic swelling assay (R(2)=0.855). The pharmacological profile of mK(ATP) (response to ATP, UDP, PIP(2), and fluoxetine) is consistent with that of an inward rectifying K(+) channel (K(IR)) and is somewhat closer to that of the K(IR)6.2 than the K(IR)6.1 isoform. The effect of fluoxetine on mK(ATP)-dependent cardioprotection has implications for the growing use of antidepressants in patients who may benefit from preconditioning.

  2. Characterization of anti-channel catfish MHC class II monoclonal antibodies

    Science.gov (United States)

    This study characterizes four monoclonal antibodies (mAb) developed against the major histocompatibility complex (MHC) class II beta chain of the channel catfish, Ictalurus punctatus. Immunoprecipitations using catfish clonal B cells revealed that each of these mAbs immunoselected proteins of appro...

  3. Time evolution of negative binomial optical field in a diffusion channel

    International Nuclear Information System (INIS)

    Liu Tang-Kun; Wu Pan-Pan; Shan Chuan-Jia; Liu Ji-Bing; Fan Hong-Yi

    2015-01-01

    We find the time evolution law of a negative binomial optical field in a diffusion channel. We reveal that by adjusting the diffusion parameter, the photon number can be controlled. Therefore, the diffusion process can be considered a quantum controlling scheme through photon addition. (paper)

  4. Dynamic Digital Channelizer Based on Spectrum Sensing.

    Science.gov (United States)

    Hu, Junpeng; Zuo, Zhen; Huang, Zhiping; Dong, Zhi

    2015-01-01

    The ability to efficiently channelize a received signal with dynamic sub-channel bandwidths is a key requirement of software defined radio (SDR) systems. The digital channelizer, which is used to split the received signal into a number of sub-channels, plays an important role in SDR systems. In this paper, a design of dynamic digital channelizer is presented. The proposed method is novel in that it employs a cosine modulated filter bank (CMFB) to divide the received signal into multiple frequency sub-bands and a spectrum sensing technique, which is mostly used in cognitive radio, is introduced to detect the presence of signal of each sub-band. The method of spectrum sensing is carried out based on the eigenvalues of covariance matrix of received signal. The ratio of maximum-minimum eigenvalue of each sub-band is vulnerable to noise fluctuation. This paper suggests an optimized method to calculate the ratio of maximum-minimum eigenvalue. The simulation results imply that the design of digital channelizer can effectively separate the received signal with dynamically changeable sub-channel signals.

  5. Renoprotective effect of calcium channel blockers

    Directory of Open Access Journals (Sweden)

    Dimković Nada

    2009-01-01

    Full Text Available The advancing chronic renal failure is at most the consequence of secondary haemodynamic and metabolic factors as intraglomerular hypertension and glomerular hypertrophy. Although tight blood pressure control is the major preventive mechanism for progressive renal failure, ACE inhibitors and angiotensin receptor blockers have some other renoprotective mechanisms beyond the blood pressure control. That is why these two groups of antihypertensive drugs traditionally have advantages in treating renal patients especially those with proteinuria over 400-1000 mg/day. Even if earlier experimental studies have shown renoprotective effect of calcium channel blockers, later clinical studies did not prove that calcium channel blockers have any advantages in renal protection over ACE inhibitors given as monotherapy or in combination with ACE inhibitors. It was explained by action of calcium channel blockers on afferent but not on efferent glomerular arterioles; a well known mechanism that leads to intraglomerular hypertension. New generations of dihydropiridine calcium channel blockers can dilate even efferent arterioles not causing unfavorable haemodynamic disturbances. This finding was confirmed in clinical studies which showed that renoprotection established by calcium channel blockers was not inferior to that of ACE inhibitors and that calcium channel blockers and ACE inhibitors have additive effect on renoprotection. Newer generation of dihydropiridine calcium channel blockers seem to offer more therapeutic possibilities in renoprotection by their dual action on afferent and efferent glomerular arterioles and, possibly by other effects beyond the blood pressure control.

  6. Molecular identity of dendritic voltage-gated sodium channels.

    Science.gov (United States)

    Lorincz, Andrea; Nusser, Zoltan

    2010-05-14

    Active invasion of the dendritic tree by action potentials (APs) generated in the axon is essential for associative synaptic plasticity and neuronal ensemble formation. In cortical pyramidal cells (PCs), this AP back-propagation is supported by dendritic voltage-gated Na+ (Nav) channels, whose molecular identity is unknown. Using a highly sensitive electron microscopic immunogold technique, we revealed the presence of the Nav1.6 subunit in hippocampal CA1 PC proximal and distal dendrites. Here, the subunit density is lower by a factor of 35 to 80 than that found in axon initial segments. A gradual decrease in Nav1.6 density along the proximodistal axis of the dendritic tree was also detected without any labeling in dendritic spines. Our results reveal the characteristic subcellular distribution of the Nav1.6 subunit, identifying this molecule as a key substrate enabling dendritic excitability.

  7. The K+ channel KZM2 is involved in stomatal movement by modulating inward K+ currents in maize guard cells.

    Science.gov (United States)

    Gao, Yong-Qiang; Wu, Wei-Hua; Wang, Yi

    2017-11-01

    Stomata are the major gates in plant leaf that allow water and gas exchange, which is essential for plant transpiration and photosynthesis. Stomatal movement is mainly controlled by the ion channels and transporters in guard cells. In Arabidopsis, the inward Shaker K + channels, such as KAT1 and KAT2, are responsible for stomatal opening. However, the characterization of inward K + channels in maize guard cells is limited. In the present study, we identified two KAT1-like Shaker K + channels, KZM2 and KZM3, which were highly expressed in maize guard cells. Subcellular analysis indicated that KZM2 and KZM3 can localize at the plasma membrane. Electrophysiological characterization in HEK293 cells revealed that both KZM2 and KZM3 were inward K + (K in ) channels, but showing distinct channel kinetics. When expressed in Xenopus oocytes, only KZM3, but not KZM2, can mediate inward K + currents. However, KZM2 can interact with KZM3 forming heteromeric K in channel. In oocytes, KZM2 inhibited KZM3 channel conductance and negatively shifted the voltage dependence of KZM3. The activation of KZM2-KZM3 heteromeric channel became slower than the KZM3 channel. Patch-clamping results showed that the inward K + currents of maize guard cells were significantly increased in the KZM2 RNAi lines. In addition, the RNAi lines exhibited faster stomatal opening after light exposure. In conclusion, the presented results demonstrate that KZM2 functions as a negative regulator to modulate the K in channels in maize guard cells. KZM2 and KZM3 may form heteromeric K in channel and control stomatal opening in maize. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  8. Distribution of cardiac sodium channels in clusters potentiates ephaptic interactions in the intercalated disc.

    Science.gov (United States)

    Hichri, Echrak; Abriel, Hugues; Kucera, Jan P

    2018-02-15

    It has been proposed that ephaptic conduction, relying on interactions between the sodium (Na + ) current and the extracellular potential in intercalated discs, might contribute to cardiac conduction when gap junctional coupling is reduced, but this mechanism is still controversial. In intercalated discs, Na + channels form clusters near gap junction plaques, but the functional significance of these clusters has never been evaluated. In HEK cells expressing cardiac Na + channels, we show that restricting the extracellular space modulates the Na + current, as predicted by corresponding simulations accounting for ephaptic effects. In a high-resolution model of the intercalated disc, clusters of Na + channels that face each other across the intercellular cleft facilitate ephaptic impulse transmission when gap junctional coupling is reduced. Thus, our simulations reveal a functional role for the clustering of Na + channels in intercalated discs, and suggest that rearrangement of these clusters in disease may influence cardiac conduction. It has been proposed that ephaptic interactions in intercalated discs, mediated by extracellular potentials, contribute to cardiac impulse propagation when gap junctional coupling is reduced. However, experiments demonstrating ephaptic effects on the cardiac Na + current (I Na ) are scarce. Furthermore, Na + channels form clusters around gap junction plaques, but the electrophysiological significance of these clusters has never been investigated. In patch clamp experiments with HEK cells stably expressing human Na v 1.5 channels, we examined how restricting the extracellular space modulates I Na elicited by an activation protocol. In parallel, we developed a high-resolution computer model of the intercalated disc to investigate how the distribution of Na + channels influences ephaptic interactions. Approaching the HEK cells to a non-conducting obstacle always increased peak I Na at step potentials near the threshold of I Na activation

  9. Interactions of gephyrotoxin with the acetylcholine receptor-ionic channel complex. I. Blockade of the ionic channel.

    Science.gov (United States)

    Souccar, C; Varanda, W A; Daly, J W; Albuquerque, E X

    1984-05-01

    The novel tricyclic alkaloid, gephyrotoxin ( GyTX ), found in the skin secretions of the frog Dendrobates histrionicus , potentiates and blocks the indirectly elicited muscle twitch in a concentration-dependent manner. GyTX prolongs the falling phase of the muscle action potential and decreases delayed rectification, supporting the idea that the alkaloid blocks the voltage-sensitive potassium conductance of the electrically excitable membrane. The peak amplitude of the end-plate currents (EPC) and miniature end-plate currents ( MEPC ) were depressed, but no significant deviation from linearity relative to control was seen in the current-voltage relationship. The decay time constant of the EPC (tau EPC) was markedly shortened by GyTX , the effect being greater at 10 degrees than at 22 degrees. The relationship between the log of tau EPC and membrane potential disclosed a linear relationship at all concentrations tested, but a progressive loss of voltage sensitivity of tau EPC was seen when GyTX concentrations were increased. Also, the plot of 1/tau EPC against GyTX concentration revealed a linear relationship. The lack of voltage and time dependence suggests that GyTX has little effect on the ACh receptor-ionic channel complex in the closed conformation. Single-channel conductance studied by means of fluctuation analysis did not change after GyTX application, but the channel lifetime decreased by about 40% at clamp potentials of -105 mV and at a toxin concentration of 7.5 microM. Repetitive nerve stimulation led to a pronounced " rundown " in the EPCs which was frequency-dependent. These findings were taken as evidence that GyTX interacts with the acetylcholine receptor complex, causing a blockade of its channel mainly in the open conformation.

  10. Electronic trade effect of marketing channels

    Directory of Open Access Journals (Sweden)

    Lovreta Stipe

    2009-01-01

    Full Text Available E-commerce has caused many significant changes in marketing channels. Consumers had obtained multiple benefits from e-commerce. In addition, it has increased the level of competition in marketing channels. However, the focus of this paper is multichannel strategy and integration of physical (store and electronic marketing channels. E-commerce has induced dynamic development of multichannel strategy. This strategy has evolved as a consequence of multichannel consumer orientation. In developed economies, consumers are multichannel entities and active marketers aim to meet their requirements by creating multichannel offer.

  11. Two-Channel Dielectric Wake Field Accelerator

    International Nuclear Information System (INIS)

    Hirshfield, Jay L.

    2012-01-01

    Experimental results are reported for test beam acceleration and deflection in a two-channel, cm-scale, rectangular dielectric-lined wakefield accelerator structure energized by a 14-MeV drive beam. The dominant waveguide mode of the structure is at ∼30 GHz, and the structure is configured to exhibit a high transformer ratio (∼12:1). Accelerated bunches in the narrow secondary channel of the structure are continuously energized via Cherenkov radiation that is emitted by a drive bunch moving in the wider primary channel. Observed energy gains and losses, transverse deflections, and changes in the test bunch charge distribution compare favorably with predictions of theory.

  12. Numerical simulation of separated flows in channels

    Science.gov (United States)

    Louda, Petr; Příhoda, Jaromír; Sváček, Petr; Kozel, Karel

    2012-04-01

    The work deals with numerical modelling of turbulent flows in channels with an expansion of the cross-section where flow separation and reattachment occur. The performance of several eddy viscosity models and an explicit algebraic Reynolds stress model (EARSM) is studied. The used test cases are flows in channels with various backward facing steps where the step is perpendicular or inclined and the top wall is parallel or deflected. Furthermore, a channel with the circular ramp is considered. The numerical solution is achieved by the finite volume method or by the finite element method. The results of both numerical approaches are compared.

  13. Estimation and Direct Equalization of Doubly Selective Channels

    NARCIS (Netherlands)

    Barhumi, I.; Leus, G.; Moonen, M.

    2006-01-01

    We propose channel estimation and direct equalization techniques for transmission over doubly selective channels. The doubly selective channel is approximated using the basis expansion model (BEM). Linear and decision feedback equalizers implemented by time-varying finite impulse response (FIR)

  14. SK2 channel expression and function in cerebellar Purkinje cells

    NARCIS (Netherlands)

    Hosy, Eric; Piochon, Claire; Teuling, Eva; Rinaldo, Lorenzo; Hansel, Christian

    2011-01-01

    Small-conductance calcium-activated K(+) channels (SK channels) regulate the excitability of neurons and their responsiveness to synaptic input patterns. SK channels contribute to the afterhyperpolarization (AHP) following action potential bursts, and curtail excitatory postsynaptic potentials

  15. Channel Measurements and Characteristics for Cooperative Positioning Applications

    DEFF Research Database (Denmark)

    Wang, Wei; Steinböck, Gerhard; Jost, Thomas

    2012-01-01

    We have conducted an indoor channel measurement campaign to characterize the propagation channel for the development of cooperative positioning algorithms. The campaign focused particularly on the characteristics of multi-link channels with applications to positioning. In this contribution we...

  16. Multi-channel software defined radio experimental evaluation and analysis

    CSIR Research Space (South Africa)

    Van der Merwe, JR

    2014-09-01

    Full Text Available Multi-channel software-defined radios (SDRs) can be utilised as inexpensive prototyping platforms for transceiver arrays. The application for multi-channel prototyping is discussed and measured results of coherent channels for both receiver...

  17. Seismic Facies of Pleistocene–Holocene Channel-fill Deposits in Bawean Island and Adjacent Waters, Southeast Java Sea

    Directory of Open Access Journals (Sweden)

    Ali Albab

    2017-08-01

    Full Text Available The late Pleistocene-Holocene stratigraphic architecture of the Bawean Island and surrounding waters, southeast Java Sea has been analyzed by using sparker seismic profiles. Geological interpretation of these seismic profiles revealed the widespread distribution of paleochannels with different shape and size in the present-day Java Sea. Two channel types can be distinguished based on its morphology: U-shaped channels in the western part and V-shaped channels in the eastern part. The stratigraphic successions were grouped into two major seismic units separated by different seismic boundaries. Characters of marine and fluvial deposits were determined based on seismic boundaries and internal reflectors. Three seismic facies can be identified within late Pleistocene – Holocene incised channel fills associated with SB2. The internal structure of incised-channels consist of chaotic reflector at the bottom, covered by parallel–sub parallel and almost reflection-free indicating the homogenous sediment deposited during the succession.

  18. Channel Planform Dynamics Monitoring and Channel Stability Assessment in Two Sediment-Rich Rivers in Taiwan

    Directory of Open Access Journals (Sweden)

    Cheng-Wei Kuo

    2017-01-01

    Full Text Available Recurrent flood events induced by typhoons are powerful agents to modify channel morphology in Taiwan’s rivers. Frequent channel migrations reflect highly sensitive valley floors and increase the risk to infrastructure and residents along rivers. Therefore, monitoring channel planforms is essential for analyzing channel stability as well as improving river management. This study analyzed annual channel changes along two sediment-rich rivers, the Zhuoshui River and the Gaoping River, from 2008 to 2015 based on satellite images of FORMOSAT-2. Channel areas were digitized from mid-catchment to river mouth (~90 km. Channel stability for reaches was assessed through analyzing the changes of river indices including braid index, active channel width, and channel activity. In general, the valley width plays a key role in braided degree, active channel width, and channel activity. These indices increase as the valley width expands whereas the braid index decreases slightly close to the river mouth due to the change of river types. This downstream pattern in the Zhuoshui River was interrupted by hydraulic construction which resulted in limited changes downstream from the weir, due to the lack of water and sediment supply. A 200-year flood, Typhoon Morakot in 2009, induced significant changes in the two rivers. The highly active landscape in Taiwan results in very sensitive channels compared to other regions. An integrated Sensitivity Index was proposed for identifying unstable reaches, which could be a useful reference for river authorities when making priorities in river regulation strategy. This study shows that satellite image monitoring coupled with river indices analysis could be an effective tool to evaluate spatial and temporal changes in channel stability in highly dynamic river systems.

  19. Dual-recycling channel management for WEEE with stochastic demand

    OpenAIRE

    Li, Chuanfa; Feng, Lipan; Wang, Xuehong

    2014-01-01

    More and more enterprises collecting e-wastes through the online recycling channel as the rapidly improving of the customer acceptance of the online recycling channel. And they are facing a problem, however, that they have to offer a higher price in the online recycling channel than the traditional recycling channel as well as reducing the searching cost by using the online recycling channel. Base on that, we incorporate a detailed consumer recycling channel choice model where the collection ...

  20. High Glucose Represses hERG K+ Channel Expression through Trafficking Inhibition

    Directory of Open Access Journals (Sweden)

    Yuan-Qi Shi

    2015-08-01

    Full Text Available Background/Aims: Abnormal QT prolongation is the most prominent cardiac electrical disturbance in patients with diabetes mellitus (DM. It is well known that the human ether-ago-go-related gene (hERG controls the rapid delayed rectifier K+ current (IKr in cardiac cells. The expression of the hERG channel is severely down-regulated in diabetic hearts, and this down-regulation is a critical contributor to the slowing of repolarization and QT prolongation. However, the intracellular mechanisms underlying the diabetes-induced hERG deficiency remain unknown. Methods: The expression of the hERG channel was assessed via western blot analysis, and the hERG current was detected with a patch-clamp technique. Results: The results of our study revealed that the expression of the hERG protein and the hERG current were substantially decreased in high-glucose-treated hERG-HEK cells. Moreover, we demonstrated that the high-glucose-mediated damage to the hERG channel depended on the down-regulation of protein levels but not the alteration of channel kinetics. These discoveries indicated that high glucose likely disrupted hERG channel trafficking. From the western blot and immunoprecipitation analyses, we found that high glucose induced trafficking inhibition through an effect on the expression of Hsp90 and its interaction with hERG. Furthermore, the high-glucose-induced inhibition of hERG channel trafficking could activate the unfolded protein response (UPR by up-regulating the expression levels of activating transcription factor-6 (ATF-6 and the ER chaperone protein calnexin. In addition, we demonstrated that 100 nM insulin up-regulated the expression of the hERG channel and rescued the hERG channel repression caused by high glucose. Conclusion: The results of our study provide the first evidence of a high-glucose-induced hERG channel deficiency resulting from the inhibition of channel trafficking. Furthermore, insulin promotes the expression of the hERG channel

  1. Superconducting muon channel at J-PARC

    International Nuclear Information System (INIS)

    Shimomura, K.; Koda, A.; Strasser, P.; Kawamura, N.; Fujimori, H.; Makimura, S.; Higemoto, W.; Nakahara, K.; Ishida, K.; Nishiyama, K.; Nagamine, K.; Miyake, Y.

    2009-01-01

    The Muon Science Laboratory at the Materials and Life Science Facility is now under construction in Japan Proton Accelerator Research Complex (J-PARC), where four types of muon channels are planned to be installed. A conventional superconducting muon channel will be installed at the first stage, which can extract surface (positive) muons and decay positive/negative muons up to 120 MeV/c, and the expected muon yield is a few 10 6 /s at 60 MeV/c (for both positive and negative). This channel will be used for various kinds of experiments like muon catalyzed fusion, μSR and nondestructive elements analysis. The present status of the superconducting muon channel is briefly reported.

  2. Subspace Analysis of Indoor UWB Channels

    Directory of Open Access Journals (Sweden)

    Rachid Saadane

    2005-03-01

    Full Text Available This work aims at characterizing the second-order statistics of indoor ultra-wideband (UWB channels using channel sounding techniques. We present measurement results for different scenarios conducted in a laboratory setting at Institut Eurécom. These are based on an eigendecomposition of the channel autocovariance matrix, which allows for the analysis of the growth in the number of significant degrees of freedom of the channel process as a function of the signaling bandwidth as well as the statistical correlation between different propagation paths. We show empirical eigenvalue distributions as a function of the signal bandwidth for both line-of-sight and non-line-of-sight situations. Furthermore, we give examples where paths from different propagation clusters (possibly arising from reflection or diffraction show strong statistical dependence.

  3. ENHANCING HSPF MODEL CHANNEL HYDRAULIC REPRESENTATION

    Science.gov (United States)

    The Hydrological Simulation Program - FORTRAN (HSPF) is a comprehensive watershed model, which employs depth-area-volume-flow relationships known as hydraulic function table (FTABLE) to represent stream channel cross-sections and reservoirs. An accurate FTABLE determination for a...

  4. Quantum channel construction with circuit quantum electrodynamics

    Science.gov (United States)

    Shen, Chao; Noh, Kyungjoo; Albert, Victor V.; Krastanov, Stefan; Devoret, M. H.; Schoelkopf, R. J.; Girvin, S. M.; Jiang, Liang

    2017-04-01

    Quantum channels can describe all transformations allowed by quantum mechanics. We adapt two existing works [S. Lloyd and L. Viola, Phys. Rev. A 65, 010101 (2001), 10.1103/PhysRevA.65.010101 and E. Andersson and D. K. L. Oi, Phys. Rev. A 77, 052104 (2008), 10.1103/PhysRevA.77.052104] to superconducting circuits, featuring a single qubit ancilla with quantum nondemolition readout and adaptive control. This construction is efficient in both ancilla dimension and circuit depth. We point out various applications of quantum channel construction, including system stabilization and quantum error correction, Markovian and exotic channel simulation, implementation of generalized quantum measurements, and more general quantum instruments. Efficient construction of arbitrary quantum channels opens up exciting new possibilities for quantum control, quantum sensing, and information processing tasks.

  5. Active Brownian motion in a narrow channel

    Science.gov (United States)

    Ao, X.; Ghosh, P. K.; Li, Y.; Schmid, G.; Hänggi, P.; Marchesoni, F.

    2014-12-01

    We review recent advances in rectification control of artificial microswimmers, also known as Janus particles, diffusing along narrow, periodically corrugated channels. The swimmer self-propulsion mechanism is modeled so as to incorporate a nonzero torque (propulsion chirality). We first summarize the effects of chirality on the autonomous current of microswimmers freely diffusing in channels of different geometries. In particular, left-right and upside-down asymmetric channels are shown to exhibit different transport properties. We then report new results on the dependence of the diffusivity of chiral microswimmers on the channel geometry and their own self-propulsion mechanism. The self-propulsion torque turns out to play a key role as a transport control parameter.

  6. Rip Channel Migration in the Nearshore

    National Research Council Canada - National Science Library

    Minetree, Courtney M

    2006-01-01

    Video imaging data generated from the Naval Postgraduate School Imaging System (NAPSIS) during November 2004 to June 2006 was analyzed to determine the location of rip channels and track their morphology...

  7. Piezo1 Channels Are Inherently Mechanosensitive

    Directory of Open Access Journals (Sweden)

    Ruhma Syeda

    2016-11-01

    Full Text Available The conversion of mechanical force to chemical signals is critical for many biological processes, including the senses of touch, pain, and hearing. Mechanosensitive ion channels play a key role in sensing the mechanical stimuli experienced by various cell types and are present in organisms from bacteria to mammals. Bacterial mechanosensitive channels are characterized thoroughly, but less is known about their counterparts in vertebrates. Piezos have been recently established as ion channels required for mechanotransduction in disparate cell types in vitro and in vivo. Overexpression of Piezos in heterologous cells gives rise to large mechanically activated currents; however, it is unclear whether Piezos are inherently mechanosensitive or rely on alternate cellular components to sense mechanical stimuli. Here, we show that mechanical perturbations of the lipid bilayer alone are sufficient to activate Piezo channels, illustrating their innate ability as molecular force transducers.

  8. Theory of Alike Selectivity in Biological Channels

    Science.gov (United States)

    Luchinsky, Dmitry G.; Gibby, Will A. T.; Kaufman, Igor Kh.; Eisenberg, Robert S.; McClintock, Peter V. E.

    2016-01-01

    We introduce a statistical mechanical model of the selectivity filter that accounts for the interaction between ions within the channel and derive Eisenman equation of the filter selectivity directly from the condition of barrier-less conduction.

  9. 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.

  10. Flame Dynamics inside Rectangular Meso scale Channels

    Science.gov (United States)

    Anwar, Muzammil; Naseer Mohammad, Abdul; Mohammad, Akram; Juhany, Khalid A.

    2018-03-01

    The present work is focused on the experimental study of flame dynamics in preheated meso-scale straight channels of various aspect ratios (2, 5, 12 and 15) and inlet dimensions.Premixed methane-air mixture were used for the reported experiments. To maintain a positive wall temperature gradient inside the channel, the lower part of the rectangular channels were heated at a constant temperature using an external electric heater. Laminar premixed flames were stabilized inside these channels. Various flame propagation modes such as concave, planar, and convex flames with respect to unburned mixture. Concave flames lead to flashback whereas convex flames lead to blowout. Increase in aspect ratio and decrease of flow velocity leads to flame flashback.

  11. Lossy Channel Games under Incomplete Information

    Directory of Open Access Journals (Sweden)

    Rayna Dimitrova

    2013-03-01

    Full Text Available In this paper we investigate lossy channel games under incomplete information, where two players operate on a finite set of unbounded FIFO channels and one player, representing a system component under consideration operates under incomplete information, while the other player, representing the component's environment is allowed to lose messages from the channels. We argue that these games are a suitable model for synthesis of communication protocols where processes communicate over unreliable channels. We show that in the case of finite message alphabets, games with safety and reachability winning conditions are decidable and finite-state observation-based strategies for the component can be effectively computed. Undecidability for (weak parity objectives follows from the undecidability of (weak parity perfect information games where only one player can lose messages.

  12. Studying Kv Channels Function using Computational Methods.

    Science.gov (United States)

    Deyawe, Audrey; Kasimova, Marina A; Delemotte, Lucie; Loussouarn, Gildas; Tarek, Mounir

    2018-01-01

    In recent years, molecular modeling techniques, combined with MD simulations, provided significant insights on voltage-gated (Kv) potassium channels intrinsic properties. Among the success stories are the highlight of molecular level details of the effects of mutations, the unraveling of several metastable intermediate states, and the influence of a particular lipid, PIP 2 , in the stability and the modulation of Kv channel function. These computational studies offered a detailed view that could not have been reached through experimental studies alone. With the increase of cross disciplinary studies, numerous experiments provided validation of these computational results, which endows an increase in the reliability of molecular modeling for the study of Kv channels. This chapter offers a description of the main techniques used to model Kv channels at the atomistic level.

  13. Multi-channel gas-delivery system

    Energy Technology Data Exchange (ETDEWEB)

    Rozenzon, Yan; Trujillo, Robert T.; Beese, Steven C.

    2016-09-13

    One embodiment of the present invention provides a gas-delivery system for delivering reaction gas to a reactor chamber. The gas-delivery system includes a main gas-inlet port for receiving reaction gases and a gas-delivery plate that includes a plurality of gas channels. A gas channel includes a plurality of gas holes for allowing the reaction gases to enter the reactor chamber from the gas channel. The gas-delivery system further includes a plurality of sub-gas lines coupling together the main gas-inlet port and the gas-delivery plate, and a respective sub-gas line is configured to deliver a portion of the received reaction gases to a corresponding gas channel.

  14. Modified MIMO Cube for Enhanced Channel Capacity

    Directory of Open Access Journals (Sweden)

    Lajos Nagy

    2012-01-01

    Full Text Available This paper deals with the optimization of MIMO antenna elements' position in modified MIMO cube for getting maximal channel capacity in indoor environment. The dependence of the channel capacity on the antenna orientation was analyzed by simulations. We have also examined the effect of the frequency dependence of the antenna system (in case of conjugate matching and nonconjugate matching for the channel capacity. Based on the simulation results in the created and measured antenna system, the antennas were at a right angle to each other. At the two chosen different structures, we measured the antenna parameters and the channel capacity. In this paper, we present the results of the measurements which clearly confirm our simulations. We will point out the differences between the two antenna structures.

  15. ULYSSES JUPITER EPAC ALL DATA CHANNELS

    Data.gov (United States)

    National Aeronautics and Space Administration — This data set contains Ulysses Energetic Particle Composition Experiment (EPAC) 1 hour averaged proton and electron flux data from all data channels submitted from...

  16. Spatial Modulation in the Underwater Acoustic Communication Channel

    National Research Council Canada - National Science Library

    Kilfoyle, Daniel

    2000-01-01

    .... The technique, termed spatial modulation, seeks to control the spatial distribution of signal energy such that multiple parallel communication channels are supported by the single, physical ocean channel...

  17. Sedimentation rate and lateral migration of tidal channels in the Lagoon of Venice (Northern Italy)

    Science.gov (United States)

    Donnici, Sandra; Madricardo, Fantina; Serandrei-Barbero, Rossana

    2017-11-01

    Tidal channels are crucial for the functioning of highly valuable coastal environments, such as estuaries and lagoons. Their properties, however, are currently less understood than those of river systems. To elucidate their past behaviour, an extensive geophysical investigation was performed to reconstruct the evolution of channels and tidal surfaces in the central part of the Lagoon of Venice (Italy) over the past 5000 years. Comparing high-spatial-resolution acoustic data and sedimentary facies analyses of 41 cores, 29 of which were radiocarbon dated, revealed the sedimentation rates in different lagoonal environments and allowed the migration of two large meanders to be reconstructed. The average sedimentation rate of the study succession in the different sedimentary environments was 1.27 mm yr-1. The lateral migration rates were 13-23 m/century. This estimate is consistent with the lateral migration rates determined by comparing aerial photographs of recent channels. Comparing the buried channels with historical and current maps showed that, in general, the number of active channels is now reduced. Their morphology was sometimes simplified by artificial interventions. An understanding of the impact of the artificial interventions over time is useful for the management and conservation of tidal environments, particularly for the Lagoon of Venice, where management authorities are currently debating the possible deepening and rectification of large navigation channels.

  18. Scorpion Toxins Specific for Potassium (K+ Channels: A Historical Overview of Peptide Bioengineering

    Directory of Open Access Journals (Sweden)

    Zachary L. Bergeron

    2012-11-01

    Full Text Available Scorpion toxins have been central to the investigation and understanding of the physiological role of potassium (K+ channels and their expansive function in membrane biophysics. As highly specific probes, toxins have revealed a great deal about channel structure and the correlation between mutations, altered regulation and a number of human pathologies. Radio- and fluorescently-labeled toxin isoforms have contributed to localization studies of channel subtypes in expressing cells, and have been further used in competitive displacement assays for the identification of additional novel ligands for use in research and medicine. Chimeric toxins have been designed from multiple peptide scaffolds to probe channel isoform specificity, while advanced epitope chimerization has aided in the development of novel molecular therapeutics. Peptide backbone cyclization has been utilized to enhance therapeutic efficiency by augmenting serum stability and toxin half-life in vivo as a number of K+-channel isoforms have been identified with essential roles in disease states ranging from HIV, T-cell mediated autoimmune disease and hypertension to various cardiac arrhythmias and Malaria. Bioengineered scorpion toxins have been monumental to the evolution of channel science, and are now serving as templates for the development of invaluable experimental molecular therapeutics.

  19. RIM determines Ca2+ channel density and vesicle docking at the presynaptic active zone

    Science.gov (United States)

    Han, Yunyun; Kaeser, Pascal S.; Südhof, Thomas C.; Schneggenburger, Ralf

    2012-01-01

    At presynaptic active zones, neurotransmitter release is initiated by the opening of voltage-gated Ca2+ channels close to docked vesicles. The mechanisms that enrich Ca2+ channels at active zones are, however, largely unknown, possibly because of the limited presynaptic accessibility of most synapses. Here, we have established a Cre-lox based conditional knock-out approach at a presynaptically accessible CNS synapse, the calyx of Held, to directly study the functions of RIM proteins. Removal of all RIM1/2 isoforms strongly reduced the presynaptic Ca2+ channel density, revealing a new role of RIM proteins in Ca2+ channel targeting. Removal of RIMs also reduced the readily-releasable pool, paralleled by a similar reduction of the number of docked vesicles, and the Ca2+ channel - vesicle coupling was decreased. Thus, RIM proteins co-ordinately regulate key functions for fast transmitter release: enabling a high presynaptic Ca2+ channel density, and vesicle docking at the active zone. PMID:21262468

  20. Cortisone Dissociates the Shaker Family K Channels from their Beta Subunit

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Y.; Weng, J; Kabaleeswaran, V; Li, H; Cao, Y; Bholse, R; Zhou, M

    2008-01-01

    The Shaker family voltage-dependent potassium channels (Kv1) are expressed in a wide variety of cells and are essential for cellular excitability. In humans, loss-of-function mutations of Kv1 channels lead to hyperexcitability and are directly linked to episodic ataxia and atrial fibrillation. All Kv1 channels assemble with {Beta} subunits (Kv{Beta}s), and certain Kv{Beta}s, for example Kv{Beta}1, have an N-terminal segment that closes the channel by the N-type inactivation mechanism. In principle, dissociation of Kv{Beta}1, although never reported, should eliminate inactivation and thus potentiate Kv1 current. We found that cortisone increases rat Kv1 channel activity by binding to Kv{Beta}1. A crystal structure of the K{Beta}v-cortisone complex was solved to 1.82-{angstrom}resolution and revealed novel cortisone binding sites. Further studies demonstrated that cortisone promotes dissociation of Kv{Beta}. The new mode of channel modulation may be explored by native or synthetic ligands to fine-tune cellular excitability.