Sample records for channel task-1 contributions

  1. Genetic variation in the two-pore domain potassium channel, TASK-1, may contribute to an atrial substrate for arrhythmogenesis

    DEFF Research Database (Denmark)

    Liang, Bo; Soka, Magdalena; Christensen, Alex Horby;


    The two-pore domain potassium channel, K2P3.1 (TASK-1) modulates background conductance in isolated human atrial cardiomyocytes and has been proposed as a potential drug target for atrial fibrillation (AF). TASK-1 knockout mice have a predominantly ventricular phenotype however, and effects of TASK......-1 inactivation on atrial structure and function have yet to be demonstrated in vivo. The extent to which genetic variation in KCNK3, that encodes TASK-1, might be a determinant of susceptibility to AF is also unknown. To address these questions, we first evaluated the effects of transient knockdown...... diameter (p=0.01) when compared with control-injected embryos. We next performed genetic screening of KCNK3 in two independent AF cohorts (373 subjects) and identified three novel KCNK3 variants. Two of these variants, present in one proband with familial AF, were located at adjacent nucleotides...

  2. Kv1.5 blockers preferentially inhibit TASK-1 channels: TASK-1 as a target against atrial fibrillation and obstructive sleep apnea? (United States)

    Kiper, Aytug K; Rinné, Susanne; Rolfes, Caroline; Ramírez, David; Seebohm, Guiscard; Netter, Michael F; González, Wendy; Decher, Niels


    Atrial fibrillation and obstructive sleep apnea are responsible for significant morbidity and mortality in the industrialized world. There is a high medical need for novel drugs against both diseases, and here, Kv1.5 channels have emerged as promising drug targets. In humans, TASK-1 has an atrium-specific expression and TASK-1 is also abundantly expressed in the hypoglossal motor nucleus. We asked whether known Kv1.5 channel blockers, effective against atrial fibrillation and/or obstructive sleep apnea, modulate TASK-1 channels. Therefore, we tested Kv1.5 blockers with different chemical structures for their TASK-1 affinity, utilizing two-electrode voltage clamp (TEVC) recordings in Xenopus oocytes. Despite the low structural conservation of Kv1.5 and TASK-1 channels, we found all Kv1.5 blockers analyzed to be even more effective on TASK-1 than on Kv1.5. For instance, the half-maximal inhibitory concentration (IC50) values of AVE0118 and AVE1231 (A293) were 10- and 43-fold lower on TASK-1. Also for MSD-D, ICAGEN-4, S20951 (A1899), and S9947, the IC50 values were 1.4- to 70-fold lower than for Kv1.5. To describe this phenomenon on a molecular level, we used in silico models and identified unexpected structural similarities between the two drug binding sites. Kv1.5 blockers, like AVE0118 and AVE1231, which are promising drugs against atrial fibrillation or obstructive sleep apnea, are in fact potent TASK-1 blockers. Accordingly, block of TASK-1 channels by these compounds might contribute to the clinical effectiveness of these drugs. The higher affinity of these blockers for TASK-1 channels suggests that TASK-1 might be an unrecognized molecular target of Kv1.5 blockers effective in atrial fibrillation or obstructive sleep apnea.

  3. The two-pore domain K+ channel TASK-1 is closely associated with brain barriers and meninges. (United States)

    Kanjhan, Refik; Pow, David V; Noakes, Peter G; Bellingham, Mark C


    Impairment of the blood-brain barrier (BBB), the blood-cerebrospinal fluid (CSF) barrier and brain-CSF barrier has been implicated in neuropathology of several brain disorders, such as amyotrophic lateral sclerosis, cerebral edema, multiple sclerosis, neural inflammation, ischemia and stroke. Two-pore domain weakly inward rectifying K+ channel (TWIK)-related acid-sensitive potassium (TASK)-1 channels (K2p3.1; KCNK3) are among the targets that contribute to the development of these pathologies. For example TASK-1 activity is inhibited by acidification, ischemia, hypoxia and several signaling molecules released under pathologic conditions. We have used immuno-histochemistry to examine the distribution of the TASK-1 protein in structures associated with the BBB, blood-CSF barrier, brain-CSF barrier, and in the meninges of adult rat. Dense TASK-1 immuno-reactivity (TASK-1-IR) was observed in ependymal cells lining the fourth ventricle at the brain-CSF interface, in glial cells that ensheath the walls of blood vessels at the glio-vascular interface, and in the meninges. In these structures, TASK-1-IR often co-localized with glial fibrillary associated protein (GFAP) or vimentin. This study provides anatomical evidence for localization of TASK-1 K+ channels in cells that segregate distinct fluid compartments within and surrounding the brain. We suggest that TASK-1 channels, in coordination with other ion channels (e.g., aquaporins and chloride channels) and transporters (e.g., Na+-K+-ATPase and Na+-K+-2Cl⁻ and by virtue of its heterogeneous distribution, may differentially contribute to the varying levels of K+ vital for cellular function in these compartments. Our findings are likely to be relevant to recently reported roles of TASK-1 in cerebral ischemia, stroke and inflammatory brain disorders.

  4. Cooperative endocytosis of the endosomal SNARE protein syntaxin-8 and the potassium channel TASK-1. (United States)

    Renigunta, Vijay; Fischer, Thomas; Zuzarte, Marylou; Kling, Stefan; Zou, Xinle; Siebert, Kai; Limberg, Maren M; Rinné, Susanne; Decher, Niels; Schlichthörl, Günter; Daut, Jürgen


    The endosomal SNARE protein syntaxin-8 interacts with the acid-sensitive potassium channel TASK-1. The functional relevance of this interaction was studied by heterologous expression of these proteins (and mutants thereof) in Xenopus oocytes and in mammalian cell lines. Coexpression of syntaxin-8 caused a fourfold reduction in TASK-1 current, a corresponding reduction in the expression of TASK-1 at the cell surface, and a marked increase in the rate of endocytosis of the channel. TASK-1 and syntaxin-8 colocalized in the early endosomal compartment, as indicated by the endosomal markers 2xFYVE and rab5. The stimulatory effect of the SNARE protein on the endocytosis of the channel was abolished when both an endocytosis signal in TASK-1 and an endocytosis signal in syntaxin-8 were mutated. A syntaxin-8 mutant that cannot assemble with other SNARE proteins had virtually the same effect as wild-type syntaxin-8. Total internal reflection fluorescence microscopy showed formation and endocytosis of vesicles containing fluorescence-tagged clathrin, TASK-1, and/or syntaxin-8. Our results suggest that the unassembled form of syntaxin-8 and the potassium channel TASK-1 are internalized via clathrin-mediated endocytosis in a cooperative manner. This implies that syntaxin-8 regulates the endocytosis of TASK-1. Our study supports the idea that endosomal SNARE proteins can have functions unrelated to membrane fusion.

  5. The pungent substances piperine, capsaicin, 6-gingerol and polygodial inhibit the human two-pore domain potassium channels TASK-1, TASK-3 and TRESK. (United States)

    Beltrán, Leopoldo R; Dawid, Corinna; Beltrán, Madeline; Gisselmann, Guenter; Degenhardt, Katharina; Mathie, Klaus; Hofmann, Thomas; Hatt, Hanns


    For a long time, the focus of trigeminal chemoperception has rested almost exclusively on TRP channels. However, two-pore domain (K2P) potassium channels have recently been identified as targets for substances associated with typical trigeminal sensations, such as numbing and tingling. In addition, they have been shown to be modulated by several TRP agonists. We investigated whether the pungent substances piperine, capsaicin, 6-gingerol and polygodial have an effect on human K2P channels. For this purpose, we evaluated the effects of these pungent substances on both wild-type and mutant K2P channels by means of two-electrode voltage-clamp experiments using Xenopus laevis oocytes. All four pungent substances were found to inhibit the basal activity of TASK-1 (K2P 3.1), TASK-3 (K2P 9.1), and TRESK (K2P 18.1) channels. This inhibitory effect was dose-dependent and, with the exception of polygodial on TASK-1, fully reversible. However, only piperine exhibited an IC50 similar to its reported EC50 on TRP channels. Finally, we observed for TASK-3 that mutating H98 to E markedly decreased the inhibition induced by piperine, capsaicin, and 6-gingerol, but not by polygodial. Our data contribute to the relatively sparse knowledge concerning the pharmacology of K2P channels and also raise the question of whether K2P channels could be involved in the pungency perception of piperine.

  6. The pungent substances piperine, capsaicin, 6-gingerol and polygodial inhibit the human two-pore domain potassium channels TASK-1, TASK-3 and TRESK

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    Leopoldo Raul Beltran


    Full Text Available For a long time, the focus of trigeminal chemoperception has rested almost exclusively on TRP channels. However, two-pore domain (K2P potassium channels have recently been identified as targets for substances associated with typical trigeminal sensations, such as numbing and tingling. In addition, they have been shown to be modulated by several TRP agonists. We investigated whether the pungent substances piperine, capsaicin, 6-gingerol and polygodial have an effect on human K2P channels. For this purpose, we evaluated the effects of these pungent substances on both wild-type and mutant K2P channels by means of two-electrode voltage-clamp experiments using Xenopus laevis oocytes. All four pungent substances were found to inhibit the basal activity of TASK-1 (K2P 3.1, TASK-3 (K2P 9.1, and TRESK (K2P 18.1 channels. This inhibitory effect was dose-dependent and, with the exception of polygodial on TASK-1, fully reversible. However, only piperine exhibited an IC50 similar to its reported EC50 on TRP channels. Finally, we observed for TASK-3 that mutating H98 to E markedly decreases the inhibition induced by piperine, capsaicin, and 6-gingerol, but not by polygodial. Our data contribute to the relatively sparse knowledge concerning the pharmacology of K2P channels and also raise the question of whether K2P channels could be involved in the pungency perception of piperine.

  7. A specific two-pore domain potassium channel blocker defines the structure of the TASK-1 open pore. (United States)

    Streit, Anne K; Netter, Michael F; Kempf, Franca; Walecki, Magdalena; Rinné, Susanne; Bollepalli, Murali K; Preisig-Müller, Regina; Renigunta, Vijay; Daut, Jürgen; Baukrowitz, Thomas; Sansom, Mark S P; Stansfeld, Phillip J; Decher, Niels


    Two-pore domain potassium (K(2P)) channels play a key role in setting the membrane potential of excitable cells. Despite their role as putative targets for drugs and general anesthetics, little is known about the structure and the drug binding site of K(2P) channels. We describe A1899 as a potent and highly selective blocker of the K(2P) channel TASK-1. As A1899 acts as an open-channel blocker and binds to residues forming the wall of the central cavity, the drug was used to further our understanding of the channel pore. Using alanine mutagenesis screens, we have identified residues in both pore loops, the M2 and M4 segments, and the halothane response element to form the drug binding site of TASK-1. Our experimental data were used to validate a K(2P) open-pore homology model of TASK-1, providing structural insights for future rational design of drugs targeting K(2P) channels.

  8. A Specific Two-pore Domain Potassium Channel Blocker Defines the Structure of the TASK-1 Open Pore* (United States)

    Streit, Anne K.; Netter, Michael F.; Kempf, Franca; Walecki, Magdalena; Rinné, Susanne; Bollepalli, Murali K.; Preisig-Müller, Regina; Renigunta, Vijay; Daut, Jürgen; Baukrowitz, Thomas; Sansom, Mark S. P.; Stansfeld, Phillip J.; Decher, Niels


    Two-pore domain potassium (K2P) channels play a key role in setting the membrane potential of excitable cells. Despite their role as putative targets for drugs and general anesthetics, little is known about the structure and the drug binding site of K2P channels. We describe A1899 as a potent and highly selective blocker of the K2P channel TASK-1. As A1899 acts as an open-channel blocker and binds to residues forming the wall of the central cavity, the drug was used to further our understanding of the channel pore. Using alanine mutagenesis screens, we have identified residues in both pore loops, the M2 and M4 segments, and the halothane response element to form the drug binding site of TASK-1. Our experimental data were used to validate a K2P open-pore homology model of TASK-1, providing structural insights for future rational design of drugs targeting K2P channels. PMID:21362619

  9. Functional and molecular identification of a TASK-1 potassium channel regulating chloride secretion through CFTR channels in the shark rectal gland: implications for cystic fibrosis. (United States)

    Telles, Connor J; Decker, Sarah E; Motley, William W; Peters, Alexander W; Mehr, Ali Poyan; Frizzell, Raymond A; Forrest, John N


    In the shark rectal gland (SRG), apical chloride secretion through CFTR channels is electrically coupled to a basolateral K(+) conductance whose type and molecular identity are unknown. We performed studies in the perfused SRG with 17 K(+) channel inhibitors to begin this search. Maximal chloride secretion was markedly inhibited by low-perfusate pH, bupivicaine, anandamide, zinc, quinidine, and quinine, consistent with the properties of an acid-sensitive, four-transmembrane, two-pore-domain K(+) channel (4TM-K2P). Using PCR with degenerate primers to this family, we identified a TASK-1 fragment in shark rectal gland, brain, gill, and kidney. Using 5' and 3' rapid amplification of cDNA ends PCR and genomic walking, we cloned the full-length shark gene (1,282 bp), whose open reading frame encodes a protein of 375 amino acids that was 80% identical to the human TASK-1 protein. We expressed shark and human TASK-1 cRNA in Xenopus oocytes and characterized these channels using two-electrode voltage clamping. Both channels had identical current-voltage relationships (outward rectifying) and a reversal potential of -90 mV. Both were inhibited by quinine, bupivicaine, and acidic pH. The pKa for current inhibition was 7.75 for shark TASK-1 vs. 7.37 for human TASK-1, values similar to the arterial pH for each species. We identified this protein in SRG by Western blot and confocal immunofluorescent microscopy and detected the protein in SRG and human airway cells. Shark TASK-1 is the major K(+) channel coupled to chloride secretion in the SRG, is the oldest 4TM 2P family member identified, and is the first TASK-1 channel identified to play a role in setting the driving force for chloride secretion in epithelia. The detection of this potassium channel in mammalian lung tissue has implications for human biology and disease.

  10. Molecular modeling and structural analysis of two-pore domain potassium channels TASK1 interactions with the blocker A1899

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    David Mauricio Ramirez


    Full Text Available A1899 is a potent and highly selective blocker of the Two-pore domain potassium (K2P channel TASK-1, it acts as an antagonist blocking the K+ flux and binds to TASK-1 in the inner cavity and shows an activity in nanomolar order. This drug travels through the central cavity and finally binds in the bottom of the selectivity filter with some threonines and waters molecules forming a H-bond network and several hydrophobic interactions. Using alanine mutagenesis screens the binding site was identify involving residues in the P1 and P2 pore loops, the M2 and M4 transmembrane segments, and the halothane response element; mutations were introduced in the human TASK-1 (KCNK3, NM_002246 expressed in Oocytes from anesthetized Xenopus laevis frogs. Based in molecular modeling and structural analysis as such as molecular docking and binding free energy calculations a pose was suggested using a TASK-1 homology models. Recently, various K2P crystal structures have been obtained. We want redefined – from a structural point of view – the binding mode of A1899 in TASK-1 homology models using as a template the K2P crystal structures. By computational structural analysis we describe the molecular basis of the A1899 binding mode, how A1899 travel to its binding site and suggest an interacting pose (Figure 1. after 100 ns of molecular dynamics simulation (MDs we found an intra H-Bond (80% of the total MDs, a H-Bond whit Thr93 (42% of the total MDs, a pi-pi stacking interaction between a ring and Phe125 (88% of the total MDs and several water bridges. Our experimental and computational results allow the molecular understanding of the structural binding mechanism of the selective blocker A1899 to TASK-1 channels. We identified the structural common and divergent features of TASK-1 channel through our theoretical and experimental studies of A1899 drug action.

  11. Acid-sensing ion channels contribute to neurotoxicity. (United States)

    Chu, Xiang-Ping; Grasing, Kenneth A; Wang, John Q


    Acidosis that occurs under pathological conditions not only affects intracellular signaling molecules, but also directly activates a unique family of ligand-gated ion channels: acid-sensing ion channels (ASICs). ASICs are widely expressed throughout the central and peripheral nervous systems and play roles in pain sensation, learning and memory, and fear conditioning. Overactivation of ASICs contributes to neurodegenerative diseases such as ischemic brain/spinal cord injury, multiple sclerosis, Parkinson's disease, and Huntington's disease. Thus, targeting ASICs might be a potential therapeutic strategy for these conditions. This mini-review focuses on the electrophysiology and pharmacology of ASICs and roles of ASICs in neuronal toxicity.

  12. Contributions of Kv3 channels to neuronal excitability. (United States)

    Rudy, B; Chow, A; Lau, D; Amarillo, Y; Ozaita, A; Saganich, M; Moreno, H; Nadal, M S; Hernandez-Pineda, R; Hernandez-Cruz, A; Erisir, A; Leonard, C; Vega-Saenz de Miera, E


    Four mammalian Kv3 genes have been identified, each of which generates, by alternative splicing, multiple protein products differing in their C-terminal sequence. Products of the Kv3.1 and Kv3.2 genes express similar delayed-rectifier type currents in heterologous expression systems, while Kv3.3 and Kv3.4 proteins express A-type currents. All Kv3 currents activate relatively fast at voltages more positive than -10 mV, and deactivate very fast. The distribution of Kv3 mRNAs in the rodent CNS was studied by in situ hybridization, and the localization of Kv3.1 and Kv3.2 proteins has been studied by immunohistochemistry. Most Kv3.2 mRNAs (approximately 90%) are present in thalamic-relay neurons throughout the dorsal thalamus. The protein is expressed mainly in the axons and terminals of these neurons. Kv3.2 channels are thought to be important for thalamocortical signal transmission. Kv3.1 and Kv3.2 proteins are coexpressed in some neuronal populations such as in fast-spiking interneurons of the cortex and hippocampus, and neurons in the globus pallidus. Coprecipitation studies suggest that in these cells the two types of protein form heteromeric channels. Kv3 proteins appear to mediate, in native neurons, similar currents to those seen in heterologous expression systems. The activation voltage and fast deactivation rates are believed to allow these channels to help repolarize action potentials fast without affecting the threshold for action potential generation. The fast deactivating current generates a quickly recovering after hyperpolarization, thus maximizing the rate of recovery of Na+ channel inactivation without contributing to an increase in the duration of the refractory period. These properties are believed to contribute to the ability of neurons to fire at high frequencies and to help regulate the fidelity of synaptic transmission. Experimental evidence has now become available showing that Kv3.1-Kv3.2 channels play critical roles in the generation of fast

  13. TASK-1 and TASK-3 may form heterodimers in human atrial cardiomyocytes. (United States)

    Rinné, Susanne; Kiper, Aytug K; Schlichthörl, Günter; Dittmann, Sven; Netter, Michael F; Limberg, Sven H; Silbernagel, Nicole; Zuzarte, Marylou; Moosdorf, Rainer; Wulf, Hinnerk; Schulze-Bahr, Eric; Rolfes, Caroline; Decher, Niels


    TASK-1 channels have emerged as promising drug targets against atrial fibrillation, the most common arrhythmia in the elderly. While TASK-3, the closest relative of TASK-1, was previously not described in cardiac tissue, we found a very prominent expression of TASK-3 in right human auricles. Immunocytochemistry experiments of human right auricular cardiomyocytes showed that TASK-3 is primarily localized at the plasma membrane. Single-channel recordings of right human auricles in the cell-attached mode, using divalent-cation-free solutions, revealed a TASK-1-like channel with a single-channel conductance of about 30pS. While homomeric TASK-3 channels were not found, we observed an intermediate single-channel conductance of about 55pS, possibly reflecting the heteromeric channel formed by TASK-1 and TASK-3. Subsequent experiments with TASK-1/TASK-3 tandem channels or with co-expressed TASK-1 and TASK-3 channels in HEK293 cells or Xenopus oocytes, supported that the 55pS channels observed in right auricles have electrophysiological characteristics of TASK-1/TASK-3 heteromers. In addition, co-expression experiments and single-channel recordings suggest that heteromeric TASK-1/TASK-3 channels have a predominant surface expression and a reduced affinity for TASK-1 blockers. In summary, the evidence for heteromeric TASK-1/TASK-3 channel complexes together with an altered pharmacologic response to TASK-1 blockers in vitro is likely to have further impact for studies isolating ITASK-1 from cardiomyocytes and for the development of drugs specifically targeting TASK-1 in atrial fibrillation treatment.


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    Samuel eGoodchild


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

  15. Contributions in Radio Channel Sounding, Modeling, and Estimation

    DEFF Research Database (Denmark)

    Pedersen, Troels


    the necessary and sufficient conditions for  spatio-temporal apertures to minimize the Cramer-Rao lower bound on the joint bi-direction and Doppler frequency estimation. The spatio-temporal aperture also impacts on the accuracy of MIMO-capacity estimation from measurements impaired by colored phase noise. We......, than corresponding results from literature. These findings indicate that the per-path directional spreads (or cluster spreads) assumed in standard models are set too large. Finally, we propose a model of the specular-to-diffuse transition observed in measurements of reverberant channels.  The model...

  16. The unique contribution of ion channels to platelet and megakaryocyte function. (United States)

    Mahaut-Smith, M P


    Ion channels are transmembrane proteins that play ubiquitous roles in cellular homeostasis and activation. In addition to their recognized role in the regulation of ionic permeability and thus membrane potential, some channel proteins possess intrinsic kinase activity, directly interact with integrins or are permeable to molecules up to ≈1000 Da. The small size and anuclear nature of the platelet has often hindered progress in understanding the role of specific ion channels in hemostasis, thrombosis and other platelet-dependent events. However, with the aid of transgenic mice and 'surrogate' patch clamp recordings from primary megakaryocytes, important unique contributions to platelet function have been identified for several classes of ion channel. Examples include ATP-gated P2X1 channels, Orai1 store-operated Ca2+ channels, voltage-gated Kv1.3 channels, AMPA and kainate glutamate receptors and connexin gap junction channels. Furthermore, evidence exists that some ion channels, such as NMDA glutamate receptors, contribute to megakaryocyte development. This review examines the evidence for expression of a range of ion channels in the platelet and its progenitor cell, and highlights the distinct roles that these proteins may play in health and disease.

  17. Rapport in Negotiation: The Contribution of the Verbal Channel (United States)

    Bronstein, Ilan; Nelson, Noa; Livnat, Zohar; Ben-Ari, Rachel


    This study examined the contribution of verbal behavior to the creation of rapport in negotiation, while methodologically addressing the issue of dependence between dyadic measures, which is inherent to the concept of rapport, with the Actor-Partner Interdependence model. The approach adopted is substantially different from that of past research,…


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    LUCA Cornelia


    Full Text Available Semi products used in the shoe manufacturing are mostly made through polymer blend injecting in moulds. The injection moulds are designed with one or more cavities. When the mould has only one cavity the injection is made straight in cavity through one canal or through one main canal and more auxiliary canals. In multiple cavity injection always uses the primary canal and more auxiliary canals. The cavities of the mould may be posted symmetrically or asymmetrically refer ring to the main canal. The correct dimensioning of the injection system determines the quality of the injected pieces and the productivity of the manufacturing process. In the same time, the injection parameters have a lot of values depending of the injected plastic mass. The aspects of the designing of the moulds for shoe manufacturing are complex. The paper presents some contributions in the designing of the injection systems of the mould cavities in shoe industry. It develops some aspects about the optimization of the principal and secondary injection canals placing confronted by the mould cavities, some aspects about the injection canals placing straight contactly with the mould cavities depending on the shape and the dimension of the cavities and some aspects about the dimensioning of the injection canals.

  19. The S4-S5 loop contributes to the ion-selective pore of potassium channels. (United States)

    Slesinger, P A; Jan, Y N; Jan, L Y


    Mutagenesis experiments on voltage-gated K+ channels have suggested that the ion-selective pore is comprised mostly of H5 segments. To see whether regions outside of the H5 segment might also contribute to the pore structure, we have studied the effect of single amino acid substitutions in the segment that connects the S4 and S5 putative transmembrane segments (S4-S5 loop) on various permeation properties of Shaker K+ channels. Mutations in the S4-S5 loop alter the Rb+ selectivity, the single-channel K+ and Rb+ conductances, and the sensitivity to open channel block produced by intracellular tetraethylammonium ion, Ba2+, and Mg2+. The block of Shaker K+ channels by intracellular Mg2+ is surprising, but is reminiscent of the internal Mg2+ blockade of inward rectifier K+ channels. The results suggest that the S4-S5 loop constitutes part of the ion-selective pore. Thus, the S4-S5 loop and the H5 segment are likely to contribute to the long pore characteristic of voltage-gated K+ channels.

  20. Can rice field channels contribute to biodiversity conservation in Southern Brazilian wetlands? (United States)

    Maltchik, Leonardo; Rolon, Ana Silvia; Stenert, Cristina; Machado, Iberê Farina; Rocha, Odete


    Conservation of species in agroecosystems has attracted attention. Irrigation channels can improve habitats and offer conditions for freshwater species conservation. Two questions from biodiversity conservation point of view are: 1) Can the irrigated channels maintain a rich diversity of macrophytes, macroinvertebrates and amphibians over the cultivation cycle? 2) Do richness, abundance and composition of aquatic species change over the rice cultivation cycle? For this, a set of four rice field channels was randomly selected in Southern Brazilian wetlands. In each channel, six sample collection events were carried out over the rice cultivation cycle (June 2005 to June 2006). A total of 160 taxa were identified in irrigated channels, including 59 macrophyte species, 91 taxa of macroinvertebrate and 10 amphibian species. The richness and abundance of macrophytes, macroinvertebrates and amphibians did not change significantly over the rice cultivation cycle. However, the species composition of these groups in the irrigation channels varied between uncultivated and cultivated periods. Our results showed that the species diversity found in the irrigation channels, together with the permanence of water enables these man-made aquatic networks to function as important systems that can contribute to the conservation of biodiversity in regions where the wetlands were converted into rice fields. The conservation of the species in agriculture, such as rice field channels, may be an important alternative for biodiversity conservation in Southern Brazil, where more than 90% of wetland systems have already been lost and the remaining ones are still at high risk due to the expansion of rice production.

  1. Asymmetric functional contributions of acidic and aromatic side chains in sodium channel voltage-sensor domains

    DEFF Research Database (Denmark)

    Pless, Stephan Alexander; Elstone, Fisal D; Niciforovic, Ana P


    functional phenotypes that are different from those observed previously in Kv VSDs. In contrast, and similar to results obtained with Kv channels, individually neutralizing acidic side chains with synthetic derivatives and with natural amino acid substitutions in the INC had little or no effect......Voltage-gated sodium (NaV) channels mediate electrical excitability in animals. Despite strong sequence conservation among the voltage-sensor domains (VSDs) of closely related voltage-gated potassium (KV) and NaV channels, the functional contributions of individual side chains in Nav VSDs remain...... largely enigmatic. To this end, natural and unnatural side chain substitutions were made in the S2 hydrophobic core (HC), the extracellular negative charge cluster (ENC), and the intracellular negative charge cluster (INC) of the four VSDs of the skeletal muscle sodium channel isoform (NaV1...

  2. TRESK channel contribution to nociceptive sensory neurons excitability: modulation by nerve injury

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    Serra Jordi


    Full Text Available Abstract Background Neuronal hyperexcitability is a crucial phenomenon underlying spontaneous and evoked pain. In invertebrate nociceptors, the S-type leak K+ channel (analogous to TREK-1 in mammals plays a critical role of in determining neuronal excitability following nerve injury. Few data are available on the role of leak K2P channels after peripheral axotomy in mammals. Results Here we describe that rat sciatic nerve axotomy induces hyperexcitability of L4-L5 DRG sensory neurons and decreases TRESK (K2P18.1 expression, a channel with a major contribution to total leak current in DRGs. While the expression of other channels from the same family did not significantly change, injury markers ATF3 and Cacna2d1 were highly upregulated. Similarly, acute sensory neuron dissociation (in vitro axotomy produced marked hyperexcitability and similar total background currents compared with neurons injured in vivo. In addition, the sanshool derivative IBA, which blocked TRESK currents in transfected HEK293 cells and DRGs, increased intracellular calcium in 49% of DRG neurons in culture. Most IBA-responding neurons (71% also responded to the TRPV1 agonist capsaicin, indicating that they were nociceptors. Additional evidence of a biological role of TRESK channels was provided by behavioral evidence of pain (flinching and licking, in vivo electrophysiological evidence of C-nociceptor activation following IBA injection in the rat hindpaw, and increased sensitivity to painful pressure after TRESK knockdown in vivo. Conclusions In summary, our results clearly support an important role of TRESK channels in determining neuronal excitability in specific DRG neurons subpopulations, and show that axonal injury down-regulates TRESK channels, therefore contributing to neuronal hyperexcitability.

  3. Transient Receptor Potential Channels Contribute to Pathological Structural and Functional Remodeling After Myocardial Infarction (United States)

    Davis, Jennifer; Correll, Robert N.; Trappanese, Danielle M.; Hoffman, Nicholas E.; Troupes, Constantine D.; Berretta, Remus M.; Kubo, Hajime; Madesh, Muniswamy; Chen, Xiongwen; Gao, Erhe; Molkentin, Jeffery D.; Houser, Steven R.


    Rationale The cellular and molecular basis for post myocardial infarction (MI) structural and functional remodeling is not well understood. Objective To determine if Ca2+ influx through transient receptor potential (canonical) (TRPC) channels contributes to post-MI structural and functional remodeling. Methods and Results TRPC1/3/4/6 channel mRNA increased after MI in mice and was associated with TRPC-mediated Ca2+ entry. Cardiac myocyte specific expression of a dominant negative (dn: loss of function) TRPC4 channel increased basal myocyte contractility and reduced hypertrophy and cardiac structural and functional remodeling after MI while increasing survival. We used adenovirus-mediated expression of TRPC3/4/6 channels in cultured adult feline myocytes (AFMs) to define mechanistic aspects of these TRPC-related effects. TRPC3/4/6 over expression in AFMs induced calcineurin (Cn)-Nuclear Factor of Activated T cells (NFAT) mediated hypertrophic signaling, which was reliant on caveolae targeting of TRPCs. TRPC3/4/6 expression in AFMs increased rested state contractions and increased spontaneous sarcoplasmic reticulum (SR) Ca2+ sparks mediated by enhanced phosphorylation of the ryanodine receptor. TRPC3/4/6 expression was associated with reduced contractility and response to catecholamines during steady state pacing, likely due to enhanced SR Ca2+ leak. Conclusions Ca2+ influx through TRPC channels expressed after MI activates pathological cardiac hypertrophy and reduces contractility reserve. Blocking post-MI TRPC activity improved post-MI cardiac structure and function. PMID:25047165

  4. Antisymmetry and channel coupling contributions to the absorption for $p + \\alpha /d + ^{3}He$

    CERN Document Server

    Cooper, S G


    To understand recently established empirical p + alpha potentials, RGM calculations followed by inversion are made to study contributions of the d + 3He reaction channels and deuteron distortion effects to the p + alpha potential. An equivalent study of the d + 3He potential is also presented. The contributions of exchange non-locality to the absorption are simulated by including an phenomenological imaginary potential in the RGM. These effects alone strongly influence the shape of the imaginary potentials for both p + alpha and d + 3He. The potentials local-equivalent to the fully antisymmetrised-coupled channels calculations have a significant parity-dependence in both real and imaginary components, which for p + alpha is qualitatively similar to that found empirically. The effects on the potentials of the further inclusion of deuteron distortion are also presented. The inclusion of a spin-orbit term in the RGM, adds additional terms to the phase-equivalent potential, most notably the comparatively large im...

  5. Mapping ECoG channel contributions to trajectory and muscle activity prediction in human sensorimotor cortex (United States)

    Nakanishi, Yasuhiko; Yanagisawa, Takufumi; Shin, Duk; Kambara, Hiroyuki; Yoshimura, Natsue; Tanaka, Masataka; Fukuma, Ryohei; Kishima, Haruhiko; Hirata, Masayuki; Koike, Yasuharu


    Studies on brain-machine interface techniques have shown that electrocorticography (ECoG) is an effective modality for predicting limb trajectories and muscle activity in humans. Motor control studies have also identified distributions of “extrinsic-like” and “intrinsic-like” neurons in the premotor (PM) and primary motor (M1) cortices. Here, we investigated whether trajectories and muscle activity predicted from ECoG were obtained based on signals derived from extrinsic-like or intrinsic-like neurons. Three participants carried objects of three different masses along the same counterclockwise path on a table. Trajectories of the object and upper arm muscle activity were predicted using a sparse linear regression. Weight matrices for the predictors were then compared to determine if the ECoG channels contributed more information about trajectory or muscle activity. We found that channels over both PM and M1 contributed highly to trajectory prediction, while a channel over M1 was the highest contributor for muscle activity prediction. PMID:28361947

  6. Relative incapacitation contributions of pressure wave and wound channel in the Marshall and Sanow data set

    CERN Document Server

    Courtney, M; Courtney, Amy; Courtney, Michael


    The Marshall and Sanow data set is the largest and most comprehensive data set available quantifying handgun bullet effectiveness in humans. This article presents an empirical model for relative incapacitation probability in humans hit in the thoracic cavity by handgun bullets. The model is constructed by employing the hypothesis that the wound channel and ballistic pressure wave effects each have an associated independent probability of incapacitation. Combining models for these two independent probabilities using the elementary rules of probability and performing a least-squares fit to the Marshall and Sanow data provides an empirical model with only two adjustable parameters for modeling bullet effectiveness with a standard error of 5.6% and a correlation coefficient R = 0.939. This supports the hypothesis that wound channel and pressure wave effects are independent (within the experimental error), and it also allows assignment of the relative contribution of each effect for a given handgun load. This mode...

  7. Nutrient contributions to the Santa Barbara Channel, California, from the ephemeral Santa Clara River (United States)

    Warrick, J.A.; Washburn, L.; Brzezinski, Mark A.; Siegel, D.A.


    The Santa Clara River delivers nutrient rich runoff to the eastern Santa Barbara Channel during brief (???1-3 day) episodic events. Using both river and oceanographic measurements, we evaluate river loading and dispersal of dissolved macronutrients (silicate, inorganic N and P) and comment on the biological implications of these nutrient contributions. Both river and ocean observations suggest that river nutrient concentrations are inversely related to river flow rates. Land use is suggested to influence these concentrations, since runoff from a subwatershed with substantial agriculture and urban areas had much higher nitrate than runoff from a wooded subwatershed. During runoff events, river nutrients were observed to conservatively mix into the buoyant, surface plume immediately seaward of the Santa Clara River mouth. Dispersal of these river nutrients extended 10s of km into the channel. Growth of phytoplankton and nutrient uptake was low during our observations (1-3 days following runoff), presumably due to the very low light levels resulting from high turbidity. However, nutrient quality of runoff (Si:N:P = 16:5:1) was found to be significantly different than upwelling inputs (13:10:1), which may influence different algal responses once sediments settle. Evaluation of total river nitrate loads suggests that most of the annual river nutrient fluxes to the ocean occur during the brief winter flooding events. Wet winters (such as El Nin??o) contribute nutrients at rates approximately an order-of-magnitude greater than "average" winters. Although total river nitrate delivery is considerably less than that supplied by upwelling, the timing and location of these types of events are very different, with river discharge (upwelling) occurring predominantly in the winter (summer) and in the eastern (western) channel. ?? 2004 Elsevier Ltd. All rights reserved.

  8. A Shab potassium channel contributes to action potential broadening in peptidergic neurons. (United States)

    Quattrocki, E A; Marshall, J; Kaczmarek, L K


    We have cloned the gene for a potassium channel, Aplysia Shab, that is expressed in the bag cell neurons of Aplysia. The voltage dependence and kinetics of the Aplysia Shab current in oocytes match those of IK2, one of the two delayed rectifiers in these neurons. Like IK2, but in contrast with other members of the Shab subfamily, the Aplysia Shab current inactivates within several hundred milliseconds. This inactivation occurs by a process whose properties do not match those previously described for C-type and N-type mechanisms. Neither truncation of the N-terminus nor block by tetraethylammonium alters the time course of inactivation. By incorporating the characteristics of Aplysia Shab into a computational model, we have shown how this current contributes to the normal enhancement of action potentials that occurs in the bag cell neurons at the onset of neuropeptide secretion.

  9. Contribution of microfinance to economic growth: Transmission channel and the ways to test it

    Directory of Open Access Journals (Sweden)

    Nargiza Alimukhamedova


    Full Text Available Since its birth in 1970s microfinance has been growing rapidly with the aim to lift people out of poverty and promote economic growth. Its role and importance has been amplified amidst the global financial crisis when trust into formal banking is shaken. Despite global recognition and popularity of microfinance there is mixed evidence of its net benefits and very limited work on its contribution to financial intermediation and economic growth. This paper first, identifies and discusses possible transmission channels for microfinance and second, establishes the choice of appropriate methodology for robust empirical test. Adapted for panel data the Arellano-Bond (1991 technique allows for the Granger-Causality type test to reveal the direction of causality and overcome endogeneity issue. The main purpose of the estimation is to check whether microfinance matters for financial sector development and economic growth.

  10. The contributions of Donald Lee Johnson to understanding the Quaternary geologic and biogeographic history of the California Channel Islands (United States)

    Muhs, Daniel R.


    Over a span of 50 years, native Californian Donald Lee Johnson made a number of memorable contributions to our understanding of the California Channel Islands. Among these are (1) recognizing that carbonate dunes, often cemented into eolianite and derived from offshore shelf sediments during lowered sea level, are markers of glacial periods on the Channel Islands; (2) identifying beach rock on the Channel Islands as the northernmost occurrence of this feature on the Pacific Coast of North America; (3) recognizing of the role of human activities in historic landscape modification; (4) identifying both the biogenic and pedogenic origins of caliche “ghost forests” and laminar calcrete forms on the Channel Islands; (5) providing the first soil maps of several of the islands, showing diverse pathways of pedogenesis; (6) pointing out the importance of fire in Quaternary landscape history on the Channel Islands, based on detailed stratigraphic studies; and (7), perhaps his greatest contribution, clarifying the origin of Pleistocene pygmy mammoths on the Channel Islands, due not to imagined ancient land bridges, but rather the superb swimming abilities of proboscideans combined with lowered sea level, favorable paleowinds, and an attractive paleovegetation on the Channel Islands. Don was a classic natural historian in the great tradition of Charles Darwin and George Gaylord Simpson, his role models. Don’s work will remain important and useful for many years and is an inspiration to those researching the California Channel Islands today.

  11. Increased expression of HERG K(+) channels contributes to myelodysplastic syndrome progression and displays correlation with prognosis stratification. (United States)

    Lu, Li; Du, Wen; Liu, Wei; Guo, Dongmei; He, Xiaoqi; Li, Huiyu


    Human ether-a-go-go-related gene (HERG) K(+) channels are shown to be aberrantly expressed in a variety of cancer cells where they play roles in contributing to cancer progression. Myelodysplastic syndromes (MDS) are a group of clinical heterogeneous disorders characterized by bone marrow failure and dysplasia of blood cells. However, the involvement of HERG K(+) channels in MDS development is poorly understood. The expression of HERG K(+) channels in untreated MDS, acute myeloid leukemia (AML) patients and the control group was detected by flow cytometry. The roles of HERG K(+) channels in regulation of SKM-1 cell proliferation, apoptosis, and cell cycle were determined by CCK-8 assay and flow cytometry, respectively. We found that expression of HERG K(+) channels in MDS patients was significantly higher than controls and was lower than AML. Percentage of HERG K(+) channels on CD34+CD38- cells gradually increased from controls to high-grade MDS subtypes. And HERG K(+) channel levels showed an ascending tendency from low-risk to high-risk MDS group. In addition, the CCK-8 assay, apoptosis and cell cycle analysis were performed and showed that blockage of HERG K(+) channels decreased the proliferation of MDS cells but rarely had effects on cell apoptosis and cell cycle distribution. Our study demonstrated that HERG K(+) channels might be a potential tumor marker of MDS. These channels were likely to contribute to MDS progression and were helpful for predicting prognosis of MDS. Inhibition of HERG K(+) channels might be a novel therapeutic measure for MDS.

  12. The contribution of TRPM8 and TRPA1 channels to cold allodynia and neuropathic pain.

    Directory of Open Access Journals (Sweden)

    Ombretta Caspani

    Full Text Available Cold allodynia is a common feature of neuropathic pain however the underlying mechanisms of this enhanced sensitivity to cold are not known. Recently the transient receptor potential (TRP channels TRPM8 and TRPA1 have been identified and proposed to be molecular sensors for cold. Here we have investigated the expression of TRPM8 and TRPA1 mRNA in the dorsal root ganglia (DRG and examined the cold sensitivity of peripheral sensory neurons in the chronic construction injury (CCI model of neuropathic pain in mice.In behavioral experiments, chronic constriction injury (CCI of the sciatic nerve induced a hypersensitivity to both cold and the TRPM8 agonist menthol that developed 2 days post injury and remained stable for at least 2 weeks. Using quantitative RT-PCR and in situ hybridization we examined the expression of TRPM8 and TRPA1 in DRG. Both channels displayed significantly reduced expression levels after injury with no change in their distribution pattern in identified neuronal subpopulations. Furthermore, in calcium imaging experiments, we detected no alterations in the number of cold or menthol responsive neurons in the DRG, or in the functional properties of cold transduction following injury. Intriguingly however, responses to the TRPA1 agonist mustard oil were strongly reduced.Our results indicate that injured sensory neurons do not develop abnormal cold sensitivity after chronic constriction injury and that alterations in the expression of TRPM8 and TRPA1 are unlikely to contribute directly to the pathogenesis of cold allodynia in this neuropathic pain model.

  13. Acid sensing ion channel 1 in lateral hypothalamus contributes to breathing control.

    Directory of Open Access Journals (Sweden)

    Nana Song

    Full Text Available Acid-sensing ion channels (ASICs are present in neurons and may contribute to chemoreception. Among six subunits of ASICs, ASIC1 is mainly expressed in the central nervous system. Recently, multiple sites in the brain including the lateral hypothalamus (LH have been found to be sensitive to extracellular acidification. Since LH contains orexin neurons and innervates the medulla respiratory center, we hypothesize that ASIC1 is expressed on the orexin neuron and contributes to acid-induced increase in respiratory drive. To test this hypothesis, we used double immunofluorescence to determine whether ASIC1 is expressed on orexin neurons in the LH, and assessed integrated phrenic nerve discharge (iPND in intact rats in response to acidification of the LH. We found that ASIC1 was co-localized with orexinA in the LH. Microinjection of acidified artificial cerebrospinal fluid increased the amplitude of iPND by 70% (pH 7.4 v.s. pH 6.5:1.05±0.12 v.s. 1.70±0.10, n = 6, P<0.001 and increased the respiratory drive (peak amplitude of iPND/inspiratory time, PA/Ti by 40% (1.10±0.23 v.s. 1.50±0.38, P<0.05. This stimulatory effect was abolished by blocking ASIC1 with a nonselective inhibitor (amiloride 10 mM, a selective inhibitor (PcTX1, 10 nM or by damaging orexin neurons in the LH. Current results support our hypothesis that the orexin neuron in the LH can exert an excitation on respiration via ASIC1 during local acidosis. Since central acidification is involved in breathing dysfunction in a variety of pulmonary diseases, understanding its underlying mechanism may improve patient management.

  14. Transient receptor potential channel M2 contributes to neointimal hyperplasia in vascular walls. (United States)

    Ru, Xiaochen; Zheng, Changbo; Zhao, Qiannan; Lan, Hui-Yao; Huang, Yu; Wan, Song; Mori, Yasuo; Yao, Xiaoqiang


    A hallmark of atherosclerosis is progressive intimal thickening (namely neointimal hyperplasia), which leads to occlusive vascular diseases. Over-production of reactive oxygen species (ROS) and alteration of Ca2+ signaling are among the key factors contributing to neointimal growth. In the present study, we investigated the role of TRPM2, a ROS-sensitive Ca2+ entry channel, in neointimal hyperplasia. Perivascular cuffs were used to induce neointimal hyperplasia in rat/mouse arteries. Immunostaining showed numerous TRPM2-positive smooth muscle cells in neointimal regions. ROS were over-produced and PCNA-positive proliferating cells were numerous in the neointimal regions. The neointimal hyperplasia was substantially reduced in Trpm2 knockout mice compared with wild-type mice. In the cultured rat/mouse aortic smooth muscle cells, H2O2 treatment was found to stimulate cell proliferation and migration. The effect of H2O2 was reduced by a TRPM2-specific blocking antibody TM2E3 or Trpm2 knockout. The signaling molecules downstream of TRPM2 were found to be Axl and Akt. These data suggest a critical functional role of TRPM2 in the progression of neointimal hyperplasia. The study also highlights the possibility of targeting TRPM2 as a potential therapeutic option for the treatment of occlusive vascular diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. The water channel aquaporin-1 contributes to renin cell recruitment during chronic stimulation of renin production. (United States)

    Tinning, Anne R; Jensen, Boye L; Schweda, Frank; Machura, Katharina; Hansen, Pernille B L; Stubbe, Jane; Gramsbergen, Jan Bert; Madsen, Kirsten


    Both the processing and release of secretory granules involve water movement across granule membranes. It was hypothesized that the water channel aquaporin (AQP)1 directly contributes to the recruitment of renin-positive cells in the afferent arteriole. AQP1(-/-) and AQP1(+/+) mice were fed a low-salt (LS) diet [0.004% (wt/wt) NaCl] for 7 days and given enalapril [angiotensin-converting enzyme inhibitor (ACEI), 0.1 mg/ml] in drinking water for 3 days. There were no differences in plasma renin concentration at baseline. After LS-ACEI, plasma renin concentrations increased markedly in both genotypes but was significantly lower in AQP1(-/-) mice compared with AQP1(+/+) mice. Tissue renin concentrations were higher in AQP1(-/-) mice, and renin mRNA levels were not different between genotypes. Mean arterial blood pressure was not different at baseline and during LS diet but decreased significantly in both genotypes after the addition of ACEI; the response was faster in AQP1(-/-) mice but then stabilized at a similar level. Renin release after 200 μl blood withdrawal was not different. Isoprenaline-stimulated renin release from isolated perfused kidneys did not differ between genotypes. Cortical tissue norepinephrine concentrations were lower after LS-ACEI compared with baseline with no difference between genotypes. Plasma nitrite/nitrate concentrations were unaffected by genotype and LS-ACEI. In AQP1(-/-) mice, the number of afferent arterioles with recruitment was significantly lower compared with AQP1(+/+) mice after LS-ACEI. We conclude that AQP1 is not necessary for acutely stimulated renin secretion in vivo and from isolated perfused kidneys, whereas recruitment of renin-positive cells in response to chronic stimulation is attenuated or delayed in AQP1(-/-) mice.

  16. Novel HCN2 mutation contributes to febrile seizures by shifting the channel's kinetics in a temperature-dependent manner.

    Directory of Open Access Journals (Sweden)

    Yuki Nakamura

    Full Text Available Hyperpolarization-activated cyclic nucleotide-gated (HCN channel-mediated currents, known as I h, are involved in the control of rhythmic activity in neuronal circuits and in determining neuronal properties including the resting membrane potential. Recent studies have shown that HCN channels play a role in seizure susceptibility and in absence and limbic epilepsy including temporal lobe epilepsy following long febrile seizures (FS. This study focused on the potential contributions of abnormalities in the HCN2 isoform and their role in FS. A novel heterozygous missense mutation in HCN2 exon 1 leading to p.S126L was identified in two unrelated patients with FS. The mutation was inherited from the mother who had suffered from FS in a pedigree. To determine the effect of this substitution we conducted whole-cell patch clamp electrophysiology. We found that mutant channels had elevated sensitivity to temperature. More specifically, they displayed faster kinetics at higher temperature. Kinetic shift by change of temperature sensitivity rather than the shift of voltage dependence led to increased availability of I h in conditions promoting FS. Responses to cyclic AMP did not differ between wildtype and mutant channels. Thus, mutant HCN2 channels cause significant cAMP-independent enhanced availability of I h during high temperatures, which may contribute to hyperthermia-induced neuronal hyperexcitability in some individuals with FS.

  17. Ca2+-activated K+ (BK) channel inactivation contributes to spike broadening during repetitive firing in the rat lateral amygdala. (United States)

    Faber, E S Louise; Sah, Pankaj


    In many neurons, trains of action potentials show frequency-dependent broadening. This broadening results from the voltage-dependent inactivation of K+ currents that contribute to action potential repolarisation. In different neuronal cell types these K+ currents have been shown to be either slowly inactivating delayed rectifier type currents or rapidly inactivating A-type voltage-gated K+ currents. Recent findings show that inactivation of a Ca2+-dependent K+ current, mediated by large conductance BK-type channels, also contributes to spike broadening. Here, using whole-cell recordings in acute slices, we examine spike broadening in lateral amygdala projection neurons. Spike broadening is frequency dependent and is reversed by brief hyperpolarisations. This broadening is reduced by blockade of voltage-gated Ca2+ channels and BK channels. In contrast, broadening is not blocked by high concentrations of 4-aminopyridine (4-AP) or alpha-dendrotoxin. We conclude that while inactivation of BK-type Ca2+-activated K+ channels contributes to spike broadening in lateral amygdala neurons, inactivation of another as yet unidentified outward current also plays a role.

  18. Non-equilibrium dynamics contribute to ion selectivity in the KcsA channel.

    Directory of Open Access Journals (Sweden)

    Van Ngo

    Full Text Available The ability of biological ion channels to conduct selected ions across cell membranes is critical for the survival of both animal and bacterial cells. Numerous investigations of ion selectivity have been conducted over more than 50 years, yet the mechanisms whereby the channels select certain ions and reject others are not well understood. Here we report a new application of Jarzynski's Equality to investigate the mechanism of ion selectivity using non-equilibrium molecular dynamics simulations of Na(+ and K(+ ions moving through the KcsA channel. The simulations show that the selectivity filter of KcsA adapts and responds to the presence of the ions with structural rearrangements that are different for Na(+ and K(+. These structural rearrangements facilitate entry of K(+ ions into the selectivity filter and permeation through the channel, and rejection of Na(+ ions. A mechanistic model of ion selectivity by this channel based on the results of the simulations relates the structural rearrangement of the selectivity filter to the differential dehydration of ions and multiple-ion occupancy and describes a mechanism to efficiently select and conduct K(+. Estimates of the K(+/Na(+ selectivity ratio and steady state ion conductance for KcsA from the simulations are in good quantitative agreement with experimental measurements. This model also accurately describes experimental observations of channel block by cytoplasmic Na(+ ions, the "punch through" relief of channel block by cytoplasmic positive voltages, and is consistent with the knock-on mechanism of ion permeation.

  19. DECOVALEX ll PROJECT. Technical Report Task 1C

    Energy Technology Data Exchange (ETDEWEB)

    Jing, L.; Stephansson, O. [Royal Inst. of Tech., Stockholm (Sweden). Dept. of Civil and Environmental Engineering; Knight, L.J. [United Kingdom Nirex Ltd., Harwell (United Kingdom); Kautsky, F. [Swedish Nuclear Power Inspectorate, Stockholm (Sweden); Tsang, C-F. [Lawrence Berkeley National Lab., Berkeley, CA (United States). Earth Science Division


    The DECOVALEX II project is an international co-operative research project supported by eleven funding organizations from seven countries. The project studied four tasks: Task 1: numerical simulation of the RCF3 pump test at Sellafield, UK; Task 2: numerical simulation if the in situ T-H-M experiment at Kamaishi Mine, Japan; Task 3: monitoring of current development in rock fracture research; and Task 4: report on treatment of T-H-M processes in Performance Assessment works for nuclear waste repositories. The project started in 1995 and is scheduled to be finalised in June 1999. This report concerns the Task 1 of the DECOVALEX 11 project. Task 1 consists of three subtasks: i) Task 1 A - the blind numerical prediction to the hydraulic response of the rock mass of the in-situ RCF3 pump test in the Borrowdale Volcanic Group (BVG) at Sellafield, UK; ii) Task 1B -calibration of the numerical models of Task 1A against measured results of the RCF3 pump test; iii) Task 1C - the numerical predictions of the hydro-mechanical effects of the BVG rock mass to the excavation of a shaft along the axis of the RCF3 borehole, without actual excavation of the shaft and associated experiments and measurements. The aim of the subtasks 1 (A+B) was to characterise the hydro-mechanical property field of the fractured rock mass at the RCF3 test site, which could then be used to predict the hydro-mechanical responses of the rock mass to the excavation of a shaft centred on the RCF3 borehole. Task 1C involves a numerical simulation of an assumed excavation of a single shaft on the line of the RCF3 borehole used for Task 1 (A+B). The subtask is basically a generic prediction, with realistic site geology and hydrogeology data but without feedback from an actual excavation of the shaft and associated measurements. A model calibration is not possible due to lack of measured results. On the other hand, some additional components were introduced into the subtask, such as studies of EDZ formation

  20. Contribution of the t-channel N*(1535) exchange for the pp¯→ϕϕ reaction (United States)

    Shi, Jun; Dai, Jian-Ping; Zou, Bing-Song


    Since the N*(1535) resonance was found to have large coupling to the strangeness due to its possible large ss¯ component, we investigate the possible contribution of the t-channel N*(1535) exchange for the pp¯→ϕϕ reaction. Our calculation indicates that the new mechanism may give significant contribution for the energies above 2.25 GeV and may be an important source for evading the Okubo-Zweig-Iizuka rule in the ϕ production from NN¯ annihilation.

  1. Contribution of the t-channel $N^*(1535)$ exchange for the $p\\bar p \\to \\phi\\phi$ reaction

    CERN Document Server

    Shi, Jun; Zou, Bing-Song


    Since the $N^*(1535)$ resonance was found to have large coupling to the strangeness due to its possible large $s\\bar s$ component, we investigate the possible contribution of the t-channel $N^*(1535)$ exchange for the $p\\bar p \\to \\phi\\phi$ reaction. Our calculation indicates that the new mechanism gives very significant contribution for the energies above 2.25 GeV and may be an important source for evading the Okubo-Zweig-Iizuka rule in the $\\phi$ production from $N \\bar{N}$ annihilation.

  2. Unique contributions of an arginine side chain to ligand recognition in a glutamate-gated chloride channel

    DEFF Research Database (Denmark)

    Lynagh, Timothy; Komnatnyy, Vitaly V; Pless, Stephan A


    -gated chloride channel from the nematode Haemonchus contortus. Our data unveil a surprisingly small contribution of charge at a conserved arginine side chain previously suggested to form a salt bridge with the ligand, glutamate. Instead, our data show that Arg contributes crucially to ligand sensitivity via...... a hydrogen bond network, where Arg interacts both with agonist and with a conserved Thr side chain within the receptor. Together, the data provide a new explanation for the reliance of neurotransmitter receptors on Arg side chains and highlight the exceptional capacity of unnatural amino acid incorporation...

  3. IEA PVPS Task 1 - UK Expert. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Gunning, R.


    The paper relates to work carried out under contract to the UK Renewable Energy Programme, and describes the terms of reference of the UK representation in the IEA PVPS Task 1 which provides a forum for exchange of information on photovoltaic (PV) technology between 21 participating countries. The main benefit derived by the UK is access to international expertise in PV technology. Using information obtained from participation in Task 1, the UK produces a National Survey Report which reports on developments in PV technology in the UK over the previous 12 months. The report covers installed capacity, prices, budgets and costs: it is freely available on the UK PVPS website. The newsletter PV Power, is prepared and distributed biannually - 18 issues have been published by mid-2003. IT Power is currently the UK representative on the IEA PVPS Task 1.

  4. Contribution of Kv7 channels to natriuretic peptide mediated vasodilation in normal and hypertensive rats

    DEFF Research Database (Denmark)

    Stott, Jennifer B; Barrese, Vincenzo; Jepps, Thomas Andrew;


    -cAMP-linked vasodilator pathways has not been investigated. Natriuretic peptides are potent vasodilators, which operate primarily through the activation of a cGMP-dependent signaling pathway. This study investigated the putative role of Kv7 channels in natriuretic peptide-dependent relaxations in the vasculature...

  5. Contributions of counter-charge in a potassium channel voltage-sensor domain

    DEFF Research Database (Denmark)

    Pless, Stephan Alexander; Galpin, Jason D; Niciforovic, Ana P


    Voltage-sensor domains couple membrane potential to conformational changes in voltage-gated ion channels and phosphatases. Highly coevolved acidic and aromatic side chains assist the transfer of cationic side chains across the transmembrane electric field during voltage sensing. We investigated...

  6. Growth and contribution of stocked channel catfish, Ictalurus punctatus (Rafinesque, 1818): the importance of measuring post-stocking performance (United States)

    Stewart, David R.; Long, James M.


    In this study it was sought to quantify post-stocking growth, survival, and contribution of advanced size (178 mm total length [TL]) channel catfish Ictalurus punctatus fingerlings, something rarely done. Channel catfish populations were evaluated before (May 2010) and after (May to August 2011 and 2012) stocking. Relative abundance, stocking contribution, and growth were different (P < 0.05) in the two study impoundments (lakes Lone Chimney and Greenleaf, Oklahoma). For fish stocked in Lake Lone Chimney, stocking contribution was lower (3–35%), and average length and weight of stocked fish by age-2 reached 230 mm TL and 85 g, whereas the stocking contribution (84–98%) and growth in length (340 mm TL) and weight (280 g) were higher by age-2 in Lake Greenleaf. Given these unambiguous differences of post-stocking performance, benchmark metrics that represent population-level information such as relative abundance and average length and weight of the sample masked these significant differences, highlighting the importance of marking hatchery-fish and then following them through time to determine the effectiveness of stocking. These results suggest that stock enhancement programmes would benefit from studies that quantify post-stocking performance of hatchery fish.

  7. Contribution of a lysine residue in the first transmembrane segment to the selectivity filter region in the CFTR chloride channel. (United States)

    Negoda, Alexander; El Hiani, Yassine; Cowley, Elizabeth A; Linsdell, Paul


    The anion selectivity and conductance of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel are determined predominantly by interactions between permeant anions and the narrow region of the channel pore. This narrow region has therefore been described as functioning as the "selectivity filter" of the channel. Multiple pore-lining transmembrane segments (TMs) have previously been shown to contribute to the selectivity filter region. However, little is known about the three-dimensional organization of this region, or how multiple TMs combine to determine its functional properties. In the present study we have used patch clamp recording to identify changes in channel function associated with the formation of disulfide cross-links between cysteine residues introduced into different TMs within the selectivity filter. Cysteine introduced at position L102 in TM1 was able to form disulfide bonds with F337C and T338C in TM6, two positions that are known to play key roles in determining anion permeation properties. Consistent with this proximal arrangement of L102, F337 and T338, different mutations at L102 altered anion selectivity and conductance properties in a way that suggests that this residue plays an important role in determining selectivity filter function, albeit a much lesser role than that of F337. These results suggest an asymmetric three-dimensional arrangement of the key selectivity filter region of the pore, as well as having important implications regarding the molecular mechanism of anion permeation.

  8. Contribution of KV7 Channels to Basal Coronary Flow and Active Response to Ischemia

    DEFF Research Database (Denmark)

    Khanamiri, Saereh; Soltysinska, Ewa; Jepps, Thomas A


    .5 activators produced relaxations, which were considerably less in arteries from hypertensive rats and were not mimicked by the KV7.1-specific activator R-L3. In isolated, perfused heart preparations, coronary flow rate increased in response to the KV7.2 to 7.5 activator (S)-1 and was diminished......The goal of the present study was to determine the role of KCNQ-encoded KV channels (KV7 channels) in the passive and active regulation of coronary flow in normotensive and hypertensive rats. In left anterior descending coronary arteries from normotensive rats, structurally different KV7.2 to 7....... Application of adenosine or A2A receptor agonist CGS-21680 produced concentration-dependent relaxations of coronary arteries from normotensive rats, which were attenuated by application of KV7 inhibitors. KV7 blockers also attenuated the ischemia-induced increase in coronary perfusion in Langendorff studies...

  9. Acidotoxicity and acid-sensing ion channels contribute to motoneuron degeneration. (United States)

    Behan, A T; Breen, B; Hogg, M; Woods, I; Coughlan, K; Mitchem, M; Prehn, J H M


    Amyotrophic lateral sclerosis (ALS) is a fatal neurological condition with no cure. Mitochondrial dysfunction, Ca(2+) overloading and local hypoxic/ischemic environments have been implicated in the pathophysiology of ALS and are conditions that may initiate metabolic acidosis in the affected tissue. We tested the hypothesis that acidotoxicity and acid-sensing ion channels (ASICs) are involved in the pathophysiology of ALS. We found that motoneurons were selectively vulnerable to acidotoxicity in vitro, and that acidotoxicity was partially reduced in asic1a-deficient motoneuron cultures. Cross-breeding of SOD1(G93A) ALS mice with asic1a-deficient mice delayed the onset and progression of motor dysfunction in SOD1 mice. Interestingly, we also noted a strong increase in ASIC2 expression in motoneurons of SOD1 mice and sporadic ALS patients during disease progression. Pharmacological pan-inhibition of ASIC channels with the lipophilic amiloride derivative, 5-(N,N-dimethyl)-amiloride hydrochloride, potently protected cultured motoneurons against acidotoxicity, and, given post-symptom onset, significantly improved lifespan, motor performance and motoneuron survival in SOD1 mice. Together, our data provide strong evidence for the involvement of acidotoxicity and ASIC channels in motoneuron degeneration, and highlight the potential of ASIC inhibitors as a new treatment approach for ALS.

  10. SK2 channel modulation contributes to compartment-specific dendritic plasticity in cerebellar Purkinje cells. (United States)

    Ohtsuki, Gen; Piochon, Claire; Adelman, John P; Hansel, Christian


    Small-conductance Ca(2+)-activated K(+) channels (SK channels) modulate excitability and curtail excitatory postsynaptic potentials (EPSPs) in neuronal dendrites. Here, we demonstrate long-lasting plasticity of intrinsic excitability (IE) in dendrites that results from changes in the gain of this regulatory mechanism. Using dendritic patch-clamp recordings from rat cerebellar Purkinje cells, we find that somatic depolarization or parallel fiber (PF) burst stimulation induce long-term amplification of synaptic responses to climbing fiber (CF) or PF stimulation and enhance the amplitude of passively propagated sodium spikes. Dendritic plasticity is mimicked and occluded by the SK channel blocker apamin and is absent in Purkinje cells from SK2 null mice. Triple-patch recordings from two dendritic sites and the soma and confocal calcium imaging studies show that local stimulation limits dendritic plasticity to the activated compartment of the dendrite. This plasticity mechanism allows Purkinje cells to adjust the SK2-mediated control of dendritic excitability in an activity-dependent manner.

  11. Differential contribution of TRPM4 and TRPM5 nonselective cation channels to the slow afterdepolarization in mouse prefrontal cortex neurons

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    Ya-Ting eLei


    Full Text Available In certain neurons from different brain regions, a brief burst of action potentials can activate a slow afterdepolarization (sADP in the presence of muscarinic acetylcholine receptor agonists. The sADP, if suprathreshold, can contribute to persistent non-accommodating firing in some of these neurons. Previous studies have characterized a Ca2+-activated non-selective cation (CAN current (ICAN that is thought to underlie the sADP. ICAN depends on muscarinic receptor stimulation and exhibits a dependence on neuronal activity, membrane depolarization and Ca2+-influx similar to that observed for the sADP. Despite the widespread occurrence of sADPs in neurons throughout the brain, the molecular identity of the ion channels underlying these events, as well as ICAN, remains uncertain. Here we used a combination of genetic, pharmacological and electrophysiological approaches to characterize the molecular mechanisms underlying the muscarinic receptor-dependent sADP in layer 5 pyramidal neurons of mouse prefrontal cortex. First, we confirmed that in the presence of the cholinergic agonist carbachol a brief burst of action potentials triggers a prominent sADP in these neurons. Second, we confirmed that this sADP requires activation of a PLC signaling cascade and intracellular calcium signaling. Third, we obtained direct evidence that the transient receptor potential melastatin 5 channel (TRPM5, which is thought to function as a CAN channel in non-neural cells, contributes importantly to the sADP in the layer 5 neurons. In contrast, the closely related TRPM4 channel may play only a minor role in the sADP.

  12. Transient receptor potential vanilloid type-1 (TRPV-1) channels contribute to cutaneous thermal hyperaemia in humans. (United States)

    Wong, Brett J; Fieger, Sarah M


    The initial, rapid increase in skin blood flow in response to direct application of heat is thought to be mediated by an axon reflex, which is dependent on intact cutaneous sensory nerves. We tested the hypothesis that inhibition of transient receptor potential vanilloid type 1 (TRPV-1) channels, which are putative channels located on sensory nerves, would attenuate the skin blood flow response to local heating in humans. Ten subjects were equipped with four microdialysis fibres which were randomly assigned one of four treatments: (1) vehicle control (90% propylene glycol + 10% lactated Ringer solution); (2) 20 mm capsazepine to inhibit TRPV-1 channels; (3) 10 mm l-NAME to inhibit NO synthase; and (4) combined 20 mm capsazepine + 10 mm l-NAME. Following baseline measurements, the temperature of skin heaters was increased from 33°C to 42°C at a rate of 1.0°C every 10 s and local temperature was held at 42°C for 20-30 min until a stable plateau in skin blood flow was achieved. An index of skin blood flow was measured directly over each microdialysis site via laser-Doppler flowmetry (LDF). Beat-by-beat blood pressure was measured via photoplethysmography and verified via automated brachial auscultation. At the end of the local heating protocol, temperature of the heaters was increased to 43°C and 28 mm nitroprusside was infused to achieve maximal vasodilatation. Cutaneous vascular conductance (CVC) was calculated as LDF/mean arterial pressure and normalized to maximal values (%CVCmax). Initial peak in capsazepine (44 ± 4%CVCmax), l-NAME (56 ± 4%CVCmax) and capsazepine + l-NAME (32 ± 6%CVCmax) sites was significantly attenuated compared to control (87 ± 5%CVCmax; P thermal hyperaemia was significantly attenuated in capsazepine (73 ± 6%CVCmax), l-NAME (47 ± 5%CVCmax) and capsazepine + l-NAME (31 ± 7%CVCmax) sites compared to control (92 ± 5%CVCmax; P thermal hyperaemia. These data further suggest a portion of the NO component of thermal hyperaemia may be

  13. Sodium leak channel, non-selective contributes to the leak current in human myometrial smooth muscle cells from pregnant women. (United States)

    Reinl, Erin L; Cabeza, Rafael; Gregory, Ismail A; Cahill, Alison G; England, Sarah K


    Uterine contractions are tightly regulated by the electrical activity of myometrial smooth muscle cells (MSMCs). These cells require a depolarizing current to initiate Ca(2+) influx and induce contraction. Cationic leak channels, which permit a steady flow of cations into a cell, are known to cause membrane depolarization in many tissue types. Previously, a Gd(3+)-sensitive, Na(+)-dependent leak current was identified in the rat myometrium, but the presence of such a current in human MSMCs and the specific ion channel conducting this current was unknown. Here, we report the presence of a Na(+)-dependent leak current in human myometrium and demonstrate that the Na(+)-leak channel, NALCN, contributes to this current. We performed whole-cell voltage-clamp on fresh and cultured MSMCs from uterine biopsies of term, non-laboring women and isolated the leak currents by using Ca(2+) and K(+) channel blockers in the bath solution. Ohmic leak currents were identified in freshly isolated and cultured MSMCs with normalized conductances of 14.6 pS/pF and 10.0 pS/pF, respectively. The myometrial leak current was significantly reduced (P < 0.01) by treating cells with 10 μM Gd(3+) or by superfusing the cells with a Na(+)-free extracellular solution. Reverse transcriptase PCR and immunoblot analysis of uterine biopsies from term, non-laboring women revealed NALCN messenger RNA and protein expression in the myometrium. Notably, ∼90% knockdown of NALCN protein expression with lentivirus-delivered shRNA reduced the Gd(3+)-sensitive leak current density by 42% (P < 0.05). Our results reveal that NALCN, in part, generates the leak current in MSMCs and provide the basis for future research assessing NALCN as a potential molecular target for modulating uterine excitability.

  14. Contributions to a first measurement of the W-boson mass in the electron channel with the ATLAS detector

    CERN Document Server


    In this document, I present my contributions to a first measurement of the W-mass in the LHC using 4.7 fb−1 of 7 TeV data, taken in 2011. I focus on the electron decay channel, W → eν. In the first part, I discuss a study regarding the performance of the electromagnetic calorimeter of the ATLAS detector, presenting a novel method to correct the lateral profiles of electron energy deposit, along with various studies of the different Geant4 physics lists versions. In the second part, I introduce the global methodology for the W-mass measurement used in ATLAS, and discuss my contributions in details. I show in a first step the assessment of uncertainties coming from the parton shower modeling in Pythia8, and the optimization of the lepton's transverse momentum fitting range in order to reduce the systematic uncertainty. In a second step, I present an elaborate data-driven method for the estimation of the multijet background in the W → eν channel, as well as the corresponding results in terms of event yie...

  15. N-terminal tetrapeptide T/SPLH motifs contribute to multimodal activation of human TRPA1 channel (United States)

    Hynkova, Anna; Marsakova, Lenka; Vaskova, Jana; Vlachova, Viktorie


    Human transient receptor potential ankyrin channel 1 (TRPA1) is a polymodal sensor implicated in pain, inflammation and itching. An important locus for TRPA1 regulation is the cytoplasmic N-terminal domain, through which various exogenous electrophilic compounds such as allyl-isothiocyanate from mustard oil or cinnamaldehyde from cinnamon activate primary afferent nociceptors. This major region is comprised of a tandem set of 17 ankyrin repeats (AR1-AR17), five of them contain a strictly conserved T/SPLH tetrapeptide motif, a hallmark of an important and evolutionarily conserved contribution to conformational stability. Here, we characterize the functional consequences of putatively stabilizing and destabilizing mutations in these important structural units and identify AR2, AR6, and AR11-13 to be distinctly involved in the allosteric activation of TRPA1 by chemical irritants, cytoplasmic calcium, and membrane voltage. Considering the potential involvement of the T/SP motifs as putative phosphorylation sites, we also show that proline-directed Ser/Thr kinase CDK5 modulates the activity of TRPA1, and that T673 outside the AR-domain is its only possible target. Our data suggest that the most strictly conserved N-terminal ARs define the energetics of the TRPA1 channel gate and contribute to chemical-, calcium- and voltage-dependence.

  16. Photoproduction of Λ*(1405 ) with the N* and the t -channel Regge contributions (United States)

    Kim, Sang-Ho; Nam, Seung-il; Jido, Daisuke; Kim, Hyun-Chul


    We investigate the photoproduction of the Λ (1405 )≡Λ* hyperon resonance, i.e., γ p →K+Λ*, employing the effective Lagrangian approach with the t -channel Regge trajectories at tree level. We extensively explore the effects from the nucleon resonances in the vicinity of the threshold √{s}th≈1900 MeV , i.e., N*(2000 ), N*(2030 ), N*(2055 ), N*(2095 ), and N*(2100 ), and observe that they are of great importance to reproduce the recent CLAS experimental data. Total and differential cross sections are given as numerical results and compared with the experimental data, in addition to the photon-beam asymmetry. The invariant-mass distributions for γ p →K+π0Σ0 via Λ* are also extracted from the two-body process results, showing a qualitative agreement with the data. We also discuss the constituent-counting rule for the internal structure of Λ*, resulting in that Λ* appears to be different from a simple three-quark (u d s ) state.

  17. Control Problems in Distribution Channels: Empirical Evidence of Management Control Systems Contributions.

    Directory of Open Access Journals (Sweden)

    José M. Sánchez Vázqez


    Full Text Available As part of the supply chain, manufacturing firms are increasingly placing greater emphasis on the management of their outsourced distribution channels (DCs. However, the role that interorganizational Management Control Systems (MCS can play in managing DC problems is still not clearly understood. Through an exploratory case study, we show how intra-organizational control problems persist in an inter-organizational context, rooted in informational asymmetries and conflicts of interest and aggravated by interdependencies. Likewise, the case study illustrates the way in which MCS assists the manufacturing firm to communicate to its representatives what the organization wants from them, motivating them and transferring capabilities. Thus, MCS can help to complement and re-orientate inter-firm agreements and constitutes a key tool for managing DCs in a flexible way.Como parte de la cadena de suministros, las empresas productoras están poniendo mayor énfasis en la gestión de sus canales de distribución externalizados (DCs. Sin embargo, aún no existe una clara comprensión sobre el papel que los Sistemas de Control de Gestión inter-organizativos (MCS pueden desarrollar en la gestión de los problemas de los DCs. A través de un estudio de caso, se muestra cómo los problemas de control intra-organizativos persisten en un contexto inter-organizativo, causados por las asimetrías informativas y el conflicto de intereses, y agravándose por las interdependencias. Asimismo, se expone cómo los MCS ayudan a la empresa productora a comunicar a sus distribuidores lo que la organización desea de ellos, motivándolos y capacitándolos. De esta forma, los MCS pueden ayudar a completar y redirigir acuerdos entre firmas y constituir una herramienta clave en la gestión flexible de los DCs.

  18. Tracing the contribution of debris flow-dominated channels to gravel-bed torrential river channel: implementing pit-tags in the upper Guil River (French Alps) (United States)

    Arnaud-Fassetta, Gilles; Lissak, Candide; Fort, Monique; Bétard, François; Carlier, Benoit; Cossart, Etienne; Madelin, Malika; Viel, Vincent; Charnay, Bérengère; Bletterie, Xavier


    In the upper, wider reaches of Alpine valleys, shaping of active channels is usually subject to rapid change. It mostly depends upon hydro-climatic variability, runoff concentration and sediment supply, and may result in alternating sequences of fluvial and debris-flow pulses, as recorded in alluvial fans and terraces. Our study, carried in the frame of SAMCO (ANR) project, focuses on the upper Guil River Valley (Queyras, Southern French Alps) cut into the slaty shale "schistes lustrés". Steep, lower order drains carry a contrasted solid discharge, including predominantly sandy-loam particles mixed with gravels and boulders (sandstone schists, ophiolites). Abundant sediment supply by frost shattering, snow avalanche and landslides is then reworked during snowmelt or summer storm runoff events, and may result in catastrophic, very destructive floods along the main channel, as shown by historical records. Following the RI-30 year 2000 flood, our investigations included sediment budgets, i.e. balance of erosion and deposition, and the mapping of the source, transport and storage of various sediments (talus, colluvium, torrential fans, terraces). To better assess sediment fluxes and sediment delivery into the main channel network, we implemented tracers (pit-tags) in selected sub-catchments, significantly contributing to the sediment yield of the valley bottoms during the floods and/or avalanches: Maloqueste, Combe Morel, Bouchouse and Peyronnelle catchments. The first three are direct tributaries of the Guil River whereas the Peyronnelle is a left bank tributary of the Peynin River, which joins the Guil River via an alluvial cone with high human and material stakes. The Maloqueste and the Combe Morel are two tributaries facing each other in the Guil valley, representing a double lateral constraint for the road during flood events of the Guil River. After pit-tag initialisation in laboratory, we set them up along the four tributaries: Maloqueste (20 pit-tags), Combe

  19. Contribution of sodium channel neuronal isoform Nav1.1 to late sodium current in ventricular myocytes from failing hearts (United States)

    Mishra, Sudhish; Reznikov, Vitaliy; Maltsev, Victor A; Undrovinas, Nidas A; Sabbah, Hani N; Undrovinas, Albertas


    Late Na+ current (INaL) contributes to action potential (AP) duration and Ca2+ handling in cardiac cells. Augmented INaL was implicated in delayed repolarization and impaired Ca2+ handling in heart failure (HF). We tested if Na+ channel (Nav) neuronal isoforms contribute to INaL and Ca2+ cycling defects in HF in 17 dogs in which HF was achieved via sequential coronary artery embolizations. Six normal dogs served as control. Transient Na+ current (INaT) and INaL in left ventricular cardiomyocytes (VCMs) were recorded by patch clamp while Ca2+ dynamics was monitored using Fluo-4. Virally delivered short interfering RNA (siRNA) ensured Nav1.1 and Nav1.5 post-transcriptional silencing. The expression of six Navs was observed in failing VCMs as follows: Nav1.5 (57.3%) > Nav1.2 (15.3%) > Nav1.1 (11.6%) > Nav2.1 (10.7%) > Nav1.3 (4.6%) > Nav1.6 (0.5%). Failing VCMs showed up-regulation of Nav1.1 expression, but reduction of Nav1.6 mRNA. A similar Nav expression pattern was found in samples from human hearts with ischaemic HF. VCMs with silenced Nav1.5 exhibited residual INaT and INaL (∼30% of control) with rightwardly shifted steady-state activation and inactivation. These currents were tetrodotoxin sensitive but resistant to MTSEA, a specific Nav1.5 blocker. The amplitude of the tetrodotoxin-sensitive INaL was 0.1709 ± 0.0299 pA pF–1 (n = 7 cells) and the decay time constant was τ = 790 ± 76 ms (n = 5). This INaL component was lacking in VCMs with a silenced Nav1.1 gene, indicating that, among neuronal isoforms, Nav1.1 provides the largest contribution to INaL. At –10 mV this contribution is ∼60% of total INaL. Our further experimental and in silico examinations showed that this new Nav1.1 INaL component contributes to Ca2+ accumulation in failing VCMs and modulates AP shape and duration. In conclusion, we have discovered an Nav1.1-originated INaL component in dog heart ventricular cells. This component is physiologically relevant to

  20. The concerted contribution of the S4-S5 linker and the S6 segment to the modulation of a Kv channel by 1-alkanols. (United States)

    Bhattacharji, Aditya; Kaplan, Benjamin; Harris, Thanawath; Qu, Xiaoguang; Germann, Markus W; Covarrubias, Manuel


    Gating of voltage-gated K(+) channels (K(v) channels) depends on the electromechanical coupling between the voltage sensor and activation gate. The main activation gate of K(v) channels involves the COOH-terminal section of the S6 segment (S6-b) and the S4-S5 linker at the intracellular mouth of the pore. In this study, we have expanded our earlier work to probe the concerted contribution of these regions to the putative amphipathic 1-alkanol site in the Shaw2 K(+) channel. In the S4-S5 linker, we found a direct energetic correlation between alpha-helical propensity and the inhibition of the Shaw2 channel by 1-butanol. Spectroscopic structural analyses of the S4-S5 linker supported this correlation. Furthermore, the analysis of chimeric Shaw2 and K(v)3.4 channels that exchanged their corresponding S4-S5 linkers showed that the potentiation induced by 1-butanol depends on the combination of a single mutation in the S6 PVPV motif (PVAV) and the presence of the Shaw2 S4-S5 linker. Then, using tandem-heterodimer subunits, we determined that this potentiation also depends on the number of S4-S5 linkers and PVAV mutations in the K(v) channel tetramer. Consistent with the critical contribution of the Shaw2 S4-S5 linker, the equivalent PVAV mutation in certain mammalian K(v) channels with divergent S4-S5 linkers conferred weak potentiation by 1-butanol. Overall, these results suggest that 1-alkanol action in Shaw2 channels depends on interactions involving the S4-S5 linker and the S6-b segment. Therefore, we propose that amphiphilic general anesthetic agents such as 1-alkanols may modulate gating of the Shaw2 K(+) channel by an interaction with its activation gate.

  1. Functional upregulation of nav1.8 sodium channels on the membrane of dorsal root Ganglia neurons contributes to the development of cancer-induced bone pain.

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    Xiao-Dan Liu

    Full Text Available We have previously reported that enhanced excitability of dorsal root ganglia (DRG neurons contributes to the development of bone cancer pain, which severely decreases the quality of life of cancer patients. Nav1.8, a tetrodotoxin-resistant (TTX-R sodium channel, contributes most of the sodium current underlying the action potential upstroke and accounts for most of the current in later spikes in a train. We speculate that the Nav1.8 sodium channel is a potential candidate responsible for the enhanced excitability of DRG neurons in rats with bone cancer pain. Here, using electrophysiology, Western blot and behavior assays, we documented that the current density of TTX-R sodium channels, especially the Nav1.8 channel, increased significantly in DRG neurons of rats with cancer-induced bone pain. This increase may be due to an increased expression of Nav1.8 on the membrane of DRG neurons. Accordantly, blockade of Nav1.8 sodium channels by its selective blocker A-803467 significantly alleviated the cancer-induced mechanical allodynia and thermal hyperalgesia in rats. Taken together, these results suggest that functional upregulation of Nav1.8 channels on the membrane of DRG neurons contributes to the development of cancer-induced bone pain.

  2. Acid-sensing ion channels contribute to the effect of extracellular acidosis on proliferation and migration of A549 cells. (United States)

    Wu, Yu; Gao, Bo; Xiong, Qiu-Ju; Wang, Yu-Chan; Huang, Da-Ke; Wu, Wen-Ning


    Acid-sensing ion channels, a proton-gated cation channel, can be activated by low extracellular pH and involved in pathogenesis of some tumors such as glioma and breast cancer. However, the role of acid-sensing ion channels in the growth of lung cancer cell is unclear. In this study, we investigated the expression of acid-sensing ion channels in human lung cancer cell line A549 and their possible role in proliferation and migration of A549 cells. The results show that acid-sensing ion channel 1, acid-sensing ion channel 2, and acid-sensing ion channel 3 are expressed in A549 cells at the messenger RNA and protein levels, and acid-sensing ion channel-like currents were elicited by extracellular acid stimuli. Moreover, we found that acidic extracellular medium or overexpressing acid-sensing ion channel 1a promotes proliferation and migration of A549 cells. In addition psalmotoxin 1, a specific acid-sensing ion channel 1a inhibitor, or acid-sensing ion channel 1a knockdown can abolish the effect of acid stimuli on A549 cells. In addition, acid-sensing ion channels mediate increase of [Ca(2+)]i induced by low extracellular pH in A549 cells. All these results indicate that acid-sensing ion channel-calcium signal mediate lung cancer cell proliferation and migration induced by extracellular acidosis, and acid-sensing ion channels may serve as a prognostic marker and a therapeutic target for lung cancer.

  3. Melanopsin Phototransduction Contributes to Light-Evoked Choroidal Expansion and Rod L-Type Calcium Channel Function In Vivo (United States)

    Berkowitz, Bruce A.; Schmidt, Tiffany; Podolsky, Robert H.; Roberts, Robin


    Purpose In humans, rodents, and pigeons, the dark → light transition signals nonretinal brain tissue to increase choroidal thickness, a major control element of choroidal blood flow, and thus of photoreceptor and retinal pigment epithelium function. However, it is unclear which photopigments in the retina relay the light signal to the brain. Here, we test the hypothesis that melanopsin (Opn4)-regulated phototransduction modulates light-evoked choroidal thickness expansion in mice. Methods Two-month-old C57Bl/6 wild-type (B6), 4- to 5-month-old C57Bl/6/129S6 wild-type (B6 + S6), and 2-month-old melanopsin knockout (Opn4−/−) on a B6 + S6 background were studied. Retinal anatomy was evaluated in vivo by optical coherence tomography and MRI. Choroidal thickness in dark and light were measured by diffusion-weighted MRI. Rod cell L-type calcium channel (LTCC) function in dark and light (manganese-enhanced MRI [MEMRI]) was also measured. Results Opn4−/− mice did not show the light-evoked expansion of choroidal thickness observed in B6 and B6 + S6 controls. Additionally, Opn4−/− mice had lower than normal rod cell and inner retinal LTCC function in the dark but not in the light. These deficits were not due to structural abnormalities because retinal laminar architecture and thickness, and choroidal thickness in the Opn4−/− mice were similar to controls. Conclusions First time evidence is provided that melanopsin phototransduction contributes to dark → light control of murine choroidal thickness. The data also highlight a contribution in vivo of melanopsin phototransduction to rod cell and inner retinal depolarization in the dark. PMID:27727394

  4. Modulation of BK channels contributes to activity-dependent increase of excitability through MTORC1 activity in CA1 pyramidal cells of mouse hippocampus

    Directory of Open Access Journals (Sweden)

    Steven eSpringer


    Full Text Available Memory acquisition and synaptic plasticity are accompanied by changes in the intrinsic excitability of CA1 pyramidal neurons. These activity-dependent changes in excitability are mediated by modulation of intrinsic currents which alters the responsiveness of the cell to synaptic inputs. The afterhyperpolarization, a major contributor to the regulation of neuronal excitability, is reduced in animals that have acquired several types of hippocampus-dependent memory tasks and also following synaptic potentiation by high frequency stimulation. BK channels underlie the fast afterhyperpolarization and contribute to spike repolarization, and this afterhyperpolarization is reduced in animals that successfully acquired trace-eyeblink conditioning. This suggests that BK channel function is activity-dependent, but the mechanisms are unknown. In this study, we found that blockade of BK channels with paxilline (10µM increased spike half-width and instantaneous frequency in response to a +100pA depolarization. In addition, induction of LTP by theta burst stimulation (TBS in CA1 pyramidal neurons reduced BK channel’s contribution to spike repolarization and instantaneous frequency. This result indicates that BK channel activity is decreased following synaptic potentiation. Interestingly, blockade of mammalian target of rapamycin (MTORC1 with rapamycin (400 nM following synaptic potentiation restored BK channel function, suggesting a role for protein translation in signaling events which decreased postsynaptic BK channel activity following synaptic potentiation.

  5. Upregulation of SK3 and IK1 channels contributes to the enhanced endothelial calcium signaling and the preserved coronary relaxation in obese Zucker rats.

    Directory of Open Access Journals (Sweden)

    Belén Climent

    Full Text Available BACKGROUND AND AIMS: Endothelial small- and intermediate-conductance KCa channels, SK3 and IK1, are key mediators in the endothelium-derived hyperpolarization and relaxation of vascular smooth muscle and also in the modulation of endothelial Ca2+ signaling and nitric oxide (NO release. Obesity is associated with endothelial dysfunction and impaired relaxation, although how obesity influences endothelial SK3/IK1 function is unclear. Therefore we assessed whether the role of these channels in the coronary circulation is altered in obese animals. METHODS AND RESULTS: In coronary arteries mounted in microvascular myographs, selective blockade of SK3/IK1 channels unmasked an increased contribution of these channels to the ACh- and to the exogenous NO- induced relaxations in arteries of Obese Zucker Rats (OZR compared to Lean Zucker Rats (LZR. Relaxant responses induced by the SK3/IK1 channel activator NS309 were enhanced in OZR and NO- endothelium-dependent in LZR, whereas an additional endothelium-independent relaxant component was found in OZR. Fura2-AM fluorescence revealed a larger ACh-induced intracellular Ca2+ mobilization in the endothelium of coronary arteries from OZR, which was inhibited by blockade of SK3/IK1 channels in both LZR and OZR. Western blot analysis showed an increased expression of SK3/IK1 channels in coronary arteries of OZR and immunohistochemistry suggested that it takes place predominantly in the endothelial layer. CONCLUSIONS: Obesity may induce activation of adaptive vascular mechanisms to preserve the dilator function in coronary arteries. Increased function and expression of SK3/IK1 channels by influencing endothelial Ca2+ dynamics might contribute to the unaltered endothelium-dependent coronary relaxation in the early stages of obesity.

  6. The interference effects of multi-channel pion-pion scattering contributions to the final states of $\\Psi$- and $\\Upsilon$-meson family decays

    CERN Document Server

    Surovtsev, Yu S; Gutsche, T; Kamiński, R; Lyubovitskij, V E; Nagy, M


    It is shown that the basic shape of dipion mass distributions in the two-pion transitions of both charmonia and bottomonia states are explained by an unified mechanism based on the contribution of the $\\pi\\pi$, $K\\overline{K}$ and $\\eta\\eta$ coupled channels including their interference.

  7. Acid-sensing ion channels in trigeminal ganglion neurons innervating the orofacial region contribute to orofacial inflammatory pain. (United States)

    Fu, Hui; Fang, Peng; Zhou, Hai-Yun; Zhou, Jun; Yu, Xiao-Wei; Ni, Ming; Zheng, Jie-Yan; Jin, You; Chen, Jian-Guo; Wang, Fang; Hu, Zhuang-Li


    Orofacial pain is a common clinical symptom that is accompanied by tooth pain, migraine and gingivitis. Accumulating evidence suggests that acid-sensing ion channels (ASICs), especially ASIC3, can profoundly affect the physiological properties of nociception in peripheral sensory neurons. The aim of this study is to examine the contribution of ASICs in trigeminal ganglion (TG) neurons to orofacial inflammatory pain. A Western blot (WB), immunofluorescence assay of labelled trigeminal ganglion neurons, orofacial formalin test, cell preparation and electrophysiological experiments are performed. This study demonstrated that ASIC1, ASIC2a and ASIC3 are highly expressed in TG neurons innervating the orofacial region of rats. The amplitude of ASIC currents in these neurons increased 119.72% (for ASIC1-like current) and 230.59% (for ASIC3-like current) in the formalin-induced orofacial inflammatory pain model. In addition, WB and immunofluorescence assay demonstrated a significantly augmented expression of ASICs in orofacial TG neurons during orofacial inflammation compared with the control group. The relative protein density of ASIC1, ASIC2a and ASIC3 also increased 58.82 ± 8.92%, 45.30 ± 11.42% and 55.32 ± 14.71%, respectively, compared with the control group. Furthermore, pharmacological blockade of ASICs and genetic deletion of ASIC1 attenuated the inflammation response. These findings indicate that peripheral inflammation can induce the upregulation of ASICs in TG neurons, causing orofacial inflammatory pain. Additionally, the specific inhibitor of ASICs may have a significant analgesic effect on orofacial inflammatory pain.

  8. The effect of resveratrol on contractility of non-pregnant rat uterus: the contribution of K(+) channels. (United States)

    Novakovic, R; Ilic, B; Beleslin-Cokic, B; Radunovic, N; Heinle, H; Scepanovic, R; Gojkovic-Bukarica, L


    This study was aimed to evaluate resveratrol (1-100 μM) effect on the spontaneous rhythmic contractions (SRC), oxytocin-induced (0.2 nM, POxC) phasic and tonic (20 nM, TOxC) contractions of isolated rat uterus. The SRC and POxC were more sensitive to resveratrol than TOxC (pD2 values: 4.53 and 4.66 versus 4.06). Different blockers of K(+) channels (glibenclamide, tetraethylamonium, iberiotoxin, 4-aminopyridine) antagonized the response to resveratrol on the SRC and phasic contractions, but did not antagonize the effect of resveratrol on the TOxC. In order to compare the relaxant activities of resveratrol on the TOxC with that of potassium channel openers, a separate experiments with NS 1619, a highly specific big Ca(2+)-sensitive K(+) (BKCa) channels opener and pinacidil, a predominant opener of ATP-sensitive K(+) (KATP) channels were done. NS 1619 (10-100 μM) and pinacidil (10-100 μM) produced more potent inhibition of TOxC than resveratrol (pD2 values were 6.00 and 5.29). Iberiotoxin, a highly selective BKCa channels blocker, antagonized the response to NS 1619 and glibenclamide, a highly selective KATP channels blocker, antagonized the response to pinacidil on the TOxC. To test K(+)- and extracellular Ca(2+)- independent mechanism(s) of resveratrol on TOxC, a K(+)-rich, Ca(2+)-free solution was used. Under this condition, only high concentrations (≥30 μM) of resveratrol inhibited TOxC. Western blots analysis confirmed expression of Kir6.1, Kir6.2, KCa1.1, Kv2.1 and Kv4.2. channel proteins in myometrium. Thus, the effect of resveratrol is dependent on the types of contractions. The inhibitory response of resveratrol on the SRC and phasic contractions involves different myometrial K(+)- channels. When applied in high concentrations, resveratrol has an additional K(+)- channels independent mechanism(s) of action. As the effects of NS 1619, pinacidil and resveratrol on the TOxC are different, we can conclud that resveratrol does not behave as a classical

  9. Contribution of K(+) channels to endothelium-derived hypolarization-induced renal vasodilation in rats in vivo and in vitro. (United States)

    Rasmussen, Kasper Moller Boje; Braunstein, Thomas Hartig; Salomonsson, Max; Brasen, Jens Christian; Sorensen, Charlotte Mehlin


    We investigated the mechanisms behind the endothelial-derived hyperpolarization (EDH)-induced renal vasodilation in vivo and in vitro in rats. We assessed the role of Ca(2+)-activated K(+) channels and whether K(+) released from the endothelial cells activates inward rectifier K(+) (Kir) channels and/or the Na(+)/K(+)-ATPase. Also, involvement of renal myoendothelial gap junctions was evaluated in vitro. Isometric tension in rat renal interlobar arteries was measured using a wire myograph. Renal blood flow was measured in isoflurane anesthetized rats. The EDH response was defined as the ACh-induced vasodilation assessed after inhibition of nitric oxide synthase and cyclooxygenase using L-NAME and indomethacin, respectively. After inhibition of small conductance Ca(2+)-activated K(+) channels (SKCa) and intermediate conductance Ca(2+)-activated K(+) channels (IKCa) (by apamin and TRAM-34, respectively), the EDH response in vitro was strongly attenuated whereas the EDH response in vivo was not significantly reduced. Inhibition of Kir channels and Na(+)/K(+)-ATPases (by ouabain and Ba(2+), respectively) significantly attenuated renal vasorelaxation in vitro but did not affect the response in vivo. Inhibition of gap junctions in vitro using carbenoxolone or 18α-glycyrrhetinic acid significantly reduced the endothelial-derived hyperpolarization-induced vasorelaxation. We conclude that SKCa and IKCa channels are important for EDH-induced renal vasorelaxation in vitro. Activation of Kir channels and Na(+)/K(+)-ATPases plays a significant role in the renal vascular EDH response in vitro but not in vivo. The renal EDH response in vivo is complex and may consist of several overlapping mechanisms some of which remain obscure.

  10. Contribution of spontaneous L-type Ca2+ channel activation to the genesis of Ca2+ sparks in resting cardiac myocytes

    Institute of Scientific and Technical Information of China (English)

    ZHANG Guangqin; FU Yu; YANG Dongmei; HAO Xuemei; BAI Shuhua; TANG Yiqun; Edward G LAKATTA; WU Caihong; CHENG Heping


    Ca2+ sparks are the elementary events of intracellular Ca2+ release from the sarcoplasmic reticulum in cardiac myocytes. In order to investigate whether spontaneous L-type Ca2+ channel activation contributes to the genesis of spontaneous Ca2+ sparks, we used confocal laser scanning microscopy and fluo-4 to visualize local Ca2+ sparks in intact rat ventricular myocytes. In the presence of 0.2 mmol/L CdCl2 which inhibits spontaneous L-type Ca2+ channel activation, the rate of occurrence of spontaneous Ca2+ sparks was halved from 4.20 to 2.04 events/(100 μm·s), with temporal and spatial properties of individual Ca2+ sparks unchanged. Analysis of the Cd2+-sensitive spark production revealed an open probability of ~10-5 for L-type channels at the rest membrane potentials (-80 mV). Thus, infrequent and stochastic openings of sarcolemmal L-type Ca2+ channels in resting heart cells contribute significantly to the production of spontaneous Ca2+ sparks.

  11. Antagonism of Nav channels and α1-adrenergic receptors contributes to vascular smooth muscle effects of ranolazine. (United States)

    Virsolvy, Anne; Farah, Charlotte; Pertuit, Nolwenn; Kong, Lingyan; Lacampagne, Alain; Reboul, Cyril; Aimond, Franck; Richard, Sylvain


    Ranolazine is a recently developed drug used for the treatment of patients with chronic stable angina. It is a selective inhibitor of the persistent cardiac Na(+) current (INa), and is known to reduce the Na(+)-dependent Ca(2+) overload that occurs in cardiomyocytes during ischemia. Vascular effects of ranolazine, such as vasorelaxation,have been reported and may involve multiple pathways. As voltage-gated Na(+) channels (Nav) present in arteries play a role in contraction, we hypothesized that ranolazine could target these channels. We studied the effects of ranolazine in vitro on cultured aortic smooth muscle cells (SMC) and ex vivo on rat aortas in conditions known to specifically activate or promote INa. We observed that in the presence of the Nav channel agonist veratridine, ranolazine inhibited INa and intracellular Ca(2+) calcium increase in SMC, and arterial vasoconstriction. In arterial SMC, ranolazine inhibited the activity of tetrodotoxin-sensitive voltage-gated Nav channels and thus antagonized contraction promoted by low KCl depolarization. Furthermore, the vasorelaxant effects of ranolazine, also observed in human arteries and independent of the endothelium, involved antagonization of the α1-adrenergic receptor. Combined α1-adrenergic antagonization and inhibition of SMCs Nav channels could be involved in the vascular effects of ranolazine.

  12. Calcium-sensing receptor activation contributed to apoptosis stimulates TRPC6 channel in rat neonatal ventricular myocytes

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Yi-hua [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China); Li, Yong-quan [Harbin Medical University, Harbin 150086 (China); Feng, Shan-li [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China); Li, Bao-xin; Pan, Zhen-wei [Department of Pharmacology, Harbin Medical University, Harbin 150086 (China); Xu, Chang-qing [Department of Pathophysiology, Harbin Medical University, Harbin 150086 (China); Li, Ting-ting [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China); Yang, Bao-feng, E-mail: [Department of Pharmacology, Harbin Medical University, Harbin 150086 (China)


    Capacitative calcium entry (CCE) refers to the influx of calcium through plasma membrane channels activated on depletion of endoplasmic sarcoplasmic/reticulum (ER/SR) Ca{sup 2+} stores, which is performed mainly by the transient receptor potential (TRP) channels. TRP channels are expressed in cardiomyocytes. Calcium-sensing receptor (CaR) is also expressed in rat cardiac tissue and plays an important role in mediating cardiomyocyte apoptosis. However, there are no data regarding the link between CaR and TRP channels in rat heart. In this study, in rat neonatal myocytes, by Ca{sup 2+} imaging, we found that the depletion of ER/SR Ca{sup 2+} stores by thapsigargin (TG) elicited a transient rise in cytoplasmic Ca{sup 2+} ([Ca{sup 2+}]{sub i}), followed by sustained increase depending on extracellular Ca{sup 2+}. But, TRP channels inhibitor (SKF96365), not L-type channels or the Na{sup +}/Ca{sup 2+} exchanger inhibitors, inhibited [Ca{sup 2+}]{sub i} relatively high. Then, we found that the stimulation of CaR with its activator gadolinium chloride (GdCl{sub 3}) or by an increased extracellular Ca{sup 2+}([Ca{sup 2+}]{sub o}) increased the concentration of intracelluar Ca{sup 2+}, whereas, the sustained elevation of [Ca{sup 2+}]{sub i} was reduced in the presence of SKF96365. Similarly, the duration of [Ca{sup 2+}]{sub i} increase was also shortened in the absence of extracellular Ca{sup 2+}. Western blot analysis showed that GdCl{sub 3} increased the expression of TRPC6, which was reversed by SKF96365. Additionally, SKF96365 reduced cardiomyocyte apoptosis induced by GdCl{sub 3}. Our results suggested that CCE exhibited in rat neonatal myocytes and CaR activation induced Ca{sup 2+}-permeable cationic channels TRPCs to gate the CCE, for which TRPC6 was one of the most likely candidates. TRPC6 channel was functionally coupled with CaR to enhance the cardiomyocyte apoptosis.

  13. DECOVALEX II PROJECT. Technical report - Task 1A and 1B

    Energy Technology Data Exchange (ETDEWEB)

    Lanru Jing; Stephansson, Ove [Royal Inst. of Tech., Stockholm (Sweden). Dept. of Civil and Environmental Engineering; Chin-Fu Tsang [Lawrence Berkeley National Laboratory, Berkeley, CA (United States). Earth Science Division; Knight, J.L. [Nirex Ltd, Harwell (United Kingdom); Kautsky, F. [Swedish Nuclear Power lnspectorate (SKI), Stockholm (Sweden)


    DECOVALEX II project started in November 1995 as a continuation of the DECOVALEX I project, which was completed at the end of 1994. The project was initiated by recognizing the fact that a proper evaluation of the current capacities of numerical modelling of the coupled T-H-M processes in fractured media is needed not only for small scale, well controlled laboratory test cases such as those studied in DECOVALEX I, but also for less characterised, more complex and realistic in-situ experiments. This will contribute to validation and confidence building in the current mathematical models, numerical methods and computer codes. Four tasks were defined in the DECOVALEX II project: TASK 1 - numerical study of the RCF3 pumping test and shaft excavation at Sellafield by Nirex, UK; TASK 2 - numerical study of the in-situ T-H-M experiments at Kamaishi Mine by PNC, Japan; TASK 3 - review of current state-of-the-art of rock joint research and TASK 4 - report on the coupled T-H-M issues related to repository design and performance assessment. This report is one of the technical reports of the DECOVALEX II project, describing the work performed for TASK 1A and 1B - the predictions and model calibrations for the RCF 3 pumping test at Sellafield. Presented in this report are the descriptions of the project, tasks, approaches, methods and results of numerical modelling work carried out by the research teams. The report is a summary of the research reports written by the research teams and submitted to the project secretariat, and the discussions held during project workshops and task force group meetings. The opinions and conclusions in this report, however, reflect only ideas of the authors, not necessarily a collective representation of the funding organisations of the project. 21 refs, figs, tabs

  14. Inhibition of mitochondrial permeability transition pore contributes to the neuroprotection induced by activation of mitochondrial ATP-sensitive potassium channel

    Institute of Scientific and Technical Information of China (English)

    Li-pingWU; FangSHEN; QiangXIA


    AIM: To investigate whether the neuroprotection via activating mitochondrial ATP-sensitive potassium channel (mitoKTP) is mediated by the inhibition of mitochondrial permeability transition pore (MPTP). METHODS: Adult male Sprague-Dawleyrats were undergoing 90 min of middle cerebral artery occlusion(MCAO) by introducing a nylon monofilament through the external

  15. Role of nitric oxide in the regulation of mechanosensitive ionic channels in cardiomyocytes: contribution of NO-synthases. (United States)

    Kazanski, V E; Kamkin, A G; Makarenko, E Yu; Lysenko, N N; Sutiagin, P V; Kiseleva, I S


    The role of NO in the regulation of currents passing through ion channels activated by cell stretching (mechanically gated channels, MGC), particularly through cation-selective K(+)-channels TRPC6, TREK1 (K(2P)2.1), and TREK2 (K(2P)10.1), was studied on isolated mouse, rat, and guinea pig cardiomyocytes using whole-cell patch-clamp technique. In non-deformed cells, binding of endogenous NO with PTIO (2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-1-oxy-3-oxide) irreversibly shifted the diastolic membrane potential towards negative values, modulates K(ir)-channels by reducing I(K1), and blocks MGC. Perfusion of stretched cells with PTIO solution completely blocked MG-currents. NO-synthase inhibitors L-NAME and L-NMMA completely blocked MGC. Stretching of cardiomyocytes isolated from wild type mice and from NOS1(-/-)- and NOS2(-/-)- knockout mice led to the appearance in MG-currents typical for the specified magnitude of stretching, while stretching of cardiomyocytes from NOS3(-/-)- knockout mice did not produce in MG-current. These findings suggest that NO plays a role in the regulation of MGC activity and that endothelial NO-synthase predominates as NO source in cardiomyocyte response to stretching.

  16. Contribution of N- and C-terminal Kv4.2 channel domains to KChIP interaction [corrected]. (United States)

    Callsen, Britta; Isbrandt, Dirk; Sauter, Kathrin; Hartmann, L Sven; Pongs, Olaf; Bähring, Robert


    Association of Shal gene-related voltage-gated potassium (Kv4) channels with cytoplasmic Kv channel interacting proteins (KChIPs) influences inactivation gating and surface expression. We investigated both functional and biochemical consequences of mutations in cytoplasmic N and C-terminal Kv4.2 domains to characterize structural determinants for KChIP interaction. We performed a lysine-scanning mutagenesis within the proximal 40 amino acid portion and a structure-based mutagenesis in the tetramerization 1 (T1) domain of Kv4.2. In addition, the cytoplasmic Kv4.2 C-terminus was truncated at various positions. Wild-type and mutant Kv4.2 channels were coexpressed with KChIP2 isoforms in mammalian cell lines. The KChIP2-induced modulation of Kv4.2 currents was studied with whole-cell patch clamp and the binding of KChIP2 isoforms to Kv4.2 channels with coimmunoprecipitation experiments. Our results define one major interaction site for KChIPs, including amino acids in the proximal N-terminus between residues 11 and 23, where binding and functional modulation are essentially equivalent. A further interaction site includes residues in the T1 domain. Notably, C-terminal deletions also had marked effects on KChIP2-dependent gating modulation and KChIP2 binding, revealing a previously unknown involvement of domains within the cytoplasmic Kv4.2 C-terminus in KChIP interaction. Less coincidence of binding and functional modulation indicates a more loose 'anchoring' at T1- and C-terminal interaction sites. Our results refine and extend previously proposed structural models for Kv4.2/KChIP complex formation.

  17. Cav1.4 L-Type Calcium Channels Contribute to Calpain Activation in Degenerating Photoreceptors of rd1 Mice.

    Directory of Open Access Journals (Sweden)

    Christian Schön

    Full Text Available Retinitis pigmentosa is an inherited blinding disorder characterized by progressive degeneration and loss of photoreceptors. The exact mechanism of degeneration and cell death of photoreceptors is not known, but is thought to involve disturbed Ca2+-signaling. Ca2+ can enter the photoreceptor cell via outer segment cyclic nucleotide-gated (CNG channels or synaptic Cav1.4 L-type voltage-gated calcium channels (VGCC. Previously, we have shown that genetic ablation of the Cngb1 gene encoding the B subunit of the rod CNG channel delays the fast progressing degeneration in the rd1 mutant mouse model of retinitis pigmentosa. In this study, we crossbred rd1 mice with the Cacna1f-deficient mouse lacking the Cav1.4 α1 subunit of the L-type VGCC. Longitudinal in vivo examinations of photoreceptor layer thickness by optical coherence tomography revealed a significant, but not sustained delay of retinal degeneration in Cacna1f x rd1 double mutant mice compared to rd1 mice. This was accompanied by a reduction of TUNEL positive cells in the early phase of rod degeneration. Remarkably, Cacna1f x rd1 double mutant mice displayed a strong decrease in the activation of the Ca2+-dependent protease calpain during photoreceptor loss. Our results show that genetic deletion of the synaptic Cav1.4 L-type VGCCs impairs calpain activation and leads to a short-term preservation of photoreceptors in the rd1 mouse.

  18. Suspended sediment load and mechanical erosion in the Senegal Basin — Estimation of the surface runoff concentration and relative contributions of channel and slope erosion (United States)

    Kattan, Z.; Gac, J. Y.; Probst, J. L.


    The main purpose of this paper is to propose a method to better understand the suspended sediment dynamics in the Senegal Basin, and the behaviour of the river particulate load at Bakel gauging station (218,000 km 2) during the period 1979-1984. The method is based on the estimation of surface discharge using a simple hydrological model which allows separation of the different flow components of the annual hydrograph. Then the suspended sediment loads can be correlated with the surface discharge. During the study period, the mean annual flow (330 m 3s -1) represented only 46% of the mean long-term flow (1903-1984), and the mean yearly particulate load carried by the Senegal River was about 1.9 million tons. Two approaches are used to estimate the different contributions to the river's suspended sediment transport. The main contribution originates from slope erosion, which supplies 50-80% of the total sediment transport and the second originates from channel erosion. The suspended sediment concentration in the surface runoff, primarily calculated by a global annual method, ranges from 0.9 to 1.6 gl -1 and averages 1.3 gl -1. After correction for channel erosion input, this concentration is reduced to 1.1 gl -1.

  19. PRP training shows Task1 response selection is the locus of the backward response compatibility effect. (United States)

    Thomson, Sandra J; Danis, Lila K; Watter, Scott


    The present study investigates the effect of practice in a psychological refractory period (PRP) paradigm on the backward compatibility effect (BCE), in order to determine the locus of this response priming effect on Task1 performance. In two experiments, we show that the size of the BCE is closely associated with the duration of the response selection stage in Task1. When this stage is shortened through PRP practice, the magnitude of the BCE decreases. Subsequently increasing the duration of Task1 response selection results in a larger BCE, but manipulating the same stage in Task2 does not. Our results suggest that the BCE reflects crosstalk of unattended response information for Task2 acting on the response selection stage in Task1, and that response information for two tasks may be activated simultaneously.

  20. On the importance of Task 1 and error performance measures in PRP dual-task studies

    Directory of Open Access Journals (Sweden)

    Tilo eStrobach


    Full Text Available The Psychological Refractory Period (PRP paradigm is a dominant research tool in the literature on dual-task performance. In this paradigm a first and second component task (i.e., Task 1 and 2 are presented with variable stimulus onset asynchronies (SOAs and priority to perform Task 1. The main indicator of dual-task impairment in PRP situations is an increasing Task 2-RT with decreasing SOAs. This impairment is typically explained with some task components being processed strictly sequentially in the context of the prominent central bottleneck theory. This assumption could implicitly suggest that processes of Task 1 are unaffected by Task 2 and bottleneck processing, i.e. decreasing SOAs do not increase RTs and error rates of the first task. The aim of the present review is to assess whether PRP dual-task studies included both RT and error data presentations and statistical analyses and whether studies including both data types (i.e., RTs and error rates show data consistent with this assumption (i.e., decreasing SOAs and unaffected RTs and/ or error rates in Task 1. This review demonstrates that, in contrast to RT presentations and analyses, error data is underrepresented in a substantial number of studies. Furthermore, a substantial number of studies with RT and error data showed a statistically significant impairment of Task 1 performance with decreasing SOA. Thus, these studies produced data that is not primarily consistent with the strong assumption that processes of Task 1 are unaffected by Task 2 and bottleneck processing in the context of PRP dual-task situations; this calls for a more careful report and analysis of Task 1 performance in PRP studies and for a more careful consideration of theories proposing additions to the bottleneck assumption, which are sufficiently general to explain Task 1 and Task 2 effects.

  1. MicroRNA-Mediated Downregulation of the Potassium Channel Kv4.2 Contributes to Seizure Onset

    Directory of Open Access Journals (Sweden)

    Christina Gross


    Full Text Available Seizures are bursts of excessive synchronized neuronal activity, suggesting that mechanisms controlling brain excitability are compromised. The voltage-gated potassium channel Kv4.2, a major mediator of hyperpolarizing A-type currents in the brain, is a crucial regulator of neuronal excitability. Kv4.2 expression levels are reduced following seizures and in epilepsy, but the underlying mechanisms remain unclear. Here, we report that Kv4.2 mRNA is recruited to the RNA-induced silencing complex shortly after status epilepticus in mice and after kainic acid treatment of hippocampal neurons, coincident with reduction of Kv4.2 protein. We show that the microRNA miR-324-5p inhibits Kv4.2 protein expression and that antagonizing miR-324-5p is neuroprotective and seizure suppressive. MiR-324-5p inhibition also blocks kainic-acid-induced reduction of Kv4.2 protein in vitro and in vivo and delays kainic-acid-induced seizure onset in wild-type but not in Kcnd2 knockout mice. These results reveal an important role for miR-324-5p-mediated silencing of Kv4.2 in seizure onset.

  2. The M4 Transmembrane α-Helix Contributes Differently to Both the Maturation and Function of Two Prokaryotic Pentameric Ligand-gated Ion Channels. (United States)

    Hénault, Camille M; Juranka, Peter F; Baenziger, John E


    The role of the outermost transmembrane α-helix in both the maturation and function of the prokaryotic pentameric ligand-gated ion channels, GLIC and ELIC, was examined by Ala scanning mutagenesis, deletion mutations, and mutant cycle analyses. Ala mutations at the M4-M1/M3 interface lead to loss-of-function phenotypes in GLIC, with the largest negative effects occurring near the M4 C terminus. In particular, two aromatic residues at the M4 C terminus form a network of π-π and/or cation-π interactions with residues on M3 and the β6-β7 loop that is essential for both maturation and function. M4-M1/M3 interactions appear to be optimized in GLIC with even subtle structural changes at this interface leading to detrimental effects. In contrast, mutations along the M4-M1/M3 interface of ELIC typically lead to gain-of-function phenotypes, suggesting that these interactions in ELIC are not optimized for channel function. In addition, no cluster of interacting residues involving the M4 C terminus, M3, and the β6-β7 loop was found, suggesting that the M4 C terminus plays little role in ELIC maturation or function. This study shows that M4 makes distinct contributions to the maturation and gating of these two closely related homologs, suggesting that GLIC and ELIC exhibit divergent features of channel function. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. LHCb: Measurements of the relative branching fractions of the decay channel $B^{\\pm}\\to p \\bar{p} K^{\\pm}$ including charmonium contributions at LHCb

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    Cardinale, Roberta


    The study of the $B^{\\pm}\\to p \\bar{p} K^{\\pm}$ decay channel at LHCb is of great interest since it gives the possibility to study different aspects of the Standard Model and possibly Beyond Standard Model physics. A measurement of the direct CP asymmetry can be performed. Moreover intermediate states such as charmonium and "charmonium-like" resonances in the $p \\bar{p}$ final state can be observed and studied along with their characteristics. A multivariate selection has been implemented to select the interesting events using kinematic and topological variables and the particle identification information using the Ring Imaging Cherenkov detectors. The selection has a high signal efficiency and high background rejection capability. The ratios of the branching fractions of the $B^{\\pm}\\to p \\bar{p} K^{\\pm}$ decay channel, of the charmless component with $M_{p \\bar{p}} < 2.85 \\,{\\rm GeV/}c^{2}$ and of the charmonium contribution $\\eta_{c}$, ${\\mathcal B} (B^{\\pm}\\to \\eta_{c} K^{\\pm})\\times {\\mathcal B} (\\eta...

  4. Contribution of SK and BK channels in the control of catecholamine release by electrical stimulation of the cat adrenal gland. (United States)

    Montiel, C; López, M G; Sánchez-García, P; Maroto, R; Zapater, P; García, A G


    on catecholamine release induced by electrical stimulation was observed at low but not at high [Ca2+]o. 6. Simultaneous release of acetylcholine and catecholamines upon electrical stimulation was achieved in glands in which the endogenous acetylcholine stores in the splanchnic nerve terminals had been prelabelled by perfusion with [3H]choline. While apamin enhanced more than 2-fold the postsynaptic release of catecholamines, the presynaptic release of acetylcholine remained unaffected. 7. The results are compatible with the hypothesis that, under physiological conditions, Ca(2+)-activated SK channels present in chromaffin cells control the firing patterns of action potentials induced by the acetylcholine released from splanchnic nerves during stress.(ABSTRACT TRUNCATED AT 400 WORDS)

  5. Contribution of SK and BK channels in the control of catecholamine release by electrical stimulation of the cat adrenal gland. (United States)

    Montiel, C; López, M G; Sánchez-García, P; Maroto, R; Zapater, P; García, A G


    on catecholamine release induced by electrical stimulation was observed at low but not at high [Ca2+]o. 6. Simultaneous release of acetylcholine and catecholamines upon electrical stimulation was achieved in glands in which the endogenous acetylcholine stores in the splanchnic nerve terminals had been prelabelled by perfusion with [3H]choline. While apamin enhanced more than 2-fold the postsynaptic release of catecholamines, the presynaptic release of acetylcholine remained unaffected. 7. The results are compatible with the hypothesis that, under physiological conditions, Ca(2+)-activated SK channels present in chromaffin cells control the firing patterns of action potentials induced by the acetylcholine released from splanchnic nerves during stress.(ABSTRACT TRUNCATED AT 400 WORDS) Images Figure 3 Figure 4 Figure 6 PMID:7473208

  6. Activation of the KCa3.1 channel contributes to traumatic scratch injury-induced reactive astrogliosis through the JNK/c-Jun signaling pathway. (United States)

    Yi, Mengni; Dou, Fangfang; Lu, Qin; Yu, Zhihua; Chen, Hongzhuan


    Reactive astrogliosis is widely considered to contribute to pathogenic responses to stress and brain injury and to diseases as diverse as ischemia and neurodegeneration. We previously found that expression of the intermediate-conductance calcium-activated potassium channel (KCa3.1) involved in TGF-β-activated astrogliosis. In the present study, we investigated whether migration of cortical astrocytes following mechanical scratch injury involves the KCa3.1 channel, which contributes to Ca(2+)-mediated migration in other cells. We found that scratch injury increased the expression of KCa3.1 protein in reactive astrocytes. Application of the KCa3.1 blocker TRAM-34 decreased glial fibrillary acidic protein (GFAP) expression and slowed migration in a concentration-dependent manner. Application of the Ca(2+) chelators, EGTA and BAPTA-AM, also slowed the migration of astrocytes. Blockade or genetic deletion of KCa3.1 both slowed and dramatically reduced the scratch injuries induced the sharp rise in astrocytes Ca(2+) concentrations. The scratch injury-induced phosphorylation of JNK and c-Jun proteins was also attenuated both by blockade of KCa3.1 with TRAM-34 and in KCa3.1(-/-) astrocytes. Using KCa3.1 knockout mice, we further confirmed that deletion of KCa3.1 reduced expression of GFAP in an in vivo stab wound model. Taken together, our findings highlight a novel role for KCa3.1 in phenotypic modulation of reactive astrocytes and in astrocyte mobilization in response to mechanical stress, providing a potential target for therapeutic intervention in brain injuries.

  7. Functional Contributions of Positive Charges in the Pore-Lining Helix 3 of the Bordetella pertussis CyaA-Hemolysin to Hemolytic Activity and Ion-Channel Opening

    Directory of Open Access Journals (Sweden)

    Chattip Kurehong


    Full Text Available The Bordetella pertussis CyaA-hemolysin (CyaA-Hly domain was previously demonstrated to be an important determinant for hemolysis against target erythrocytes and ion-channel formation in planar lipid bilayers (PLBs. Here, net-charge variations in the pore-lining helix of thirteen related RTX cytolysins including CyaA-Hly were revealed by amino acid sequence alignments, reflecting their different degrees of hemolytic activity. To analyze possible functional effects of net-charge alterations on hemolytic activity and channel formation of CyaA-Hly, specific mutations were made at Gln574 or Glu581 in its pore-lining α3 of which both residues are highly conserved Lys in the three highly active RTX cytolysins (i.e., Escherichia coli α-hemolysin, Actinobacillus pleuropneumoniae toxin, and Aggregatibacter actinomycetemcomitans leukotoxin. All six constructed CyaA-Hly mutants that were over-expressed in E. coli as 126 kDa His-tagged soluble proteins were successfully purified via immobilized Ni2+-affinity chromatography. Both positive-charge substitutions (Q574K, Q574R, E581K, E581R and negative-charge elimination (E581Q appeared to increase the kinetics of toxin-induced hemolysis while the substitution with a negatively-charged side-chain (Q574E completely abolished its hemolytic activity. When incorporated into PLBs under symmetrical conditions (1.0 M KCl, pH 7.4, all five mutant toxins with the increased hemolytic activity produced clearly-resolved single channels with higher open probability and longer lifetime than the wild-type toxin, albeit with a half decrease in their maximum conductance. Molecular dynamics simulations for 50 ns of a trimeric CyaA-Hly pore model comprising three α2-loop-α3 transmembrane hairpins revealed a significant role of the positive charge at both target positions in the structural stability and enlarged diameter of the simulated pore. Altogether, our present data have disclosed functional contributions of positively

  8. Volume regulated anion channel currents of rat hippocampal neurons and their contribution to oxygen-and-glucose deprivation induced neuronal death.

    Directory of Open Access Journals (Sweden)

    Huaqiu Zhang

    Full Text Available Volume-regulated anion channels (VRAC are widely expressed chloride channels that are critical for the cell volume regulation. In the mammalian central nervous system, the physiological expression of neuronal VRAC and its role in cerebral ischemia are issues largely unknown. We show that hypoosmotic medium induce an outwardly rectifying chloride conductance in CA1 pyramidal neurons in rat hippocampal slices. The induced chloride conductance was sensitive to some of the VRAC inhibitors, namely, IAA-94 (300 µM and NPPB (100 µM, but not to tamoxifen (10 µM. Using oxygen-and-glucose deprivation (OGD to simulate ischemic conditions in slices, VRAC activation appeared after OGD induced anoxic depolarization (AD that showed a progressive increase in current amplitude over the period of post-OGD reperfusion. The OGD induced VRAC currents were significantly inhibited by inhibitors for glutamate AMPA (30 µM NBQX and NMDA (40 µM AP-5 receptors in the OGD solution, supporting the view that induction of AD requires an excessive Na(+-loading via these receptors that in turn to activate neuronal VRAC. In the presence of NPPB and DCPIB in the post-OGD reperfusion solution, the OGD induced CA1 pyramidal neuron death, as measured by TO-PRO-3-I staining, was significantly reduced, although DCPIB did not appear to be an effective neuronal VRAC blocker. Altogether, we show that rat hippocampal pyramidal neurons express functional VRAC, and ischemic conditions can initial neuronal VRAC activation that may contribute to ischemic neuronal damage.

  9. Classical-Nova Contribution to the Milky Way's $^{26}$Al Abundance: Exit Channel of the Key $^{25}$Al($p,\\gamma$)$^{26}$Si Resonance

    CERN Document Server

    Bennett, M B; Chipps, K A; José, J; Liddick, S N; Santia, M; Bowe, A; Chen, A A; Cooper, N; Irvine, D; McNeice, E; Montes, F; Naqvi, F; Ortez, R; Pain, S D; Pereira, J; Prokop, C; Quaglia, J; Quinn, S J; Schwartz, S B; Shanab, S; Simon, A; Spyrou, A; Thiagalingam, E


    Classical novae are expected to contribute to the 1809-keV Galactic $\\gamma$-ray emission by producing its precursor $^{26}$Al, but the yield depends on the thermonuclear rate of the unmeasured $^{25}$Al($p,\\gamma$)$^{26}$Si reaction. Using the $\\beta$ decay of $^{26}$P to populate the key $J^{\\pi}=3^+$ resonance in this reaction, we report the first evidence for the observation of its exit channel via a $1741.6 \\pm 0.6 (\\textrm{stat}) \\pm 0.3 (\\textrm{syst})$ keV primary $\\gamma$ ray, where the uncertainties are statistical and systematic, respectively. By combining the measured $\\gamma$-ray energy and intensity with other experimental data on $^{26}$Si, we find the center-of-mass energy and strength of the resonance to be $E_r = 414.9 \\pm 0.6(\\textrm{stat}) \\pm 0.3 (\\textrm{syst}) \\pm 0.6(\\textrm{lit.})$ keV and $\\omega\\gamma = 23 \\pm 6 (\\textrm{stat})^{+11}_{-10}(\\textrm{lit.})$ meV, respectively, where the last uncertainties are from adopted literature data. We use hydrodynamic nova simulations to model $...

  10. Distinct Kv channel subtypes contribute to differences in spike signaling properties in the axon initial segment and presynaptic boutons of cerebellar interneurons. (United States)

    Rowan, Matthew J M; Tranquil, Elizabeth; Christie, Jason M


    The discrete arrangement of voltage-gated K(+) (Kv) channels in axons may impart functional advantages in action potential (AP) signaling yet, in compact cell types, the organization of Kv channels is poorly understood. We find that in cerebellar stellate cell interneurons of mice, the composition and influence of Kv channels populating the axon is diverse and depends on location allowing axonal compartments to differentially control APs in a local manner. Kv1 channels determine AP repolarization at the spike initiation site but not at more distal sites, limiting the expression of use-dependent spike broadening to the most proximal axon region, likely a key attribute informing spiking phenotype. Local control of AP repolarization at presynaptic boutons depends on Kv3 channels keeping APs brief, thus limiting Ca(2+) influx and synaptic strength. These observations suggest that AP repolarization is tuned by the local influence of distinct Kv channel types, and this organization enhances the functional segregation of axonal compartments.

  11. Assessment of Fleet Inventory for Naval Air Station Whidbey Island. Task 1

    Energy Technology Data Exchange (ETDEWEB)

    Schey, Stephen [Idaho National Lab. (INL), Idaho Falls, ID (United States); Francfort, Jim [Idaho National Lab. (INL), Idaho Falls, ID (United States)


    Task 1includes a survey of the inventory of non-tactical fleet vehicles at Naval Air Station Whidbey Island (NASWI) to characterize the fleet. This information and characterization are used to select vehicles for monitoring that takes place during Task 2. This monitoring involves data logging of vehicle operation in order to identify the vehicle’s mission and travel requirements. Individual observations of these selected vehicles provide the basis for recommendations related to PEV adoption. It also identifies whether a battery electric vehicle or plug-in hybrid electric vehicle (collectively referred to as PEVs) can fulfill the mission requirements and provide observations related to placement of PEV charging infrastructure. This report provides the results of the assessments and observations of the current non-tactical fleet, fulfilling the Task 1 requirements.

  12. US-UK Phase 3 Task 1 Oxidation in Supercritical Fluids

    Energy Technology Data Exchange (ETDEWEB)

    Holcomb, Gordon R. [National Energy Technology Lab. (NETL), Albany, OR (United States)


    A presentation of the US-UK Phase 3 Task 1 Oxidation in Supercritical Fluids. Includes slides on Supercritical Steam, sCO2 Power Cycles – Indirect, sCO2 Power Cycles – Direct, Experimental Exposures, Alloys, Why Si, Results—Ni-xCr Alloys (5-24Cr), Fatigue Crack Growth$-$Experiment, and Alloys and Samples, Fatigue Crack Growth—Results (H282).

  13. H2O2 generated by NADPH oxidase 4 contributes to transient receptor potential vanilloid 1 channel-mediated mechanosensation in the rat kidney. (United States)

    Lin, Chian-Shiung; Lee, Shang-Hsing; Huang, Ho-Shiang; Chen, Yih-Sharng; Ma, Ming-Chieh


    The presence of NADPH oxidase (Nox) in the kidney, especially Nox4, results in H2O2 production, which regulates Na(+) excretion and urine formation. Redox-sensitive transient receptor potential vanilloid 1 channels (TRPV1s) are distributed in mechanosensory fibers of the renal pelvis and monitor changes in intrapelvic pressure (IPP) during urine formation. The present study tested whether H2O2 derived from Nox4 affects TRPV1 function in renal sensory responses. Perfusion of H2O2 into the renal pelvis dose dependently increased afferent renal nerve activity and substance P (SP) release. These responses were attenuated by cotreatment with catalase or TRPV1 blockers. In single unit recordings, H2O2 activated afferent renal nerve activity in response to rising IPP but not high salt. Western blots revealed that Nox2 (gp91(phox)) and Nox4 are both present in the rat kidney, but Nox4 is abundant in the renal pelvis and originates from dorsal root ganglia. This distribution was associated with expression of the Nox4 regulators p22(phox) and polymerase δ-interacting protein 2. Coimmunoprecipitation experiments showed that IPP increases polymerase δ-interacting protein 2 association with Nox4 or p22(phox) in the renal pelvis. Interestingly, immunofluorescence labeling demonstrated that Nox4 colocalizes with TRPV1 in sensory fibers of the renal pelvis, indicating that H2O2 generated from Nox4 may affect TRPV1 activity. Stepwise increases in IPP and saline loading resulted in H2O2 and SP release, sensory activation, diuresis, and natriuresis. These effects, however, were remarkably attenuated by Nox inhibition. Overall, these results suggest that Nox4-positive fibers liberate H2O2 after mechanostimulation, thereby contributing to a renal sensory nerve-mediated diuretic/natriuretic response.

  14. Suppression of KCNQ/M (Kv7) potassium channels in the spinal cord contributes to the sensitization of dorsal horn WDR neurons and pain hypersensitivity in a rat model of bone cancer pain. (United States)

    Cai, Jie; Fang, Dong; Liu, Xiao-Dan; Li, Song; Ren, Juan; Xing, Guo-Gang


    Primary and metastatic cancers that affect bones are frequently associated with severe and intractable pain. The mechanisms underlying the development of bone cancer pain are largely unknown. In the present study, we investigated whether inhibition of KCNQ/M (Kv7) potassium channels in the spinal cord contributes to the development of bone cancer pain via sensitization of dorsal horn wide dynamic range (WDR) neurons. Using a rat model of bone cancer pain based on intratibial injection of MRMT-1 tumor cells, we observed a significant increase in C-fiber responses of dorsal horn WDR neurons in the MRMT-1 injected rats, indicating sensitization of spinal WDR neurons in bone cancer rats. Furthermore, we discovered that blockade of KCNQ/M channels in the spinal cord by local administration of XE-991, a specific KCNQ/M channel blocker, caused a robust increase in excitability of dorsal horn WDR neurons, while, producing obvious pain hypersensitivity in normal rats. On the contrary, activation of spinal KCNQ/M channels by retigabine, a selective KCNQ/M channel opener, not only inhibited the bone cancer‑induced hyperexcitability of dorsal horn WDR neurons, but also alleviated mechanical allodynia and thermal hyperalgesia in the bone cancer rats, while all of these effects of retigabine could be blocked by KCNQ/M-channel antagonist XE-991. All things considered, these results suggest that suppression of KCNQ/M channels in the spinal cord likely contributes to the development of bone cancer pain via sensitization of dorsal horn WDR neurons in rats following tumor cell inoculation.

  15. Molecular cloning of ion channels in Felis catus that are related to periodic paralyses in man: a contribution to the understanding of the genetic susceptibility to feline neck ventroflexion and paralysis (United States)

    Zapata, Marlyn; Kunii, Ilda S.; Paninka, Rolf M.; Simões, Denise M. N.; Castillo, Víctor A.; Reche, Archivaldo; Maciel, Rui M. B.; Dias da Silva, Magnus R.


    ABSTRACT Neck ventroflexion in cats has different causes; however, the most common is the hypokalemia associated with flaccid paralysis secondary to chronic renal failure. In humans, the most common causes of acute flaccid paralysis are hypokalemia precipitated by thyrotoxicosis and familial forms linked to mutations in sodium, potassium, and calcium channel genes. Here, we describe the sequencing and analysis of skeletal muscle ion channels in Felis catus that could be related to periodic paralyses in humans, contributing to the understanding of the genetic susceptibility to feline neck ventroflexion and paralysis. We studied genomic DNA from eleven cats, including five animals that were hyperthyroid with hypokalemia, although only one presented with muscle weakness, and six healthy control domestic cats. We identified the ion channel ortholog genes KCNJ2, KCNJ12, KCNJ14, CACNA1S and SCN4A in the Felis catus genome, together with several polymorphic variants. Upon comparative alignment with other genomes, we found that Felis catus provides evidence for a high genomic conservation of ion channel sequences. Although we hypothesized that neck ventroflexion in cats could be associated with a thyrotoxic or familial periodic paralysis channel mutation, we did not identify any previously detected human channel mutation in the hyperthyroid cat presenting hypokalemia. However, based on the small number of affected cats in this study, we cannot yet rule out this molecular mechanism. Notwithstanding, hyperthyroidism should still be considered as a differential diagnosis in hypokalemic feline paralysis. PMID:25063199

  16. Molecular cloning of ion channels in Felis catus that are related to periodic paralyses in man: a contribution to the understanding of the genetic susceptibility to feline neck ventroflexion and paralysis

    Directory of Open Access Journals (Sweden)

    Marlyn Zapata


    Full Text Available Neck ventroflexion in cats has different causes; however, the most common is the hypokalemia associated with flaccid paralysis secondary to chronic renal failure. In humans, the most common causes of acute flaccid paralysis are hypokalemia precipitated by thyrotoxicosis and familial forms linked to mutations in sodium, potassium, and calcium channel genes. Here, we describe the sequencing and analysis of skeletal muscle ion channels in Felis catus that could be related to periodic paralyses in humans, contributing to the understanding of the genetic susceptibility to feline neck ventroflexion and paralysis. We studied genomic DNA from eleven cats, including five animals that were hyperthyroid with hypokalemia, although only one presented with muscle weakness, and six healthy control domestic cats. We identified the ion channel ortholog genes KCNJ2, KCNJ12, KCNJ14, CACNA1S and SCN4A in the Felis catus genome, together with several polymorphic variants. Upon comparative alignment with other genomes, we found that Felis catus provides evidence for a high genomic conservation of ion channel sequences. Although we hypothesized that neck ventroflexion in cats could be associated with a thyrotoxic or familial periodic paralysis channel mutation, we did not identify any previously detected human channel mutation in the hyperthyroid cat presenting hypokalemia. However, based on the small number of affected cats in this study, we cannot yet rule out this molecular mechanism. Notwithstanding, hyperthyroidism should still be considered as a differential diagnosis in hypokalemic feline paralysis.

  17. Overview of BioCreAtIvE task 1B: normalized gene lists


    Hirschman, Lynette; Colosimo, Marc; Morgan, Alexander; Yeh, Alexander


    Background Our goal in BioCreAtIve has been to assess the state of the art in text mining, with emphasis on applications that reflect real biological applications, e.g., the curation process for model organism databases. This paper summarizes the BioCreAtIvE task 1B, the "Normalized Gene List" task, which was inspired by the gene list supplied for each curated paper in a model organism database. The task was to produce the correct list of unique gene identifiers for the genes and gene product...

  18. US-UK Collaboration on Fossil Energy Advanced Materials: Task 1—Steam Oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Holcomb, Gordon R. [National Energy Technology Lab. (NETL), Albany, OR (United States); Tylczak, Joseph [National Energy Technology Lab. (NETL), Albany, OR (United States); Carney, Casey [National Energy Technology Lab. (NETL), Albany, OR (United States)


    This presentation goes over the following from the US-UK collaboration on Fossil Energy Advanced Materials: Task 1, Steam Oxidation: US-led or co-led deliverables, Phase II products (US), 2011-present, Phase III products, Phase III Plan, an explanation of sCO2 compared with sH2O, an explanation of Ni-base Alloys, an explanation of 300 Series (18Cr-8Ni)/E-Brite, an explanation of the typical Microchannel HX Fabrication process, and an explanation of diffusion bonded Ni-base superalloys.

  19. Resurgent Na+ current in pyramidal neurones of rat perirhinal cortex: axonal location of channels and contribution to depolarizing drive during repetitive firing (United States)

    Castelli, Loretta; Biella, Gerardo; Toselli, Mauro; Magistretti, Jacopo


    The perirhinal cortex (PRC) is a supra-modal cortical area that collects and integrates information originating from uni- and multi-modal neocortical regions and directed to the hippocampus. The mechanisms that underlie the specific excitable properties of the different PRC neuronal types are still largely unknown, and their elucidation may be important in understanding the integrative functions of PRC. In this study we investigated the expression and properties of resurgent Na+ current (INaR) in pyramidal neurones of rat PRC area 35 (layer II). Patch-clamp experiments in acute PRC slices were first carried out. A measurable INaR was expressed by a large majority of neurones (31 out of 35 cells). INaR appeared as an inward, slowly decaying current elicited upon step repolarization after depolarizations sufficient to induce nearly complete inactivation of the transient Na+ current (INaT). INaR had a peak amplitude of ∼2.5% that of INaT, and showed the typical biophysical properties also observed in other neuronal types (i.e. cerebellar Purkinje and granule cells), including a bell-shaped current–voltage relationship with a peak at approximately −40 mV, and a characteristic acceleration of activation and decay speed at potentials negative to −45 mV. Current-clamp experiments were then carried out in which repetitive action-potential discharge at various frequencies was induced with depolarizing current injection. The voltage signals thus obtained were then used as command waveforms for voltage-clamp recordings. These experiments showed that a Na+ current identifiable as INaR activates in the early interspike phase even at relatively high firing frequencies (20 Hz), thereby contributing to the depolarizing drive and possibly enhancing repetitive discharge. In acutely dissociated area 35 layer II neurones, as well as in nucleated patches from the same neurones, INaR was never observed, despite the presence of typical INaTs. Since in both preparations neuronal

  20. Channel Choice: A Literature Review

    DEFF Research Database (Denmark)

    Østergaard Madsen, Christian; Kræmmergaard, Pernille


    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....

  1. Electric Vehicle Preparedness: Task 1, Assessment of Fleet Inventory for Marine Corps Base Camp Lejeune

    Energy Technology Data Exchange (ETDEWEB)

    Schey, Stephen [Idaho National Lab. (INL), Idaho Falls, ID (United States); Francfort, Jim [Idaho National Lab. (INL), Idaho Falls, ID (United States)


    Several U.S. Department of Defense-based studies were conducted to identify potential U.S. Department of Defense transportation systems that are strong candidates for introduction or expansion of plug-in electric vehicles (PEVs). Task 1 included a survey of the inventory of non-tactical fleet vehicles at the Marine Corps Base Camp Lejeune (MCBCL) to characterize the fleet. This information and characterization will be used to select vehicles for monitoring that takes place during Task 2. This monitoring involves data logging of vehicle operation in order to identify the vehicle’s mission and travel requirements. Individual observations of these selected vehicles provide the basis for recommendations related to PEV adoption. It also identifies whether a battery electric vehicle or plug-in hybrid electric vehicle (collectively referred to as PEVs) can fulfill the mission requirements and provides observations related to placement of PEV charging infrastructure.

  2. Evolutionary trajectory of channel planforms in the middle Garonne River (Toulouse, SW France) over a 130-year period: Contribution of mixed multiple factor analysis (MFAmix) (United States)

    David, Mélodie; Labenne, Amaury; Carozza, Jean-Michel; Valette, Philippe


    The purpose of this study is to propose a methodological essay for defining evolutionary trajectories of channel planforms and to examine the channel change in the middle Garonne River (southwest France) over a 130-year period. The study focuses on a reach of ~ 90 km situated downstream from the city of Toulouse. A set of four historical maps (1868, 1940s, 1970s, and 2000s) is used to build a geomorphometric diachronic database. Data processing through mixed multiple factor analysis (MFAmix) and hierarchical cluster analysis (HCA) allows distinction between four homogeneous zones within the study reach, depending on their evolutionary trajectories. Channel behavior in the upstream and median zones evolved as of the beginning of the study period (narrowing of the fluvial area, colonization by vegetation, and removal of alluvial bars), likely owing to punctual anthropogenic actions. The downstream zone is characterized by stabilization of the channel and alluvial bar removal over the second half of the twentieth century, coinciding with the campaign undertaken by French local authorities between 1960 and 1984 to protect river banks. The role of climate transition between the Little Ice Age (LIA) and the onset of the Global Warming period (GW) is also discussed. Results generally are consistent with the chronology established for most European rivers.

  3. Enhanced large conductance K+ channel activity contributes to the impaired myogenic response in the cerebral vasculature of Fawn Hooded Hypertensive rats (United States)

    Pabbidi, Mallikarjuna R.; Mazur, Olga; Fan, Fan; Farley, Jerry M.; Gebremedhin, Debebe; Harder, David R.


    Recent studies have indicated that the myogenic response (MR) in cerebral arteries is impaired in Fawn Hooded Hypertensive (FHH) rats and that transfer of a 2.4 megabase pair region of chromosome 1 (RNO1) containing 15 genes from the Brown Norway rat into the FHH genetic background restores MR in a FHH.1BN congenic strain. However, the mechanisms involved remain to be determined. The present study examined the role of the large conductance calcium-activated potassium (BK) channel in impairing the MR in FHH rats. Whole-cell patch-clamp studies of cerebral vascular smooth muscle cells (VSMCs) revealed that iberiotoxin (IBTX; BK inhibitor)-sensitive outward potassium (K+) channel current densities are four- to fivefold greater in FHH than in FHH.1BN congenic strain. Inside-out patches indicated that the BK channel open probability (NPo) is 10-fold higher and IBTX reduced NPo to a greater extent in VSMCs isolated from FHH than in FHH.1BN rats. Voltage sensitivity of the BK channel is enhanced in FHH as compared with FHH.1BN rats. The frequency and amplitude of spontaneous transient outward currents are significantly greater in VSMCs isolated from FHH than in FHH.1BN rats. However, the expression of the BK-α and -β-subunit proteins in cerebral vessels as determined by Western blot is similar between the two groups. Middle cerebral arteries (MCAs) isolated from FHH rats exhibited an impaired MR, and administration of IBTX restored this response. These results indicate that there is a gene on RNO1 that impairs MR in the MCAs of FHH rats by enhancing BK channel activity. PMID:24464756

  4. Contribution of the S5-pore-S6 domain to the gating characteristics of the cation channels TRPM2 and TRPM8. (United States)

    Kühn, Frank J P; Witschas, Katja; Kühn, Cornelia; Lückhoff, Andreas


    The closely related cation channels TRPM2 and TRPM8 show completely different requirements for stimulation and are regulated by Ca(2+) in an opposite manner. TRPM8 is basically gated in a voltage-dependent process enhanced by cold temperatures and cooling compounds such as menthol and icilin. The putative S4 voltage sensor of TRPM8 is closely similar to that of TRPM2, which, however, is mostly devoid of voltage sensitivity. To gain insight into principal interactions of critical channel domains during the gating process, we created chimeras in which the entire S5-pore-S6 domains were reciprocally exchanged. The chimera M2-M8P (i.e. TRPM2 with the pore of TRPM8) responded to ADP-ribose and hydrogen peroxide and was regulated by extracellular and intracellular Ca(2+) as was wild-type TRPM2. Single-channel recordings revealed the characteristic pattern of TRPM2 with extremely long open times. Only at far-negative membrane potentials (-120 to -140 mV) did differences become apparent because currents were reduced by hyperpolarization in M2-M8P but not in TRPM2. The reciprocal chimera, M8-M2P, showed currents after stimulation with high concentrations of menthol and icilin, but these currents were only slightly larger than in controls. The transfer of the NUDT9 domain to the C terminus of TRPM8 produced a channel sensitive to cold, menthol, or icilin but insensitive to ADP-ribose or hydrogen peroxide. We conclude that the gating processes in TRPM2 and TRPM8 differ in their requirements for specific structures within the pore. Moreover, the regulation by extracellular and intracellular Ca(2+) and the single-channel properties in TRPM2 are not determined by the S5-pore-S6 region.

  5. Effects of a no-go Task 2 on Task 1 performance in dual - tasking: From benefits to costs. (United States)

    Janczyk, Markus; Huestegge, Lynn


    When two tasks are combined in a dual-task experiment, characteristics of Task 2 can influence Task 1 performance, a phenomenon termed the backward crosstalk effect (BCE). Besides instances depending on the (spatial) compatibility of both responses, a particularly interesting example was introduced by Miller (2006): If Task 2 was a no-go task (i.e., one not requiring any action at all), responses were slowed in Task 1. Subsequent work, however, also reported the opposite result-that is, faster Task 1 responses in cases of no-go Task 2 trials. We report three experiments aiming to more precisely identify the conditions under which a no-go Task 2 facilitates or impedes Task 1 performance. The results suggest that an adverse no-go BCE is only observed when the Task 2 response(s) are sufficiently prepared in advance, yielding strong inhibitory control demands for Task 2 that eventually hamper Task 1 processing as well (i.e., inhibitory costs). If this is not the case, encountering a no-go Task 2 trial facilitates Task 1 performance, suggesting that the underlying task representation is reduced to a single - task. These results are discussed in the context of other recent work on BCEs and of recently suggested accounts of the no-go BCE.

  6. Measurement of the $s$-channel Single Top Quark Cross Section at the CDF Experiment and Contributions to the Evidence of $H\\rightarrow bb$ at the Tevatron

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Hao [Univ. of Virginia, Charlottesville, VA (United States)


    In this thesis, we present the measurement of the s-channel single top quark production cross section. In the cross section measurement we use data generated by protonantiproton collisions at the center-of-mass energy √s = 1.96 TeV and collected by the CDF Run II detector. The total data set corresponds to an integrated luminosity of 9.4 fb-1.

  7. Chronic deficit in nitric oxide elicits oxidative stress and augments T-type calcium-channel contribution to vascular tone of rodent arteries and arterioles

    DEFF Research Database (Denmark)

    Howitt, Lauren; Kuo, Ivana Y; Ellis, Anthie;


    AIMS: As cardiovascular disease is characterized by reduced nitric oxide bioavailability, our aim was to determine the impact of this change on the mechanism underlying vascular tone of pressurized arteries in vitro and in vivo. METHODS AND RESULTS: We used pressurized cerebral and mesenteric......, by regulating the bioavailability of reactive oxygen species produced by NADPH oxidase. Our data provide evidence for a novel causal link between nitric oxide deficit, oxidative stress, and T-type calcium channel function....

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

    Directory of Open Access Journals (Sweden)

    Alex M. Dopico


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

  9. Genetic contribution to iron status: SNPs related to iron deficiency anaemia and fine mapping of CACNA2D3 calcium channel subunit. (United States)

    Baeza-Richer, Carlos; Arroyo-Pardo, Eduardo; Blanco-Rojo, Ruth; Toxqui, Laura; Remacha, Angel; Vaquero, M Pilar; López-Parra, Ana M


    Numerous studies associate genetic markers with iron- and erythrocyte-related parameters, but few relate them to iron-clinical phenotypes. Novel SNP rs1375515, located in a subunit of the calcium channel gene CACNA2D3, is associated with a higher risk of anaemia. The aim of this study is to further investigate the association of this SNP with iron-related parameters and iron-clinical phenotypes, and to explore the potential role of calcium channel subunit region in iron regulation. Furthermore, we aim to replicate the association of other SNPs reported previously in our population. We tested 45 SNPs selected via systematic review and fine mapping of CACNA2D3 region, with haematological and biochemical traits in 358 women of reproductive age. Multivariate analyses include back-step logistic regression and decision trees. The results replicate the association of SNPs with iron-related traits, and also confirm the protective effect of both A allele of rs1800562 (HFE) and G allele of rs4895441 (HBS1L-MYB). The risk of developing anaemia is increased in reproductive age women carriers of A allele of rs1868505 (CACNA2D3) and/or T allele of rs13194491 (HIST1H2BJ). Association of SNPs from fine mapping with ferritin and serum iron suggests that calcium channels could be a potential pathway for iron uptake in physiological conditions.

  10. Instrumentation Needs for Integral Primary System Reactors (IPSRs) - Task 1 Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Gary D. Storrick; Bojan Petrovic; Luca Oriani; Lawrence E. Conway; Diego Conti


    This report presents the results of the Westinghouse work performed under Task 1 of this Financial Assistance Award and satisfies a Level 2 Milestone for the project. While most of the signals required for control of IPSRs are typical of other PWRs, the integral configuration poses some new challenges in the design or deployment of the sensors/instrumentation and, in some cases, requires completely new approaches. In response to this consideration, the overall objective of Task 1 was to establish the instrumentation needs for integral reactors, provide a review of the existing solutions where available, and, identify research and development needs to be addressed to enable successful deployment of IPSRs. The starting point for this study was to review and synthesize general characteristics of integral reactors, and then to focus on a specific design. Due to the maturity of its design and availability of design information to Westinghouse, IRIS (International Reactor Innovative and Secure) was selected for this purpose. The report is organized as follows. Section 1 is an overview. Section 2 provides background information on several representative IPSRs, including IRIS. A review of the IRIS safety features and its protection and control systems is used as a mechanism to ensure that all critical safety-related instrumentation needs are addressed in this study. Additionally, IRIS systems are compared against those of current advanced PWRs. The scope of this study is then limited to those systems where differences exist, since, otherwise, the current technology already provides an acceptable solution. Section 3 provides a detailed discussion on instrumentation needs for the representative IPSR (IRIS) with detailed qualitative and quantitative requirements summarized in the exhaustive table included as Appendix A. Section 3 also provides an evaluation of the current technology and the instrumentation used for measurement of required parameters in current PWRs. Section 4

  11. Ion Fluxes through KCa2 (SK) and Cav1 (L-type) Channels Contribute to Chronoselectivity of Adenosine A1 Receptor-Mediated Actions in Spontaneously Beating Rat Atria (United States)

    Bragança, Bruno; Oliveira-Monteiro, Nádia; Ferreirinha, Fátima; Lima, Pedro A.; Faria, Miguel; Fontes-Sousa, Ana P.; Correia-de-Sá, Paulo


    Impulse generation in supraventricular tissue is inhibited by adenosine and acetylcholine via the activation of A1 and M2 receptors coupled to inwardly rectifying GIRK/KIR3.1/3.4 channels, respectively. Unlike M2 receptors, bradycardia produced by A1 receptors activation predominates over negative inotropy. Such difference suggests that other ion currents may contribute to adenosine chronoselectivity. In isolated spontaneously beating rat atria, blockade of KCa2/SK channels with apamin and Cav1 (L-type) channels with nifedipine or verapamil, sensitized atria to the negative inotropic action of the A1 agonist, R-PIA, without affecting the nucleoside negative chronotropy. Patch-clamp experiments in the whole-cell configuration mode demonstrate that adenosine, via A1 receptors, activates the inwardly-rectifying GIRK/KIR3.1/KIR3.4 current resulting in hyperpolarization of atrial cardiomyocytes, which may slow down heart rate. Conversely, the nucleoside inactivates a small conductance Ca2+-activated KCa2/SK outward current, which eventually reduces the repolarizing force and thereby prolong action potentials duration and Ca2+ influx into cardiomyocytes. Immunolocalization studies showed that differences in A1 receptors distribution between the sinoatrial node and surrounding cardiomyocytes do not afford a rationale for adenosine chronoselectivity. Immunolabelling of KIR3.1, KCa2.2, KCa2.3, and Cav1 was also observed throughout the right atrium. Functional data indicate that while both A1 and M2 receptors favor the opening of GIRK/KIR3.1/3.4 channels modulating atrial chronotropy, A1 receptors may additionally restrain KCa2/SK activation thereby compensating atrial inotropic depression by increasing the time available for Ca2+ influx through Cav1 (L-type) channels. PMID:27014060

  12. Non-charged amino acids from three different domains contribute to link agonist binding to channel gating in alpha7 nicotinic acetylcholine receptors. (United States)

    Aldea, Marcos; Mulet, José; Sala, Salvador; Sala, Francisco; Criado, Manuel


    Binding of agonists to nicotinic acetylcholine receptors results in channel opening. Previously, we have shown that several charged residues at three different domains of the alpha7 nicotinic receptor are involved in coupling binding and gating, probably through a network of electrostatic interactions. This network, however, could also be integrated by other residues. To test this hypothesis, non-charged amino acids were mutated and expression levels and electrophysiological responses of mutant receptors were determined. Mutants at positions Asn47 and Gln48 (loop 2), Ile130, Trp134, and Gln140 (loop 7), and Thr264 (M2-M3 linker) showed poor or null functional responses, despite significant membrane expression. By contrast, mutants F137A and S265A exhibited a gain of function effect. In all cases, changes in dose-response relationships were small, EC(50) values being between threefold smaller and fivefold larger, arguing against large modifications of agonist binding. Peak currents decayed at the same rate in all receptors except two, excluding large effects on desensitization. Thus, the observed changes could be mostly caused by alterations of the gating characteristics. Moreover, analysis of double mutants showed an interconnection between some residues in these domains, especially Gln48 with Ile130, suggesting a potential coupling between agonist binding and channel gating through these amino acids.

  13. DECOVALEX III PROJECT. Modelling of FEBEX In-Situ Test. Task1 Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Alonso, E.E.; Alcoverro, J. [Univ. Politecnica de Catalunya, Barcelona (Spain)] (comps.)


    Task 1 of DECOVALEX III was conceived as a benchmark exercise supported by all field and laboratory data generated during the performance of the FEBEX experiment designed to study thermo-hydro-mechanical and thermo-hydro-geochemical processes of the buffer and rock in the near field. The task was defined as a series of three successive blind prediction exercises (Parts A, B and C), which cover the behaviour of both the rock and bentonite barrier. Research teams participating in the FEBEX task were given, for each of the three parts, a set of field and laboratory data theoretically sufficient to generate a proper model and were asked to submit predictions, at given locations and time, for some of the measured variables. The merits and limitations of different modeling approaches were therefore established. The teams could perform additional calculations, once the actual 'solution' was disclosed. Final calculations represented the best approximation that a given team could provide, always within the general time constraints imposed by the General DECOVALEX III Organization. This report presents the works performed for Task 1. It contains the case definitions and evaluations of modelling results for Part A, B and C, and the overall evaluation of the works performed. The report is completed by a CD-ROM containing a set of final reports provided by the modeling teams participating in each of the three parts defined. These reports provide the necessary details to better understand the nature of the blind or final predictions included in this report. The report closes with a set of conclusions, which provides a summary of the main findings and highlights the lessons learned, some of which were summarized below. The best predictions of the water inflow into the excavated tunnel are found when the hydro geological model is properly calibrated on the basis of other known flow measurements in the same area. The particular idealization of the rock mass (equivalent

  14. Radioactive waste management: the contribution of expert assessments to the implementation of safe management channels; La gestion des dechets radioactifs: l'apport de l'expertise a la mise en oeuvre de filieres sures

    Energy Technology Data Exchange (ETDEWEB)

    Besnus, F.; Jouve, A.C. [Institut de Radioprotection et de Surete Nucleaire - IRSN, Service d' evaluation de la surete des irradiateurs, des accelerateurs et des installations de gestion des dechets, 92 - Clamart (France)


    The national Radioactive Materials and Waste Management (PNGMDR) sets objectives and defines waste management channels for all radioactive wastes produced in France. Within this framework, IRSN (Institute for Radioprotection and Nuclear Safety) expertise aims at assessing the consistency and robustness of the technical solutions set in place by the plan. As a result of this assessment, the main safety issues and priorities for upgrading the safety of the various facilities that will receive and treat waste are identified on the one hand, while possible foreseen weaknesses in terms of storage or treatment capacities are put into light on the other hand. To carry out such assessment, IRSN backs on its 'in depth' knowledge of facilities, acquired through the examination of each major step of waste management facility life (creation, commissioning, re-examination of safety...). This knowledge feeds in turn the examination of the waste management strategies implemented by operators. In addition, special attention is given to the achievement of waste packages of favourable properties as well as to the conditions for their safe disposal, since these two aspects are most often key factors for optimizing the safety of the whole management channel. By its capacity to overlook all steps of waste management channels, from production to final disposal, IRSN intends to contribute to the objective of enhancing the global safety of the management of radioactive waste. (authors)

  15. Applications of hydrogeological modelling methodology using NAMMU and CONNECTFLOW. Task 1, 2, 3 and 4

    Energy Technology Data Exchange (ETDEWEB)

    Gylling, Bjoern; Marsic, Niko [Kemakta Konsult AB, Stockholm (Sweden); Hartley, Lee; Holton, David [Serco Assurance Ltd, Risley (United Kingdom)


    concept, show the work flow from data to model, and create generic though realistic models that can be adapted for later studies. Models for Task 1, 2, 3 and 4 have been set up. In all cases nested models have been created using CONNECTFLOW. Task 1 and 2 consider the case of a repository-scale DFN model nested within an embedded CPM model that includes both the site-scale and regional scales. Task 1 demonstrates how such models can be constructed. Task 2 shows what results can be obtained using such a model by applying the model to Beberg and comparing the results for canister flux and transport statistics with results from pure CPM models as used in SR 97. Several realisations of the model were performed and analysed to obtain statistics of repository performance measures such as groundwater travel time and flux at starting positions. The results show good consistency in the mean values when compared to SR 97, but the variance is increased in the new nested model. This is to be expected since a DFN model offers much greater resolution in local-scale variability since it represents individual fractures on a few metres scale rather than the CPM approach where flows are effectively averaged out over a larger volume (e.g. 35 m cuboid elements). Task 2 gave also an opportunity to test the recently developed method to calculate F-quotients directly in CONNECTFLOW. For Task 3 the converse arrangement of nesting was used where a rather complex CPM model was nested within a DFN model. The CPM model represents a tunnel system with an access tunnel, six deposition tunnels and 162 deposition holes. A generic DFN model serves as a framework and makes it possible to study fracture and repository intersections. The goal is to obtain detailed near-field flow rates and possibility to address design issues. In Task 4, the CONNECTFLOW concept is used to calculate more realistic input to a near field model since it models explicitly the flow in the fracture system around the canisters

  16. Epigenetic regulation of Kcna3-encoding Kv1.3 potassium channel by cereblon contributes to regulation of CD4+ T-cell activation. (United States)

    Kang, Jung-Ah; Park, Sang-Heon; Jeong, Sang Phil; Han, Min-Hee; Lee, Cho-Rong; Lee, Kwang Min; Kim, Namhee; Song, Mi-Ryoung; Choi, Murim; Ye, Michael; Jung, Guhung; Lee, Won-Woo; Eom, Soo Hyun; Park, Chul-Seung; Park, Sung-Gyoo


    The role of cereblon (CRBN) in T cells is not well understood. We generated mice with a deletion in Crbn and found cereblon to be an important antagonist of T-cell activation. In mice lacking CRBN, CD4(+) T cells show increased activation and IL-2 production on T-cell receptor stimulation, ultimately resulting in increased potassium flux and calcium-mediated signaling. CRBN restricts T-cell activation via epigenetic modification of Kcna3, which encodes the Kv1.3 potassium channel required for robust calcium influx in T cells. CRBN binds directly to conserved DNA elements adjacent to Kcna3 via a previously uncharacterized DNA-binding motif. Consequently, in the absence of CRBN, the expression of Kv1.3 is derepressed, resulting in increased Kv1.3 expression, potassium flux, and CD4(+) T-cell hyperactivation. In addition, experimental autoimmune encephalomyelitis in T-cell-specific Crbn-deficient mice was exacerbated by increased T-cell activation via Kv1.3. Thus, CRBN limits CD4(+) T-cell activation via epigenetic regulation of Kv1.3 expression.

  17. Objective assessment of the contribution of the RECOPESCA network to the monitoring of 3D coastal ocean variables in the Bay of Biscay and the English Channel (United States)

    Lamouroux, Julien; Charria, Guillaume; De Mey, Pierre; Raynaud, Stéphane; Heyraud, Catherine; Craneguy, Philippe; Dumas, Franck; Le Hénaff, Matthieu


    In the Bay of Biscay and the English Channel, in situ observations represent a key element to monitor and to understand the wide range of processes in the coastal ocean and their direct impacts on human activities. An efficient way to measure the hydrological content of the water column over the main part of the continental shelf is to consider ships of opportunity as the surface to cover is wide and could be far from the coast. In the French observation strategy, the RECOPESCA programme, as a component of the High frequency Observation network for the environment in coastal SEAs (HOSEA), aims to collect environmental observations from sensors attached to fishing nets. In the present study, we assess that network using the Array Modes (ArM) method (a stochastic implementation of Le Hénaff et al. Ocean Dyn 59: 3-20. doi: 10.1007/s10236-008-0144-7, 2009). That model ensemble-based method is used here to compare model and observation errors and to quantitatively evaluate the performance of the observation network at detecting prior (model) uncertainties, based on hypotheses on error sources. A reference network, based on fishing vessel observations in 2008, is assessed using that method. Considering the various seasons, we show the efficiency of the network at detecting the main model uncertainties. Moreover, three scenarios, based on the reference network, a denser network in 2010 and a fictive network aggregated from a pluri-annual collection of profiles, are also analysed. Our sensitivity study shows the importance of the profile positions with respect to the sheer number of profiles for ensuring the ability of the network to describe the main error modes. More generally, we demonstrate the capacity of this method, with a low computational cost, to assess and to design new in situ observation networks.

  18. Enhanced pre-synaptic glutamate release in deep-dorsal horn contributes to calcium channel alpha-2-delta-1 protein-mediated spinal sensitization and behavioral hypersensitivity

    Directory of Open Access Journals (Sweden)

    Dickenson Anthony H


    Full Text Available Abstract Nerve injury-induced expression of the spinal calcium channel alpha-2-delta-1 subunit (Cavα2δ1 has been shown to mediate behavioral hypersensitivity through a yet identified mechanism. We examined if this neuroplasticity modulates behavioral hypersensitivity by regulating spinal glutamatergic neurotransmission in injury-free transgenic mice overexpressing the Cavα2δ1 proteins in neuronal tissues. The transgenic mice exhibited hypersensitivity to mechanical stimulation (allodynia similar to the spinal nerve ligation injury model. Intrathecally delivered antagonists for N-methyl-D-aspartate (NMDA and α-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA/kainate receptors, but not for the metabotropic glutamate receptors, caused a dose-dependent allodynia reversal in the transgenic mice without changing the behavioral sensitivity in wild-type mice. This suggests that elevated spinal Cavα2δ1 mediates allodynia through a pathway involving activation of selective glutamate receptors. To determine if this is mediated by enhanced spinal neuronal excitability or pre-synaptic glutamate release in deep-dorsal horn, we examined wide-dynamic-range (WDR neuron excitability with extracellular recording and glutamate-mediated excitatory postsynaptic currents with whole-cell patch recording in deep-dorsal horn of the Cavα2δ1 transgenic mice. Our data indicated that overexpression of Cavα2δ1 in neuronal tissues led to increased frequency, but not amplitude, of miniature excitatory post synaptic currents mediated mainly by AMPA/kainate receptors at physiological membrane potentials, and also by NMDA receptors upon depolarization, without changing the excitability of WDR neurons to high intensity stimulation. Together, these findings support a mechanism of Cavα2δ1-mediated spinal sensitization in which elevated Cavα2δ1 causes increased pre-synaptic glutamate release that leads to reduced excitation thresholds of post-synaptic dorsal

  19. Activation of mammalian target of rapamycin contributes to pain nociception induced in rats by BmK I, a sodium channel-specific modulator. (United States)

    Jiang, Feng; Hua, Li-Ming; Jiao, Yun-Lu; Ye, Pin; Fu, Jin; Cheng, Zhi-Jun; Ding, Gang; Ji, Yong-Hua


    The mammalian target of rapamycin (mTOR) pathway is essential for maintenance of the sensitivity of certain adult sensory neurons. Here, we investigated whether the mTOR cascade is involved in scorpion envenomation-induced pain hypersensitivity in rats. The results showed that intraplantar injection of a neurotoxin from Buthus martensii Karsch, BmK I (10 μg), induced the activation of mTOR, as well as its downstream molecules p70 ribosomal S6 protein kinase (p70 S6K) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), in lumbar 5-6 dorsal root ganglia neurons on both sides in rats. The activation peaked at 2 h and recovered 1 day after injection. Compared with the control group, the ratios of p-mTOR/p-p70 S6K/p-4EBP1 in three types of neurons changed significantly. The cell typology of p-mTOR/p-p70 S6K/p-4E-BP1 immuno-reactive neurons also changed. Intrathecal administration of deforolimus, a specific inhibitor of mTOR, attenuated BmK I-induced pain responses (spontaneous flinching, paroxysmal pain-like behavior, and mechanical hypersensitivity). Together, these results imply that the mTOR signaling pathway is mobilized by and contributes to experimental scorpion sting-induced pain.

  20. Superconducting Gamma/Neutron Spectrometer Task 1 Completion Report Evaluation of Candidate Neutron-Sensitive Materials

    CERN Document Server

    Bell, Z W


    A review of the scientific literature regarding boron- and lithium-containing compounds was completed. Information such as Debye temperature, heat capacity, superconductivity properties, physical and chemical characteristics, commercial availability, and recipes for synthesis was accumulated and evaluated to develop a list of neutron-sensitive materials likely to perform properly in the spectrometer. The best candidate borides appear to be MgB sub 2 (a superconductor with T sub c = 39 K), B sub 6 Si, B sub 4 C, and elemental boron; all are commercially available. Among the lithium compounds are LiH, LiAl, Li sub 1 sub 2 Si sub 7 , and Li sub 7 Sn sub 2. These materials have or are expected to have high Debye temperatures and sufficiently low heat capacities at 100 mK to produce a useful signal. The responses of sup 1 sup 0 B and sup 6 Li to a fission neutron spectrum were also estimated. These demonstrated that the contribution of scattering events is no more than 3% in a boron-based system and 1.5% in a lith...

  1. Two-pore Domain Potassium Channels in Astrocytes (United States)

    Ryoo, Kanghyun


    Two-pore domain potassium (K2P) channels have a distinct structure and channel properties, and are involved in a background K+ current. The 15 members of the K2P channels are identified and classified into six subfamilies on the basis of their sequence similarities. The activity of the channels is dynamically regulated by various physical, chemical, and biological effectors. The channels are expressed in a wide variety of tissues in mammals in an isoform specific manner, and play various roles in many physiological and pathophysiological conditions. To function as channels, the K2P channels form dimers, and some isoforms form heterodimers that provide diversity in channel properties. In the brain, TWIK1, TREK1, TREK2, TRAAK, TASK1, and TASK3 are predominantly expressed in various regions, including the cerebral cortex, dentate gyrus, CA1-CA3, and granular layer of the cerebellum. TWIK1, TREK1, and TASK1 are highly expressed in astrocytes, where they play specific cellular roles. Astrocytes keep leak K+ conductance, called the passive conductance, which mainly involves TWIK1-TREK1 heterodimeric channel. TWIK1 and TREK1 also mediate glutamate release from astrocytes in an exocytosis-independent manner. The expression of TREK1 and TREK2 in astrocytes increases under ischemic conditions, that enhance neuroprotection from ischemia. Accumulated evidence has indicated that astrocytes, together with neurons, are involved in brain function, with the K2P channels playing critical role in these astrocytes. PMID:27790056

  2. Golgi and plasma membrane pools of PI(4)P contribute to plasma membrane PI(4,5)P2 and maintenance of KCNQ2/3 ion channel current. (United States)

    Dickson, Eamonn J; Jensen, Jill B; Hille, Bertil


    Plasma membrane (PM) phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] regulates the activity of many ion channels and other membrane-associated proteins. To determine precursor sources of the PM PI(4,5)P2 pool in tsA-201 cells, we monitored KCNQ2/3 channel currents and translocation of PHPLCδ1 domains as real-time indicators of PM PI(4,5)P2, and translocation of PHOSH2×2, and PHOSH1 domains as indicators of PM and Golgi phosphatidylinositol 4-phosphate [PI(4)P], respectively. We selectively depleted PI(4)P pools at the PM, Golgi, or both using the rapamycin-recruitable lipid 4-phosphatases. Depleting PI(4)P at the PM with a recruitable 4-phosphatase (Sac1) results in a decrease of PI(4,5)P2 measured by electrical or optical indicators. Depleting PI(4)P at the Golgi with the 4-phosphatase or disrupting membrane-transporting motors induces a decline in PM PI(4,5)P2. Depleting PI(4)P simultaneously at both the Golgi and the PM induces a larger decrease of PI(4,5)P2. The decline of PI(4,5)P2 following 4-phosphatase recruitment takes 1-2 min. Recruiting the endoplasmic reticulum (ER) toward the Golgi membranes mimics the effects of depleting PI(4)P at the Golgi, apparently due to the trans actions of endogenous ER Sac1. Thus, maintenance of the PM pool of PI(4,5)P2 appears to depend on precursor pools of PI(4)P both in the PM and in the Golgi. The decrease in PM PI(4,5)P2 when Sac1 is recruited to the Golgi suggests that the Golgi contribution is ongoing and that PI(4,5)P2 production may be coupled to important cell biological processes such as membrane trafficking or lipid transfer activity.

  3. A preliminary investigation of the efficacy of riparian fencing schemes for reducing contributions from eroding channel banks to the siltation of salmonid spawning gravels across the south west UK. (United States)

    Collins, Adrian L; Walling, Desmond E; McMellin, Grant K; Zhang, Yusheng; Gray, Janina; McGonigle, Daniel; Cherrington, Ross


    The low productivity of salmonids in many river systems across the UK is testament to their intolerance of water quality perturbations including those associated with excessive sedimentation. Catchment and fishery managers concerned with combating such issues require reliable information on the key sources of the sediment problem to target management and on the efficacy of the mitigation options being implemented. In recognition of the latter requirement, a pre- and post-remediation sediment sourcing survey was used to examine the potential for using sediment tracing to assemble preliminary information on the efficacy of riparian fencing schemes for reducing sediment contributions from eroding channel banks to salmonid spawning gravels in the Rivers Camel, Fal, Lynher, Plym, Tamar and Tavy in the south west of the UK. Respective estimates of the overall mean proportion (+/-95% confidence limits) of the interstitial sediment input to salmonid spawning gravels originating from eroding channel banks during the pre- (1999-2000) and post-remediation (2008-2009) study periods were computed at 97+/-1% vs. 69+/-1%, 94+/-1% vs. 91+/-1%, 12+/-1% vs. 10+/-1%, 92+/-1% vs. 34+/-1%, 31+/-1% vs. 16+/-1% and 90+/-1% vs. 66+/-1%. Whilst the study demonstrates the potential utility of the fingerprinting approach for helping to assemble important information on the efficacy of bank fencing as a sediment source control measure at catchment scale, a number of limitations of the work and some suggestions for improving experimental design are discussed. Equivalent data are urgently required for many sediment mitigation options to help inform the development of water quality policy packages designed to protect aquatic ecosystems.

  4. Contribution of intracellular calcium and pH in ischemic uncoupling of cardiac gap junction channels formed of connexins 43, 40, and 45: a critical function of C-terminal domain.

    Directory of Open Access Journals (Sweden)

    Giriraj Sahu

    Full Text Available Ischemia is known to inhibit gap junction (GJ mediated intercellular communication. However the detail mechanisms of this inhibition are largely unknown. In the present study, we determined the vulnerability of different cardiac GJ channels formed of connexins (Cxs 43, 40, and 45 to simulated ischemia, by creating oxygen glucose deprived (OGD condition. 5 minutes of OGD decreased the junctional conductance (Gj of Cx43, Cx40 and Cx45 by 53±3%, 64±1% and 85±2% respectively. Reduction of Gj was prevented completely by restricting the change of both intracellular calcium ([Ca(2+]i and pH (pHi with potassium phosphate buffer. Clamping of either [Ca(2+]i or pHi, through BAPTA (2 mM or HEPES (80 mM respectively, offered partial resistance to ischemic uncoupling. Anti-calmodulin antibody attenuated the uncoupling of Cx43 and Cx45 significantly but not of Cx40. Furthermore, OGD could reduce only 26±2% of Gj in C-terminus (CT truncated Cx43 (Cx43-Δ257. Tethering CT of Cx43 to the CT-truncated Cx40 (Cx40-Δ249, and Cx45 (Cx45-Δ272 helped to resist OGD mediated uncoupling. Moreover, CT domain played a significant role in determining the junction current density and plaque diameter. Our results suggest; OGD mediated uncoupling of GJ channels is primarily due to elevated [Ca(2+]i and acidic pHi, though the latter contributes more. Among Cx43, Cx40 and Cx45, Cx43 is the most resistant to OGD while Cx45 is the most sensitive one. CT of Cx43 has major necessary elements for OGD induced uncoupling and it can complement CT of Cx40 and Cx45.

  5. Task 1.5 Genomic Shift and Drift Trends of Emerging Pathogens

    Energy Technology Data Exchange (ETDEWEB)

    Borucki, M


    The Lawrence Livermore National Laboratory (LLNL) Bioinformatics group has recently taken on a role in DTRA's Transformation Medical Technologies Initiative (TMTI). The high-level goal of TMTI is to accelerate the development of broad-spectrum countermeasures. To achieve those goals, TMTI has a near term need to conduct analyses of genomic shift and drift trends of emerging pathogens, with a focused eye on select agent pathogens, as well as antibiotic and virulence markers. Most emerging human pathogens are zoonotic viruses with a genome composed of RNA. The high mutation rate of the replication enzymes of RNA viruses contributes to sequence drift and provides one mechanism for these viruses to adapt to diverse hosts (interspecies transmission events) and cause new human and zoonotic diseases. Additionally, new viral pathogens frequently emerge due to genetic shift (recombination and segment reassortment) which allows for dramatic genotypic and phenotypic changes to occur rapidly. Bacterial pathogens also evolve via genetic drift and shift, although sequence drift generally occurs at a much slower rate for bacteria as compared to RNA viruses. However, genetic shift such as lateral gene transfer and inter- and intragenomic recombination enables bacteria to rapidly acquire new mechanisms of survival and antibiotic resistance. New technologies such as rapid whole genome sequencing of bacterial genomes, ultra-deep sequencing of RNA virus populations, metagenomic studies of environments rich in antibiotic resistance genes, and the use of microarrays for the detection and characterization of emerging pathogens provide mechanisms to address the challenges posed by the rapid emergence of pathogens. Bioinformatic algorithms that enable efficient analysis of the massive amounts of data generated by these technologies as well computational modeling of protein structures and evolutionary processes need to be developed to allow the technology to fulfill its potential.

  6. NRL Technical Year End Progress Report for MCSC PM-ICE FY11 SOW Tasks 1 and 2 - Hearing Loss (United States)


    2 — Hearing Loss Research May 18, 2012 Approved for public release; distribution is unlimited. Peter C. HerdiC James W. mCmaHon daniel l. amon...Technical Year End Progress Report for MCSC PM-ICE FY11 SOW Tasks 1 and 2 — Hearing Loss Research Peter C. Herdic, James W. McMahon, Daniel L. Amon...deemed relevant to the warfighter. 18-05-2012 Memorandum Report Hearing loss Human ear Small weapons fire Shooter’s notch Program Manager, Infantry Combat

  7. Channel Measurements and Characteristics for Cooperative Positioning Applications

    DEFF Research Database (Denmark)

    Wang, Wei; Steinböck, Gerhard; Jost, Thomas


    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...

  8. Beyond the Manual Channel

    DEFF Research Database (Denmark)

    the manual channel. Not surprisingly, most papers deal with non-manuals on the face. Once again, the papers at this workshop clearly identify the potentials of even closer cooperation between sign linguists and sign language engineers, and we think it is events like this that contribute a lot to a better...

  9. National Survey Report of PV Power Applications in Australia 2009. Task 1. Exchange and dissemination of information on PV power systems

    Energy Technology Data Exchange (ETDEWEB)

    Watt, M.; Wyder, J. [IT Power Australia, 6/9 Mackay Street Turner ACT 2612 (Australia)


    The objective of Task 1 of the IEA Photovoltaic Power Systems Programme is to facilitate the exchange and dissemination of information on the technical, economic, environmental and social aspects of photovoltaic power systems. An important deliverable of Task 1 is the annual Trends in photovoltaic applications report. In parallel, National Survey Reports are produced annually by each Task 1 participant. This document is the Australian National Survey Report for the year 2009. Information from this document will be used as input to the annual Trends in photovoltaic applications report.

  10. Enhancing Sensing and Channel Access in Cognitive Radio Networks

    KAUST Repository

    Hamza, Doha R.


    Cognitive radio technology is a promising technology to solve the wireless spectrum scarcity problem by intelligently allowing secondary, or unlicensed, users access to the primary, licensed, users\\' frequency bands. Cognitive technology involves two main tasks: 1) sensing the wireless medium to assess the presence of the primary users and 2) designing secondary spectrum access techniques that maximize the secondary users\\' benefits while maintaining the primary users\\' privileged status. On the spectrum sensing side, we make two contributions. First, we maximize a utility function representing the secondary throughput while constraining the collision probability with the primary below a certain value. We optimize therein the channel sensing time, the sensing decision threshold, the channel probing time, together with the channel sensing order for wideband primary channels. Second, we design a cooperative spectrum sensing technique termed sensing with equal gain combining whereby cognitive radios simultaneously transmit their sensing results to the fusion center over multipath fading reporting channels. The proposed scheme is shown to outperform orthogonal reporting systems in terms of achievable secondary throughput and to be robust against phase and synchronization errors. On the spectrum access side, we make four contributions. First, we design a secondary scheduling scheme with the goal of minimizing the secondary queueing delay under constraints on the average secondary transmit power and the maximum tolerable primary outage probability. Second, we design another secondary scheduling scheme based on the spectrum sensing results and the primary automatic repeat request feedback. The optimal medium access probabilities are obtained via maximizing the secondary throughput subject to constraints that guarantee quality of service parameters for the primary. Third, we propose a three-message superposition coding scheme to maximize the secondary throughput without

  11. Quarternary tectonics, Task 1

    Energy Technology Data Exchange (ETDEWEB)

    Bell, J.W.


    Activities conducted for the evaluation of the geology and seismotectonics stability of Yucca Mountain as a potential site for the underground disposal of high-level radioactive wastes continued. Tasks concerned with quaternary tectonics include: scheduling of photography of Little Skull Mountain area; the collection and dating of rock varnish samples from the 1932 Cedar Mountain earthquake area for carbon 14 AMS and cation-ratio analysis; collection of samples for thermoluminescence dating from the 1932 Cedar Mountain earthquake area; mapping of the northern area of Crater Flat; and surveying of the May 17, 1993 Eureka the Valley earthquake area.

  12. Task 1 quarternary tectonics

    Energy Technology Data Exchange (ETDEWEB)

    Bell, J.W.


    Activities on the task of quarternary tectonics for the Yucca Mountain Site investigations are described. Technical topics include: A preliminary reveiw of Bare Mountain Trench; A preliminary detailed lineament map of the Southwestern part of the proposed repository; A discussion on the 1994 Double Spring Flat, Nevada earthquake; and evidence for temporal clustering.

  13. FLOAT Project - Task 1

    DEFF Research Database (Denmark)

    Marchalot, Tanguy; Kofoed, Jens Peter; Sørensen, Eigil V.

    The objective of the FLOAT project is to study the reliability of high-performance fibre-reinforced concrete, also known as Compact Reinforced Composite (CRC), for the floats of wave energy converters. In order to reach commercial breakthrough, wave energy converters need to achieve a lower price...... of energy produced, comparable to prices currently obtained from offshore wind power, and this can be done by the use of more suitable materials. The flotation device is a key part of converters, as it accounts for a considerable share of initial investment, up to 27% depending on the converter (, 2011). CRC floats could be a very cost-effective technology with enhanced loading capacity and environmental resistance, and very low maintenance requirements, affecting directly the final energy price. The project involves DEXA Wave Energy Ltd, Wave Star A/S, Aalborg University and Hi-Con A...

  14. Differences between three inbred rat strains in number of K+ channel-immunoreactive neurons in the medullary raphé nucleus. (United States)

    Riley, D; Dwinell, M; Qian, B; Krause, K L; Bonis, J M; Neumueller, S; Marshall, B D; Hodges, M R; Forster, H V


    Ventilatory sensitivity to hypercapnia is greater in Dahl salt-sensitive (SS) rats than in Fawn Hooded hypertensive (FHH) and Brown Norway (BN) inbred rats. Since pH-sensitive potassium ion (K(+)) channels are postulated to contribute to the sensing and signaling of changes in CO(2)-H(+) in chemosensitive neurons, we tested the hypothesis that there are more pH-sensitive K(+) channel-immunoreactive (ir) neurons within the medullary raphé nuclei of the highly chemosensitive SS rats than in the other two strains. Medullary tissues from male and female BN, FHH, and SS rats were stained with cresyl violet or with antibodies targeting TASK-1, K(v)1.4, and Kir2.3 channels. K(+) channel-ir neurons were quantified and compared with the total neurons in the region. The total number of neurons in the medullary raphé 1) was greater in male FHH than the other male rats, 2) did not differ among the female rats, and 3) did not differ between sexes. The average number of K(+) channel-ir neurons per section was 30-60 neurons higher in the male SS than in the other rat strains. In contrast, for the females, the number of K(+) channel-ir neurons was greatest in the BN. We also found significant differences in the number of K(+) channel-ir neurons between sexes in SS (males > females) and BN (females > males) rats, but not the FHH strain. Our findings support the hypothesis for males but not for females, suggesting that both genetic background and sex are determinants of K(+) channel immunoreactivity of medullary raphé neurons, and that the expression of pH-sensitive K(+) channels in the medullary raphé does not correlate with the ventilatory sensitivity to hypercapnia.

  15. Mechanosensitive Channels (United States)

    Martinac, Boris

    Living cells are exposed to a variety of mechanical stimuli acting throughout the biosphere. The range of the stimuli extends from thermal molecular agitation to potentially destructive cell swelling caused by osmotic pressure gradients. Cellular membranes present a major target for these stimuli. To detect mechanical forces acting upon them cell membranes are equipped with mechanosensitive (MS) ion channels. Functioning as molecular mechanoelectrical transducers of mechanical forces into electrical and/or chemical intracellular signals these channels play a critical role in the physiology of mechanotransduction. Studies of prokaryotic MS channels and recent work on MS channels of eukaryotes have significantly increased our understanding of their gating mechanism, physiological functions, and evolutionary origins as well as their role in the pathology of disease.

  16. Potassium channels in pulmonary arterial hypertension. (United States)

    Boucherat, Olivier; Chabot, Sophie; Antigny, Fabrice; Perros, Frédéric; Provencher, Steeve; Bonnet, Sébastien


    Pulmonary arterial hypertension (PAH) is a devastating cardiopulmonary disorder with various origins. All forms of PAH share a common pulmonary arteriopathy characterised by vasoconstriction, remodelling of the pre-capillary pulmonary vessel wall, and in situ thrombosis. Although the pathogenesis of PAH is recognised as a complex and multifactorial process, there is growing evidence that potassium channels dysfunction in pulmonary artery smooth muscle cells is a hallmark of PAH. Besides regulating many physiological functions, reduced potassium channels expression and/or activity have significant effects on PAH establishment and progression. This review describes the molecular mechanisms and physiological consequences of potassium channel modulation. Special emphasis is placed on KCNA5 (Kv1.5) and KCNK3 (TASK1), which are considered to play a central role in determining pulmonary vascular tone and may represent attractive therapeutic targets in the treatment of PAH.

  17. Asp residues of the Glu-Glu-Asp-Asp pore filter contribute to ion permeation and selectivity of the Ca(v)3.2 T-type channel. (United States)

    Park, Hyun-Jee; Park, So-Jung; Ahn, Eun-Joo; Lee, So-Young; Seo, Haengsoo; Lee, Jung-Ha


    Voltage-activated Ca2+ channels are membrane protein machinery performing selective permeation of external calcium ions. The main Ca2+ selective filters of all high-voltage-activated Ca2+ channel isoforms are commonly composed of four Glu residues (EEEE), while those of low-voltage-activated T-type Ca2+ channel isoforms are made up of two Glu and two Asp residues (EEDD). We here investigate how the Asp residues at the pore loops of domains III and IV affect biophysical properties of the Ca(v)3.2 channel. Electrophysiological characterization of the pore mutant channels in which the pore Asp residue(s) were replaced with Glu, showed that both Asp residues critically control the biophysical properties of Ca(v)3.2, including relative permeability between Ba2+ and Ca2+, anomalous mole fraction effect (AMFE), voltage dependency of channel activation, Cd2+ blocking sensitivity, and pH effects, in distinctive ways. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Methods development for measuring and classifying flammability/combustibility of refrigerants. Interim report, Task 1 -- Annotated bibliography and summary

    Energy Technology Data Exchange (ETDEWEB)

    Heinonen, E.W.; Tapscott, R.E. [New Mexico Univ., Albuquerque, NM (United States). Center for Global Enviromental Technology


    For Task 1 of the flammable refrigerant methods development contract, NMERI performed a literature search to identify references on the flammability of refrigerants. A database to store a bibliographic record of the literature search was then developed. This database is contained in the Microsoft Access{reg_sign} relational database management system for Windows{trademark}. Searches for applicable sources were made on-line using the STN{reg_sign} scientific and technical network; off-line using the National Technical Information Service (NTIS) database; WorldCat CD-rom database; the University of New Mexico library search; the Air-Conditioning and Refrigeration institute (ARI) Refrigerant Database; and personal contacts. Three specific areas were searched: refrigerant properties, flammability test methods, and ignition technology. Many of the articles retrieved fall into multiple categories. Ignition technology was included as a separate category because of the importance of the ignition process to flammability and the vast amount of information available on ignition of gaseous fuels, especially hydrocarbons. Over 90 separate references have been entered into the database. Two separate report formats have been developed to display the results of the literature search. Appendix B is the short report format--without abstract, while Appendix C is the long format--with abstract.

  19. Task 1. Monitoring real time materials degradation. NRC extended In-situ and real-time Monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Bakhtiari, Sasan [Argonne National Lab. (ANL), Argonne, IL (United States)


    The overall objective of this project was to perform a scoping study to identify, in concert with the nuclear industry, those sensors and techniques that have the most promising commercial viability and fill a critical inspection or monitoring need. Candidates to be considered include sensors to monitor real-time material degradation, characterize residual stress, monitor and inspect component fabrication, assess radionuclide and associated chemical species concentrations in ground water and soil, characterize fuel properties, and monitor severe accident conditions. Under Task 1—Monitoring Real-Time Materials Degradation—scoping studies were conducted to assess the feasibility of potential inspection and monitoring technologies (i.e., a combination of sensors, advanced signal processing techniques, and data analysis methods) that could be utilized in LWR and/or advanced reactor applications for continuous monitoring of degradation in-situ. The goal was to identify those techniques that appear to be the most promising, i.e., those that are closest to being both technically and commercially viable and that the nuclear industry is most likely to pursue. Current limitations and associated issues that must be overcome before commercial application of certain techniques have also been addressed.

  20. Positron Channeling

    CERN Document Server

    Badikyan, Karen


    The possibility of channeling the low-energy relativistic positrons around separate crystallographic axes with coaxial symmetry of negative ions in some types of crystals is shown. The process of annihilation of positrons with electrons of medium was studied in detail.

  1. Brands & Channels

    Institute of Scientific and Technical Information of China (English)

    Alice Yang


    @@ "Brands" and "Channels" are the two most important things in Ku-Hai Chen's eyes when doing business with Main-land China. Ku-Hai Chen, Executive Director of the International Trade Institute of Taiwan External Trade Development Council (TAITRA), flies frequently between Chinese Taipei and Mainland China, and was in Beijing earlier this month for his seminar.

  2. Channel Power in Multi-Channel Environments

    NARCIS (Netherlands)

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


    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 compon

  3. Channel Power in Multi-Channel Environments

    NARCIS (Netherlands)

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


    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

  4. Nonlinear channelizer (United States)

    In, Visarath; Longhini, Patrick; Kho, Andy; Neff, Joseph D.; Leung, Daniel; Liu, Norman; Meadows, Brian K.; Gordon, Frank; Bulsara, Adi R.; Palacios, Antonio


    The nonlinear channelizer is an integrated circuit made up of large parallel arrays of analog nonlinear oscillators, which, collectively, serve as a broad-spectrum analyzer with the ability to receive complex signals containing multiple frequencies and instantaneously lock-on or respond to a received signal in a few oscillation cycles. The concept is based on the generation of internal oscillations in coupled nonlinear systems that do not normally oscillate in the absence of coupling. In particular, the system consists of unidirectionally coupled bistable nonlinear elements, where the frequency and other dynamical characteristics of the emergent oscillations depend on the system's internal parameters and the received signal. These properties and characteristics are being employed to develop a system capable of locking onto any arbitrary input radio frequency signal. The system is efficient by eliminating the need for high-speed, high-accuracy analog-to-digital converters, and compact by making use of nonlinear coupled systems to act as a channelizer (frequency binning and channeling), a low noise amplifier, and a frequency down-converter in a single step which, in turn, will reduce the size, weight, power, and cost of the entire communication system. This paper covers the theory, numerical simulations, and some engineering details that validate the concept at the frequency band of 1-4 GHz.

  5. Transient receptor potential channels encode volatile chemicals sensed by rat trigeminal ganglion neurons.

    Directory of Open Access Journals (Sweden)

    Matthias Lübbert

    Full Text Available Primary sensory afferents of the dorsal root and trigeminal ganglia constantly transmit sensory information depicting the individual's physical and chemical environment to higher brain regions. Beyond the typical trigeminal stimuli (e.g. irritants, environmental stimuli comprise a plethora of volatile chemicals with olfactory components (odorants. In spite of a complete loss of their sense of smell, anosmic patients may retain the ability to roughly discriminate between different volatile compounds. While the detailed mechanisms remain elusive, sensory structures belonging to the trigeminal system seem to be responsible for this phenomenon. In order to gain a better understanding of the mechanisms underlying the activation of the trigeminal system by volatile chemicals, we investigated odorant-induced membrane potential changes in cultured rat trigeminal neurons induced by the odorants vanillin, heliotropyl acetone, helional, and geraniol. We observed the dose-dependent depolarization of trigeminal neurons upon application of these substances occurring in a stimulus-specific manner and could show that distinct neuronal populations respond to different odorants. Using specific antagonists, we found evidence that TRPA1, TRPM8, and/or TRPV1 contribute to the activation. In order to further test this hypothesis, we used recombinantly expressed rat and human variants of these channels to investigate whether they are indeed activated by the odorants tested. We additionally found that the odorants dose-dependently inhibit two-pore potassium channels TASK1 and TASK3 heterologously expressed In Xenopus laevis oocytes. We suggest that the capability of various odorants to activate different TRP channels and to inhibit potassium channels causes neuronal depolarization and activation of distinct subpopulations of trigeminal sensory neurons, forming the basis for a specific representation of volatile chemicals in the trigeminal ganglia.

  6. Estimation real number of road accident casualties. SafetyNet, Building the European Road Safety Observatory, Deliverable D.1.15 : final report on task 1.5.

    NARCIS (Netherlands)

    Broughton, J. Amoros, E. Bos, N.M. Evgenikos, P. Hoeglinger, S. Holló, P. Pérez, C. & Tecl, J.


    The objective of Task 1.5 of the SafetyNet IP has been to estimate the actual numbers of road accident casualties in Europe from the CARE database by addressing two issues: • the under-reporting in national accident databases and • the differences between countries of the definitions used to

  7. ``Just Another Distribution Channel?'' (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.

  8. Functional mutagenesis screens reveal the 'cap structure' formation in disulfide-bridge free TASK channels. (United States)

    Goldstein, Matthias; Rinné, Susanne; Kiper, Aytug K; Ramírez, David; Netter, Michael F; Bustos, Daniel; Ortiz-Bonnin, Beatriz; González, Wendy; Decher, Niels


    Two-pore-domain potassium (K2P) channels have a large extracellular cap structure formed by two M1-P1 linkers, containing a cysteine for dimerization. However, this cysteine is not present in the TASK-1/3/5 subfamily. The functional role of the cap is poorly understood and it remained unclear whether K2P channels assemble in the domain-swapped orientation or not. Functional alanine-mutagenesis screens of TASK-1 and TRAAK were used to build an in silico model of the TASK-1 cap. According to our data the cap structure of disulfide-bridge free TASK channels is similar to that of other K2P channels and is most likely assembled in the domain-swapped orientation. As the conserved cysteine is not essential for functional expression of all K2P channels tested, we propose that hydrophobic residues at the inner leaflets of the cap domains can interact with each other and that this way of stabilizing the cap is most likely conserved among K2P channels.

  9. Molecular dissection of the contribution of negatively and positively charged residues in S2, S3, and S4 to the final membrane topology of the voltage sensor in the K+ channel, KAT1. (United States)

    Sato, Yoko; Sakaguchi, Masao; Goshima, Shinobu; Nakamura, Tatsunosuke; Uozumi, Nobuyuki


    Voltage-dependent ion channels control changes in ion permeability in response to membrane potential changes. The voltage sensor in channel proteins consists of the highly positively charged segment, S4, and the negatively charged segments, S2 and S3. The process involved in the integration of the protein into the membrane remains to be elucidated. In this study, we used in vitro translation and translocation experiments to evaluate interactions between residues in the voltage sensor of a hyperpolarization-activated potassium channel, KAT1, and their effect on the final topology in the endoplasmic reticulum (ER) membrane. A D95V mutation in S2 showed less S3-S4 integration into the membrane, whereas a D105V mutation allowed S4 to be released into the ER lumen. These results indicate that Asp(95) assists in the membrane insertion of S3-S4 and that Asp(105) helps in preventing S4 from being releasing into the ER lumen. The charge reversal mutation, R171D, in S4 rescued the D105R mutation and prevented S4 release into the ER lumen. A series of constructs containing different C-terminal truncations of S4 showed that Arg(174) was required for correct integration of S3 and S4 into the membrane. Interactions between Asp(105) and Arg(171) and between negative residues in S2 or S3 and Arg(174) may be formed transiently during membrane integration. These data clarify the role of charged residues in S2, S3, and S4 and identify posttranslational electrostatic interactions between charged residues that are required to achieve the correct voltage sensor topology in the ER membrane.

  10. Conceptual Design of a Space-Based Multimegawatt MHD Power System, Task 1 Topical Report; Volume 1: Technical Discussion (United States)


    TemD (K) Temp. (Min.) Shutdown KIWI -B4D 2222 1 Hydrogen Fire KIWI -B4E 2389 8, 2.5 Normal NRX-A2 >2200 3.4 Normal NRX-A3 >2400 16.3 Normal PH0EBUS-1A...development team with contributions to the successful KIWI reactor core lateral support design and on-line reactor test monitoring procedures

  11. Sol-Gel Technology for Low-VOC, Nonchromated Adhesive Bonding Applications SERDP; Project PP-1113, Task 1 (United States)


    Steve Risser of Battelle and Henry Zheng of Chemat Technology, Inc. were team members who contributed to PP-1113 efforts that are not documented in...High Volume Low Pressure (HVLP) spray gun (Binks Model M1-G). Baseline specimens were bonded with 3M Company AF 163-2M (0.06 pounds per square foot ...first experiment. During that experiment, a nearly flat -top beam spatial profile was used. Two laser fluence levels were evaluated: a level

  12. IPIRG-2 task 1 - pipe system experiments with circumferential cracks in straight-pipe locations. Final report, September 1991--November 1995

    Energy Technology Data Exchange (ETDEWEB)

    Scott, P.; Olson, R.; Marschall, C.; Rudland, D. [and others


    This report presents the results from Task 1 of the Second International Piping Integrity Research Group (IPIRG-2) program. The IPIRG-2 program is an international group program managed by the US Nuclear Regulatory Commission (US NRC) and funded by a consortium of organizations from 15 nations including: Bulgaria, Canada, Czech Republic, France, Hungary, Italy, Japan, Republic of Korea, Lithuania, Republic of China, Slovak Republic, Sweden, Switzerland, the United Kingdom, and the United States. The objective of the program was to build on the results of the IPIRG-1 and other related programs by extending the state-of-the-art in pipe fracture technology through the development of data needed to verify engineering methods for assessing the integrity of nuclear power plant piping systems that contain defects. The IPIRG-2 program included five main tasks: Task 1 - Pipe System Experiments with Flaws in Straight Pipe and Welds Task 2 - Fracture of Flawed Fittings Task 3 - Cyclic and Dynamic Load Effects on Fracture Toughness Task 4 - Resolution of Issues From IPIRG-1 and Related Programs Task 5 - Information Exchange Seminars and Workshops, and Program Management. The scope of this report is to present the results from the experiments and analyses associated with Task 1 (Pipe System Experiments with Flaws in Straight Pipe and Welds). The rationale and objectives of this task are discussed after a brief review of experimental data which existed after the IPIRG-1 program.

  13. RING1B contributes to Ewing sarcoma development by repressing the NaV1.6 sodium channel and the NF-κB pathway, independently of the fusion oncoprotein (United States)

    Hernandez-Muñoz, Inmaculada; Rodriguez, Eva; Fernández-Mariño, Ana Isabel; Pardo-Pastor, Carlos; Bahamonde, María Isabel; Fernández-Fernández, José M.; García-Domínguez, Daniel J.; Hontecillas-Prieto, Lourdes; Lavarino, Cinzia; Carcaboso, Angel M.; de Torres, Carmen; Tirado, Oscar M.; de Alava, Enrique; Mora, Jaume


    Ewing sarcoma (ES) is an aggressive tumor defined by EWSR1 gene fusions that behave as an oncogene. Here we demonstrate that RING1B is highly expressed in primary ES tumors, and its expression is independent of the fusion oncogene. RING1B-depleted ES cells display an expression profile enriched in genes functionally involved in hematological development but RING1B depletion does not induce cellular differentiation. In ES cells, RING1B directly binds the SCN8A sodium channel promoter and its depletion results in enhanced Nav1.6 expression and function. The signaling pathway most significantly modulated by RING1B is NF-κB. RING1B depletion results in enhanced p105/p50 expression, which sensitizes ES cells to apoptosis by FGFR/SHP2/STAT3 blockade. Reduced NaV1.6 function protects ES cells from apoptotic cell death by maintaining low NF-κB levels. Our findings identify RING1B as a trait of the cell-of-origin and provide a potential targetable vulnerability. PMID:27317769

  14. Coupled-channel analysis for phi photoproduction with Lambda

    NARCIS (Netherlands)

    Ozaki, S.; Hosaka, A.; Nagahiro, H.; Scholten, O.


    We investigate photoproduction of phi mesons off protons within a coupled-channel effective-Lagrangian method which is based on the K-matrix approach. Since the threshold energy of the K Lambda(1520) channel is close to that of phi N, the contribution of this channel to f photoproduction near the th

  15. Functional mutagenesis screens reveal the ‘cap structure’ formation in disulfide-bridge free TASK channels (United States)

    Goldstein, Matthias; Rinné, Susanne; Kiper, Aytug K.; Ramírez, David; Netter, Michael F.; Bustos, Daniel; Ortiz-Bonnin, Beatriz; González, Wendy; Decher, Niels


    Two-pore-domain potassium (K2P) channels have a large extracellular cap structure formed by two M1-P1 linkers, containing a cysteine for dimerization. However, this cysteine is not present in the TASK-1/3/5 subfamily. The functional role of the cap is poorly understood and it remained unclear whether K2P channels assemble in the domain-swapped orientation or not. Functional alanine-mutagenesis screens of TASK-1 and TRAAK were used to build an in silico model of the TASK-1 cap. According to our data the cap structure of disulfide-bridge free TASK channels is similar to that of other K2P channels and is most likely assembled in the domain-swapped orientation. As the conserved cysteine is not essential for functional expression of all K2P channels tested, we propose that hydrophobic residues at the inner leaflets of the cap domains can interact with each other and that this way of stabilizing the cap is most likely conserved among K2P channels. PMID:26794006

  16. Beyond the Manual Channel

    DEFF Research Database (Denmark)

    , the main focus there is on spoken languages in their written and spoken forms. This series of workshops, however, offers a forum for researchers focussing on sign languages. For the fourth time, the workshop had sign language corpora as its main topic. This time, the focus was on any aspect beyond......This collection of papers stems from the Sixth Workshop on the Representation and Processing of Sign Languages, held in May 2014 as a satellite to the Language Resources and Evaluation Conference in Reykjavik. While there has been occasional attention for sign languages at the main LREC conference...... the manual channel. Not surprisingly, most papers deal with non-manuals on the face. Once again, the papers at this workshop clearly identify the potentials of even closer cooperation between sign linguists and sign language engineers, and we think it is events like this that contribute a lot to a better...

  17. Cell volume-regulated cation channels. (United States)

    Wehner, Frank


    Considering the enormous turnover rates of ion channels when compared to carriers it is quite obvious that channel-mediated ion transport may serve as a rapid and efficient mechanism of cell volume regulation. Whenever studied in a quantitative fashion the hypertonic activation of non-selective cation channels is found to be the main mechanism of regulatory volume increase (RVI). Some channels are inhibited by amiloride (and may be related to the ENaC), others are blocked by Gd(3) and flufenamate (and possibly linked to the group of transient receptor potential (TRP) channels). Nevertheless, the actual architecture of hypertonicity-induced cation channels remains to be defined. In some preparations, hypertonic stress decreases K(+) channel activity so reducing the continuous K(+) leak out of the cell; this is equivalent to a net gain of cell osmolytes facilitating RVI. The hypotonic activation of K(+) selective channels appears to be one of the most common principles of regulatory volume decrease (RVD) and, in most instances, the actual channels involved could be identified on the molecular level. These are BKCa (or maxi K(+)) channels, IK(Ca) and SK(Ca) channels (of intermediate and small conductance, respectively), the group of voltage-gated (Kv) channels including their Beta (or Kv ancilliary) subunits, two-pore K(2P) channels, as well as inwardly rectifying K(+) (Kir) channels (also contributing to K(ATP) channels). In some cells, hypotonicity activates non-selective cation channels. This is surprising, at first sight, because of the inside negative membrane voltage and the sum of driving forces for Na(+) and K(+) diffusion across the cell membrane rather favouring net cation uptake. Some of these channels, however, exhibit a P(K)/P(Na) significantly higher than 1, whereas others are Ca(++) permeable linking hypotonic stress to the activation of Ca(++) dependent ion channels. In particular, the latter holds for the group of TRPs which are specialised in the

  18. District heating and cooling systems for communities through power-plant retrofit and distribution network. Volume 2. Tasks 1-3. Final report. [Downtown Toledo steam system

    Energy Technology Data Exchange (ETDEWEB)

    Watt, J.R.; Sommerfield, G.A.


    Each of the tasks is described separately: Task 1 - Demonstration Team; Task 2 - Identify Thermal Energy Source(s) and Potential Service Area(s); and Task 3 - Energy Market Analysis. The purpose of the project is to establish and implement measures in the downtown Toledo steam system for conserving scarce fuel supplies through cogeneration, by retrofit of existing base- or intermediate-loaded electric-generating plants to provide for central heating and cooling systems, with the ultimate purpose of applying the results to other communities. For Task 1, Toledo Edison Company has organized a Demonstration Team (Battelle Columbus Laboratories; Stone and Webster; Ohio Dept. of Energy; Public Utilities Commission of Ohio; Toledo Metropolitan Area Council of Governments; and Toledo Edison) that it hopes has the expertise to evaluate the technical, legal, economic, and marketing issues related to the utilization of by-product heat from power generation to supply district heating and cooling services. Task 2 gives a complete technical description of the candidate plant(s), its thermodynamic cycle, role in load dispatch, ownership, and location. It is concluded that the Toledo steam distribution system can be the starting point for developing a new district-heating system to serve an expanding market. Battelle is a member of the team employed as a subcontractor to complete the energy market analysis. The work is summarized in Task 3. (MCW)

  19. Mobile radio channels

    CERN Document Server

    Pätzold, Matthias


    Providing a comprehensive overview of the modelling, analysis and simulation of mobile radio channels, this book gives a detailed understanding of fundamental issues and examines state-of-the-art techniques in mobile radio channel modelling. It analyses several mobile fading channels, including terrestrial and satellite flat-fading channels, various types of wideband channels and advanced MIMO channels, providing a fundamental understanding of the issues currently being investigated in the field. Important classes of narrowband, wideband, and space-time wireless channels are explored in deta

  20. Channel nut tool

    Energy Technology Data Exchange (ETDEWEB)

    Olson, Marvin


    A method, system, and apparatus for installing channel nuts includes a shank, a handle formed on a first end of a shank, and an end piece with a threaded shaft configured to receive a channel nut formed on the second end of the shaft. The tool can be used to insert or remove a channel nut in a channel framing system and then removed from the channel nut.

  1. Vehicular Channel Characterization and Modeling


    Oestges, Claude; 10th European Conference on Antennas and Propagation (EuCAP)


    Vehicle-to-vehicle transmissions have emerged as a key component of future communication standards, whose design and testing critically depends upon the understanding of propagation mechanisms. An important and specific aspect of vehicular communication channels lies in the fact that these are essentially non-stationary. Hence, this communication addresses two recent contributions in the field of non-stationary vehicular propagation, based on extensive measurements conducted at 5.3 GHz in sub...

  2. Multi-Channel Retailing

    Directory of Open Access Journals (Sweden)

    Dirk Morschett, Dr.,


    Full Text Available Multi-channel retailing entails the parallel use by retailing enterprises of several sales channels. The results of an online buyer survey which has been conducted to investigate the impact of multi-channel retailing (i.e. the use of several retail channels by one retail company on consumer behaviour show that the frequently expressed concern that the application of multi-channel systems in retailing would be associated with cannibalization effects, has proven unfounded. Indeed, the appropriate degree of similarity, consistency, integration and agreement achieves the exact opposite. Different channels create different advantages for consumers. Therefore the total benefit an enterprise which has a multi-channel system can offer to its consumers is larger, the greater the number of available channels. The use of multi-channel systems is associated with additional purchases in the different channels. Such systems are thus superior to those offering only one sales channel to their customers. Furthermore, multi-channel systems with integrated channels are superior to those in which the channels are essentially autonomous and independent of one another. In integrated systems, consumers can achieve synergy effects in the use of sales-channel systems. Accordingly, when appropriately formulated, multi-channel systems in retailing impact positively on consumers. They use the channels more frequently, buy more from them and there is a positive customer-loyalty impact. Multi-channel systems are strategic options for achieving customer loyalty, exploiting customer potential and for winning new customers. They are thus well suited for approaching differing and varied target groups.

  3. Field Laboratory in the Osage Reservation -- Determination of the Status of Oil and Gas Operations: Task 1. Development of Survey Procedures and Protocols

    Energy Technology Data Exchange (ETDEWEB)

    Carroll, Herbert B.; Johnson, William I.


    Procedures and protocols were developed for the determination of the status of oil, gas, and other mineral operations on the Osage Mineral Reservation Estate. The strategy for surveying Osage County, Oklahoma, was developed and then tested in the field. Two Osage Tribal Council members and two Native American college students (who are members of the Osage Tribe) were trained in the field as a test of the procedures and protocols developed in Task 1. Active and inactive surface mining operations, industrial sites, and hydrocarbon-producing fields were located on maps of the county, which was divided into four more or less equal areas for future investigation. Field testing of the procedures, protocols, and training was successful. No significant damage was found at petroleum production operations in a relatively new production operation and in a mature waterflood operation.

  4. Channel Capacity Estimation using Free Probability Theory

    CERN Document Server

    Ryan, Øyvind


    In many channel measurement applications, one needs to estimate some characteristics of the channels based on a limited set of measurements. This is mainly due to the highly time varying characteristics of the channel. In this contribution, it will be shown how free probability can be used for channel capacity estimation in MIMO systems. Free probability has already been applied in various application fields such as digital communications, nuclear physics and mathematical finance, and has been shown to be an invaluable tool for describing the asymptotic behaviour of many systems when the dimensions of the system get large (i.e. the number of antennas). In particular, introducing the notion of free deconvolution, we provide hereafter an asymptotically (in the number of antennas) unbiased capacity estimator (w.r.t. the number of observations) for MIMO channels impaired with noise. Another unbiased estimator (for any number of observations) is also constructed by slightly modifying the free probability based est...

  5. Ion channels regulating mast cell biology. (United States)

    Ashmole, I; Bradding, P


    Mast cells play a central role in the pathophysiology of asthma and related allergic conditions. Mast cell activation leads to the degranulation of preformed mediators such as histamine and the secretion of newly synthesised proinflammatory mediators such as leukotrienes and cytokines. Excess release of these mediators contributes to allergic disease states. An influx of extracellular Ca2+ is essential for mast cell mediator release. From the Ca2+ channels that mediate this influx, to the K+ , Cl- and transient receptor potential channels that set the cell membrane potential and regulate Ca2+ influx, ion channels play a critical role in mast cell biology. In this review we provide an overview of our current knowledge of ion channel expression and function in mast cells with an emphasis on how channels interact to regulate Ca2+ signalling.

  6. Coal combustion science: Task 1, Coal char combustion: Task 2, Fate of mineral matter. Quarterly progress report, July--September 1993

    Energy Technology Data Exchange (ETDEWEB)

    Hardesty, D.R. [ed.; Hurt, R.H.; Davis, K.A.; Baxter, L.L.


    Progress reports are presented for the following tasks: (1) kinetics and mechanisms of pulverized coal char combustion and (2) fate of inorganic material during coal combustion. The objective of Task 1 is to characterize the combustion behavior of selected US coals under conditions relevant to industrial pulverized coal-fired furnaces. In Sandia`s Coal Combustion Laboratory (CCL), optical techniques are used to obtain high-resolution images of individual burning coal char particles and to measure, in situ, their temperatures, sizes, and velocities. Detailed models of combustion transport processes are then used to determine kinetic parameters describing the combustion behavior as a function of coal type and combustion environment. Partially reacted char particles are also sampled and characterized with advanced materials diagnostics to understand the critical physical and chemical transformations that influence reaction rates and burnout times. The ultimate goal of the task is the establishment of a data base of the high temperature reactivities of chars from strategic US coals, from which important trends may be identified and predictive capabilities developed. The overall objectives for task 2 are: (1) to complete experimental and theoretical investigation of ash release mechanisms; (2) to complete experimental work on char fragmentation; (3) to establish the extent of coal (as opposed to char) fragmentation as a function of coal type and particle size; (4) to develop diagnostic capabilities for in situ, real-time, qualitative indications of surface species composition during ash deposition, with work continuing into FY94; (5) to develop diagnostic capabilities for in situ, real-time qualitative detection of inorganic vapor concentrations; and (6) to conduct a literature survey on the current state of understanding of ash deposition, with work continuing into FY94.

  7. Hadamard quantum broadcast channels (United States)

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


    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.

  8. Omni-channel Retail Information Systems

    DEFF Research Database (Denmark)

    Tambo, Torben


    key players in the industry of retailing (Wilson, 2012; Verizon, 2012) and covers the idea that anything can be sold anywhere with consistent marketing, reasonable efficiency of the supply chain channels and responsible customer service. This article aims at contributing to a characterisation...... and digital sales channels by the use of technology, thus providing uniform customer experience and operational effectiveness across the channels (Hansen and Tambo, 2011). The vision of OCRIS remains largely at a conceptual level. Selected point-of-sale (“cash registers”) products and retail management...

  9. USACE Navigation Channels 2012 (United States)

    California Department of Resources — This dataset represents both San Francisco and Los Angeles District navigation channel lines. All San Francisco District channel lines were digitized from CAD files...

  10. Channelling versus inversion

    DEFF Research Database (Denmark)

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


    . Within this channel were smaller erosional structures (hardgrounds, and locally have a basal fill of granular phosphorite. The entire channel system was progressively infilled by chalk, as demonstrated by the expanded succession...

  11. Maritime Channel Modeling and Simulation for Efficient Wideband Communications between Autonomous Unmanned Surface Vehicles (United States)


    5 4.1 NAKAGAMI -M FADING CHANNEL MODEL ...................................................................... 6 5. SIMULATION...modeled using a Nakagami -m distribution. A special instance of the Nakagami -m multipath fading channel is the Rayleigh fading channel, which is...decomposed into the following contributions and losses: , (7) where LAPM is the propagation loss calculated by APM. 4.1 NAKAGAMI -M FADING CHANNEL

  12. Hidden systematics of fission channels

    Directory of Open Access Journals (Sweden)

    Schmidt Karl-Heinz


    Full Text Available It is a common procedure to describe the fission-fragment mass distributions of fissioning systems in the actinide region by a sum of at least 5 Gaussian curves, one for the symmetric component and a few additional ones, together with their complementary parts, for the asymmetric components. These components have been attributed to the influence of fragment shells, e.g. in the statistical scission-point model of Wilkins, Steinberg and Chasman. They have also been associated with valleys in the potential-energy landscape between the outer saddle and the scission configuration in the multi-channel fission model of Brosa. When the relative yields, the widths and the mean mass-asymmetry values of these components are fitted to experimental data, the mass distributions can be very well reproduced. Moreover, these fission channels are characterised by specific values of charge polarisation, total kinetic energy and prompt-neutron yields. The present contribution investigates the systematic variation of the characteristic fission-channel properties as a function of the composition and the excitation energy of the fissioning system. The mean position of the asymmetric fission channels in the heavy fragment is almost constant in atomic number. The deformation of the nascent fragments at scission, which is the main source of excitation energy of the separated fission fragments ending up in prompt-neutron emission, is found to be a unique function of Z for the light and the heavy fragment of the asymmetric fission channels. A variation of the initial excitation energy of the fissioning system above the fission saddle is only seen in the neutron yield of the heavy fragment. The charge polarisation in the two most important asymmetric fission channels is found to be constant and to appreciably exceed the macroscopic value. The variation of the relative yields and of the positions of the fission channels as a function of the composition and excitation energy

  13. Quantum Multiple Access Channel

    Institute of Scientific and Technical Information of China (English)

    侯广; 黄民信; 张永德


    We consider the transmission of classical information over a quantum channel by many senders, which is a generalization of the two-sender case. The channel capacity region is shown to be a convex hull bound by the yon Neumann entropy and the conditional yon Neumann entropies. The result allows a reasonable distribution of channel capacity over the senders.

  14. Poster contributions; Contributions par affiches

    Energy Technology Data Exchange (ETDEWEB)

    Allegraud, K.; Gatilova, I.; Guaitella, O.; Ionikh, Y.; Roepcke, J.; Rousseau, A.; Aranchuk, L.E.; Larour, J.; Asad, S.; Tendero, C.; Tixier, C.; Jaoul, C.; Tristant, P.; Boisse-Laporte, C.; Leprince, P.; Leniniven, C.; Assouar, M.B.; Jimenez Rioboo, R.J.; Aubert, X.; Rousseau, A.; Sadeghi, N.; Bekstein, A.; Benhenni, M.; Yousfi, M.; Bousquet, A.; Granier, A.; Cartry, G.; Calafat, M.; Escaich, D.; Raynaud, P.; Clergereaux, R.; Cardoso, R.P.; Belmonte, T.; Henrion, G.; Sadeghi, N.; Cavarroc, M.; Mikikian, M.; Tessier, Y.; Boufendi, I.; Celestin, S.; Guaitella, O.; Bourdon, A.; Rousseau, A.; Cernogora, G.; Szopa, C.; Cavarroc, M.; Boufendi, I.; Commaux, N.; Geraud, A.; Pegourie, B.; Clairet, F.; Gil, C.; Gros, G.; Gunn, J.; Joffrin, E.; Hertout, P.; Costin, C.; Choimet, J.B.; Minea, T.; Couedel, L.; Mikikian, M.; Tessier, Y.; Boufendi, I.; Samarian, A.A.; Cousin, R.; Larour, J.; Gouard, P.; Raymond, P.; Curley, G.A.; Booth, J.P.; Corr, C.S.; Foldes, T.; Guillon, J.; Czarny, O.; Huysmans, G.; Daniel, A.; Belmonte, T.; Poucques, L. de; Imbert, J.C.; Teule-Gay, L.; Boisse-Laporte, C.; Devaux, S.; Manfredi, G.; Dif-Pradalier, G.; Grandgirard, V.; Sarazin, Y.; Garbet, X.; Ghendrih, Ph.; Dong, B.; Bauchire, J.M.; Pouvesle, J.M.; Magnier, P.; Hong, D.; Duluard, C.; Tillocher, T.; Mekkakia Maaza, N.; Dussart, R.; Mellhaoui, X.; Lefaucheux, P.; Puech, M.; Ranson, P.; Faudot, E.; Heuraux, S.; Colas, L.; Fubiani, G.; Boilson, D.; Hemsworth, R.S.; Gatilova, L.; Allegraud, K.; Ionikh, Y.; Roepcke, J.; Cartry, G.; Rousseau, A.; Gauthier, J.C.; Fourment, C.; Schurtz, G.; Nicolai, Ph.; Peyrusse, O.; Feugeas, J.L


    This document gathers the poster contributions among which 11 are relevant for fusion plasmas or particle acceleration: 1) the spectral study of a micro plasma from an X-pinch explosion; 2) experiments with a plasma density greater than the Greenwald value via the injection of icicles in Tore-Supra; 3) Bezier's surfaces and finite elements method for non-linear MHD; 4) 2-dimensional simulation of the RF casings before the ICRF antennas in tokamaks; 5) negative ion sources for ITER; 6) experimental characterization of electron heat transport on the laser integration line; 7) comparison of fluctuation measurement methods of plasma density via reflectometry in mode-o and mode-x in Tore-Supra; 8) water-bag model applied to kinetics equations of magnetic fusion plasmas; 9) computerized simulation of electron acceleration in plasma waves generated in a capillary pipe through laser wakefield; 10) the slowing-down of an alpha particle in a strongly magnetized dense plasma; and 11) stochastic processes of particle trapping by a wave in a magnetized plasma. (A.C.)

  15. Flavonoid Regulation of HCN2 Channels* (United States)

    Carlson, Anne E.; Rosenbaum, Joel C.; Brelidze, Tinatin I.; Klevit, Rachel E.; Zagotta, William N.


    The hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels are pacemaker channels whose currents contribute to rhythmic activity in the heart and brain. HCN channels open in response to hyperpolarizing voltages, and the binding of cAMP to their cyclic nucleotide-binding domain (CNBD) facilitates channel opening. Here, we report that, like cAMP, the flavonoid fisetin potentiates HCN2 channel gating. Fisetin sped HCN2 activation and shifted the conductance-voltage relationship to more depolarizing potentials with a half-maximal effective concentration (EC50) of 1.8 μm. When applied together, fisetin and cAMP regulated HCN2 gating in a nonadditive fashion. Fisetin did not potentiate HCN2 channels lacking their CNBD, and two independent fluorescence-based binding assays reported that fisetin bound to the purified CNBD. These data suggest that the CNBD mediates the fisetin potentiation of HCN2 channels. Moreover, binding assays suggest that fisetin and cAMP partially compete for binding to the CNBD. NMR experiments demonstrated that fisetin binds within the cAMP-binding pocket, interacting with some of the same residues as cAMP. Together, these data indicate that fisetin is a partial agonist for HCN2 channels. PMID:24085296

  16. Seismic imaging and evaluation of channels modeled by boolean approach

    Energy Technology Data Exchange (ETDEWEB)

    Spinola, M.; Aggio, A. [PETROBRAS, Rio de Janeiro, RJ (Brazil). Centro de Pesquisas


    The seismic method attempt to image the subsurface architecture and has been able to significantly contribute to detect areal and vertical changes in rock properties. This work presents a seismic imaging study of channel objects generated using the boolean technique. Three channels having different thicknesses were simulated, using the same width, sinuosity and direction. A velocity model was constructed in order to allow seismic contrasts between the interior of channels and the embedding rock. To examine the seismic response for different channel thicknesses, a 3D ray tracing with a normal incident point survey was performed. The three channels were resolved and the way the seismic could image them was studied. (author)

  17. Ion channels in plants (United States)

    Baluška, František; Mancuso, Stefano


    In his recent opus magnum review paper published in the October issue of Physiology Reviews, Rainer Hedrich summarized the field of plant ion channels.1 He started from the earliest electric recordings initiated by Charles Darwin of carnivorous Dionaea muscipula,1,2 known as Venus flytrap, and covered the topic extensively up to the most recent discoveries on Shaker-type potassium channels, anion channels of SLAC/SLAH families, and ligand-activated channels of glutamate receptor-like type (GLR) and cyclic nucleotide-gated channels (CNGC).1 PMID:23221742

  18. Protocol channels as a new design alternative of covert channels

    CERN Document Server

    Wendzel, Steffen


    Covert channel techniques are used by attackers to transfer hidden data. There are two main categories of covert channels: timing channels and storage channels. This paper introduces a third category called protocol channels. A protocol channel switches one of at least two protocols to send a bit combination to a destination while sent packets include no hidden information themselves.

  19. Surface vacancy channels through ion channeling

    Energy Technology Data Exchange (ETDEWEB)

    Redinger, Alex; Standop, Sebastian; Michely, Thomas [II. Physikalisches Institut, Universitaet Koeln, Zuelpicher Strasse 77, 50937 Koeln (Germany); Rosandi, Yudi; Urbassek, Herbert M. [Fachbereich Physik, Technische Universitaet Kaiserslautern, Erwin-Schroedinger-Strasse, D-67663 Kaiserslautern (Germany)


    Damage patterns of single ion impacts on Pt(111) have been studied by scanning tunneling microscopy (STM) and molecular dynamics simulations (MD). Low temperature experiments, where surface diffusion is absent, have been performed for argon and xenon ions with energies between 1 keV and 15 keV at an angle of incidence of 86 {sup circle} measured with respect to the surface normal. Ions hitting preexisting illuminated step edges penetrate into the crystal and are guided in open crystallographic directions, one or more layers underneath the surface (subsurface channeling). In the case of argon channeling the resulting surface damage consists of adatom and vacancy pairs aligned in ion beam direction. After xenon channeling thin surface vacancy trenches along the ion trajectories - surface vacancy channels - are observed. They result from very efficient sputtering and adatom production along the ion trajectory. This phenomena is well reproduced in molecular dynamics simulations of single ion impacts at 0 K. The damage patterns of Argon and Xenon impacts can be traced back to the different energy losses of the particles in the channel. Channeling distances exceeding 1000 A for 15 keV xenon impacts are observed.

  20. Activation of TRPV1 channels inhibits mechanosensitive Piezo channel activity by depleting membrane phosphoinositides. (United States)

    Borbiro, Istvan; Badheka, Doreen; Rohacs, Tibor


    Capsaicin is an activator of the heat-sensitive TRPV1 (transient receptor potential vanilloid 1) ion channels and has been used as a local analgesic. We found that activation of TRPV1 channels with capsaicin either in dorsal root ganglion neurons or in a heterologous expression system inhibited the mechanosensitive Piezo1 and Piezo2 channels by depleting phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and its precursor phosphatidylinositol 4-phosphate [PI(4)P] from the plasma membrane through Ca(2+)-induced phospholipase Cδ (PLCδ) activation. Experiments with chemically inducible phosphoinositide phosphatases and receptor-induced activation of PLCβ indicated that inhibition of Piezo channels required depletion of both PI(4)P and PI(4,5)P2. The mechanically activated current amplitudes decreased substantially in the excised inside-out configuration, where the membrane patch containing Piezo1 channels is removed from the cell. PI(4,5)P2 and PI(4)P applied to these excised patches inhibited this decrease. Thus, we concluded that Piezo channel activity requires the presence of phosphoinositides, and the combined depletion of PI(4,5)P2 and PI(4)P reduces channel activity. In addition to revealing a role for distinct membrane lipids in mechanosensitive ion channel regulation, these data suggest that inhibition of Piezo2 channels may contribute to the analgesic effect of capsaicin.

  1. Compressed air energy storage: preliminary design and site development program in an aquifer. Final draft, Task 1: establish facility design criteria and utility benefits

    Energy Technology Data Exchange (ETDEWEB)



    Compressed air energy storage (CAES) has been identified as one of the principal new energy storage technologies worthy of further research and development. The CAES system stores mechanical energy in the form of compressed air during off-peak hours, using power supplied by a large, high-efficiency baseload power plant. At times of high electrical demand, the compressed air is drawn from storage and is heated in a combustor by the burning of fuel oil, after which the air is expanded in a turbine. In this manner, essentially all of the turbine output can be applied to the generation of electricity, unlike a conventional gas turbine which expends approximately two-thirds of the turbine shaft power in driving the air compressor. The separation of the compression and generation modes in the CAES system results in increased net generation and greater premium fuel economy. The use of CAES systems to meet the utilities' high electrical demand requirements is particularly attractive in view of the reduced availability of premium fuels such as oil and natural gas. This volume documents the Task 1 work performed in establishing facility design criteria for a CAES system with aquifer storage. Information is included on: determination of initial design bases; preliminary analysis of the CAES system; development of data for site-specific analysis of the CAES system; detailed analysis of the CAES system for three selected heat cycles; CAES power plant design; and an economic analysis of CAES.

  2. Equipment Design and Cost Estimation for Small Modular Biomass Systems, Synthesis Gas Cleanup, and Oxygen Separation Equipment; Task 1: Cost Estimates of Small Modular Systems

    Energy Technology Data Exchange (ETDEWEB)

    Nexant Inc.


    This deliverable is the Final Report for Task 1, Cost Estimates of Small Modular Systems, as part of NREL Award ACO-5-44027, ''Equipment Design and Cost Estimation for Small Modular Biomass Systems, Synthesis Gas Cleanup and Oxygen Separation Equipment''. Subtask 1.1 looked into processes and technologies that have been commercially built at both large and small scales, with three technologies, Fluidized Catalytic Cracking (FCC) of refinery gas oil, Steam Methane Reforming (SMR) of Natural Gas, and Natural Gas Liquids (NGL) Expanders, chosen for further investigation. These technologies were chosen due to their applicability relative to other technologies being considered by NREL for future commercial applications, such as indirect gasification and fluidized bed tar cracking. Research in this subject is driven by an interest in the impact that scaling has on the cost and major process unit designs for commercial technologies. Conclusions from the evaluations performed could be applied to other technologies being considered for modular or skid-mounted applications.

  3. Review of state-of-the-art of solar collector corrosion processes. Task 1 of solar collector studies for solar heating and cooling applications. Final technical progress report

    Energy Technology Data Exchange (ETDEWEB)

    Clifford, J E; Diegle, R B


    The state-of-the-art of solar collector corrosion processes is reviewed, and Task 1 of a current research program on use of aqueous heat transfer fluids for solar heating and cooling is summarized. The review of available published literature has indicated that lack of quantitative information exists relative to collector corrosion at the present time, particularly for the higher temperature applications of solar heating and cooling compared to domestic water heating. Solar collector systems are reviewed from the corrosion/service life viewpoint, with emphasis on various applications, collector design, heat transfer fluids, and freeze protection methods. Available information (mostly qualitative) on collector corrosion technology is reviewed to indicate potential corrosion problem areas and corrosion prevention practices. Sources of limited quantitative data that are reviewed are current solar applications, research programs on collector corrosion, and pertinent experience in related applications of automotive cooling and non-solar heating and cooling. A data bank was developed to catalog corrosion information. Appendix A of this report is a bibliography of the data bank, with abstracts reproduced from presently available literature accessions (about 220). This report is presented as a descriptive summary of information that is contained in the data bank.

  4. Trafficking of ThermoTRP Channels

    Directory of Open Access Journals (Sweden)

    Clotilde Ferrandiz-Huertas


    Full Text Available ThermoTRP channels (thermoTRPs define a subfamily of the transient receptor potential (TRP channels that are activated by changes in the environmental temperature, from noxious cold to injurious heat. Acting as integrators of several stimuli and signalling pathways, dysfunction of these channels contributes to several pathological states. The surface expression of thermoTRPs is controlled by both, the constitutive and regulated vesicular trafficking. Modulation of receptor surface density during pathological processes is nowadays considered as an interesting therapeutic approach for management of diseases, such as chronic pain, in which an increased trafficking is associated with the pathological state. This review will focus on the recent advances trafficking of the thermoTRP channels, TRPV1, TRPV2, TRPV4, TRPM3, TRPM8 and TRPA1, into/from the plasma membrane. Particularly, regulated membrane insertion of thermoTRPs channels contributes to a fine tuning of final channel activity, and indeed, it has resulted in the development of novel therapeutic approaches with successful clinical results such as disruption of SNARE-dependent exocytosis by botulinum toxin or botulinomimetic peptides.

  5. Dysfunctional HCN ion channels in neurological diseases. (United States)

    DiFrancesco, Jacopo C; DiFrancesco, Dario


    Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are expressed as four different isoforms (HCN1-4) in the heart and in the central and peripheral nervous systems. HCN channels are activated by membrane hyperpolarization at voltages close to resting membrane potentials and carry the hyperpolarization-activated current, dubbed If (funny current) in heart and Ih in neurons. HCN channels contribute in several ways to neuronal activity and are responsible for many important cellular functions, including cellular excitability, generation, and modulation of rhythmic activity, dendritic integration, transmission of synaptic potentials, and plasticity phenomena. Because of their role, defective HCN channels are natural candidates in the search for potential causes of neurological disorders in humans. Several data, including growing evidence that some forms of epilepsy are associated with HCN mutations, support the notion of an involvement of dysfunctional HCN channels in different experimental models of the disease. Additionally, some anti-epileptic drugs are known to modify the activity of the Ih current. HCN channels are widely expressed in the peripheral nervous system and recent evidence has highlighted the importance of the HCN2 isoform in the transmission of pain. HCN channels are also present in the midbrain system, where they finely regulate the activity of dopaminergic neurons, and a potential role of these channels in the pathogenesis of Parkinson's disease has recently emerged. The function of HCN channels is regulated by specific accessory proteins, which control the correct expression and modulation of the neuronal Ih current. Alteration of these proteins can severely interfere with the physiological channel function, potentially predisposing to pathological conditions. In this review we address the present knowledge of the association between HCN dysfunctions and neurological diseases, including clinical, genetic, and physiopathological

  6. Dysfunctional HCN ion channels in neurological diseases

    Directory of Open Access Journals (Sweden)

    Jacopo C. DiFrancesco


    Full Text Available Hyperpolarization-activated cyclic nucleotide-gated (HCN channels are expressed as four different isoforms (HCN1-4 in the heart and in the central and peripheral nervous systems. HCN channels are activated by membrane hyperpolarization at voltages close to resting membrane potentials and carry the hyperpolarization-activated current, dubbed If (funny current in heart and Ih in neurons. HCN channels contribute in several ways to neuronal activity and are responsible for many important cellular functions, including cellular excitability, generation and modulation of rhythmic activity, dendritic integration, transmission of synaptic potentials and plasticity phenomena. Because of their role, defective HCN channels are natural candidates in the search for potential causes of neurological disorders in humans. Several data, including growing evidence that some forms of epilepsy are associated with HCN mutations, support the notion of an involvement of dysfunctional HCN channels in different experimental models of the disease. Additionally, some anti-epileptic drugs are known to modify the activity of the Ih current. HCN channels are widely expressed in the peripheral nervous system and recent evidence has highlighted the importance of the HCN2 isoform in the transmission of pain. HCN channels are also present in the midbrain system, where they finely regulate the activity of dopaminergic neurons, and a potential role of these channels in the pathogenesis of Parkinson’s disease has recently emerged. The function of HCN channels is regulated by specific accessory proteins, which control the correct expression and modulation of the neuronal Ih current. Alteration of these proteins can severely interfere with the physiological channel function, potentially predisposing to pathological conditions. In this review we address the present knowledge of the association between HCN dysfunctions and neurological diseases, including clinical, genetic and

  7. Molecular origins of conduction channels observed in shot-noise measurements. (United States)

    Solomon, Gemma C; Gagliardi, Alessio; Pecchia, Alessandro; Frauenheim, Thomas; Di Carlo, Aldo; Reimers, Jeffrey R; Hush, Noel S


    Measurements of shot noise from single molecules have indicated the presence of various conduction channels. We present three descriptions of these channels in molecular terms showing that the number of conduction channels is limited by bottlenecks in the molecule and that the channels can be linked to transmission through different junction states. We introduce molecular-conductance orbitals, which allow the transmission to be separated into contributions from individual orbitals and contributions from interference between pairs of orbitals.

  8. X-ray radiation channeling in micro-channel plates: Spectroscopy with a synchrotron radiation beam

    Energy Technology Data Exchange (ETDEWEB)

    Mazuritskiy, M.I. [Physics Department, Southern Federal University, Rostov-on-Don (Russian Federation); Dabagov, S.B. [INFN Laboratori Nazionali di Frascati, 00044 Frascati (Italy); RAS P.N. Lebedev Physical Institute, Leninsky pr. 53, 119991 Moscow (Russian Federation); National Research Nuclear University MEPhI, Kashirskoe shosse 31, 115409 Moscow (Russian Federation); Marcelli, A. [INFN Laboratori Nazionali di Frascati, 00044 Frascati (Italy); RICMASS, Rome International Center for Materials Science Superstripes, via dei Sabelli 119A, 00185 Rome (Italy); Dziedzic-Kocurek, K. [M. Smoluchowski Institute of Physics, Jagiellonian University, Krakow (Poland); Lerer, A.M. [Physics Department, Southern Federal University, Rostov-on-Don (Russian Federation)


    We present here the angular distribution of the radiation propagated inside MultiChannel Plates with micro-channels of ∼3 μm diameter. The spectra collected at the exit of the channels present a complex distribution with contributions that can be assigned to the fluorescence radiation, originated from the excitation of the micro-channel walls. For radiation above the absorption edge, when the monochromatic energy in the region of the Si L-edge hits the micro-channel walls with a grazing angle θ ⩾ 5°, or at the O K-edge when θ ⩾ 2° a fluorescence radiation is detected. Additional information associated to the fine structures of the XANES spectra detected at the exit of MCPs are also presented and discussed.

  9. Quantum broadcast channels

    CERN Document Server

    Yard, J; Devetak, I; Yard, Jon; Hayden, Patrick; Devetak, Igor


    We analyze quantum broadcast channels, which are quantum channels with a single sender and many receivers. Focusing on channels with two receivers for simplicity, we generalize a number of results from the network Shannon theory literature which give the rates at which two senders can receive a common message, while a personalized one is sent to one of them. Our first collection of results applies to channels with a classical input and quantum outputs. The second class of theorems we prove concern sending a common classical message over a quantum broadcast channel, while sending quantum information to one of the receivers. The third group of results we obtain concern communication over an isometry, giving the rates at quantum information can be sent to one receiver, while common quantum information is sent to both, in the sense that tripartite GHZ entanglement is established. For each scenario, we provide an additivity proof for an appropriate class of channels, yielding single-letter characterizations of the...

  10. Volume Regulated Channels

    DEFF Research Database (Denmark)

    Klausen, Thomas Kjær

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

  11. Cardiac ion channels in health and disease. (United States)

    Amin, Ahmad S; Tan, Hanno L; Wilde, Arthur A M


    Cardiac electrical activity depends on the coordinated propagation of excitatory stimuli through the heart and, as a consequence, the generation of action potentials in individual cardiomyocytes. Action potential formation results from the opening and closing (gating) of ion channels that are expressed within the sarcolemma of cardiomyocytes. Ion channels possess distinct genetic, molecular, pharmacologic, and gating properties and exhibit dissimilar expression levels within different cardiac regions. By gating, ion channels permit ion currents across the sarcolemma, thereby creating the different phases of the action potential (e.g., resting phase, depolarization, repolarization). The importance of ion channels in maintaining normal heart rhythm is reflected by the increased incidence of arrhythmias in inherited diseases that are linked to mutations in genes encoding ion channels or their accessory proteins and in acquired diseases that are associated with changes in ion channel expression levels or gating properties. This review discusses ion channels that contribute to action potential formation in healthy hearts and their role in inherited and acquired diseases.

  12. Voltage-Gated Calcium Channels in Nociception (United States)

    Yasuda, Takahiro; Adams, David J.

    Voltage-gated calcium channels (VGCCs) are a large and functionally diverse group of membrane ion channels ubiquitously expressed throughout the central and peripheral nervous systems. VGCCs contribute to various physiological processes and transduce electrical activity into other cellular functions. This chapter provides an overview of biophysical properties of VGCCs, including regulation by auxiliary subunits, and their physiological role in neuronal functions. Subsequently, then we focus on N-type calcium (Cav2.2) channels, in particular their diversity and specific antagonists. We also discuss the role of N-type calcium channels in nociception and pain transmission through primary sensory dorsal root ganglion neurons (nociceptors). It has been shown that these channels are expressed predominantly in nerve terminals of the nociceptors and that they control neurotransmitter release. To date, important roles of N-type calcium channels in pain sensation have been elucidated genetically and pharmacologically, indicating that specific N-type calcium channel antagonists or modulators are particularly useful as therapeutic drugs targeting chronic and neuropathic pain.

  13. Acid-sensitive channel inhibition prevents fetal alcohol spectrum disorders cerebellar Purkinje cell loss. (United States)

    Ramadoss, Jayanth; Lunde, Emilie R; Ouyang, Nengtai; Chen, Wei-Jung A; Cudd, Timothy A


    Ethanol is now considered the most common human teratogen. Educational campaigns have not reduced the incidence of ethanol-mediated teratogenesis, leading to a growing interest in the development of therapeutic prevention or mitigation strategies. On the basis of the observation that maternal ethanol consumption reduces maternal and fetal pH, we hypothesized that a pH-sensitive pathway involving the TWIK-related acid-sensitive potassium channels (TASKs) is implicated in ethanol-induced injury to the fetal cerebellum, one of the most sensitive targets of prenatal ethanol exposure. Pregnant ewes were intravenously infused with ethanol (258+/-10 mg/dl peak blood ethanol concentration) or saline in a "3 days/wk binge" pattern throughout the third trimester. Quantitative stereological analysis demonstrated that ethanol resulted in a 45% reduction in the total number of fetal cerebellar Purkinje cells, the cell type most sensitive to developmental ethanol exposure. Extracellular pH manipulation to create the same degree and pattern of pH fall caused by ethanol (manipulations large enough to inhibit TASK 1 channels), resulted in a 24% decrease in Purkinje cell number. We determined immunohistochemically that TASK 1 channels are expressed in Purkinje cells and that the TASK 3 isoform is expressed in granule cells of the ovine fetal cerebellum. Pharmacological blockade of both TASK 1 and TASK 3 channels simultaneous with ethanol effectively prevented any reduction in fetal cerebellar Purkinje cell number. These results demonstrate for the first time functional significance of fetal cerebellar two-pore domain pH-sensitive channels and establishes them as a potential therapeutic target for prevention of ethanol teratogenesis.

  14. Ion channels in asthma. (United States)

    Valverde, Miguel A; Cantero-Recasens, Gerard; Garcia-Elias, Anna; Jung, Carole; Carreras-Sureda, Amado; Vicente, Rubén


    Ion channels are specialized transmembrane proteins that permit the passive flow of ions following their electrochemical gradients. In the airways, ion channels participate in the production of epithelium-based hydroelectrolytic secretions and in the control of intracellular Ca(2+) levels that will ultimately activate almost all lung cells, either resident or circulating. Thus, ion channels have been the center of many studies aiming to understand asthma pathophysiological mechanisms or to identify therapeutic targets for better control of the disease. In this minireview, we focus on molecular, genetic, and animal model studies associating ion channels with asthma.

  15. Quantum feedback channels

    CERN Document Server

    Bowen, G


    In classical information theory the capacity of a noisy communication channel cannot be increased by the use of feedback. In quantum information theory the no-cloning theorem means that noiseless copying and feedback of quantum information cannot be achieved. In this paper, quantum feedback is defined as the unlimited use of a noiseless quantum channel from receiver to sender. Given such quantum feedback, it is shown to provide no increase in the entanglement-assisted capacities of a noisy quantum channel, in direct analogy to the classical case. It is also shown that in various cases of non-assisted capacities, feedback can increase the capacity of many quantum channels.

  16. TRP channels in schistosomes

    Directory of Open Access Journals (Sweden)

    Swarna Bais


    Full Text Available Praziquantel (PZQ is effectively the only drug currently available for treatment and control of schistosomiasis, a disease affecting hundreds of millions of people worldwide. Many anthelmintics, likely including PZQ, target ion channels, membrane protein complexes essential for normal functioning of the neuromusculature and other tissues. Despite this fact, only a few classes of parasitic helminth ion channels have been assessed for their pharmacological properties or for their roles in parasite physiology. One such overlooked group of ion channels is the transient receptor potential (TRP channel superfamily. TRP channels share a common core structure, but are widely diverse in their activation mechanisms and ion selectivity. They are critical to transducing sensory signals, responding to a wide range of external stimuli. They are also involved in other functions, such as regulating intracellular calcium and organellar ion homeostasis and trafficking. Here, we review current literature on parasitic helminth TRP channels, focusing on those in schistosomes. We discuss the likely roles of these channels in sensory and locomotor activity, including the possible significance of a class of TRP channels (TRPV that is absent in schistosomes. We also focus on evidence indicating that at least one schistosome TRP channel (SmTRPA has atypical, TRPV1-like pharmacological sensitivities that could potentially be exploited for future therapeutic targeting.

  17. KV7 potassium channels

    DEFF Research Database (Denmark)

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


    identified as being crucial mediators of this process in a variety of smooth muscle. Recently, KV7 channels have been shown to be involved in the pathogenesis of hypertension, as well as being implicated in other smooth muscle disorders, providing a new and inviting target for smooth muscle disorders.......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...

  18. Radio Channel Modelling Using Stochastic Propagation Graphs

    DEFF Research Database (Denmark)

    Pedersen, Troels; Fleury, Bernard Henri


    In this contribution the radio channel model proposed in [1] is extended to include multiple transmitters and receivers. The propagation environment is modelled using random graphs where vertices of a graph represent scatterers and edges model the wave propagation between scatterers. Furthermore...

  19. Optimization of Spatiotemporal Apertures in Channel Sounding

    DEFF Research Database (Denmark)

    Pedersen, Troels; Pedersen, Claus; Yin, Xuefeng;


    In this paper we investigate the impact of the spatio-temporal aperture of a channel sounding system equipped with antenna arrays at the transmitter and receiver on the accuracy of joint estimation of Doppler frequency and bi-direction. The contribution of this work is three-fold. Firstly, we sta...

  20. Functional diversity and evolutionary dynamics of thermoTRP channels. (United States)

    Saito, Shigeru; Tominaga, Makoto


    Animals have evolved sophisticated physiological systems for sensing ambient temperature since changes in environmental temperatures affect various biological processes. Thermosensitive transient receptor potential (thermoTRP) channels serve as thermal sensors in diverse animal species. They are multimodal receptors that are activated by temperature as well as other physical and chemical stimuli. Since thermoTRP channels are calcium permeable non-selective cation channels, their activation leads to an influx of calcium and sodium ions into the cell and triggers downstream signal transduction. ThermoTRP channels have been characterized in diverse animal species over the past several years, illuminating the diversification of thermoTRP channels in the course of evolution. The gene repertoires of thermoTRP channels differ among animal species. Additionally, in some cases, the temperature and chemical sensitivities among orthologous thermoTRP channels vary among species. The evolutionary flexibility of thermoTRP channels enabled them to contribute to unique physiological systems such as infrared sensation in snakes and bats and seasonal adaptation in silk moth. On the other hand, the functional differences of thermoTRP channels among species have been utilized for understanding the molecular basis for their activation (or inhibition) mechanisms, and amino acid residues (or domains) responsible for the respective channel properties have been identified in various thermoTRP channels. Here we summarize the current understanding of the functional diversity and evolutionary dynamics of thermoTRP channels.

  1. Secret-Key Generation using Correlated Sources and Channels

    CERN Document Server

    Khisti, Ashish; Wornell, Gregory


    We study the problem of generating a shared secret key between two terminals in a joint source-channel setup -- the sender communicates to the receiver over a discrete memoryless wiretap channel and additionally the terminals have access to correlated discrete memoryless source sequences. We establish lower and upper bounds on the secret-key capacity. These bounds coincide, establishing the capacity, when the underlying channel consists of independent, parallel and reversely degraded wiretap channels. In the lower bound, the equivocation terms of the source and channel components are functionally additive. The secret-key rate is maximized by optimally balancing the the source and channel contributions. This tradeoff is illustrated in detail for the Gaussian case where it is also shown that Gaussian codebooks achieve the capacity. When the eavesdropper also observes a source sequence, the secret-key capacity is established when the sources and channels of the eavesdropper are a degraded version of the legitima...

  2. Transmission channels through Na and Al atom wire

    DEFF Research Database (Denmark)

    Kobayashi, N.; Brandbyge, Mads; Tsukada, M.


    First-principles calculations of the transmission channels of single-atom-width Na and Al atom wires bridged between metallic jellium electrodes are presented. For the Na wire, a single channel contributes to the conduction with an almost full quantization value, 2e(2)/h. The conductance...

  3. A model for the distribution channels planning process

    NARCIS (Netherlands)

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


    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 c

  4. A linearization of quantum channels (United States)

    Crowder, Tanner


    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.

  5. Ion channels in toxicology. (United States)

    Restrepo-Angulo, Iván; De Vizcaya-Ruiz, Andrea; Camacho, Javier


    Ion channels play essential roles in human physiology and toxicology. Cardiac contraction, neural transmission, temperature sensing, insulin release, regulation of apoptosis, cellular pH and oxidative stress, as well as detection of active compounds from chilli, are some of the processes in which ion channels have an important role. Regulation of ion channels by several chemicals including those found in air, water and soil represents an interesting potential link between environmental pollution and human diseases; for instance, de novo expression of ion channels in response to exposure to carcinogens is being considered as a potential tool for cancer diagnosis and therapy. Non-specific binding of several drugs to ion channels is responsible for a huge number of undesirable side-effects, and testing guidelines for several drugs now require ion channel screening for pharmaceutical safety. Animal toxins targeting human ion channels have serious effects on the population and have also provided a remarkable tool to study the molecular structure and function of ion channels. In this review, we will summarize the participation of ion channels in biological processes extensively used in toxicological studies, including cardiac function, apoptosis and cell proliferation. Major findings on the adverse effects of drugs on ion channels as well as the regulation of these proteins by different chemicals, including some pesticides, are also reviewed. Association of ion channels and toxicology in several biological processes strongly suggests these proteins to be excellent candidates to follow the toxic effects of xenobiotics, and as potential early indicators of life-threatening situations including chronic degenerative diseases.

  6. Quantum biological channel modeling and capacity calculation. (United States)

    Djordjevic, Ivan B


    Quantum mechanics has an important role in photosynthesis, magnetoreception, and evolution. There were many attempts in an effort to explain the structure of genetic code and transfer of information from DNA to protein by using the concepts of quantum mechanics. The existing biological quantum channel models are not sufficiently general to incorporate all relevant contributions responsible for imperfect protein synthesis. Moreover, the problem of determination of quantum biological channel capacity is still an open problem. To solve these problems, we construct the operator-sum representation of biological channel based on codon basekets (basis vectors), and determine the quantum channel model suitable for study of the quantum biological channel capacity and beyond. The transcription process, DNA point mutations, insertions, deletions, and translation are interpreted as the quantum noise processes. The various types of quantum errors are classified into several broad categories: (i) storage errors that occur in DNA itself as it represents an imperfect storage of genetic information, (ii) replication errors introduced during DNA replication process, (iii) transcription errors introduced during DNA to mRNA transcription, and (iv) translation errors introduced during the translation process. By using this model, we determine the biological quantum channel capacity and compare it against corresponding classical biological channel capacity. We demonstrate that the quantum biological channel capacity is higher than the classical one, for a coherent quantum channel model, suggesting that quantum effects have an important role in biological systems. The proposed model is of crucial importance towards future study of quantum DNA error correction, developing quantum mechanical model of aging, developing the quantum mechanical models for tumors/cancer, and study of intracellular dynamics in general.

  7. Quantum Biological Channel Modeling and Capacity Calculation

    Directory of Open Access Journals (Sweden)

    Ivan B. Djordjevic


    Full Text Available Quantum mechanics has an important role in photosynthesis, magnetoreception, and evolution. There were many attempts in an effort to explain the structure of genetic code and transfer of information from DNA to protein by using the concepts of quantum mechanics. The existing biological quantum channel models are not sufficiently general to incorporate all relevant contributions responsible for imperfect protein synthesis. Moreover, the problem of determination of quantum biological channel capacity is still an open problem. To solve these problems, we construct the operator-sum representation of biological channel based on codon basekets (basis vectors, and determine the quantum channel model suitable for study of the quantum biological channel capacity and beyond. The transcription process, DNA point mutations, insertions, deletions, and translation are interpreted as the quantum noise processes. The various types of quantum errors are classified into several broad categories: (i storage errors that occur in DNA itself as it represents an imperfect storage of genetic information, (ii replication errors introduced during DNA replication process, (iii transcription errors introduced during DNA to mRNA transcription, and (iv translation errors introduced during the translation process. By using this model, we determine the biological quantum channel capacity and compare it against corresponding classical biological channel capacity. We demonstrate that the quantum biological channel capacity is higher than the classical one, for a coherent quantum channel model, suggesting that quantum effects have an important role in biological systems. The proposed model is of crucial importance towards future study of quantum DNA error correction, developing quantum mechanical model of aging, developing the quantum mechanical models for tumors/cancer, and study of intracellular dynamics in general.

  8. Generalized channeled polarimetry. (United States)

    Alenin, Andrey S; Tyo, J Scott


    Channeled polarimeters measure polarization by modulating the measured intensity in order to create polarization-dependent channels that can be demodulated to reveal the desired polarization information. A number of channeled systems have been described in the past, but their proposed designs often unintentionally sacrifice optimality for ease of algebraic reconstruction. To obtain more optimal systems, a generalized treatment of channeled polarimeters is required. This paper describes methods that enable handling of multi-domain modulations and reconstruction of polarization information using linear algebra. We make practical choices regarding use of either Fourier or direct channels to make these methods more immediately useful. Employing the introduced concepts to optimize existing systems often results in superficial system changes, like changing the order, orientation, thickness, or spacing of polarization elements. For the two examples we consider, we were able to reduce noise in the reconstruction to 34.1% and 57.9% of the original design values.

  9. Athermalized channeled spectropolarimeter enhancement.

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  10. Cardiac potassium channel subtypes

    DEFF Research Database (Denmark)

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


    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......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...... drive the late repolarization of the ventricle with some redundancy, and in atria this repolarization reserve is supplemented by the fairly atrial-specific KV1.5, Kir3, KCa, and K2P channels. The role of the latter two subtypes in atria is currently being clarified, and several findings indicate...

  11. New Role of P/Q-type Voltage-gated Calcium Channels

    DEFF Research Database (Denmark)

    Hansen, Pernille B L


    Voltage-gated calcium channels are important for the depolarization-evoked contraction of vascular smooth muscle cells (SMCs), with L-type channels being the classical channel involved in this mechanism. However, it has been demonstrated that the CaV2.1 subunit, which encodes a neuronal isoform...... of the voltage-gated calcium channels (P/Q-type), is also expressed and contributes functionally to contraction of renal blood vessels in both mice and humans. Furthermore, preglomerular vascular SMCs and aortic SMCs coexpress L-, P-, and Q-type calcium channels within the same cell. Calcium channel blockers...... are widely used as pharmacological treatments. However, calcium channel antagonists vary in their selectivity for the various calcium channel subtypes, and the functional contribution from P/Q-type channels as compared with L-type should be considered. Confirming the presence of P/Q-type voltage...

  12. Flow Routing for Delineating Supraglacial Meltwater Channel Networks

    Directory of Open Access Journals (Sweden)

    Leonora King


    Full Text Available Growing interest in supraglacial channels, coupled with the increasing availability of high-resolution remotely sensed imagery of glacier surfaces, motivates the development and testing of new approaches to delineating surface meltwater channels. We utilized a high-resolution (2 m digital elevation model of parts of the western margin of the Greenland Ice Sheet (GrIS and retention of visually identified sinks (i.e., moulins to investigate the ability of a standard D8 flow routing algorithm to delineate supraglacial channels. We compared these delineated channels to manually digitized channels and to channels extracted from multispectral imagery. We delineated GrIS supraglacial channel networks in six high-elevation (above 1000 m and one low-elevation (below 1000 m catchments during and shortly after peak melt (July and August 2012, and investigated the effect of contributing area threshold on flow routing performance. We found that, although flow routing is sensitive to data quality and moulin identification, it can identify 75% to 99% of channels observed with multispectral analysis, as well as low-order, high-density channels (up to 15.7 km/km2 with a 0.01 km2 contributing area threshold in greater detail than multispectral methods. Additionally, we found that flow routing can delineate supraglacial channel networks on rough ice surfaces with widespread crevassing. Our results suggest that supraglacial channel density is sufficiently high during peak melt that low contributing area thresholds can be employed with little risk of overestimating the channel network extent.

  13. 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.

  14. Connexin channels and phospholipids: association and modulation

    Directory of Open Access Journals (Sweden)

    Harris Andrew L


    This study is the first to identify (endogenous phospholipids that tightly associate with connexin channels. The finding that specific phospholipids are associated with different connexin isoforms suggests connexin-specific regulatory and/or structural interactions with lipid membranes. The results are interpreted in light of connexin channel function and cell biology, as informed by current knowledge of lipid-protein interactions and membrane biophysics. The intimate involvement of distinct phospholipids with different connexins contributes to channel structure and/or function, as well as plaque integrity, and to modulation of connexin channels by lipophilic agents.

  15. Minireview: potassium channels and aldosterone dysregulation: is primary aldosteronism a potassium channelopathy? (United States)

    Gomez-Sanchez, Celso E; Oki, Kenji


    Primary aldosteronism is the most common form of secondary hypertension and has significant cardiovascular consequences. Aldosterone-producing adenomas (APAs) are responsible for half the cases of primary aldosteronism, and about half have mutations of the G protein-activated inward rectifying potassium channel Kir3.4. Under basal conditions, the adrenal zona glomerulosa cells are hyperpolarized with negative resting potentials determined by membrane permeability to K(+) mediated through various K(+) channels, including the leak K(+) channels TASK-1, TASK-3, and Twik-Related Potassium Channel 1, and G protein inward rectifying potassium channel Kir3.4. Angiotensin II decreases the activity of the leak K(+) channels and Kir3.4 channel and decreases the expression of the Kir3.4 channel, resulting in membrane depolarization, increased intracellular calcium, calcium-calmodulin pathway activation, and increased expression of cytochrome P450 aldosterone synthase (CYP11B2), the last enzyme for aldosterone production. Somatic mutations of the selectivity filter of the Kir3.4 channel in APA results in loss of selectivity for K(+) and entry of sodium, resulting in membrane depolarization, calcium mobilization, increased CYP11B2 expression, and hyperaldosteronism. Germ cell mutations cause familial hyperaldosteronism type 3, which is associated with adrenal zona glomerulosa hyperplasia, rather than adenoma. Less commonly, somatic mutations of the sodium-potassium ATPase, calcium ATPase, or the calcium channel calcium channel voltage-dependent L type alpha 1D have been found in some APAs. The regulation of aldosterone secretion is exerted to a significant degree by activation of membrane K(+) and calcium channels or pumps, so it is not surprising that the known causes of disorders of aldosterone secretion in APA have been channelopathies, which activate mechanisms that increase aldosterone synthesis.

  16. The contribution of bank and surface sediments to fluvial sediment ...

    African Journals Online (AJOL)

    The contribution of bank and surface sediments to fluvial sediment transport of the Pra River. ... Sediment source studies involving a simple mixing model was undertaken in the ... For bank erosion, river channel bank materials were sampled.

  17. Controls on plan-form evolution of submarine channels (United States)

    Imran, J.; Mohrig, D. C.


    types. The in-channel suspended-load deposition occurs at sites of flow separation along the inner banks of bends. The relative contribution of inner-bank deposition from bed-load versus suspended load affects the plan-form evolution of both river and submarine channels.

  18. Computation over Mismatched Channels

    CERN Document Server

    Karamchandani, Nikhil; Diggavi, Suhas


    We consider the problem of distributed computation of a target function over a multiple-access channel. If the target and channel functions are matched (i.e., compute the same function), significant performance gains can be obtained by jointly designing the computation and communication tasks. However, in most situations there is mismatch between these two functions. In this work, we analyze the impact of this mismatch on the performance gains achievable with joint computation and communication designs over separation-based designs. We show that for most pairs of target and channel functions there is no such gain, and separation of computation and communication is optimal.

  19. Channel Access in Erlang

    Energy Technology Data Exchange (ETDEWEB)

    Nicklaus, Dennis J. [Fermilab


    We have developed an Erlang language implementation of the Channel Access protocol. Included are low-level functions for encoding and decoding Channel Access protocol network packets as well as higher level functions for monitoring or setting EPICS process variables. This provides access to EPICS process variables for the Fermilab Acnet control system via our Erlang-based front-end architecture without having to interface to C/C++ programs and libraries. Erlang is a functional programming language originally developed for real-time telecommunications applications. Its network programming features and list management functions make it particularly well-suited for the task of managing multiple Channel Access circuits and PV monitors.

  20. Integrin receptors and ligand-gated channels. (United States)

    Morini, Raffaella; Becchetti, Andrea


    Plastic expression of different integrin subunits controls the different stages of neural development, whereas in the adult integrins regulate synaptic stability. Evidence of integrin-channel crosstalk exists for ionotropic glutamate receptors. As is often the case in other tissues, integrin engagement regulates channel activity through complex signaling pathways that often include tyrosine phosphorylation cascades. The specific pathways recruited by integrin activation depend on cerebral region and cell type. In turn, ion channels control integrin expression onto the plasma membrane and their ligand binding affinity. The most extensive studies concern the hippocampus and suggest implications for neuronal circuit plasticity. The physiological relevance of these findings depends on whether adhesion molecules, aside from determining tissue stability, contribute to synaptogenesis and the responsiveness of mature synapses, thus contributing to long-term circuit consolidation. Little evidence is available for other ligand-gated channels, with the exception of nicotinic receptors. These exert a variety of functions in neurons and non neural tissue, both in development and in the adult, by regulating cell cycle, synaptogenesis and synaptic circuit refinement. Detailed studies in epidermal keratinocytes have shed some light on the possible mechanisms through which ACh can regulate cell motility, which may be of general relevance for morphogenetic processes. As to the control of mature synapses, most results concern the integrinic control of nicotinic receptors in the neuromuscular junction. Following this lead, a few studies have addressed similar topics in adult cerebral synapses. However, pursuing and interpreting these results in the brain is especially difficult because of the complexity of the nicotinic roles and the widespread contribution of nonsynaptic, paracrine transmission. From a pathological point of view, considering the well-known contribution of both

  1. An Insight to Covert Channels


    Salwan, Nitish; Singh, Sandeep; Arora, Suket; Singh, Amarpreet


    This paper presents an overview of different concepts regarding covert channels. It discusses the various classifications and the detailing of various fields used to manipulate for the covert channel execution.Different evaluation criterias are presented for measuring the strength of covert channels. The defenses and prevention schemes for this covert channel will also be discussed. This paper also discuss about an advanced timing channel i.e.Temperature Based Covert Channel.

  2. Insight toward epithelial Na+ channel mechanism revealed by the acid-sensing ion channel 1 structure. (United States)

    Stockand, James D; Staruschenko, Alexander; Pochynyuk, Oleh; Booth, Rachell E; Silverthorn, Dee U


    The epithelial Na(+) channel/degenerin (ENaC/DEG) protein family includes a diverse group of ion channels, including nonvoltage-gated Na(+) channels of epithelia and neurons, and the acid-sensing ion channel 1 (ASIC1). In mammalian epithelia, ENaC helps regulate Na(+) and associated water transport, making it a critical determinant of systemic blood pressure and pulmonary mucosal fluidity. In the nervous system, ENaC/DEG proteins are related to sensory transduction. While the importance and physiological function of these ion channels are established, less is known about their structure. One hallmark of the ENaC/DEG channel family is that each channel subunit has only two transmembrane domains connected by an exceedingly large extracellular loop. This subunit structure was recently confirmed when Jasti and colleagues determined the crystal structure of chicken ASIC1, a neuronal acid-sensing ENaC/DEG channel. By mapping ENaC to the structural coordinates of cASIC1, as we do here, we hope to provide insight toward ENaC structure. ENaC, like ASIC1, appears to be a trimeric channel containing 1alpha, 1beta, and 1gamma subunit. Heterotrimeric ENaC and monomeric ENaC subunits within the trimer possibly contain many of the major secondary, tertiary, and quaternary features identified in cASIC1 with a few subtle but critical differences. These differences are expected to have profound effects on channel behavior. In particular, they may contribute to ENaC insensitivity to acid and to its constitutive activity in the absence of time- and ligand-dependent inactivation. Experiments resulting from this comparison of cASIC1 and ENaC may help clarify unresolved issues related to ENaC architecture, and may help identify secondary structures and residues critical to ENaC function.

  3. Analytical study of parameters affecting entropy generation of nanofluid turbulent flow in channel and micro-channel

    Directory of Open Access Journals (Sweden)

    Sheikhzadeh Ghanbarali


    Full Text Available In this study, thermo-physical and geometrical parameters affecting entropy generation of nanofluid turbulent flow such as the volume fraction, Reynolds number and diameter of the channel and micro-channel with circular cross section under constant flux are examined analytically. Water is used as a base fluid of nanofluid with nanoparticles of Ag, Cu, CuO and TiO2. The study is conducted for Reynolds numbers of 20000, 40000 and 100000, volume fractions of 0, 0.01, 0.02, 0.03 and 0.04, channel diameters of 2, 4, 6 and 8 cm and micro-channel diameters of 20, 40, 60 and 80 micrometers. Based on the results, the most of the generated entropy in channel is due to heat transfer, and also, with increasing the diameter of the channel, Bejan number increases. The contribution of entropy generation due to heat transfer in the micro-channel is very poor and the major contribution of entropy generation is due to friction. The maximum amount of entropy generation in channel belongs to nanofluids with Ag, Cu, CuO and TiO2 nanoparticles, respectively, while in the micro-channel this behavior is reversed; and the minimum entropy generation happens in nanofluids with Ag, Cu, CuO and TiO2 nanoparticles, respectively. In channel and micro-channel, for all nanofluids except for the water-TiO2, with increasing volume fraction of nanoparticles, the entropy generation decreases. In channel and micro-channel, the total entropy generation increases as Reynolds number augments.

  4. Cooperative gating between ion channels. (United States)

    Choi, Kee-Hyun


    Cooperative gating between ion channels, i.e. the gating of one channel directly coupled to the gating of neighboring channels, has been observed in diverse channel types at the single-channel level. Positively coupled gating could enhance channel-mediated signaling while negative coupling may effectively reduce channel gating noise. Indeed, the physiological significance of cooperative channel gating in signal transduction has been recognized in several in vivo studies. Moreover, coupled gating of ion channels was reported to be associated with some human disease states. In this review, physiological roles for channel cooperativity and channel clustering observed in vitro and in vivo are introduced, and stimulation-induced channel clustering and direct channel cross linking are suggested as the physical mechanisms of channel assembly. Along with physical clustering, several molecular mechanisms proposed as the molecular basis for functional coupling of neighboring channels are covered: permeant ions as a channel coupling mediator, concerted channel activation through the membrane, and allosteric mechanisms. Also, single-channel analysis methods for cooperative gating such as the binomial analysis, the variance analysis, the conditional dwell time density analysis, and the maximum likelihood fitting analysis are reviewed and discussed.

  5. Channelized Streams in Iowa (United States)

    Iowa State University GIS Support and Research Facility — This draft dataset consists of all ditches or channelized pieces of stream that could be identified using three input datasets; namely the1:24,000 National...

  6. Covert Channels within IRC (United States)


    Communications ....................................... 2 1.3 Steganography and Covert Channels .......................................................... 3...Internet Relay Chat ..................................................................................... 7 2.2 Steganography ...13 2.2.2 Encrypted Steganographic Systems .............................................. 15 2.2.3 Text-Based Steganography

  7. 28-Channel rotary transformer (United States)

    Mclyman, W. T.


    Transformer transmits power and digital data across rotating interface. Array has many parallel data channels, each with potential l megabaud data rate. Ferrite-cored transformers are spaced along rotor; airgap between them reduces crosstalk.

  8. Calcium channel blocker poisoning

    Directory of Open Access Journals (Sweden)

    Miran Brvar


    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.

  9. Volume Regulated Channels

    DEFF Research Database (Denmark)

    Klausen, Thomas Kjær

    - serves a multitude of functions in the mammalian cell, regulating the membrane potential (Em), cell volume, protein activity and the driving force for facilitated transporters giving Cl- and Cl- channels a major potential of regulating cellular function. These functions include control of the cell cycle...... of volume perturbations evolution have developed system of channels and transporters to tightly control volume homeostasis. In the past decades evidence has been mounting, that the importance of these volume regulated channels and transporters are not restricted to the defense of cellular volume......, 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...

  10. Authentication over Noisy Channels

    CERN Document Server

    Lai, Lifeng; Poor, H Vincent


    In this work, message authentication over noisy channels is studied. The model developed in this paper is the authentication theory counterpart of Wyner's wiretap channel model. Two types of opponent attacks, namely impersonation attacks and substitution attacks, are investigated for both single message and multiple message authentication scenarios. For each scenario, information theoretic lower and upper bounds on the opponent's success probability are derived. Remarkably, in both scenarios, lower and upper bounds are shown to match, and hence the fundamental limit of message authentication over noisy channels is fully characterized. The opponent's success probability is further shown to be smaller than that derived in the classic authentication model in which the channel is assumed to be noiseless. These results rely on a proposed novel authentication scheme in which key information is used to provide simultaneous protection again both types of attacks.

  11. Coding for optical channels

    CERN Document Server

    Djordjevic, Ivan; Vasic, Bane


    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.

  12. Cl- channels in apoptosis

    DEFF Research Database (Denmark)

    Wanitchakool, Podchanart; Ousingsawat, Jiraporn; Sirianant, Lalida


    , 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......(-) channels or as regulators of other apoptotic Cl(-) channels, such as LRRC8. CFTR has been known for its proapoptotic effects for some time, and this effect may be based on glutathione release from the cell and increase in cytosolic reactive oxygen species (ROS). Although we find that CFTR is activated...... by cell swelling, it is possible that CFTR serves RVD/AVD through accumulation of ROS and activation of independent membrane channels such as ANO6. Thus activation of ANO6 will support cell shrinkage and induce additional apoptotic events, such as membrane phospholipid scrambling....

  13. Sensing with Ion Channels

    CERN Document Server

    Martinac, Boris


    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.

  14. Charges in the cytoplasmic pore control intrinsic inward rectification and single-channel properties in Kir1.1 and Kir2.1 channels. (United States)

    Chang, Hsueh-Kai; Yeh, Shih-Hao; Shieh, Ru-Chi


    An E224G mutation of the Kir2.1 channel generates intrinsic inward rectification and single-channel fluctuations in the absence of intracellular blockers. In this study, we showed that positively charged residues H226, R228 and R260, near site 224, regulated the intrinsic inward rectification and single-channel properties of the E224G mutant. By carrying out systematic mutations, we found that the charge effect on the intrinsic inward rectification and single-channel conductance is consistent with a long-range electrostatic mechanism. A Kir1.1 channel where the site equivalent to E224 in the Kir2.1 channel is a glycine residue does not show inward rectification or single-channel fluctuations. The G223K and N259R mutations of the Kir1.1 channel induced intrinsic inward rectification and reduced the single-channel conductance but did not generate large open-channel fluctuations. Substituting the cytoplasmic pore of the E224G mutant into the Kir1.1 channel induced open-channel fluctuations and intrinsic inward rectification. The single-channel conductance of the E224G mutant showed inward rectification. Also, a voltage-dependent gating mechanism decreased open probability during depolarization and contributed to the intrinsic inward rectification in the E224G mutant. In addition to an electrostatic effect, a close interaction of K(+) with channel pore may be required for generating open-channel fluctuations in the E224G mutant.

  15. Chloride channels in stroke

    Institute of Scientific and Technical Information of China (English)

    Ya-ping ZHANG; Hao ZHANG; Dayue Darrel DUAN


    Vascular remodeling of cerebral arterioles,including proliferation,migration,and apoptosis of vascular smooth muscle cells (VSMCs),is the major cause of changes in the cross-sectional area and diameter of the arteries and sudden interruption of blood flow or hemorrhage in the brain,ie,stroke.Accumulating evidence strongly supports an important role for chloride (Clˉ) channels in vascular remodeling and stroke.At least three Clˉ channel genes are expressed in VSMCs:1) the TMEM16A (or Ano1),which may encode the calcium-activated Clˉ channels (CACCs); 2) the CLC-3 Clˉ channel and Clˉ/H+ antiporter,which is closely related to the volume-regulated Clˉ channels (VRCCs); and 3) the cystic fibrosis transmembrane conductance regulator (CFTR),which encodes the PKA-and PKC-activated Clˉ channels.Activation of the CACCs by agonist-induced increase in intracellular Ca2+ causes membrane depolarization,vasoconstriction,and inhibition of VSMC proliferation.Activation of VRCCs by cell volume increase or membrane stretch promotes the production of reactive oxygen species,induces proliferation and inhibits apoptosis of VSMCs.Activation of CFTR inhibits oxidative stress and may prevent the development of hypertension.In addition,Clˉ current mediated by gammaaminobutyric acid (GABA) receptor has also been implicated a role in ischemic neuron death.This review focuses on the functional roles of Clˉ channels in the development of stroke and provides a perspective on the future directions for research and the potential to develop Clˉ channels as new targets for the prevention and treatment of stroke.

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

    NARCIS (Netherlands)

    Slaats, Gisela G; Wheway, Gabrielle; Foletto, Veronica; Szymanska, Katarzyna; van Balkom, Bas W M; Logister, Ive; Den Ouden, Krista; Keijzer-Veen, Mandy G; Lilien, Marc R; Knoers, Nine V; Johnson, Colin A; Giles, Rachel H


    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.

  17. Alternatively spliced isoforms of TRIP8b differentially control h channel trafficking and function

    NARCIS (Netherlands)

    Lewis, A.S.; Schwartz, E.; Chan, C.S.; Noam, Y.; Shin, M.; Wadman, W.J.; Surmeier, D.J.; Baram, T.Z.; Macdonald, R.L.; Chetkovich, D.M.


    Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels (h channels) are the molecular basis for the current, I-h, which contributes crucially to intrinsic neuronal excitability. The subcellular localization and biophysical properties of h channels govern their function, but the mechanism

  18. Course on Ionic Channels

    CERN Document Server


    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...

  19. Fracture channel waves (United States)

    Nihei, Kurt T.; Yi, Weidong; Myer, Larry R.; Cook, Neville G. W.; Schoenberg, Michael


    The properties of guided waves which propagate between two parallel fractures are examined. Plane wave analysis is used to obtain a dispersion equation for the velocities of fracture channel waves. Analysis of this equation demonstrates that parallel fractures form an elastic waveguide that supports two symmetric and two antisymmetric dispersive Rayleigh channel waves, each with particle motions and velocities that are sensitive to the normal and tangential stiffnesses of the fractures. These fracture channel waves degenerate to shear waves when the fracture stiffnesses are large, to Rayleigh waves and Rayleigh-Lamb plate waves when the fracture stiffnesses are low, and to fracture interface waves when the fractures are either very closely spaced or widely separated. For intermediate fracture stiffnesses typical of fractured rock masses, fracture channel waves are dispersive and exhibit moderate to strong localization of guided wave energy between the fractures. The existence of these waves is examined using laboratory acoustic measurements on a fractured marble plate. This experiment confirms the distinct particle motion of the fundamental antisymmetric fracture channel wave (A0 mode) and demonstrates the ease with which a fracture channel wave can be generated and detected.

  20. Hydraulic geometry of cohesive channels undergoing base level drop (United States)

    Vachtman, Dina; Laronne, Jonathan B.


    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.

  1. A Survey of Fading Models for Mobile Radio Channel Characterization

    Directory of Open Access Journals (Sweden)

    L. D. Arya


    Full Text Available Future 3G and 4G mobile communication systems will be required to support wide range of data rates and quality of service matrix. For the efficient design of data link and transport protocols system designer needs knowledge of the statistical properties of physicallayer. Studies have shown that without proper characterization of the channel, blind application of existing protocols and transmission policy may results in disastrous performance unless proper measures are not being taken. Channel characterization also helps in llocation of resources, selection of transmission policy andprotocols. A feasible measure is to have an accurate and thoroughly reproducible optimum channel model which can mimic the mobile radio channel in diversities of fading error environments. Objective of channel model is to supply proper outputs for designing of upper layer protocol in such a fashion as if it were running on the actualphysical layer. The model should fit very well to the measured data and should easily handle analytically. Various approaches for characterization of fading mobile channels have appeared in iterature over last five decades. This article surveys the fading channel models for proper characterization of the radio channel andprovides approaches to classify the existing channel models. The paper also presents the contribution made by these channel models with their assumptions, suitability, applications, shortcomingsand further improvement issues. In present environment Markov Models are best suited for characterization of the fading radio channel. Inthese models radio channel is presented in terms of fading states and modeled as stochastic process. A proper constructed channel model may be valuable means to enhance the reliability and capacity of future mobile radio channel.

  2. Transfer of Physical and Hydraulic Properties Databases to the Hanford Environmental Information System - PNNL Remediation Decision Support Project, Task 1, Activity 6

    Energy Technology Data Exchange (ETDEWEB)

    Rockhold, Mark L.; Middleton, Lisa A.


    This report documents the requirements for transferring physical and hydraulic property data compiled by PNNL into the Hanford Environmental Information System (HEIS). The Remediation Decision Support (RDS) Project is managed by Pacific Northwest National Laboratory (PNNL) to support Hanford Site waste management and remedial action decisions by the U.S. Department of Energy and one of their current site contractors - CH2M-Hill Plateau Remediation Company (CHPRC). The objective of Task 1, Activity 6 of the RDS project is to compile all available physical and hydraulic property data for sediments from the Hanford Site, to port these data into the Hanford Environmental Information System (HEIS), and to make the data web-accessible to anyone on the Hanford Local Area Network via the so-called Virtual Library.1 These physical and hydraulic property data are used to estimate parameters for analytical and numerical flow and transport models that are used for site risk assessments and evaluation of remedial action alternatives. In past years efforts were made by RDS project staff to compile all available physical and hydraulic property data for Hanford sediments and to transfer these data into SoilVision{reg_sign}, a commercial geotechnical software package designed for storing, analyzing, and manipulating soils data. Although SoilVision{reg_sign} has proven to be useful, its access and use restrictions have been recognized as a limitation to the effective use of the physical and hydraulic property databases by the broader group of potential users involved in Hanford waste site issues. In order to make these data more widely available and useable, a decision was made to port them to HEIS and to make them web-accessible via a Virtual Library module. In FY08 the original objectives of this activity on the RDS project were to: (1) ensure traceability and defensibility of all physical and hydraulic property data currently residing in the SoilVision{reg_sign} database

  3. Functional role of anion channels in cardiac diseases

    Institute of Scientific and Technical Information of China (English)

    Da-yue DUAN; Luis LH LIU; Nathan BOZEAT; Z Maggie HUANG; Sunny Y XIANG; Guan-lei WANG; Linda YE; Joseph R HUME


    In comparison to cation (K+, Na+, and Ca2+) channels, much less is currently known about the functional role of anion (Cl-) channels in cardiovascular physiology and pathophysiology. Over the past 15 years, various types of Cl- currents have been recorded in cardiac cells from different species including humans. All cardiac Cl- channels described to date may be encoded by five different Cl- channel genes: the PKA- and PKC-activated cystic fibrosis tansmembrane conductance regulator (CFTR), the volume-regulated ClC-2 and ClC-3, and the Ca2+-activated CLCA or Bestrophin. Recent studies using multiple approaches to examine the functional role of Cl- channels in the context of health and disease have demonstrated that Cl- channels might contribute to: 1) arrhythmogenesis in myocardial injury; 2) cardiac ischemic preconditioning; and 3) the adaptive remodeling of the heart during myocardial hypertrophy and heart failure. Therefore,anion channels represent very attractive novel targets for therapeutic approaches to the treatment of heart diseases. Recent evidence suggests that Cl- channels,like cation channels, might function as a multiprotein complex or functional module.In the post-genome era, the emergence of functional proteomics has necessitated a new paradigm shift to the structural and functional assessment of integrated Cl- channel multiprotein complexes in the heart, which could provide new insight into our understanding of the underlying mechanisms responsible for heart disease and protection.

  4. Unidirectional photoreceptor-to-Muller glia coupling and unique K+ channel expression in Caiman retina.

    Directory of Open Access Journals (Sweden)

    Astrid Zayas-Santiago

    Full Text Available BACKGROUND: Müller cells, the principal glial cells of the vertebrate retina, are fundamental for the maintenance and function of neuronal cells. In most vertebrates, including humans, Müller cells abundantly express Kir4.1 inwardly rectifying potassium channels responsible for hyperpolarized membrane potential and for various vital functions such as potassium buffering and glutamate clearance; inter-species differences in Kir4.1 expression were, however, observed. Localization and function of potassium channels in Müller cells from the retina of crocodiles remain, hitherto, unknown. METHODS: We studied retinae of the Spectacled caiman (Caiman crocodilus fuscus, endowed with both diurnal and nocturnal vision, by (i immunohistochemistry, (ii whole-cell voltage-clamp, and (iii fluorescent dye tracing to investigate K+ channel distribution and glia-to-neuron communications. RESULTS: Immunohistochemistry revealed that caiman Müller cells, similarly to other vertebrates, express vimentin, GFAP, S100β, and glutamine synthetase. In contrast, Kir4.1 channel protein was not found in Müller cells but was localized in photoreceptor cells. Instead, 2P-domain TASK-1 channels were expressed in Müller cells. Electrophysiological properties of enzymatically dissociated Müller cells without photoreceptors and isolated Müller cells with adhering photoreceptors were significantly different. This suggests ion coupling between Müller cells and photoreceptors in the caiman retina. Sulforhodamine-B injected into cones permeated to adhering Müller cells thus revealing a uni-directional dye coupling. CONCLUSION: Our data indicate that caiman Müller glial cells are unique among vertebrates studied so far by predominantly expressing TASK-1 rather than Kir4.1 K+ channels and by bi-directional ion and uni-directional dye coupling to photoreceptor cells. This coupling may play an important role in specific glia-neuron signaling pathways and in a new type of K

  5. Pool spacing in forest channels (United States)

    David R. Montgomery; John M. Buffington; Richard D. Smith; Kevin M. Schmidt; George Pess


    Field surveys of stream channels in forested mountain drainage basins in southeast Alaska and Washington reveal that pool spacing depends on large woody debris (LWD) loading and channel type, slope, and width. Mean pool spacing in pool-riffle, plane-bed, and forced pool-riffle channels systematically decreases from greater than 13 channel widths per pool to less than 1...

  6. Calcium channels and migraine. (United States)

    Pietrobon, Daniela


    Missense mutations in CACNA1A, the gene that encodes the pore-forming α1 subunit of human voltage-gated Ca(V)2.1 (P/Q-type) calcium channels, cause a rare form of migraine with aura (familial hemiplegic migraine type 1: FHM1). Migraine is a common disabling brain disorder whose key manifestations are recurrent attacks of unilateral headache that may be preceded by transient neurological aura symptoms. This review, first, briefly summarizes current understanding of the pathophysiological mechanisms that are believed to underlie migraine headache, migraine aura and the onset of a migraine attack, and briefly describes the localization and function of neuronal Ca(V)2.1 channels in the brain regions that have been implicated in migraine pathogenesis. Then, the review describes and discusses i) the functional consequences of FHM1 mutations on the biophysical properties of recombinant human Ca(V)2.1 channels and native Ca(V)2.1 channels in neurons of knockin mouse models carrying the mild R192Q or severe S218L mutations in the orthologous gene, and ii) the functional consequences of these mutations on neurophysiological processes in the cerebral cortex and trigeminovascular system thought to be involved in the pathophysiology of migraine, and the insights into migraine mechanisms obtained from the functional analysis of these processes in FHM1 knockin mice. This article is part of a Special Issue entitled: Calcium channels. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. MEMS in microfluidic channels.

    Energy Technology Data Exchange (ETDEWEB)

    Ashby, Carol Iris Hill; Okandan, Murat; Michalske, Terry A.; Sounart, Thomas L.; Matzke, Carolyn M.


    Microelectromechanical systems (MEMS) comprise a new class of devices that include various forms of sensors and actuators. Recent studies have shown that microscale cantilever structures are able to detect a wide range of chemicals, biomolecules or even single bacterial cells. In this approach, cantilever deflection replaces optical fluorescence detection thereby eliminating complex chemical tagging steps that are difficult to achieve with chip-based architectures. A key challenge to utilizing this new detection scheme is the incorporation of functionalized MEMS structures within complex microfluidic channel architectures. The ability to accomplish this integration is currently limited by the processing approaches used to seal lids on pre-etched microfluidic channels. This report describes Sandia's first construction of MEMS instrumented microfluidic chips, which were fabricated by combining our leading capabilities in MEMS processing with our low-temperature photolithographic method for fabricating microfluidic channels. We have explored in-situ cantilevers and other similar passive MEMS devices as a new approach to directly sense fluid transport, and have successfully monitored local flow rates and viscosities within microfluidic channels. Actuated MEMS structures have also been incorporated into microfluidic channels, and the electrical requirements for actuation in liquids have been quantified with an elegant theory. Electrostatic actuation in water has been accomplished, and a novel technique for monitoring local electrical conductivities has been invented.

  8. Channel Identification Machines

    Directory of Open Access Journals (Sweden)

    Aurel A. Lazar


    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.

  9. Bounds on the capacity region of a class of compound interference channels

    CERN Document Server

    Raja, Adnan; Viswanath, Pramod


    We derive inner and outer bounds on the capacity region of a class of compound interference channels and quantify the gap between these bounds. From this we derive the capacity region of the compound version of El Gamal and Costa's deterministic interference channel, and characterize to within 2 bits the capacity region of scalar compound Gaussian interference channels. One of our main contributions is a novel achievable scheme for compound interference channels.

  10. Modulation of KCNQ4 channel activity by changes in cell volume

    DEFF Research Database (Denmark)

    Hougaard, Charlotte; Klaerke, Dan A; Hoffmann, Else K;


    KCNQ4 channels expressed in HEK 293 cells are sensitive to cell volume changes, being activated by swelling and inhibited by shrinkage, respectively. The KCNQ4 channels contribute significantly to the regulatory volume decrease (RVD) process following cell swelling. Under isoosmotic conditions......, the KCNQ4 channel activity is modulated by protein kinases A and C, G protein activation, and a reduction in the intracellular Ca2+ concentration, but these signalling pathways are not responsible for the increased channel activity during cell swelling....

  11. Sign ambiguity in the K Sigma channel

    CERN Document Server

    Anisovich, A V; Nikonov, V A; Sarantsev, A V; Thoma, U


    Ambiguities of the signs of $N\\to \\Sigma K$ coupling constants are studied in a multichannel partial wave analysis of a large body of pion and photo-induced reactions. It is shown that the signs are not free from some ambiguities, and further experimental data are needed. Data on the reactions $\\pi^+p\\to \\Sigma^+K^+$ and $\\gamma p\\to K^+\\Sigma^0$ define rather well the isospin 3/2 contributions to these channels. However the lack of information on polarization observables for the reactions $\\pi^-p\\to \\Sigma^0K^0$, $\\pi^-p\\to \\Sigma^-K^+$ and $\\gamma p\\to K^0\\Sigma^+$ does not allow us to fix uniquely the signs of $N\\to \\Sigma K$ coupling constants. As a consequence, also the contributions of nucleon resonances to these channels remain uncertain.

  12. Ion channels in control of pancreatic stellate cell migration (United States)

    Storck, Hannah; Hild, Benedikt; Schimmelpfennig, Sandra; Sargin, Sarah; Nielsen, Nikolaj; Zaccagnino, Angela; Budde, Thomas; Novak, Ivana; Kalthoff, Holger; Schwab, Albrecht


    Pancreatic stellate cells (PSCs) play a critical role in the progression of pancreatic ductal adenocarcinoma (PDAC). Once activated, PSCs support proliferation and metastasis of carcinoma cells. PSCs even co-metastasise with carcinoma cells. This requires the ability of PSCs to migrate. In recent years, it has been established that almost all “hallmarks of cancer” such as proliferation or migration/invasion also rely on the expression and function of ion channels. So far, there is only very limited information about the function of ion channels in PSCs. Yet, there is growing evidence that ion channels in stromal cells also contribute to tumor progression. Here we investigated the function of KCa3.1 channels in PSCs. KCa3.1 channels are also found in many tumor cells of different origin. We revealed the functional expression of KCa3.1 channels by means of Western blot, immunofluorescence and patch clamp analysis. The impact of KCa3.1 channel activity on PSC function was determined with live-cell imaging and by measuring the intracellular Ca2+ concentration ([Ca2+]i). KCa3.1 channel blockade or knockout prevents the stimulation of PSC migration and chemotaxis by reducing the [Ca2+]i and calpain activity. KCa3.1 channels functionally cooperate with TRPC3 channels that are upregulated in PDAC stroma. Knockdown of TRPC3 channels largely abolishes the impact of KCa3.1 channels on PSC migration. In summary, our results clearly show that ion channels are crucial players in PSC physiology and pathophysiology. PMID:27903970

  13. Status Report on Transfer of Physical and Hydraulic Properties Databases to the Hanford Environmental Information System - PNNL Remediation Decision Support Project, Task 1, Activity 6

    Energy Technology Data Exchange (ETDEWEB)

    Rockhold, Mark L.; Middleton, Lisa A.; Cantrell, Kirk J.


    This document provides a status report on efforts to transfer physical and hydraulic property data from PNNL to CHPRC for incorporation into HEIS. The Remediation Decision Support (RDS) Project is managed by Pacific Northwest National Laboratory (PNNL) to support Hanford Site waste management and remedial action decisions by the U.S. Department of Energy and their contractors. The objective of Task 1, Activity 6 of the RDS project is to compile all available physical and hydraulic property data for sediments from the Hanford Site, to port these data into the Hanford Environmental Information System (HEIS), and to make the data web-accessible to anyone on the Hanford Local Area Network via the so-called Virtual Library. These physical and hydraulic property data are used to estimate parameters for analytical and numerical flow and transport models that are used for site risk assessments and evaluation of remedial action alternatives. In past years efforts were made by RDS project staff to compile all available physical and hydraulic property data for Hanford sediments and to transfer these data into SoilVision{reg_sign}, a commercial geotechnical software package designed for storing, analyzing, and manipulating soils data. Although SoilVision{reg_sign} has proven to be useful, its access and use restrictions have been recognized as a limitation to the effective use of the physical and hydraulic property databases by the broader group of potential users involved in Hanford waste site issues. In order to make these data more widely available and useable, a decision was made to port them to HEIS and to make them web-accessible via a Virtual Library module. In FY08 the original objectives of this activity on the RDS project were to: (1) ensure traceability and defensibility of all physical and hydraulic property data currently residing in the SoilVision{reg_sign} database maintained by PNNL, (2) transfer the physical and hydraulic property data from the Microsoft

  14. Effect of background potassium channels on potassium homeostasis in healthy and epileptic hippocampus


    Päsler, Dennis


    In the frequent neurological disease of epilepsy, focal extracellular potassium concentration in the brain increases to pathological values. The underlying mechanisms are not yet fully understood. Two-pore-domain potassium channels (K2P channels), postulated in the 1950s and cloned and investigated in the past years, came into scientific view. A contribution of these channels on keeping membrane’s resting potential of glial cells is proven. In the present study, the contribution of K2P channe...

  15. Dequantization Via Quantum Channels (United States)

    Andersson, Andreas


    For a unital completely positive map {Φ} ("quantum channel") governing the time propagation of a quantum system, the Stinespring representation gives an enlarged system evolving unitarily. We argue that the Stinespring representations of each power {Φ^m} of the single map together encode the structure of the original quantum channel and provide an interaction-dependent model for the bath. The same bath model gives a "classical limit" at infinite time {mto∞} in the form of a noncommutative "manifold" determined by the channel. In this way, a simplified analysis of the system can be performed by making the large- m approximation. These constructions are based on a noncommutative generalization of Berezin quantization. The latter is shown to involve very fundamental aspects of quantum-information theory, which are thereby put in a completely new light.

  16. Chaos in quantum channels

    CERN Document Server

    Hosur, Pavan; Roberts, Daniel A; Yoshida, Beni


    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.

  17. Chaos in quantum channels

    Energy Technology Data Exchange (ETDEWEB)

    Hosur, Pavan; Qi, Xiao-Liang [Department of Physics, Stanford University,476 Lomita Mall, Stanford, California 94305 (United States); Roberts, Daniel A. [Center for Theoretical Physics and Department of Physics, Massachusetts Institute of Technology,77 Massachusetts Ave, Cambridge, Massachusetts 02139 (United States); Yoshida, Beni [Perimeter Institute for Theoretical Physics,31 Caroline Street North, Waterloo, Ontario N2L 2Y5 (Canada); Walter Burke Institute for Theoretical Physics, California Institute of Technology,1200 E California Blvd, Pasadena CA 91125 (United States)


    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.

  18. TRP channels and pain. (United States)

    Julius, David


    Nociception is the process whereby primary afferent nerve fibers of the somatosensory system detect noxious stimuli. Pungent irritants from pepper, mint, and mustard plants have served as powerful pharmacological tools for identifying molecules and mechanisms underlying this initial step of pain sensation. These natural products have revealed three members of the transient receptor potential (TRP) ion channel family--TRPV1, TRPM8, and TRPA1--as molecular detectors of thermal and chemical stimuli that activate sensory neurons to produce acute or persistent pain. Analysis of TRP channel function and expression has validated the existence of nociceptors as a specialized group of somatosensory neurons devoted to the detection of noxious stimuli. These studies are also providing insight into the coding logic of nociception and how specification of nociceptor subtypes underlies behavioral discrimination of noxious thermal, chemical, and mechanical stimuli. Biophysical and pharmacological characterization of these channels has provided the intellectual and technical foundation for developing new classes of analgesic drugs.


    Institute of Scientific and Technical Information of China (English)

    Zhao Zheng; Jia Ying; Yin Qinye


    Delay diversity is an effective transmit diversity technique to combat adverse ef-fects of fading. Thus far, previous work in delay diversity assumed that perfect estimates ofcurrent channel fading conditions are available at the receiver and training symbols are requiredto estimate the channel from the transmitter to the receiver. However, increasing the number ofthe antennas increases the required training interval and reduces the available time within whichdata may be transmitted. Learning the channel coefficients becomes increasingly difficult for thefrequency selective channels. In this paper, with the subspace method and the delay character ofdelay diversity, a channel estimation method is proposed, which does not use training symbols. Itaddresses the transmit diversity for a frequency selective channel from a single carrier perspectivein the form of a simple equivalent fiat fading model. Monte Carlo simulations give the perfor-mance of channel estimation and the performance comparison of our channel-estimation-baseddetector with decision feedback equalization, which uses the perfect channel information.

  20. K(v)7 channels: function, pharmacology and channel modulators. (United States)

    Dalby-Brown, William; Hansen, Henrik H; Korsgaard, Mads P G; Mirza, Naheed; Olesen, Søren-P


    K(v)7 channels are unique among K(+) channels, since four out of the five channel subtypes have well-documented roles in the development of human diseases. They have distinct physiological functions in the heart and in the nervous system, which can be ascribed to their voltage-gating properties. The K(v)7 channels also lend themselves to pharmacological modulation, and synthetic openers as well as blockers of the channels, regulating neuronal excitability, have existed even before the K(v)7 channels were identified by cloning. In the present review we give an account on the focused efforts to develop selective modulators, openers as well as blockers, of the K(v)7 channel subtypes, which have been undertaken during recent years, along with a discussion of the K(v)7 ion channel physiology and therapeutic indications for modulators of the neuronal K(v)7 channels.

  1. Ionic Channels in Thunderclouds (United States)

    Losseva, T. V.; Fomenko, A. S.; Nemtchinov, I. V.


    We proceed to study the formation and propagation of ionic channels in thunderclouds in the framework of the model of the corona discharge wave propagation (Fomenko A.S., Losseva T.V., Nemtchinov I.V. The corona discharge waves in thunderclouds and formation of ionic channels // 2004 Fall Meeting. EOS Trans. AGU. 2004. V. 85. ¹ 47. Suppl. Abstract AE23A-0835.). In this model we proposed a hypothesis that the structure of a thundercloud becomes nonuniform due to corona discharge on the drops and ice particles and formation of ionic channels with higher conductivity than the surrounding air. When the onset strength of corona discharge becomes smaller than the electric field strength the corona discharge increases concentrations of ions in a small part of the cloud (a hot spot). An additional charge at opposite ends of the hot spot forms due to polarization process. The increased electric field initiates corona discharge in other parts of the cloud on ice particles and water drops with smaller sizes. The corona discharge front moves as a wave with the velocity of the order of ion drift and formes a highly conductive channel. We model this non-stationary problem with Poisson equation which is solved simultaneously with a simplified set of kinetic equations for ions, small charged particles and electrons (at high electric fields), including ionization due to electronic impact, attachment and formation of positive ions. By applying 3D numerical simulations we obtain the parameters of formed ionic channels with respect to onset electric fields both from large particles (in hot spot) and from small particles (surrounding hot spot), microscopic currents from particles with different sizes and the external electric field in the cloud. The interaction of ionic channels is also investigated. This work was supported by Russian Foundation of Basic Research (Project No 07-05-00998-à).

  2. Communicating Under Channel Uncertainty

    CERN Document Server

    Warsi, Naqueeb; Shah, Tapan


    For a single transmit and receive antenna system, a new constellation design is proposed to combat errors in the phase estimate of the channel coefficient. The proposed constellation is a combination of PSK and PAM constellations, where PSK is used to provide protection against phase errors, while PAM is used to increase the transmission rate using the knowledge of the magnitude of the channel coefficient. The performance of the proposed constellation is shown to be significantly better than the widely used QAM in terms of probability of error. The proposed strategy can also be extended to systems using multiple transmit and receive antennas.

  3. Economic and Industrial Development: EID - EMPLOY. Final Report, task 1. Review of approaches for employment impact assessment of renewable energy deployment

    Energy Technology Data Exchange (ETDEWEB)

    Breitschopf, Barbara; Nathani, Carsten; Resch, Gustav


    The importance of renewable energy in energy systems is increasing at an impressive rate, and the expectation is that this tendency will continue in the longer term. As a consequence, there is a strong need for reliable insight into the employment benefits from renewable energy. The current knowledge on the economic impacts of large-scale deployment of renewable energy technologies is more or less derived on an ad hoc basis and consists of a variety of different methodologies with different objectives. This is why the International Energy Agency's Implementing Agreement on Renewable Energy Technology Deployment (IEA-RETD) would like to facilitate a more structural approach, which will contribute to reliable and consistent insights of employment effects from deployment of renewable energy technologies. The objectives of the EMPLOY-EID project are to: Provide guidelines based on a thorough review of best practices, which are able to contribute to a consistent, reliable framework in which to measure employment effects from renewable energy deployment and which can be replicated from one country to another; Identify data sources and/or inputs required in application of such guidelines; Provide better understanding of key parameters and mechanisms that determine contribution of renewable energy employment; Assess availability of sources for employment benefit data for all RETD member countries as well as other interesting countries; Provide concrete gross employment benefit data to countries where data is available through application of the guidelines and best practices; and, Document the economic effects of renewable energy deployment through a publishable brochure of the main project results, presentations, the guidelines and background report. This project will help achieve the IEA-RETD's objective to ''empowering policy makers and energy market actors through the provision of information, tools and resources'' by underlining the

  4. Developments in relativistic channeling

    Energy Technology Data Exchange (ETDEWEB)

    Carrigan, R.A. Jr.


    The possibility of using channeling as a tool for high energy accelerator applications and particle physics has now been extensively investigated. Bent crystals have been used for accelerator extraction and for particle deflection. Applications as accelerating devices have been discussed but have not yet been tried. 61 refs., 1 fig.

  5. Ion channels in inflammation. (United States)

    Eisenhut, Michael; Wallace, Helen


    Most physical illness in vertebrates involves inflammation. Inflammation causes disease by fluid shifts across cell membranes and cell layers, changes in muscle function and generation of pain. These disease processes can be explained by changes in numbers or function of ion channels. Changes in ion channels have been detected in diarrhoeal illnesses, pyelonephritis, allergy, acute lung injury and systemic inflammatory response syndromes involving septic shock. The key role played by changes in ion transport is directly evident in inflammation-induced pain. Expression or function of all major categories of ion channels like sodium, chloride, calcium, potassium, transient receptor potential, purinergic receptor and acid-sensing ion channels can be influenced by cyto- and chemokines, prostaglandins, leukotrienes, histamine, ATP, reactive oxygen species and protons released in inflammation. Key pathways in this interaction are cyclic nucleotide, phosphoinositide and mitogen-activated protein kinase-mediated signalling, direct modification by reactive oxygen species like nitric oxide, ATP or protons and disruption of the cytoskeleton. Therapeutic interventions to modulate the adverse and overlapping effects of the numerous different inflammatory mediators on each ion transport system need to target adversely affected ion transport systems directly and locally.


    Directory of Open Access Journals (Sweden)

    Enrique eBalderas


    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.

  7. Intermittency and exotic channels

    CERN Document Server

    Bialas, A


    It is pointed out that accurate measurements of short-range two-particle correlations in like-charge K\\pi and in \\pi^ 0\\pi^ 0 channels should be very helpful in determining the origin of the \\lq\\lq intermittency\\rq\\rq\\ phenomenon observed recently for the like-charge pion pairs.

  8. All channels open

    NARCIS (Netherlands)

    Frank Huysmans; Jos de Haan


    Original title: Alle kanalen staan open. The rapid changes taking place in the media landscape in the Netherlands - characterised by digitisation and convergence of media technologies - raise the question of how the Dutch are dealing with the many new opportunities that have opened up. All channels

  9. Chemistry in Microfluidic Channels (United States)

    Chia, Matthew C.; Sweeney, Christina M.; Odom, Teri W.


    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…

  10. TRP channels: an overview

    DEFF Research Database (Denmark)

    Pedersen, Stine Falsig; Owsianik, Grzegorz; Nilius, Bernd


    to a plethora of data on the roles of TRPs in a variety of tissues and species, including mammals, insects, and yeast. The present review summarizes the most pertinent recent evidence regarding the structural and functional properties of TRP channels, focusing on the regulation and physiology of mammalian TRPs....

  11. Nonscaling calculation of the effective diffusion coefficient in periodic channels (United States)

    Kalinay, Pavol


    An algorithm calculating the effective diffusion coefficient D(x) in 2D and 3D channels with periodically varying cross section along the longitudinal coordinate x is presented. Unlike other methods, it is not based on scaling of the transverse coordinates, or the smallness of the width of the channel. The result is expressed as an integral of specific contributions to D(x) coming from the positions neighboring to x. The method avoids the hierarchy of derivatives of the channel shaping function h(x), so it is also suitable for the channels with cusps or jumps of their width. The method describes correctly D(x) in wide channels, giving the expected behavior in the limit of infinite width (no confinement).

  12. Extending Velocity Channel Analysis for Studying Turbulence Anisotropies

    CERN Document Server

    Kandel, Dinesh; Pogosyan, Dmitri


    We extend the analysis of the fluctuations in the velocity slices of Position-Position- Velocity (PPV) spectroscopic data from Doppler broadened lines, i.e. Velocity Channel Analysis (VCA) introduced by Lazarian & Pogosyan (2000), to study anisotropy of the underlying velocity and density turbulence statistics that arises from the presence of magnetic field. In particular, we study analytically how the measurable anisotropy of the statistics of the channel map fluctuations changes with the thickness of velocity channels. In agreement with the earlier VCA studies we find that the anisotropy of the thick channels reflects the anisotropy of the density field, while the relative contribution of density and velocity fluctuations to the thin velocity channels depends on the density spectral slope. We show that the anisotropies arising from Alfven, slow and fast modes are different, in particular, the anisotropy in PPV created by fast modes is opposite to that created by Alfven and slow modes and this can be use...

  13. A New Covert Channel over Cellular Voice Channel in Smartphones


    Aloraini, Bushra; Johnson, Daryl; Stackpole, Bill; Mishra, Sumita


    Investigating network covert channels in smartphones has become increasingly important as smartphones have recently replaced the role of traditional computers. Smartphones are subject to traditional computer network covert channel techniques. Smartphones also introduce new sets of covert channel techniques as they add more capabilities and multiple network connections. This work presents a new network covert channel in smartphones. The research studies the ability to leak information from the...

  14. Physiology and Regulation of Calcium Channels in Stomatal Guard Cells

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, Julian I.


    Stomatal pores in the epidermis of leaves regulate the diffusion of CO2 into leaves for photosynthetic carbon fixation and control water loss of plants during drought periods. Guard cells sense CO2, water status, light and other environmental conditions to regulate stomatal apertures for optimization of CO2 intake and plant growth under drought stress. The cytosolic second messenger calcium contributes to stomatal movements by transducing signals and regulating ion channels in guard cells. Studies suggest that both plasma membrane Ca2+ influx channels and vacuolar/organellar Ca2+ release channels contribute to ABA-induced Ca2+ elevations in guard cells. Recent research in the P.I.'s laboratory has led to identification of a novel major cation-selective Ca2+-permeable influx channel (Ica) in the plasma membrane of Arabidopsis guard cells. These advances will allow detailed characterization of Ica plasma membrane Ca2+ influx channels in guard cells. The long term goal of this research project is to gain a first detailed characterization of these novel plasma membrane Ca2+-permeable channel currents in Arabidopsis guard cells. The proposed research will investigate the hypothesis that Ica represents an important Ca2+ influx pathway for ABA and CO2 signal transduction in Arabidopsis guard cells. These studies will lead to elucidation of key signal transduction mechanisms by which plants balance CO2 influx into leaves and transpirational water loss and may contribute to future strategies for manipulating gas exchange for improved growth of crop plants and for biomass production.

  15. DAMGO modulates two-pore domain K(+) channels in the substantia gelatinosa neurons of rat spinal cord. (United States)

    Cho, Pyung Sun; Lee, Han Kyu; Lee, Sang Hoon; Im, Jay Zoon; Jung, Sung Jun


    The analgesic mechanism of opioids is known to decrease the excitability of substantia gelatinosa (SG) neurons receiving the synaptic inputs from primary nociceptive afferent fiber by increasing inwardly rectifying K(+) current. In this study, we examined whether a µ-opioid agonist, [D-Ala2,N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO), affects the two-pore domain K(+) channel (K2P) current in rat SG neurons using a slice whole-cell patch clamp technique. Also we confirmed which subtypes of K2P channels were associated with DAMGO-induced currents, measuring the expression of K2P channel in whole spinal cord and SG region. DAMGO caused a robust hyperpolarization and outward current in the SG neurons, which developed almost instantaneously and did not show any time-dependent inactivation. Half of the SG neurons exhibited a linear I~V relationship of the DAMGO-induced current, whereas rest of the neurons displayed inward rectification. In SG neurons with a linear I~V relationship of DAMGO-induced current, the reversal potential was close to the K(+) equilibrium potentials. The mRNA expression of TWIK (tandem of pore domains in a weak inwardly rectifying K(+) channel) related acid-sensitive K(+) channel (TASK) 1 and 3 was found in the SG region and a low pH (6.4) significantly blocked the DAMGO-induced K(+) current. Taken together, the DAMGO-induced hyperpolarization at resting membrane potential and subsequent decrease in excitability of SG neurons can be carried by the two-pore domain K(+) channel (TASK1 and 3) in addition to inwardly rectifying K(+) channel.

  16. Digital communications over fading channels


    Beltz, Nathan E.; Robertson, R. Clark


    In this report, the probabilities of bit error for the most commonly used digital modulation techniques are analyzed. Analytic solutions are developed for the probability of bit error when the signal is affected by the most commonly encountered impairment to system performance for a wireless channel, the transmission of the signal over a fading channel. In this report, the effect of a slow, flat Ricean fading channel on communications systems performance is examined. Since channel fading ...

  17. Radar channel balancing with commutation

    Energy Technology Data Exchange (ETDEWEB)

    Doerry, Armin Walter


    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.

  18. 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


    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.

  19. Lipid Ion Channels

    CERN Document Server

    Heimburg, Thomas


    The interpretation electrical phenomena in biomembranes is usually based on the assumption that the experimentally found discrete ion conduction events are due to a particular class of proteins called ion channels while the lipid membrane is considered being an inert electrical insulator. The particular protein structure is thought to be related to ion specificity, specific recognition of drugs by receptors and to macroscopic phenomena as nerve pulse propagation. However, lipid membranes in their chain melting regime are known to be highly permeable to ions, water and small molecules, and are therefore not always inert. In voltage-clamp experiments one finds quantized conduction events through protein-free membranes in their melting regime similar to or even undistinguishable from those attributed to proteins. This constitutes a conceptual problem for the interpretation of electrophysiological data obtained from biological membrane preparations. Here, we review the experimental evidence for lipid ion channels...

  20. Regulated trafficking of the CFTR chloride channel. (United States)

    Kleizen, B; Braakman, I; de Jonge, H R


    The cystic fibrosis transmembrane conductance regulator (CFTR), the ABC transporter encoded by the cystic fibrosis gene, is localized in the apical membrane of epithelial cells where it functions as a cyclic AMP-regulated chloride channel and as a regulator of other ion channels and transporters. Whereas a key role of cAMP-dependent phosphorylation in CFTR-channel gating has been firmly established, more recent studies have provided clear evidence for the existence of a second level of cAMP regulation, i.e. the exocytotic recruitment of CFFR to the plasma membrane and its endocytotic retrieval. Regulated trafficking of the CFTR Cl- channel has sofar been demonstrated only in a subset of CFTR-expressing cell types. However, with the introduction of more sensitive methods to measure CFTR cycling and submembrane localization, it might turn out to be a more general phenomenon that could contribute importantly to both the regulation of CFTR-mediated chloride transport itself and to the regulation of other transporters and CFTR-modulated cellular functions. This review aims to summarize the present state of knowledge regarding polarized and regulated CFTR trafficking and endosomal recycling in epithelial cells, to discuss present gaps in our understanding of these processes at the cellular and molecular level, and to consider its possible implications for cystic fibrosis.

  1. DMT of weighted Parallel Channels: Application to Broadcast Channel

    CERN Document Server

    Mroueh, Lina; Othman, Ghaya Rekaya-Ben; Belfiore, Jean-Claude


    In a broadcast channel with random packet arrival and transmission queues, the stability of the system is achieved by maximizing a weighted sum rate capacity with suitable weights that depend on the queue size. The weighted sum rate capacity using Dirty Paper Coding (DPC) and Zero Forcing (ZF) is asymptotically equivalent to the weighted sum capacity over parallel single-channels. In this paper, we study the Diversity Multiplexing Tradeoff (DMT) of the fading broadcast channel under a fixed weighted sum rate capacity constraint. The DMT of both identical and different parallel weighted MISO channels is first derived. Finally, we deduce the DMT of a broadcast channel using DPC and ZF precoders.

  2. On partially entanglement breaking channels

    CERN Document Server

    Chruscinski, D; Chruscinski, Dariusz; Kossakowski, Andrzej


    Using well known duality between quantum maps and states of composite systems we introduce the notion of Schmidt number of a quantum channel. It enables one to define classes of quantum channels which partially break quantum entanglement. These classes generalize the well known class of entanglement breaking channels.

  3. Micro-channel plate detector (United States)

    Elam, Jeffrey W.; Lee, Seon W.; Wang, Hsien -Hau; Pellin, Michael J.; Byrum, Karen; Frisch, Henry J.


    A method and system for providing a micro-channel plate detector. An anodized aluminum oxide membrane is provided and includes a plurality of nanopores which have an Al coating and a thin layer of an emissive oxide material responsive to incident radiation, thereby providing a plurality of radiation sensitive channels for the micro-channel plate detector.

  4. 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)


    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).

  5. Secondary Flow Effects in Relatively Narrow Channels

    Institute of Scientific and Technical Information of China (English)

    Rudolf Dvo(r)ák


    Secondary flow effects were discussed in numerous papers at the past ISAIF Symposia, mainly in connection with turbine or compressor cascades[1]. This paper will complement these papers by looking at the problem from the channel (or blade passages) geometry point of view. If we describe as secondary flows any flows in planes perpendicular to the main flow direction, then there are at least three kinds of secondary flows in a typical turbine rotor cascade: - secondary flows of the 1st kind, generated by centrifugal forces in closed curved channels, - secondary flows of the 2nd kind, generated by interacting boundary layers, mainly in corners (this will include even the horseshoe vortices), - secondary flows due to mass inflow through the tip clearance. Quite often all the secondary flow vortices merge downstream into a passage vortex with a non-negligible contribution to the channel (cascade) losses, and it is worth investigating the individual contributions to these losses to take them into account in the design procedure.

  6. Molecular cell biology of KATP channels: implications for neonatal diabetes. (United States)

    Smith, Andrew J; Taneja, Tarvinder K; Mankouri, Jamel; Sivaprasadarao, Asipu


    ATP-sensitive potassium (KATP) channels play a key role in the regulation of insulin secretion by coupling glucose metabolism to the electrical activity of pancreatic beta-cells. To generate an electric signal of suitable magnitude, the plasma membrane of the beta-cell must contain an appropriate number of channels. An inadequate number of channels can lead to congenital hyperinsulinism, whereas an excess of channels can result in the opposite condition, neonatal diabetes. KATP channels are made up of four subunits each of Kir6.2 and the sulphonylurea receptor (SUR1), encoded by the genes KCNJ11 and ABCC8, respectively. Following synthesis, the subunits must assemble into an octameric complex to be able to exit the endoplasmic reticulum and reach the plasma membrane. While this biosynthetic pathway ensures supply of channels to the cell surface, an opposite pathway, involving clathrin-mediated endocytosis, removes channels back into the cell. The balance between these two processes, perhaps in conjunction with endocytic recycling, would dictate the channel density at the cell membrane. In this review, we discuss the molecular signals that contribute to this balance, and how an imbalance could lead to a disease state such as neonatal diabetes.

  7. Automatic cross-talk removal from multi-channel data

    CERN Document Server

    Allen, B; Ottewill, A; Allen, Bruce; Hua, Wensheng; Ottewill, Adrian


    A technique is described for removing interference from a signal of interest ("channel 1") which is one of a set of N time-domain instrumental signals ("channels 1 to N"). We assume that channel 1 is a linear combination of "true" signal plus noise, and that the "true" signal is not correlated with the noise. We also assume that part of this noise is produced, in a poorly-understood way, by the environment, and that the environment is monitored by channels 2 to N. Finally, we assume that the contribution of channel n to channel 1 is described by an (unknown!) linear transfer function R_n(t-t'). Our technique estimates the R_i and provides a way to subtract the environmental contamination from channel 1, giving an estimate of the "true" signal which minimizes its variance. It also provides some insights into how the environment is contaminating the signal of interest. The method is illustrated with data from a prototype interferometric gravitational-wave detector, in which the channel of interest (differential...

  8. Niflumic acid blocks native and recombinant T-type channels. (United States)

    Balderas, Enrique; Ateaga-Tlecuitl, Rogelio; Rivera, Manuel; Gomora, Juan C; Darszon, Alberto


    Voltage-dependent calcium channels are widely distributed in animal cells, including spermatozoa. Calcium is fundamental in many sperm functions such as: motility, capacitation, and the acrosome reaction (AR), all essential for fertilization. Pharmacological evidence has suggested T-type calcium channels participate in the AR. Niflumic acid (NA), a non-steroidal anti-inflammatory drug commonly used as chloride channel blocker, blocks T-currents in mouse spermatogenic cells and Cl(-) channels in testicular sperm. Here we examine the mechanism of NA blockade and explore if it can be used to separate the contribution of different Ca(V)3 members previously detected in these cells. Electrophysiological patch-clamp recordings were performed in isolated mouse spermatogenic cells and in HEK cells heterologously expressing Ca(V)3 channels. NA blocks mouse spermatogenic cell T-type currents with an IC(50) of 73.5 µM, without major voltage-dependent effects. The NA blockade is more potent in the open and in the inactivated state than in the closed state of the T-type channels. Interestingly, we found that heterologously expressed Ca(V)3.1 and Ca(V)3.3 channels were more sensitive to NA than Ca(V)3.2 channels, and this drug substantially slowed the recovery from inactivation of the three isoforms. Molecular docking modeling of drug-channel binding predicts that NA binds preferentially to the extracellular face of Ca(V)3.1 channels. The biophysical characteristics of mouse spermatogenic cell T-type currents more closely resemble those from heterologously expressed Ca(V)3.1 channels, including their sensitivity to NA. As Ca(V)3.1 null mice maintain their spermatogenic cell T-currents, it is likely that a novel Ca(V)3.2 isoform is responsible for them.

  9. Ion channels, ion channel receptors, and visceral hypersensitivity in irritable bowel syndrome. (United States)

    Fuentes, I M; Christianson, J A


    Ion channels are expressed throughout the gastrointestinal system and regulate nearly every aspect of digestion, including fluid secretion and absorption, motility, and visceral sensitivity. It is therefore not surprising that in the setting of functional bowel disorders, such as irritable bowel syndrome (IBS), ion channels are often altered in terms of expression level and function and are a target of pharmacological intervention. This is particularly true of their role in driving abdominal pain through visceral hypersensitivity (VH), which is the main reason IBS patients seek medical care. In the study by Scanzi et al., in the current issue of this journal, they provide evidence that the T-type voltage-gated calcium channel (Cav ) Cav 3.2 is upregulated in human IBS patients, and is necessary for the induction of an IBS-like disease state in mice. In this mini-review, we will discuss the contribution of specific ion channels to VH in IBS, both in human patients and rodent models. We will also discuss how Cav 3.2 may play a role as an integrator of multiple environmental stimuli contributing toward VH.

  10. Abeta ion channels. Prospects for treating Alzheimer's disease with Abeta channel blockers. (United States)

    Arispe, Nelson; Diaz, Juan C; Simakova, Olga


    The main pathological features in the Alzheimer's brain are progressive depositions of amyloid protein plaques among nerve cells, and neurofibrillary tangles within the nerve cells. The major components of plaques are Abeta peptides. Numerous reports have provided evidence that Abeta peptides are cytotoxic and may play a role in the pathogenesis of AD. An increasing number of research reports support the concept that the Abeta-membrane interaction event may be followed by the insertion of Abeta into the membrane in a structural configuration which forms an ion channel. This review summarizes experimental procedures which have been designed to test the hypothesis that the interaction of Abeta with a variety of membranes, both artificial and natural, results in the subsequent formation of Abeta ion channels We describe experiments, by ourselves and others, that support the view that Abeta is cytotoxic largely due to the action of Abeta channels in the cell membrane. The interaction of Abeta with the surface of the cell membrane may results in the activation of a chain of processes that, when large enough, become cytotoxic and induce cell death by apoptosis. Remarkably, the blockage of Abeta ion channels at the surface of the cell absolutely prevents the activation of these processes at different intracellular levels, thereby preserving the life of the cells. As a prospect for therapy for Alzheimer's disease, our findings at cellular level may be testable on AD animal models to elucidate the potential role and the magnitude of the contribution of the Abeta channels for induction of the disease.

  11. Sparse Variational Bayesian SAGE Algorithm With Application to the Estimation of Multipath Wireless Channels

    DEFF Research Database (Denmark)

    Shutin, Dmitriy; Fleury, Bernard Henri


    channels. The application context of the algorithm considered in this contribution is parameter estimation from channel sounding measurements for radio channel modeling purpose. The new sparse VB-SAGE algorithm extends the classical SAGE algorithm in two respects: i) by monotonically minimizing...... scattering, calibration and discretization errors, allowing for a robust extraction of the relevant multipath components. The performance of the sparse VB-SAGE algorithm and its advantages over conventional channel estimation methods are demonstrated in synthetic single-input-multiple-output (SIMO) time......-invariant channels. The algorithm is also applied to real measurement data in a multiple-input-multiple-output (MIMO) time-invariant context....

  12. Anion-Channel Blockers Inhibit S-Type Anion Channels and Abscisic Acid Responses in Guard Cells. (United States)

    Schwartz, A.; Ilan, N.; Schwarz, M.; Scheaffer, J.; Assmann, S. M.; Schroeder, J. I.


    The effects of anion-channel blockers on light-mediated stomatal opening, on the potassium dependence of stomatal opening, on stomatal responses to abscisic acid (ABA), and on current through slow anion channels in the plasma membrane of guard cells were investigated. The anion-channel blockers anthracene-9-carboxylic acid (9-AC) and niflumic acid blocked current through slow anion channels of Vicia faba L. guard cells. Both 9-AC and niflumic acid reversed ABA inhibition of stomatal opening in V. faba L. and Commelina communis L. The anion-channel blocker probenecid also abolished ABA inhibition of stomatal opening in both species. Additional tests of 9-AC effects on stomatal aperture in Commelina revealed that application of this anion-channel blocker allowed wide stomatal opening under low (1 mM) KCI conditions and increased the rate of stomatal opening under both low and high (100 mM) KCI conditions. These results indicate that anion channels can function as a negative regulator of stomatal opening, presumably by allowing anion efflux and depolarization, which prohibits ion up-take in guard cells. Furthermore, 9-AC prevented ABA induction of stomatal closure. A model in which ABA activation of anion channels contributes a rate-limiting mechanism during ABA-induced stomatal closure and inhibition of stomatal opening is discussed.

  13. Silicon buried channels for pixel detector cooling

    Energy Technology Data Exchange (ETDEWEB)

    Boscardin, M., E-mail: [Fondazione Bruno Kessler Trento, Via Sommarive 18, I-38123 Trento (Italy); Conci, P.; Crivellari, M.; Ronchin, S. [Fondazione Bruno Kessler Trento, Via Sommarive 18, I-38123 Trento (Italy); Bettarini, S. [Universitá di Pisa, L.go B. Pontecorvo 3, I-56127 Pisa (Italy); Istituto Nazionale di Fisica Nucleare, Sez. di Pisa, L.go B. Pontecorvo 3, I-56127 Pisa (Italy); Bosi, F. [Istituto Nazionale di Fisica Nucleare, Sez. di Pisa, L.go B. Pontecorvo 3, I-56127 Pisa (Italy)


    The support and cooling structures add important contributions to the thickness, in radiation length, of vertex detectors. In order to minimize the material budget of pixel sensors, we developed a new approach to integrate the cooling into the silicon devices. The microchannels are formed in silicon using isotropic SF{sub 6} plasma etching in a DRIE (deep reactive ion etcher) equipment. Due to their peculiar profiles, the channels can be sealed by a layer of a PECVD silicon oxide. We have realized on a silicon wafer microchannels with different geometries and hydraulic diameters. We describe the main fabrication steps of microchannels with focus on the channel definition. The experimental results are reported on the thermal characterization of several prototypes, using a mixture of glycol and water as a liquid coolant. The prototypes have shown high cooling efficiency and high-pressure breaking strength.

  14. Bayesian Inference Methods for Sparse Channel Estimation

    DEFF Research Database (Denmark)

    Pedersen, Niels Lovmand


    This thesis deals with sparse Bayesian learning (SBL) with application to radio channel estimation. As opposed to the classical approach for sparse signal representation, we focus on the problem of inferring complex signals. Our investigations within SBL constitute the basis for the development...... of Bayesian inference algorithms for sparse channel estimation. Sparse inference methods aim at finding the sparse representation of a signal given in some overcomplete dictionary of basis vectors. Within this context, one of our main contributions to the field of SBL is a hierarchical representation...... analysis of the complex prior representation, where we show that the ability to induce sparse estimates of a given prior heavily depends on the inference method used and, interestingly, whether real or complex variables are inferred. We also show that the Bayesian estimators derived from the proposed...

  15. Charm mass effects in bulk channel correlations

    CERN Document Server

    Burnier, Y


    The bulk viscosity of thermalized QCD matter at temperatures above a few hundred MeV could be significantly influenced by charm quarks because their contribution arises four perturbative orders before purely gluonic effects. In an attempt to clarify the challenges of a lattice study, we determine the relevant imaginary-time correlator (of massive scalar densities) up to NLO in perturbation theory, and compare with existing data. We find discrepancies much larger than in the vector channel; this may hint, apart from the importance of taking a continuum limit, to larger non-perturbative effects in the scalar channel. We also recall how a transport peak related to the scalar density spectral function encodes non-perturbative information concerning the charm quark chemical equilibration rate close to equilibrium.

  16. Ion Channels in Neurological Disorders. (United States)

    Kumar, Pravir; Kumar, Dhiraj; Jha, Saurabh Kumar; Jha, Niraj Kumar; Ambasta, Rashmi K


    The convergent endeavors of the neuroscientist to establish a link between clinical neurology, genetics, loss of function of an important protein, and channelopathies behind neurological disorders are quite intriguing. Growing evidence reveals the impact of ion channels dysfunctioning in neurodegenerative disorders (NDDs). Many neurological/neuromuscular disorders, viz, Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, and age-related disorders are caused due to altered function or mutation in ion channels. To maintain cell homeostasis, ion channels are playing a crucial role which is a large transmembrane protein. Further, these channels are important as it determines the membrane potential and playing critically in the secretion of neurotransmitter. Behind NDDs, losses of pathological proteins and defective ion channels have been reported and are found to aggravate the disease symptoms. Moreover, ion channel dysfunctions are eliciting a range of symptoms, including memory loss, movement disabilities, neuromuscular sprains, and strokes. Since the possible mechanistic role played by aberrant ion channels, their receptor and associated factors in neurodegeneration remained elusive; therefore, it is a challenging task for the neuroscientist to implement the therapeutics for targeting NDDs. This chapter reviews the potential role of the ion channels in membrane physiology and brain homeostasis, where ion channels and their associated factors have been characterized with their functional consequences in neurological diseases. Moreover, mechanistic role of perturbed ion channels has been identified in various NDDs, and finally, ion channel modulators have been investigated for their therapeutic intervention in treating common NDDs.

  17. HCN Channels and Heart Rate

    Directory of Open Access Journals (Sweden)

    Ilaria Dentamaro


    Full Text Available Hyperpolarization and Cyclic Nucleotide (HCN -gated channels represent the molecular correlates of the “funny” pacemaker current (If, a current activated by hyperpolarization and considered able to influence the sinus node function in generating cardiac impulses. HCN channels are a family of six transmembrane domain, single pore-loop, hyperpolarization activated, non-selective cation channels. This channel family comprises four members: HCN1-4, but there is a general agreement to consider HCN4 as the main isoform able to control heart rate. This review aims to summarize advanced insights into the structure, function and cellular regulation of HCN channels in order to better understand the role of such channels in regulating heart rate and heart function in normal and pathological conditions. Therefore, we evaluated the possible therapeutic application of the selective HCN channels blockers in heart rate control.

  18. A thermosensitive mutation alters the effects of lacosamide on slow inactivation in neuronal voltage-gated sodium channels, NaV 1.2.Mena Abdelsayed1, Stanislav Sokolov1, Peter C. Ruben*1 - These authors contributed equally to this work* - Corresponding author

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    Mena eAbdelsayed


    Full Text Available Epilepsy is a disorder characterized by seizures and convulsions. The basis of epilepsy is an increase in neuronal excitability that, in some cases, may be caused by functional defects in neuronal voltage gated sodium channels (NaVs. The C121W mutation of the β1 subunit, in particular, gives rise to the thermosensitive generalized epilepsy with febrile seizures plus (GEFS+ phenotype. Lacosamide is used to treat epileptic seizures and is distinct from other anti-seizure drugs by targeting NaV slow-inactivation. We studied the effects of 100 µM lacosamide on the biophysical properties of NaV1.2 channels associated with either WT-β1 or the mutant C121W-β1 subunit. Biophysical parameters were measured at both normal (22 °C and elevated (34 °C temperatures to elicit the differential temperature-sensitivity of C121W. Lacosamide was less effective in NaV1.2 associated with the C121W-β1 at either temperature than in NaV1.2 + WT-β1. There is also a more potent effect by lacosamide on slow inactivation at elevated temperatures. Our data suggest a modulatory role is imparted by the β1 subunit in the interaction between the drug and the channel.

  19. Sanshool on The Fingertip Interferes with Vibration Detection in a Rapidly-Adapting (RA) Tactile Channel (United States)

    Kuroki, Scinob; Hagura, Nobuhiro; Nishida, Shin’ya; Haggard, Patrick; Watanabe, Junji


    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. PMID:27935970

  20. Mechanosensitive TRP channels in cardiovascular pathophysiology. (United States)

    Inoue, Ryuji; Jian, Zhong; Kawarabayashi, Yasuhiro


    Transient receptor potential (TRP) proteins constitute a large non-voltage-gated cation channel superfamily, activated polymodally by various physicochemical stimuli, and are implicated in a variety of cellular functions. Known activators for TRP include not only chemical stimuli such as receptor stimulation, increased acidity and pungent/cooling agents, but temperature change and various forms of mechanical stimuli such as osmotic stress, membrane stretch, and shear force. Recent investigations have revealed that at least ten mammalian TRPs exhibit mechanosensitivity (TRPC1, 5, 6; TRPV1, 2, 4; TRPM3, 7; TRPA1; TRPP2), but the mechanisms underlying it appear considerably divergent and complex. The proposed mechanisms are associated with lipid bilayer mechanics, specialized force-transducing structures, biochemical reactions, membrane trafficking and transcriptional regulation. Many of mechanosensitive (MS)-TRP channel likely undergo multiple regulations via these mechanisms. In the cardiovascular system in which hemodynamic forces constantly operate, the impact of mechanical stress may be particularly significant. Extensive morphological and functional studies have indicated that several MS-TRP channels are expressed in cardiac muscle, vascular smooth muscle, endothelium and vasosensory neurons, each differentially contributing to cardiovascular (CV) functions. To further complexity, the recent evidence suggests that mechanical stress may synergize with neurohormonal mechanisms thereby amplifying otherwise marginal responses. Furthermore, the currently available data suggest that MS-TRP channels may be involved in CV pathophysiology such as cardiac arrhythmia, cardiac hypertrophy/myopathy, hypertension and aneurysms. This review will overview currently known mechanisms for mechanical activation/modulation of TRPs and possible connections of MS-TRP channels to CV disorders.

  1. Social Contributions in Romania

    Directory of Open Access Journals (Sweden)

    Attila Gyorgy


    Full Text Available Social contributions have an important impact on payroll policy. Also, social contributions represent a significant budgetary revenue item which can be viewed at the edge between taxation and insurance. Social contributions in Romania experienced many changes which ended in 2008. Nowadays, they are within a long transaction period towards partial externalization of the insurance activity to privately managed funds. The aim of this paper is to analyse the homogeneity of Romanian social security public scheme using annual data extracted from 2002-2009.The main findings reveal that social contributions reached the pinnacle of diversification, being too many, some of them with a small contribution rates; fiscal reforms which reduced contribution rates advantaged employers, and state will be interested to externalize this activity as far private sector will be able to assume this responsibility and the budgetary effects are acceptable for the public finance.

  2. Ion Channels in Leukocytes (United States)


    muscle k142), heart muscle (80), bo- are released. In recent years much has been learned vine pulmonar arter endothelial cells (251), and rat about the...b3 Zn or cytes from cystic fibrosis patients lack a Cl current that Ni (1 mM)-added to the cytoplasmic side of the mem- can be acti% ated b3 the...that at37’C hu- to be defectiv.- in cystic fibrosis (55, 277), and Chen et al. man T-cell CiL channels are active at rest, implies that (25) have shown

  3. Cholesterol binding to ion channels

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    Irena eLevitan


    Full Text Available Numerous studies demonstrated that membrane cholesterol is a major regulator of ion channel function. The goal of this review is to discuss significant advances that have been recently achieved in elucidating the mechanisms responsible for cholesterol regulation of ion channels. The first major insight that comes from growing number of studies that based on the sterol specificity of cholesterol effects, show that several types of ion channels (nAChR, Kir, BK, TRPV are regulated by specific sterol-protein interactions. This conclusion is supported by demonstrating direct saturable binding of cholesterol to a bacterial Kir channel. The second major advance in the field is the identification of putative cholesterol binding sites in several types of ion channels. These include sites at locations associated with the well-known cholesterol binding motif CRAC and its reversed form CARC in nAChR, BK, and TRPV, as well as novel cholesterol binding regions in Kir channels. Notably, in the majority of these channels, cholesterol is suggested to interact mainly with hydrophobic residues in non-annular regions of the channels being embedded in between transmembrane protein helices. We also discuss how identification of putative cholesterol binding sites is an essential step to understand the mechanistic basis of cholesterol-induced channel regulation. Clearly, however, these are only the first few steps in obtaining a general understanding of cholesterol-ion channels interactions and their roles in cellular and organ functions.

  4. Apport des expériences en canal à l'interprétation sédimentologique des dépôts de cônes détritiques sous-marins . . . Contribution of Channel Experiments to the Sedimentological Interpretation of Marine Detrital Cone Deposits

    Directory of Open Access Journals (Sweden)

    Ravenne C.


    épliques. Chaque élé-ment constitutif : banc de grès homogène plus l'intercalation argilo-silteuse suivante, ainsi que la barre massive, représente un écoulement. This article describes the results of experiments. performed in a channel at the Fluid Mechanics Laboratory in Grenoble to study turbid currents and their contribution to understanding the arrangement and composition of different elements observed in gravity deposits such as are generally encountered in deep sedimentary basins. The first part deals with the experiments and shows : (i the distinction between density current and turbid surge; (ii the different phases of a turbid flow and their mechanism (setting the initial mass in motion, forming a mass-flow, forming a debris-flow or a grain-flow, the importance of the hydraulic jump, forming a density surge, deceleration of the surge. The second part deals with interpreting the elements making up a sequence linked to turbid flows such as were observed in the Annot Sandstone Series and, in particular, made up of the following units: (a homogeneous sandstone banks; (b massive bar and its different components: - homogeneous sandstone level, - soft pebble level - erosion, - granule level, - graded-bed level, - level of water-escape marks, - level with progradation marks, (c shaly-silty interbedding. Each of these units is linked to a phase or part of a phase described in the first part. At the same time as this interpretation, a process is proposed for putting the different units in place and for arranging them sequentially, i. e. very fast strato-increasing series, massive bar and progressive strato-decreasing series. This process is based on a major catastrophic episode (earthquake or slope destabilization that was responsible for creating the massive bar. The strato-increasing series is linked to the early beginnings of this major phase, and the strato-decreasing series to its aftershocks. Each constitutive unit - very homogeneous sandstone bank plus the subsequent

  5. Mimicking multi-channel scattering with single-channel approaches


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


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

  6. Capacity of Fading Channels in the Low Power Regime

    KAUST Repository

    Benkhelifa, Fatma


    The low power regime has attracted various researchers in the information theory and communication communities to understand the performance limits of wireless systems. Indeed, the energy consumption is becoming one of the major limiting factors in wireless systems. As such, energy-efficient wireless systems are of major importance to the next generation wireless systems designers. The capacity is a metric that measures the performance limit of a wireless system. The study of the ergodic capacity of some fading channels in the low power regime is the main subject of this thesis. In our study, we consider that the receiver has always a full knowledge of the channel state information. However, we assume that the transmitter has possibly imperfect knowledge of the channel state information, i.e. he knows either perfectly the channel or only an estimated version of the channel. Both radio frequency and free space optical communication channel models are considered. The main contribution of this work is the explicit characterization of how the capacity scales as function of the signal-to-noise ratio in the low power regime. This allows us to characterize the gain due to the perfect knowledge compared to no knowledge of the channel state information at the transmitter. In particular, we show that the gain increases logarithmically for radio frequency communication. However, the gain increases as log2(Pavg) or log4(Pavg) for free-space optical communication, where Pavg is the average power constraint imposed to the input. Furthermore, we characterize the capacity of cascaded fading channels and we applied the result to Rayleigh-product fading channel and to a free-space optical link over gamma-gamma atmospheric turbulence in the presence of pointing errors. Finally, we study the capacity of Nakagami-m fading channel under quality of service constraints, namely the effective capacity. We have shown that the effective capacity converges to Shannon capacity in the very low

  7. Incentives to Encourage Scientific Web Contribution (Invited) (United States)

    Antunes, A. K.


    We suggest improvements to citation standards and creation of remuneration opportunities to encourage career scientist contributions to Web2.0 and social media science channels. At present, agencies want to accomplish better outreach and engagement with no funding, while scientists sacrifice their personal time to contribute to web and social media sites. Securing active participation by scientists requires career recognition of the value scientists provide to web knowledge bases and to the general public. One primary mechanism to encourage participation is citation standards, which let a contributor improve their reputation in a quantifiable way. But such standards must be recognized by their scientific and workplace communities. Using case studies such as the acceptance of web in the workplace and the growth of open access journals, we examine what agencies and individual can do as well as the time scales needed to secure increased active contribution by scientists. We also discuss ways to jumpstart this process.

  8. Multiuser MIMO Channel Estimation

    Directory of Open Access Journals (Sweden)



    Full Text Available In this paper, three beamforming design are considered for multi user MIMO system. First, transmit beamformers are fixed and the receive (RX beamformers are calculated. Transmit beamformer (TX-BFis projectedas a null space of appropriate channels. It reduces the interference for each user. Then the receiver beamformer is determined which maximize the SNR. This beamforming design provides less computation time. The second case is joint TX and RX beamformer for SNR maximization. In this transmitter and receiver beamformer are calculated using extended alternating optimization (EAO algorithm. The third one is joint transmitter and receiver beamforming for SNR and SINR maximization using EAO algorithm. This algorithm provides better error performance and sum rate performance. All the design cases are simulated by using standard multipath channel model. Our simulation results illustrate that compared to the least square design and zero forcing design, the joint TX and RX beamforming design using EAO algorithm provides faster beamforming and improved error performance and sum rate.

  9. Channel Wall Landslides (United States)


    [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.

  10. A Micromechanical RF Channelizer (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

  11. Rain and channel flow supplements to subsurface water beneath hyper-arid ephemeral stream channels (United States)

    Kampf, Stephanie K.; Faulconer, Joshua; Shaw, Jeremy R.; Sutfin, Nicholas A.; Cooper, David J.


    In hyper-arid regions, ephemeral stream channels are important sources of subsurface recharge and water supply for riparian vegetation, but few studies have documented the subsurface water content dynamics of these systems. This study examines ephemeral channels in the hyper-arid western Sonoran Desert, USA to determine how frequently water recharges the alluvial fill and identify variables that affect the depth and persistence of recharge. Precipitation, stream stage, and subsurface water content measurements were collected over a three-year study at six channels with varying contributing areas and thicknesses of alluvial fill. All channels contain coarse alluvium composed primarily of sands and gravels, and some locations also have localized layers of fine sediment at 2-3 m depth. Rain alone contributed 300-400 mm of water input to these channels over three years, but water content responses were only detected for 36% of the rain events at 10 cm depth, indicating that much of the rain water was either quickly evaporated or taken up by plants. Pulses of water from rain events were detected only in the top meter of alluvium. The sites each experienced ⩽5 brief flow events, which caused transient saturation that usually lasted only a few hours longer than flow. These events were the only apparent source of water to depths >1 m, and water from flow events quickly percolated past the deepest measurement depths (0.5-3 m). Sustained saturation in the shallow subsurface only developed where there was a near-surface layer of finer consolidated sediments that impeded deep percolation.

  12. Experimental study of natural circulation flow instability in rectangular channels

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Tao; Qi, Shi; Song, Mingqiang [North China Electric Power Univ., Beijing (China). School of Nuclear Science and Engineering; Passive Nuclear Safety Technology, Beijing (China). Beijing Key Lab.; Xiao, Zejun [Nuclear, Reactor Thermal Hydraulics Technology, Chengdu (China). CNNC Key Lab.


    Experiments of natural circulation flow instability were conducted in rectangular channels with 5 mm and 10 mm wide gaps. Results for different heating powers were obtained. The results showed that the flow will tend to be instable with the growing of heating power. The oscillation period of pressure D-value and volume flow are the same, but their phase positions are opposite. They both can be described by trigonometric functions. The existence of edge position and secondary flow will strengthen the disturbance of fluid flow in rectangle channels, which contributes to heat transfer. The disturbance of bubble and fluid will be strengthened, especially in the saturated boiling section, which make it possible for the mixing flow. The results also showed that the resistance in 5 mm channel is bigger than that in 10 mm channel, it is less likely to form stable natural circulation in the subcooled region.

  13. Ion channels-related diseases. (United States)

    Dworakowska, B; Dołowy, K


    There are many diseases related to ion channels. Mutations in muscle voltage-gated sodium, potassium, calcium and chloride channels, and acetylcholine-gated channel may lead to such physiological disorders as hyper- and hypokalemic periodic paralysis, myotonias, long QT syndrome, Brugada syndrome, malignant hyperthermia and myasthenia. Neuronal disorders, e.g., epilepsy, episodic ataxia, familial hemiplegic migraine, Lambert-Eaton myasthenic syndrome, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia may result from dysfunction of voltage-gated sodium, potassium and calcium channels, or acetylcholine- and glycine-gated channels. Some kidney disorders, e.g., Bartter's syndrome, policystic kidney disease and Dent's disease, secretion disorders, e.g., hyperinsulinemic hypoglycemia of infancy and cystic fibrosis, vision disorders, e.g., congenital stationary night blindness and total colour-blindness may also be linked to mutations in ion channels.

  14. Defect Distributions in Channeling Experiments

    DEFF Research Database (Denmark)

    Andersen, Hans Henrik; Sigmund, P.


    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 of radiat......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...... of radiation damage by channeled particles. As an application, one gets a necessary criterion for the occurence of super tails in channeling experiments. The theory involves some assumptions on the behaviour of Born-Mayer potentials which are verified by comparison to experimental displacement energies....

  15. Unifying Theories of Mobile Channels

    Directory of Open Access Journals (Sweden)

    Gerard Ekembe Ngondi


    Full Text Available In this paper we present the denotational semantics for channel mobility in the Unifying Theories of Programming (UTP semantics framework. The basis for the model is the UTP theory of reactive processes (precisely, the UTP semantics for Communicating Sequential Processes (CSP, which is slightly extended to allow the mobility of channels: the set of actions in which a process is authorised to participate, originally static or constant (set during the process's definition, is now made dynamic or variable: it can change during the process's execution. A channel is thus moved around by communicating it via other channels and then allowing the receiving process to extend its alphabet with the received channel. New healthiness conditions are stated to ensure an appropriate use of mobile channels.

  16. An Apical-Membrane Chloride Channel in Human Tracheal Epithelium (United States)

    Welsh, Michael J.


    The mechanism of chloride transport by airway epithelia has been of substantial interest because airway and sweat gland-duct epithelia are chloride-impermeable in cystic fibrosis. The decreased chloride permeability prevents normal secretion by the airway epithelium, thereby interfering with mucociliary clearance and contributing to the morbidity and mortality of the disease. Because chloride secretion depends on and is regulated by chloride conductance in the apical cell membrane, the patch-clamp technique was used to directly examine single-channel currents in primary cultures of human tracheal epithelium. The cells contained an anion-selective channel that was not strongly voltage-gated or regulated by calcium in cell-free patches. The channel was also blocked by analogs of carboxylic acid that decrease apical chloride conductance in intact epithelia. When attached to the cell, the channel was activated by isoproterenol, although the channel was also observed to open spontaneously. However, in some cases, the channel was only observed after the patch was excised from the cell. These results suggest that this channel is responsible for the apical chloride conductance in airway epithelia.

  17. Flow splitting modifies the helical motion in submarine channels (United States)

    Islam, M. Ashraful; Imran, Jasim; Pirmez, Carlos; Cantelli, Alessandro


    Intricately meandering channels of various scales constitute a major morphological feature of the submarine slope and fan systems. These channels act as conduits of density-driven gravity underflows and in turn are shaped by these underflows. The relationship between channel curvature and the dynamics of sediment-laden underflows commonly known as turbidity current has been an enigma, and recently, a subject of controversy. This contribution unravels the flow field of turbidity current at submarine channel bends captured from large scale laboratory experiments. The experimental results show that a mildly sloping channel bank greatly enhances the tilt of the turbidity current-ambient water interface, so much so that the current completely separates from the convex or the inside bank. We also show that irrespective of the shape of the channel cross section, two cells of helical flow appear in confined submarine bend flow. The near-bed cell has a circulation pattern similar to that observed in fluvial channels; the other cell has an opposite sense of rotation. If, on the other hand, a portion of the flow detaches from the body of the current and spills to the concave or outside overbank area, the upper circulation cell becomes suppressed by the resulting lateral convection.

  18. Molecular basis of epithelial Ca2+ and Mg2+ transport: insights from the TRP channel family

    DEFF Research Database (Denmark)

    Dimke, Henrik Anthony; Hoenderop, Joost G J; Bindels, René J M


    potential (TRP) family identified several new ion channels acting as gatekeepers of Ca(2+) and Mg(2+) transport in these epithelia, greatly increasing our understanding of the molecular processes that facilitate the movement of these minerals. In the intestine, TRP channels contribute to the saturable...... active transcellular movement of divalent cations from the lumen into the enterocyte. Furthermore, in bone, TRPV channels play important roles by influencing the osteoclastic resorption process, thereby contributing importantly to overall bone mineral content. The divalent cation-permeable TRPV5 and TRPM......6 channels are located in the renal distal convolution, the main site of active transcellular Ca(2+) and Mg(2+) transport. The channels are regulated by a multitude of factors and hormones that contribute importantly to keeping the systemic concentrations of Ca(2+) and Mg(2+) within normal limits...

  19. Upgrading a marketing channels role

    Directory of Open Access Journals (Sweden)

    Tišma-Borota Ankica


    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.

  20. Calcium ion channel and epilepsy

    Institute of Scientific and Technical Information of China (English)

    Yudan Lü; Weihong Lin; Dihui Ma


    OBJECTIVE: To review the relationship between calcium ion channel and epilepsy for well investigating the pathogenesis of epilepsy and probing into the new therapeutic pathway of epilepsy.DATA SOURCES: A computer-based online research Calcium ion channel and epilepsy related articles published between January 1994 and December 2006 in the CKNI and Wanfang database with the key words of "calcium influxion, epilepsy, calcium-channel blocker". The language was limited to Chinese. At the same time,related articles published between January 1993 and December 2006 in Pubmed were searched for on online with the key words of "calcium influxion, epilepsy" in English.STUDY SELECTION: The materials were selected firstly. Inclusive criteria: ① Studies related to calcium ion channel and the pat1hogenesis of epilepsy. ② Studies on the application of calcium ion channel blocker in the treatment of epilepsy. Exclusive criteria: repetitive or irrelated studies.DATA EXTRACTION: According to the criteria, 123 articles were retrieved and 93 were excluded due to repetitive or irrelated studies. Altogether 30 articles met the inclusive criteria, 11 of them were about the structure and characters of calcium ion channel, 10 about calcium ion channel and the pathogenesis of epilepsy and 9 about calcium blocker and the treatment of epilepsy.DATA SYNTHESIS: Calcium ion channels mainly consist of voltage dependent calcium channel and receptor operated calcium channel. Depolarization caused by voltage gating channel-induced influxion is the pathological basis of epileptic attack, and it is found in many studies that many anti-epileptic drugs have potential and direct effect to rivalizing voltage-dependent calcium ion channel.CONCLUSION: Calcium influxion plays an important role in the seizure of epilepsy. Some calcium antagonists seen commonly are being tried in the clinical therapy of epilepsy that is being explored, not applied in clinical practice. If there are enough evidences to

  1. Single-channel kinetics of BK (Slo1 channels

    Directory of Open Access Journals (Sweden)

    Yanyan eGeng


    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.

  2. T-type Ca(2+) channel modulation by otilonium bromide. (United States)

    Strege, Peter R; Sha, Lei; Beyder, Arthur; Bernard, Cheryl E; Perez-Reyes, Edward; Evangelista, Stefano; Gibbons, Simon J; Szurszewski, Joseph H; Farrugia, Gianrico


    Antispasmodics are used clinically to treat a variety of gastrointestinal disorders by inhibition of smooth muscle contraction. The main pathway for smooth muscle Ca(2+) entry is through L-type channels; however, there is increasing evidence that T-type Ca(2+) channels also play a role in regulating contractility. Otilonium bromide, an antispasmodic, has previously been shown to inhibit L-type Ca(2+) channels and colonic contractile activity. The objective of this study was to determine whether otilonium bromide also inhibits T-type Ca(2+) channels. Whole cell currents were recorded by patch-clamp technique from HEK293 cells transfected with cDNAs encoding the T-type Ca(2+) channels, Ca(V)3.1 (alpha1G), Ca(V)3.2 (alpha1H), or Ca(V)3.3 (alpha1I) alpha subunits. Extracellular solution was exchanged with otilonium bromide (10(-8) to 10(-5) M). Otilonium bromide reversibly blocked all T-type Ca(2+) channels with a significantly greater affinity for Ca(V)3.3 than Ca(V)3.1 or Ca(V)3.2. Additionally, the drug slowed inactivation in Ca(V)3.1 and Ca(V)3.3. Inhibition of T-type Ca(2+) channels may contribute to inhibition of contractility by otilonium bromide. This may represent a new mechanism of action for antispasmodics and may contribute to the observed increased clinical effectiveness of antispasmodics compared with selective L-type Ca(2+) channel blockers.

  3. T-type Ca2+ channel modulation by otilonium bromide (United States)

    Strege, Peter R.; Sha, Lei; Beyder, Arthur; Bernard, Cheryl E.; Perez-Reyes, Edward; Evangelista, Stefano; Gibbons, Simon J.; Szurszewski, Joseph H.


    Antispasmodics are used clinically to treat a variety of gastrointestinal disorders by inhibition of smooth muscle contraction. The main pathway for smooth muscle Ca2+ entry is through L-type channels; however, there is increasing evidence that T-type Ca2+ channels also play a role in regulating contractility. Otilonium bromide, an antispasmodic, has previously been shown to inhibit L-type Ca2+ channels and colonic contractile activity. The objective of this study was to determine whether otilonium bromide also inhibits T-type Ca2+ channels. Whole cell currents were recorded by patch-clamp technique from HEK293 cells transfected with cDNAs encoding the T-type Ca2+ channels, CaV3.1 (α1G), CaV3.2 (α1H), or CaV3.3 (α1I) alpha subunits. Extracellular solution was exchanged with otilonium bromide (10−8 to 10−5 M). Otilonium bromide reversibly blocked all T-type Ca2+ channels with a significantly greater affinity for CaV3.3 than CaV3.1 or CaV3.2. Additionally, the drug slowed inactivation in CaV3.1 and CaV3.3. Inhibition of T-type Ca2+ channels may contribute to inhibition of contractility by otilonium bromide. This may represent a new mechanism of action for antispasmodics and may contribute to the observed increased clinical effectiveness of antispasmodics compared with selective L-type Ca2+ channel blockers. PMID:20203058

  4. Capacities of quantum amplifier channels (United States)

    Qi, Haoyu; Wilde, Mark M.


    Quantum amplifier channels are at the core of several physical processes. Not only do they model the optical process of spontaneous parametric down-conversion, but the transformation corresponding to an amplifier channel also describes the physics of the dynamical Casimir effect in superconducting circuits, the Unruh effect, and Hawking radiation. Here we study the communication capabilities of quantum amplifier channels. Invoking a recently established minimum output-entropy theorem for single-mode phase-insensitive Gaussian channels, we determine capacities of quantum-limited amplifier channels in three different scenarios. First, we establish the capacities of quantum-limited amplifier channels for one of the most general communication tasks, characterized by the trade-off between classical communication, quantum communication, and entanglement generation or consumption. Second, we establish capacities of quantum-limited amplifier channels for the trade-off between public classical communication, private classical communication, and secret key generation. Third, we determine the capacity region for a broadcast channel induced by the quantum-limited amplifier channel, and we also show that a fully quantum strategy outperforms those achieved by classical coherent-detection strategies. In all three scenarios, we find that the capacities significantly outperform communication rates achieved with a naive time-sharing strategy.

  5. Genetic Control of Potassium Channels. (United States)

    Amin, Ahmad S; Wilde, Arthur A M


    Approximately 80 genes in the human genome code for pore-forming subunits of potassium (K(+)) channels. Rare variants (mutations) in K(+) channel-encoding genes may cause heritable arrhythmia syndromes. Not all rare variants in K(+) channel-encoding genes are necessarily disease-causing mutations. Common variants in K(+) channel-encoding genes are increasingly recognized as modifiers of phenotype in heritable arrhythmia syndromes and in the general population. Although difficult, distinguishing pathogenic variants from benign variants is of utmost importance to avoid false designations of genetic variants as disease-causing mutations.

  6. Geometric pumping in autophoretic channels

    CERN Document Server

    Michelin, Sebastien; De Canio, Gabriele; Lobato-Dauzier, Nicolas; Lauga, Eric


    Many microfluidic devices use macroscopic pressure differentials to overcome viscous friction and generate flows in microchannels. In this work, we investigate how the chemical and geometric properties of the channel walls can drive a net flow by exploiting the autophoretic slip flows induced along active walls by local concentration gradients of a solute species. We show that chemical patterning of the wall is not required to generate and control a net flux within the channel, rather channel geometry alone is sufficient. Using numerical simulations, we determine how geometric characteristics of the wall influence channel flow rate, and confirm our results analytically in the asymptotic limit of lubrication theory.

  7. TRP channels and psychiatric disorders. (United States)

    Chahl, Loris A


    Depression and schizophrenia are major psychiatric disorders that cause much human suffering. Current treatments have major limitations and new drug targets are eagerly sought. Study of transient receptor potential (TRP) channels in these disorders is at an early stage and the potential of agents that activate or inhibit these channels remains speculative. The findings that TRPC6 channels promote dendritic growth and are selectively activated by hyperforin, the key constitutent of St John's wort, suggest that TRPC6 channels might prove to be a new target for antidepressant drug development. There is now considerable evidence that TRPV1 antagonists have anxiolytic activity but there is no direct evidence that they have antidepressant activity. There is also no direct evidence that TRP channels play a role in schizophrenia. However, the findings that TRPC channels are involved in neuronal development and fundamental synaptic mechanisms, and that TRPV1 channels play a role in central dopaminergic and cannabinoid mechanisms is suggestive of potential roles of these channels in schizophrenia. Investigation of TRP channels in psychiatric disorders holds the promise of yielding further understanding of the aetiology of psychiatric disorders and the development of new drug treatments.

  8. Demystifying Mechanosensitive Piezo Ion Channels. (United States)

    Xu, X Z Shawn


    Mechanosensitive channels mediate touch, hearing, proprioception, and blood pressure regulation. Piezo proteins, including Piezo1 and Piezo2, represent a new class of mechanosensitive channels that have been reported to play key roles in most, if not all, of these modalities. The structural architecture and molecular mechanisms by which Piezos act as mechanosensitive channels, however, remain mysterious. Two new studies have now provided critical insights into the atomic structure and molecular basis of the ion permeation and mechano-gating properties of the Piezo1 channel.

  9. Ion channels generating complex spikes in cartwheel cells of the dorsal cochlear nucleus. (United States)

    Kim, Yuil; Trussell, Laurence O


    Cartwheel cells are glycinergic interneurons that modify somatosensory input to the dorsal cochlear nucleus. They are characterized by firing of mixtures of both simple and complex action potentials. To understand what ion channels determine the generation of these two types of spike waveforms, we recorded from cartwheel cells using the gramicidin perforated-patch technique in brain slices of mouse dorsal cochlear nucleus and applied channel-selective blockers. Complex spikes were distinguished by whether they arose directly from a negative membrane potential or later during a long depolarization. Ca(2+) channels and Ca(2+)-dependent K(+) channels were major determinants of complex spikes. Onset complex spikes required T-type and possibly R-type Ca(2+) channels and were shaped by BK and SK K(+) channels. Complex spikes arising later in a depolarization were dependent on P/Q- and L-type Ca(2+) channels as well as BK and SK channels. BK channels also contributed to fast repolarization of simple spikes. Simple spikes featured an afterdepolarization that is probably the trigger for complex spiking and is shaped by T/R-type Ca(2+) and SK channels. Fast spikes were dependent on Na(+) channels; a large persistent Na(+) current may provide a depolarizing drive for spontaneous activity in cartwheel cells. Thus the diverse electrical behavior of cartwheel cells is determined by the interaction of a wide variety of ion channels with a prominent role played by Ca(2+).

  10. The M2 Channel

    DEFF Research Database (Denmark)

    Santner, Paul

    and inhibition mechanisms, drug design studies were recently able to achieve successes in finding new potent inhibitors, some of which are even able to inhibit resistant M2 variants. Effective and robust methods for measuring M2 activity on the other hand are still scarce and tactics to assess the genetic...... barrier of new inhibitors as well as resistance development non-existent. Therefore we developed a fluorescence sensor based assay that directly measures proton conduction (pHlux assay) and combined it with an already established directed evolution selection and screening system of M2 to identify possible...... resistance escape routes from drug inhibition. We thereby were hopefully able to provide a platform for the large-scale evaluation of M2 channel activity, inhibitors and resistance....

  11. Channel Floor Yardangs (United States)


    [figure removed for brevity, see original site] Released 19 July 2004 The atmosphere of Mars is a dynamic system. Water-ice clouds, fog, and hazes can make imaging the surface from space difficult. Dust storms can grow from local disturbances to global sizes, through which imaging is impossible. Seasonal temperature changes are the usual drivers in cloud and dust storm development and growth. Eons of atmospheric dust storm activity has left its mark on the surface of Mars. Dust carried aloft by the wind has settled out on every available surface; sand dunes have been created and moved by centuries of wind; and the effect of continual sand-blasting has modified many regions of Mars, creating yardangs and other unusual surface forms. The yardangs in this image are forming in channel floor deposits. The channel itself is funneling the wind to cause the erosion. Image information: VIS instrument. Latitude 4.5, Longitude 229.7 East (133.3 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

  12. The Discovery Channel Telescope (United States)

    Millis, R. L.; Dunham, E. W.; Sebring, T. A.; Smith, B. W.; de Kock, M.; Wiecha, O.


    The Discovery Channel Telescope (DCT) is a 4.2-m telescope to be built at a new site near Happy Jack, Arizona. The DCT features a large prime focus mosaic CCD camera with a 2-degree-diameter field of view especially designed for surveys of KBOs, Centaurs, NEAs and other moving or time-variable targets. The telescope can be switched quickly to a Ritchey-Chretien configuration for optical/IR spectroscopy or near-IR imaging. This flexibility allows timely follow-up physical studies of high priority objects discovered in survey mode. The ULE (ultra-low-expansion) meniscus primary and secondary mirror blanks for the telescope are currently in fabrication by Corning Glass. Goodrich Aerospace, Vertex RSI, M3 Engineering and Technology Corp., and e2v Technologies have recently completed in-depth conceptual design studies of the optics, mount, enclosure, and mosaic focal plane, respectively. The results of these studies were subjected to a formal design review in July, 2004. Site testing at the 7760-ft altitude Happy Jack site began in 2001. Differential image motion observations from 117 nights since January 1, 2003 gave median seeing of 0.84 arcsec FWHM, and the average of the first quartile was 0.62 arcsec. The National Environmental Policy Act (NEPA) process for securing long-term access to this site on the Coconino National Forest is nearing completion and ground breaking is expected in the spring of 2005. The Discovery Channel Telescope is a project of the Lowell Observatory with major financial support from Discovery Communications, Inc. (DCI). DCI plans ongoing television programming featuring the construction of the telescope and the research ultimately undertaken with the DCT. An additional partner can be accommodated in the project. Interested parties should contact the lead author.

  13. Zinc transporters and dysregulated channels in cancers (United States)

    Pan, Zui; Choi, Sangyong; Ouadid-Ahidouch, Halima; Yang, Jin-Ming; Beattie, John H.; Korichneva, Irina


    As a nutritionally essential metal ion, zinc (Zn) not only constitutes a structural element for more than 3000 proteins but also plays important regulatory functions in cellular signal transduction. Zn homeostasis is tightly controlled by regulating the flux of Zn across cell membranes through specific transporters, i.e. ZnT and ZIP family proteins. Zn deficiency and malfunction of Zn transporters have been associated with many chronic diseases including cancer. However, the mechanisms underlying Zn regulatory functions in cellular signaling and their impact on the pathogenesis and progression of cancers remain largely unknown. In addition to these acknowledged multifunctions, Zn modulates a wide range of ion channels that in turn may also play an important role in cancer biology. The goal of this review is to propose how zinc deficiency, through modified Zn homeostasis, transporter activity and the putative regulatory function of Zn can influence ion channel activity, and thereby contribute to carcinogenesis and tumorigenesis. This review intends to stimulate interest in, and support for research into the understanding of Zn-modulated channels in cancers, and to search for novel biomarkers facilitating effective clinical stratification of high risk cancer patients as well as improved prevention and therapy in this emerging field. PMID:27814637

  14. Negative particle planar and axial channeling and channeling collimation

    Energy Technology Data Exchange (ETDEWEB)

    Carrigan, Richard A., Jr.; /Fermilab


    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. Preservation of meandering river channels in uniformly aggrading channel belts

    NARCIS (Netherlands)

    van de Lageweg, W.I.; Schuurman, F.; Cohen, K.M.; van Dijk, W. M.; Shimizu, Y.; Kleinhans, M.G.


    Channel belt deposits from meandering river systems commonly display an internal architecture of stacked depositional features with scoured basal contacts due to channel and bedform migration across a range of scales. Recognition and correct interpretation of these bounding surfaces is essential to


    Institute of Scientific and Technical Information of China (English)

    K. H. Sayhood; Wu Lenan


    A method of coherent detection and channel estimation for punctured convolutional coded binary Quadrature Amplitude Modulation (QAM) signals transmitted over a frequency-flat Rayleigh fading channels used for a digital radio broadcasting transmission is presented. Some known symbols are inserted in the encoded data stream to enhance the channel estimation process.The pilot symbols are used to replace the existing parity symbols so no bandwidth expansion is required. An iterative algorithm that uses decoding information as well as the information contained in the known symbols is used to improve the channel parameter estimate. The scheme complexity grows exponentially with the channel estimation filter length. The performance of the system is compared for a normalized fading rate with both perfect coherent detection (corresponding to a perfect knowledge of the fading process and noise variance) and differential detection of Differential Amplitude Phase Shift Keying (DAPSK). The tradeoff between simplicity of implementation and bit-error-rate performance of different techniques is also compared.

  17. Aperiodic Linear Networked Control Considering Variable Channel Delays: Application to Robots Coordination (+ supplementary file)

    NARCIS (Netherlands)

    Santos, C.; Espinosa, F.; Santiso, E.; Mazo, M.


    One of the main challenges in wireless cyber-physical systems is to reduce the load of the communication channel while preserving the control performance. In this way, communication resources are liberated for other applications sharing the channel bandwidth. The main contribution of this work is th

  18. Estimation of MIMO channel capacity from phase-noise impaired measurements

    DEFF Research Database (Denmark)

    Pedersen, Troels; Yin, Xuefeng; Fleury, Bernard Henri


    phase noise samples affecting measurement samples collected with real TDMMIMO channel sounders are correlated. In this contribution a capacity estimator that accounts for the phase noise correlation is proposed. The estimator is based on a linear minimum mean square error estimate of the MIMO channel...

  19. Tactile Sensitivity of Children: Effects of Frequency, Masking, and the Non-Pacinian I Psychophysical Channel (United States)

    Guclu, Burak; Oztek, Cigdem


    Tactile perception depends on the contributions of four psychophysical tactile channels mediated by four corresponding receptor systems. The sensitivity of the tactile channels is determined by detection thresholds that vary as a function of the stimulus frequency. It has been widely reported that tactile thresholds increase (i.e., sensitivity…

  20. Tactile Sensitivity of Children: Effects of Frequency, Masking, and the Non-Pacinian I Psychophysical Channel (United States)

    Guclu, Burak; Oztek, Cigdem


    Tactile perception depends on the contributions of four psychophysical tactile channels mediated by four corresponding receptor systems. The sensitivity of the tactile channels is determined by detection thresholds that vary as a function of the stimulus frequency. It has been widely reported that tactile thresholds increase (i.e., sensitivity…

  1. Aperiodic Linear Networked Control Considering Variable Channel Delays: Application to Robots Coordination (+ supplementary file)

    NARCIS (Netherlands)

    Santos, C.; Espinosa, F.; Santiso, E.; Mazo, M.


    One of the main challenges in wireless cyber-physical systems is to reduce the load of the communication channel while preserving the control performance. In this way, communication resources are liberated for other applications sharing the channel bandwidth. The main contribution of this work is

  2. Mirrored serpentine flow channels for fuel cell

    Energy Technology Data Exchange (ETDEWEB)

    Rock, Jeffrey Allan (Rochester, NY)


    A PEM fuel cell having serpentine flow field channels wherein the input/inlet legs of each channel border the input/inlet legs of the next adjacent channels in the same flow field, and the output/exit legs of each channel border the output/exit legs of the next adjacent channels in the same flow field. The serpentine fuel flow channels may be longer, and may contain more medial legs, than the serpentine oxidant flow channels.

  3. Polarization for arbitrary discrete memoryless channels


    Sasoglu, Eren; Telatar, Emre; Arikan, Erdal


    Channel polarization, originally proposed for binary-input channels, is generalized to arbitrary discrete memoryless channels. Specifically, it is shown that when the input alphabet size is a prime number, a similar construction to that for the binary case leads to polarization. This method can be extended to channels of composite input alphabet sizes by decomposing such channels into a set of channels with prime input alphabet sizes. It is also shown that all discrete memoryless channels can...

  4. Task 1 Steam Oxidation (NETL-US)

    Energy Technology Data Exchange (ETDEWEB)

    Holcomb, Gordon R. [NETL; Carney, Casey [URS


    A first high pressure test was completed: 293 hr at 267 bar and 670{degrees}C; A parallel 1 bar test was done for comparison; Mass gains were higher for all alloys at 267 bar than at 1 bar; Longer term exposures, over a range of temperatures and pressures, are planned to provide information as to the commercial implications of pressure effects; The planned tests are at a higher combination of temperatures and pressures than in the existing literature. A comparison was made with longer-term literature data: The short term exposures are largely consistent with the longer-term corrosion literature; Ferritic steels--no consistent pressure effect; Austenitic steels--fine grain alloys less able to maintain protective chromia scale as pressure increases; Ni-base alloys--more mass gains above 105 bar than below. Not based on many data points.

  5. International data collection and analysis. Task 1

    Energy Technology Data Exchange (ETDEWEB)

    Fox, J.B.; Stobbs, J.J.; Collier, D.M.; Hobbs, J.S.


    Commercial nuclear power has grown to the point where 13 nations now operate commercial nuclear power plants. Another four countries should join this list before the end of 1980. In the Nonproliferation Alternative Systems Assessment Program (NASAP), the US DOE is evaluating a series of alternate possible power systems. The objective is to determine practical nuclear systems which could reduce proliferation risk while still maintaining the benefits of nuclear power. Part of that effort is the development of a data base denoting the energy needs, resources, technical capabilities, commitment to nuclear power, and projected future trends for various non-US countries. The data are presented by country for each of 28 non-US counries. Data are compiled in this volume on Canada, Egypt, Federal Republic of Germany, Finland, and France.

  6. Task 1 Steam Oxidation (NETL-US)

    Energy Technology Data Exchange (ETDEWEB)

    Holcomb, Gordon R. [NETL; Carney, Casey [URS


    A first high pressure test was completed: 293 hr at 267 bar and 670{degrees}C; A parallel 1 bar test was done for comparison; Mass gains were higher for all alloys at 267 bar than at 1 bar; Longer term exposures, over a range of temperatures and pressures, are planned to provide information as to the commercial implications of pressure effects; The planned tests are at a higher combination of temperatures and pressures than in the existing literature. A comparison was made with longer-term literature data: The short term exposures are largely consistent with the longer-term corrosion literature; Ferritic steels--no consistent pressure effect; Austenitic steels--fine grain alloys less able to maintain protective chromia scale as pressure increases; Ni-base alloys--more mass gains above 105 bar than below. Not based on many data points.

  7. Task 1 Steam Oxidation (NETL-US)

    Energy Technology Data Exchange (ETDEWEB)

    G. R. Holcomb; J. Tylczak; R. Hu,


    Some conclusions are: (1) Increased flow rates can lower chromia activity in alloys with Ti and Mn - (a) Reduced chromia activity reduces equilibrium CrO{sub 2}(OH){sub 2}(g) vapor pressures; (2) Model is very sensitive to small decreases in chromia activity at the HP turbine - (a) Upstream partial saturation of the gas phase with CrO{sub 2}(OH){sub 2}(g) can become nearly or fully saturated at the HP turbine, (b) Can radically change breakaway oxidation times from less than a year to never happening; and (3) Thus even small chromia activity reductions from Ti and Mn additions can make evaporation issues self-correcting.

  8. International data collection and analysis. Task 1

    Energy Technology Data Exchange (ETDEWEB)


    Commercial nuclear power has grown to the point where 13 nations now operate commercial nuclear power plants. Another four countries should join this list before the end of 1980. In the Nonproliferation Alternative Systems Assessment Program (NASAP), the US DOE is evaluating a series of alternate possible power systems. The objective is to determine practical nuclear systems which could reduce proliferation risk while still maintaining the benefits of nuclear power. Part of that effort is the development of a data base denoting the energy needs, resources, technical capabilities, commitment to nuclear power, and projected future trends for various non-US countries. The data are presented by country for each of 28 non-US countries. This volume contains compiled data on Mexico, Netherlands, Pakistan, Philippines, South Africa, South Korea, and Spain.

  9. Littoral steering of deltaic channels (United States)

    Nienhuis, Jaap H.; Ashton, Andrew D.; Giosan, Liviu


    The typically single-threaded channels on wave-influenced deltas show striking differences in their orientations, with some channels oriented into the incoming waves (e.g., Ombrone, Krishna), and others oriented away from the waves (e.g., Godavari, Sao Francisco). Understanding the controls on channel orientation is important as the channel location greatly influences deltaic morphology and sedimentology, both subaerially and subaqueously. Here, we explore channel orientation and consequent feedbacks with local shoreline dynamics using a plan-form numerical model of delta evolution. The model treats fluvial sediment delivery to a wave-dominated coast in two ways: 1) channels are assumed to prograde in a direction perpendicular to the local shoreline orientation and 2) a controlled fraction of littoral sediment transport can bypass the river mouth. Model results suggest that channels migrate downdrift when there is a significant net littoral transport and alongshore transport bypassing of the river mouth is limited. In contrast, river channels tend to orient themselves into the waves when fluvial sediment flux is relatively large, causing the shoreline of the downdrift delta flank to attain the orientation of maximum potential sediment transport for the incoming wave climate. Using model results, we develop a framework to estimate channel orientations for wave-influenced deltas that shows good agreement with natural examples. An increase in fluvial sediment input can cause a channel to reorient itself into incoming waves, behavior observed, for example, in the Ombrone delta in Italy. Our results can inform paleoclimate studies by linking channel orientation to fluvial sediment flux and wave energy. In particular, our approach provides a means to quantify past wave directions, which are notoriously difficult to constrain.

  10. Contributions to industrial statistics



    This thesis is about statistics' contributions to industry. It is an article compendium comprising four articles divided in two blocks: (i) two contributions for a water supply company, and (ii) significance of the effects in Design of Experiments. In the first block, great emphasis is placed on how the research design and statistics can be applied to various real problems that a water company raises and it aims to convince water management companies that statistics can be very useful to impr...

  11. The ion channels to cytoskeleton connection as potential mechanism of mechanosensitivity. (United States)

    Martinac, Boris


    As biological force-sensing systems mechanosensitive (MS) ion channels present the best example of coupling molecular dynamics of membrane proteins to the mechanics of the surrounding cell membrane. In animal cells MS channels have over the past two decades been very much in focus of mechanotransduction research. In recent years this helped to raise awareness of basic and medical researchers about the role that abnormal MS channels may play in the pathophysiology of diseases, such as cardiac hypertrophy, atrial fibrillation, muscular dystrophy or polycystic kidney disease. To date a large number of MS channels from organisms of diverse phylogenetic origins have been identified at the molecular level; however, the structure of only few of them has been determined. Although their function has extensively been studied in a great variety of cells and tissues by different experimental approaches it is, with exception of bacterial MS channels, very little known about how these channels sense mechanical force and which cellular components may contribute to their function. By focusing on MS channels found in animal cells this article discusses the ways in which the connections between cytoskeleton and ion channels may contribute to mechanosensory transduction in these cells. This article is part of a Special Issue entitled: Reciprocal influences between cell cytoskeleton and membrane channels, receptors and transporters. This article is part of a Special Issue entitled: Reciprocal influences between cell cytoskeleton and membrane channels, receptors and transporters. Guest Editor: Jean Claude Hervé.

  12. Perceived quality of channel zapping

    NARCIS (Netherlands)

    Kooij, R.E.; Ahmed, K.; Brunnström, K.


    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

  13. Hydraulic jumps in a channel

    DEFF Research Database (Denmark)

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


    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...

  14. An improved channel assessment scheme

    KAUST Repository

    Bader, Ahmed


    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.

  15. Channel Communication and Reconfigurable Hardware

    NARCIS (Netherlands)

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


    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

  16. Bluetooth command and control channel

    CSIR Research Space (South Africa)

    Pieterse, H


    Full Text Available &C channel is executed in a controlled environment using the Android operating system as a development platform. The results show that a physical Bluetooth C&C channel is indeed possible and the paper concludes by identifying potential strengths...

  17. Channel's Concurrence and Quantum Teleportation

    Institute of Scientific and Technical Information of China (English)

    LING Yin-Sheng


    Concurrence can measure the entanglement property of a system. If the channel is a pure state, positive concurrence state can afford the good performance in the teleportation process. If the channel ia a mixed state, positive concurrence state cannot assure the good performance in the teleportation. The conditions of the positive concurrence and the quantum teleportation in the Heisenberg spin ring is derived.

  18. Channelling, a new immunization strategy. (United States)

    Gacharna Romero, M G; Silva Pizano, E; Avendano Lamo, J


    In 1981, with PAHO/WHO technical assistance, the Ministry of Health, Colombia, designed what is known as the channelling strategy, aimed at improving immunization coverage. This name was given because the strategy is designed to establish communication channels through direct action aimed at promoting health. Health workers and community leaders or guides conduct household visits to identify unvaccinated children or those with incomplete vaccination schedules and "channel" them to health centers or health posts. The channelling strategy developed in Colombia was briefly mentioned in the case study on the Colombian Vaccination Crusade of 1984. It is now being employed for ORT and other PHC components in the Colombian Child Survival and Development Plan, 1985-1987. In the meantime, other countries have adopted the channelling strategy, which is described in this article.

  19. Quantum channel capacities - multiparty communication

    CERN Document Server

    Demianowicz, M; Demianowicz, Maciej; Horodecki, Pawel


    We analyze different aspects of multiparty communication over quantum memoryless channels and generalize some of key results known from bipartite channels to that of multiparty scenario. In particular, we introduce multiparty versions of minimal subspace transmission fidelity and entanglement transmission fidelity. We also provide alternative, local, versions of fidelities and show their equivalence to the global ones in context of capacity regions defined. The equivalence of two different capacity notions with respect to two types of the fidelities is proven. In analogy to bipartite case it is shown, via sufficiency of isometric encoding theorem, that additional classical forward side channel does not increase capacity region of any quantum channel with $k$ senders and $m$ receivers which represents a compact unit of general quantum networks theory. The result proves that recently provided capacity region of multiple access channel ([M. Horodecki et al, Nature {\\bf 436} 673 (2005)], [J.Yard et al, quant-ph/0...

  20. Gender Representation on Gender-Targeted Television Channels: A Comparison of Female- and Male-Targeted TV Channels in the Netherlands. (United States)

    Daalmans, Serena; Kleemans, Mariska; Sadza, Anne


    The current study investigated the differences in the representation of gender on male- and female-targeted channels with regard to recognition (i.e., the actual presence of men and women) and respect (i.e., the nature of that representation or portrayal). To this end, the presence of men and women on two female- and two male-targeted Dutch channels (N = 115 programs, N = 1091 persons) were compared via content analysis. The expectation that men's channels would portray a less equal and more traditional image of gender than women's channels was generally supported by the results. Regardless of genre as well as country of origin of the program, women were underrepresented on men's channels, while gender distribution on women's channels was more equal. The representation of women in terms of age and occupation was more stereotypical on men's channels than on women's channels, whereas men were represented in more contra-stereotypical ways (e.g., performing household tasks) on women's channels. Since television viewing contributes to the learning and maintenance of stereotyped perceptions, the results imply that it is important to strengthen viewers' defenses against the effects of gender stereotyping when watching gendered television channels, for instance through media literacy programs in schools.

  1. The Wiretap Channel with Feedback: Encryption over the Channel

    CERN Document Server

    Lai, Lifeng; Poor, H Vincent


    In this work, the critical role of noisy feedback in enhancing the secrecy capacity of the wiretap channel is established. Unlike previous works, where a noiseless public discussion channel is used for feedback, the feed-forward and feedback signals share the same noisy channel in the present model. Quite interestingly, this noisy feedback model is shown to be more advantageous in the current setting. More specifically, the discrete memoryless modulo-additive channel with a full-duplex destination node is considered first, and it is shown that the judicious use of feedback increases the perfect secrecy capacity to the capacity of the source-destination channel in the absence of the wiretapper. In the achievability scheme, the feedback signal corresponds to a private key, known only to the destination. In the half-duplex scheme, a novel feedback technique that always achieves a positive perfect secrecy rate (even when the source-wiretapper channel is less noisy than the source-destination channel) is proposed....

  2. Voltage-gated Proton Channels (United States)

    DeCoursey, Thomas E.


    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

  3. TRPC6 channel translocation into phagosomal membrane augments phagosomal function (United States)

    Riazanski, Vladimir; Gabdoulkhakova, Aida G.; Boynton, Lin S.; Eguchi, Raphael R.; Deriy, Ludmila V.; Hogarth, D. Kyle; Loaëc, Nadège; Oumata, Nassima; Galons, Hervé; Brown, Mary E.; Shevchenko, Pavel; Gallan, Alexander J.; Yoo, Sang Gune; Naren, Anjaparavanda P.; Villereal, Mitchel L.; Beacham, Daniel W.; Bindokas, Vytautas P.; Birnbaumer, Lutz; Meijer, Laurent; Nelson, Deborah J.


    Defects in the innate immune system in the lung with attendant bacterial infections contribute to lung tissue damage, respiratory insufficiency, and ultimately death in the pathogenesis of cystic fibrosis (CF). Professional phagocytes, including alveolar macrophages (AMs), have specialized pathways that ensure efficient killing of pathogens in phagosomes. Phagosomal acidification facilitates the optimal functioning of degradative enzymes, ultimately contributing to bacterial killing. Generation of low organellar pH is primarily driven by the V-ATPases, proton pumps that use cytoplasmic ATP to load H+ into the organelle. Critical to phagosomal acidification are various channels derived from the plasma membrane, including the anion channel cystic fibrosis transmembrane conductance regulator, which shunt the transmembrane potential generated by movement of protons. Here we show that the transient receptor potential canonical-6 (TRPC6) calcium-permeable channel in the AM also functions to shunt the transmembrane potential generated by proton pumping and is capable of restoring microbicidal function to compromised AMs in CF and enhancement of function in non-CF cells. TRPC6 channel activity is enhanced via translocation to the cell surface (and then ultimately to the phagosome during phagocytosis) in response to G-protein signaling activated by the small molecule (R)-roscovitine and its derivatives. These data show that enhancing vesicular insertion of the TRPC6 channel to the plasma membrane may represent a general mechanism for restoring phagosome activity in conditions, where it is lost or impaired. PMID:26604306

  4. Based on Channel Characteristics

    Directory of Open Access Journals (Sweden)

    Zhuo Hao


    Full Text Available A number of key agreement schemes based on wireless channel characteristics have been proposed recently. However, previous key agreement schemes require that two nodes which need to agree on a key are within the communication range of each other. Hence, they are not suitable for multihop wireless networks, in which nodes do not always have direct connections with each other. In this paper, we first propose a basic multihop key agreement scheme for wireless ad hoc networks. The proposed basic scheme is resistant to external eavesdroppers. Nevertheless, this basic scheme is not secure when there exist internal eavesdroppers or Man-in-the-Middle (MITM adversaries. In order to cope with these adversaries, we propose an improved multihop key agreement scheme. We show that the improved scheme is secure against internal eavesdroppers and MITM adversaries in a single path. Both performance analysis and simulation results demonstrate that the improved scheme is efficient. Consequently, the improved key agreement scheme is suitable for multihop wireless ad hoc networks.

  5. Opening Channels of Communication

    Directory of Open Access Journals (Sweden)

    Clarice Moura Costa


    Full Text Available Psychosis, as described through a psychodynamic perspective, is conceptualized as an attempt to deny the enveloping reality to avoid contact with the other. Music therapy is a way to break this barrier of non-communication raised by the patients. The music therapy process is configured as a trinomial – action (making music/ relationship (action with the other/communication (musical or verbal voluntary expression of feelings and conflicts, which, although intrinsically connected, is perceived in a sequential process. Aulagnier asserts that psychic activity represents the conjunction of three modes of functioning: the original process, the primary process and the secondary process. The perception of sound passes through three phases, corresponding to each manner of functioning of the psychic system – the pleasure of hearing, the desire to listen (to the other and the imperative of meaning. The music therapy process offers a significant similarity with the theory proposed by Aulagnier. We propose the hypothesis that in music therapy, there is an opportunity to (reexperience very archaic phases in the constitution of the ego, but in a new manner, so helping to open communication channels. This theoretical hypothesis is illustrated by real examples of patients.

  6. Ergodic channel capacity of the spatial correlated rayleigh MIMO channel

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hui-ping; WU Ping; LIU Ai-jun


    The theoretical capacity of the spatial correlated Rayleigh multiple input multiple output (MIMO) channel is an important issue in MIMO technology. In this article, an ergodic channel capacity formula of the spatial correlated rayleigh MIMO channel is provided, which is deduced when two antennas exist at either the transmitter or the receiver. The multi-dimensional least-squares fit algorithm is employed to narrow the difference between the theoretical formula capacity and the practical capacity. Simulation results show that the theoretical capacity approaches the practical one closely.

  7. The Role of Potassium Channels in the Temperature Control of Stomatal Aperture. (United States)

    Ilan, N.; Moran, N.; Schwartz, A.


    We used the patch-clamp technique to examine the effect of temperature (13-36[deg]C) on the depolarization-activated K channels (KD channels) and on the hyperpolarization-activated channels (KH channels) in the plasma membrane of Vicia faba guard-cell protoplasts. The steady-state whole-cell conductance of both K channel types increased with temperature up to 20[deg]C. However, whereas the whole-cell conductance of the KH channels increased further and saturated at 28[deg]C, that of KD channels decreased at higher temperatures. The unitary conductance of both channel types increased with temperature like the rate of diffusion in water (temperature quotient of approximately 1.5), constituting the major contribution to the conductance increase in the whole cells. The mean number of available KH channels was not affected significantly by temperature, but the mean number of available KD channels increased significantly between 13 and 20[deg]C and declined drastically above 20[deg]C. This decrease and the reduced steady-state voltage-dependent probability of opening of the KD channels above 28[deg]C (because of a shift of voltage dependence by +21 mV) account for the depression of the whole-cell KD conductance at the higher temperatures. This may be a basic mechanism by which leaves of well-watered plants keep their stomata open during heat stress to promote cooling by transpiration.

  8. Functional expression of T-type Ca2+ channels in spinal motoneurons of the adult turtle.

    Directory of Open Access Journals (Sweden)

    Martha Canto-Bustos

    Full Text Available Voltage-gated Ca2+ (CaV channels are transmembrane proteins comprising three subfamilies named CaV1, CaV2 and CaV3. The CaV3 channel subfamily groups the low-voltage activated Ca2+ channels (LVA or T-type a significant role in regulating neuronal excitability. CaV3 channel activity may lead to the generation of complex patterns of action potential firing such as the postinhibitory rebound (PIR. In the adult spinal cord, these channels have been found in dorsal horn interneurons where they control physiological events near the resting potential and participate in determining excitability. In motoneurons, CaV3 channels have been found during development, but their functional expression has not yet been reported in adult animals. Here, we show evidence for the presence of CaV3 channel-mediated PIR in motoneurons of the adult turtle spinal cord. Our results indicate that Ni2+ and NNC55-0396, two antagonists of CaV3 channel activity, inhibited PIR in the adult turtle spinal cord. Molecular biology and biochemical assays revealed the expression of the CaV3.1 channel isotype and its localization in motoneurons. Together, these results provide evidence for the expression of CaV3.1 channels in the spinal cord of adult animals and show also that these channels may contribute to determine the excitability of motoneurons.

  9. Spatial and temporal variability in sedimentation rates associated with cutoff channel infill deposits: Ain River, France (United States)

    Piegay, H.; Hupp, C.R.; Citterio, A.; Dufour, S.; Moulin, B.; Walling, D.E.


    Floodplain development is associated with lateral accretion along stable channel geometry. Along shifting rivers, the floodplain sedimentation is more complex because of changes in channel position but also cutoff channel presence, which exhibit specific overflow patterns. In this contribution, the spatial and temporal variability of sedimentation rates in cutoff channel infill deposits is related to channel changes of a shifting gravel bed river (Ain River, France). The sedimentation rates estimated from dendrogeomorphic analysis are compared between and within 14 cutoff channel infills. Detailed analyses along a single channel infill are performed to assess changes in the sedimentation rates through time by analyzing activity profiles of the fallout radionuclides 137Cs and unsupported 210Pb. Sedimentation rates are also compared within the channel infills with rates in other plots located in the adjacent floodplain. Sedimentation rates range between 0.65 and 2.4 cm a -1 over a period of 10 to 40 years. The data provide additional information on the role of distance from the bank, overbank flow frequency, and channel geometry in controlling the sedimentation rate. Channel infills, lower than adjacent floodplains, exhibit higher sedimentation rates and convey overbank sediment farther away within the floodplain. Additionally, channel degradation, aggradation, and bank erosion, which reduce or increase the distance between the main channel and the cutoff channel aquatic zone, affect local overbank flow magnitude and frequency and therefore sedimentation rates, thereby creating a complex mosaic of sedimentation zones within the floodplain and along the cutoff channel infills. Last, the dendrogeomorphic and 137Cs approaches are cross validated for estimating the sedimentation rate within a channel infill. Copyright 2008 by the American Geophysical Union.

  10. Blockade of HERG channels by the class III antiarrhythmic azimilide: mode of action (United States)

    Busch, A E; Eigenberger, B; Jurkiewicz, N K; Salata, J J; Pica, A; Suessbrich, H; Lang, F


    The class III antiarrhythmic azimilide has previously been shown to inhibit IKs and IKr in guinea-pig cardiac myocytes and IKs (minK) channels expressed in Xenopus oocytes. Because HERG channels underly the conductance IKr in human heart, the effects of azimilide on HERG channels expressed in Xenopus oocytes were the focus of the present study.In contrast to other well characterized HERG channel blockers, azimilide blockade was reverse use-dependent, i.e., the relative block and apparent affinity of azimilide decreased with an increase in channel activation frequency. Azimilide blocked HERG channels at 0.1 and 1 Hz with IC50 s of 1.4 μM and 5.2  μM respectively.In an envelope of tail test, HERG channel blockade increased with increasing channel activation, indicating binding of azimilide to open channels.Azimilide blockade of HERG channels expressed in Xenopus oocytes and IKr in mouse AT-1 cells was decreased under conditions of high [K+]e, whereas block of slowly activating IKs channels was not affected by changes in [K+]e.In summary, azimilide is a blocker of cardiac delayed rectifier channels, IKs and HERG. Because of the distinct effects of stimulation frequency and [K+]e on azimilide block of IKr and IKs channels, we conclude that the relative contribution of block of each of these cardiac delayed rectifier channels depends on heart frequency. [K+]e and regulatory status of the respective channels. PMID:9484850

  11. Modeling Channelization in Coastal Wetlands with Ecological Feedbacks (United States)

    Hughes, Z. J.; Mahadevan, A.; Pennings, S.; FitzGerald, D.


    In coastal wetlands in Georgia and South Carolina, dendritic channel networks are actively incising headward at the rate of nearly 2 m/yr. The future geomorphic evolution of these marshes remains in question as rates of relative sea-level rise increase. Our objective is to understand the mechanisms that lead to the evolution of these channel networks through field observations and modeling. We model the geomorphological evolution of tidal creeks by viewing the wetland as a permeable medium. The porosity of the medium affects its hydraulic conductivity, which in turn is altered by erosion. Our multiphase model spontaneously generates channelization and branching networks through flow and erosion. In our field studies, we find that crabs play an active role in grazing vegetation and in the bioturbation of sediments. These effects are incorporated in our model based on field and laboratory observations of crab behavior and its effects on the marsh. We find the erosional patterns and channelization are significantly altered by the faunal feedback. Crabs enhance the growth of channels, inducing the headward erosion of creeks where flow-induced stresses are weakest. They are instrumental in generating high rates of creek extension, which channelize the marsh more effectively in response to sea-level rise. This indicates that the evolution of coastal wetlands is responding to interactions between physics and ecology and highlights the importance of the faunal contribution to these feedbacks.

  12. TRP channels in microglia: role in physiology and disease

    Directory of Open Access Journals (Sweden)

    Yolima P Torres


    Full Text Available Microglia are responsible for modulating the cellular environment in the nervous system, where they have neuroprotective effects. In these cells has been reported the expression of different ion channels, including those belonging to the transient receptor potential (TRP family. TRP are nonselective cation channels that have six transmembrane domains and both N-terminus and C-terminus domain located in the cytoplasm. These proteins can be activated by mechanical, thermal and chemical stimuli as well as pH changes. Their activation can induce calcium influx contributing to regulate the intracellular calcium concentration. Different studies describe the effect of TRP channels in cellular processes such as osmotic regulation, cytokine production, proliferation, activation, cell death and responses to oxidative stress. As a result, these channels have an important role in neurodegenerative diseases, ischemia, inflammatory responses and pain perception. Modulating the activity of the TRP channels can be a therapeutic target for various diseases associated with the central nervous system. In this review the most relevant aspects about the role of the TRP channels in the physiology of microglia and their potential use as a therapeutic target in central nervous system diseases will be described.

  13. Robust Beamforming in Interference Channels with Imperfect Transmitter Channel Information

    CERN Document Server

    Mochaourab, Rami


    We consider $K$ links operating concurrently in the same spectral band. Each transmitter has multiple antennas, while each receiver uses a single antenna. This setting corresponds to the multiple-input single-output interference channel. We assume perfect channel state information at the receivers whereas the transmitters only have estimates of the true channels. The channel estimation errors are assumed to be bounded in elliptical regions whose geometry is known at the transmitters. Robust beamforming optimizes worst-case received power gains, and a Pareto optimal point is a worst-case achievable rate tuple from which it is impossible to increase a link's performance without degrading the performance of another. We characterize the robust beamforming vectors necessary to operate at any Pareto optimal point. Moreover, these beamforming vectors are parameterized by $K(K-1)$ real-valued parameters. We analyze the system's spectral efficiency at high and low signal-to-noise ratio (SNR). Zero forcing transmission...

  14. Channel Coding in Random Access Communication over Compound Channels

    CERN Document Server

    Wang, Zheng


    Due to the short and bursty incoming messages, channel access activities in a wireless random access system are often fractional. The lack of frequent data support consequently makes it difficult for the receiver to estimate and track the time varying channel states with high precision. This paper investigates random multiple access communication over a compound wireless channel where channel realization is known neither at the transmitters nor at the receiver. An achievable rate and error probability tradeoff bound is derived under the non-asymptotic assumption of a finite codeword length. The results are then extended to the random multiple access system where the receiver is only interested in decoding messages from a user subset.

  15. Human and automatic speaker recognition over telecommunication channels

    CERN Document Server

    Fernández Gallardo, Laura


    This work addresses the evaluation of the human and the automatic speaker recognition performances under different channel distortions caused by bandwidth limitation, codecs, and electro-acoustic user interfaces, among other impairments. Its main contribution is the demonstration of the benefits of communication channels of extended bandwidth, together with an insight into how speaker-specific characteristics of speech are preserved through different transmissions. It provides sufficient motivation for considering speaker recognition as a criterion for the migration from narrowband to enhanced bandwidths, such as wideband and super-wideband.

  16. Ion channels in neuronal survival

    Institute of Scientific and Technical Information of China (English)


    The study of ion channels represents one of the most active fields in neuroscience research in China.In the last 10 years,active research in various Chinese neuroscience institutions has sought to understand the mechanisms responsible for sensory processing,neural development and neurogenesis,neural plasticity,as well as pathogenesis.In addition,extensive studies have been directed to measure ion channel activity,structure-function relationships,as well as many other biophysical and biochemical properties.This review focuses on the progress achieved in the investigation of ion channels in neuronal survival during the past 10 years in China.

  17. Skeletal Muscle Na+ Channel Disorders

    Directory of Open Access Journals (Sweden)

    Dina eSimkin


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

  18. Marine Toxins Targeting Ion Channels

    Directory of Open Access Journals (Sweden)

    Hugo R. Arias


    Full Text Available Abstract: This introductory minireview points out the importance of ion channels for cell communication. The basic concepts on the structure and function of ion channels triggered by membrane voltage changes, the so-called voltage-gated ion channels (VGICs, as well as those activated by neurotransmitters, the so-called ligand-gated ion channel (LGICs, are introduced. Among the most important VGIC superfamiles, we can name the voltage-gated Na+ (NaV, Ca2+ (CaV, and K+ (KV channels. Among the most important LGIC super families, we can include the Cys-loop or nicotinicoid, the glutamate-activated (GluR, and the ATP-activated (P2XnR receptor superfamilies. Ion channels are transmembrane proteins that allow the passage of different ions in a specific or unspecific manner. For instance, the activation of NaV, CaV, or KV channels opens a pore that is specific for Na+, Ca2+, or K+, respectively. On the other hand, the activation of certain LGICs such as nicotinic acetylcholine receptors, GluRs, and P2XnRs allows the passage of cations (e.g., Na+, K+, and/or Ca2+, whereas the activation of other LGICs such as type A γ-butyric acid and glycine receptors allows the passage of anions (e.g., Cl− and/or HCO3−. In this regard, the activation of NaV and CaV as well as ligand-gated cation channels produce membrane depolarization, which finally leads to stimulatory effects in the cell, whereas the activation of KV as well as ligand-gated anion channels induce membrane hyperpolarization that finally leads to inhibitory effects in the cell. The importance of these ion channel superfamilies is emphasized by considering their physiological functions throughout the body as well as their pathophysiological implicance in several neuronal diseases. In this regard, natural molecules, and especially marine toxins, can be potentially used as modulators (e.g., inhibitors or prolongers of ion channel functions to treat or to alleviate a specific

  19. Channel estimation in TDD mode

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yi; GU Jian; YANG Da-cheng


    An efficient solution is proposed in this article for the channel estimation in time division duplex (TDD) mode wireless communication systems. In the proposed solution, the characteristics of fading channels in TDD mode systems are fully exploited to estimate the path delay of the fading channel.The corresponding amplitude is estimated using the minimum mean square error (MMSE) criterion. As a result, it is shown that the proposed novel solution is more accurate and efficient than the traditional solution, and the improvement is beneficial to the performance of Joint Detection.

  20. Mutations Causing Slow-Channel Myasthenia Reveal That a Valine Ring in the Channel Pore of Muscle AChR is Optimized for Stabilizing Channel Gating. (United States)

    Shen, Xin-Ming; Okuno, Tatsuya; Milone, Margherita; Otsuka, Kenji; Takahashi, Koji; Komaki, Hirofumi; Giles, Elizabeth; Ohno, Kinji; Engel, Andrew G


    We identify two novel mutations in acetylcholine receptor (AChR) causing a slow-channel congenital myasthenia syndrome (CMS) in three unrelated patients (Pts). Pt 1 harbors a heterozygous βV266A mutation (p.Val289Ala) in the second transmembrane domain (M2) of the AChR β subunit (CHRNB1). Pts 2 and 3 carry the same mutation at an equivalent site in the ε subunit (CHRNE), εV265A (p.Val285Ala). The mutant residues are conserved across all AChR subunits of all species and are components of a valine ring in the channel pore, which is positioned four residues above the leucine ring. Both βV266A and εV265A reduce the amino acid size and lengthen the channel opening bursts by fourfold by enhancing gating efficiency by approximately 30-fold. Substitution of alanine for valine at the corresponding position in the δ and α subunit prolongs the burst duration four- and eightfold, respectively. Replacing valine at ε codon 265 either by a still smaller glycine or by a larger leucine also lengthens the burst duration. Our analysis reveals that each valine in the valine ring contributes to channel kinetics equally, and the valine ring has been optimized in the course of evolution to govern channel gating.

  1. Infinitely many kinds of quantum channels

    Energy Technology Data Exchange (ETDEWEB)

    Hastings, Matthew B [Los Alamos National Laboratory


    We define the ability of a quantum channel to simulate another by means of suitable encoding and decoding operations. While classical channels have only two equivalence classes under simulation (channels with non-vanishing capacity and those with vanishing capacity), we show that there are an uncountable infinity of different equivalence classes of quantum channels using the example of the quantum erasure channel. Our results also imply a kind of 'Matthew principle' for error correction on certain channels.

  2. Promotion through Marketing Channels : The Case of Kosovo

    Directory of Open Access Journals (Sweden)

    MSc. Hidajet Karaxha


    Full Text Available In order for a product to be put in the hands of the customer, requires a mechanism which is called distribution channel and which enables the connection between the consumer and producer. One of the many strategies applied by Kosovar companies for the involvement of the members of the channel is also the promotion through distribution channels. Therefore, the strategies which involve the members of the channel have a higher probability to be positively accepted by the members of the channel, when they are part of a general program of supporting the needs of the producers. The process of realizing a marketing strategy of a company does not concise only of achieving specific goals of production during the realization of the promotion phase, but it also requires identifying the target market and achieving it. The purpose of this paper is to review the promotion strategy of distribution channels, which emphasize the support by the members of the channel, initiated by the producers through cooperative advertisements, promotional salaries, slotting taxes, incentives, promotions in markets and also special promotional agreements. The theoretical and practical side of the study are very important, especially regarding to new theoretical and practical views in the study context. Besides the theoretical contribution that will be offered by this paper, there will also be interesting findings in the practical aspect where through this paper, the owners, managers, firms will be able to understand the role and importance of promotion through distribution channels. Knowing that there are only few studies offered in this field, this paper offers help for everyone interested in this field. This paper contains empirical data collected by questionnaires and interviews.

  3. Voltage-dependent gating of hERG potassium channels

    Directory of Open Access Journals (Sweden)

    Yen May eCheng


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

  4. A deterministic equivalent for the capacity analysis of correlated multi-user MIMO channels

    CERN Document Server

    Couillet, Romain; Silverstein, Jack W


    This paper provides the analysis of capacity expressions in multi-user and multi-cell systems when the transmitters and receivers have a large number of correlated antennas. Our main contribution mathematically translates into a deterministic equivalent of the Shannon transform of a class of large dimensional random matrices. This class of large matrices is used in this contribution to model (i) multi-antenna multiple access (MAC) and broadcast channels (BC) with transmit and receive channel correlation, (ii) multiple-input multiple-output (MIMO) communications with inter-cell interference and channel correlation both at the base stations and at the receiver. These models extend the classical results on multi-user MIMO capacities in independent and identically distributed (i.i.d.) Gaussian channels to the more realistic Gaussian channels with separable variance profile. On an information theoretical viewpoint, this article provides: in scenario (i), an asymptotic description of the MAC and BC rate regions as ...

  5. Modelling debris flows down general channels

    Directory of Open Access Journals (Sweden)

    S. P. Pudasaini


    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

  6. BIOPROTA: Key issues in biosphere aspects of assessment of the long-term impact of contaminant releases associated with radioactive waste management. Theme 2 Task 1: Model review and comparison for spray irrigation pathway

    Energy Technology Data Exchange (ETDEWEB)

    Bergstroem, U.; Albrecht, A.; Kanyar, B.; Smith, G.; Thorne, M.C.; Yoshida, H.; Wasiolek, M.


    The objective of Task 1 within Theme 2 was to investigate the modelling of the concentrations of radionuclides on vegetation arising from interception by growing crops using contaminated irrigation water and the consequent contamination of the food consumed by humans. This Task 1 report includes model descriptions provided by participants and the specification and results of model test calculations designed to investigate the significance of the different model assumptions. A significant array of modelling methods has been presented and explained. The equations used and the data adopted have also been presented. This compilation may be useful for future reference. Although the methods vary, most assessment results are within a factor of ten of each other. This is not a large range given the generic nature of the assessment question asked. This is generally due to compensating effects. For example, a high initial assumed retention factor is compensated for when weathering and translocation are then taken into account. That is to say, while different modelling approaches are taken, each conceptual model is internally consistent. Overall, the results lend considerable confidence to the assessment community's ability to assess doses as a result of food contamination due to the direct effects of irrigation. The biggest reasons for discrepancies in results are associated with the treatment of weathering and translocation, post deposition. Values for translocation vary considerably between the participants and there are different interpretations of weathering and translocation data. Another significant reason for differences in models and in results concerns the different irrigation practices used in different areas. These are largely climate driven. Overall it appears that relatively simple models provide very similar results to the more process orientated and data demanding models. Further consideration of the adequacy of the data for assessment purposes will

  7. FMCG companies specific distribution channels

    Directory of Open Access Journals (Sweden)

    Ioana Barin


    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.

  8. The Degraded Poisson Wiretap Channel

    CERN Document Server

    Laourine, Amine


    Providing security guarantees for wireless communication is critically important for today's applications. While previous work in this area has concentrated on radio frequency (RF) channels, providing security guarantees for RF channels is inherently difficult because they are prone to rapid variations due small scale fading. Wireless optical communication, on the other hand, is inherently more secure than RF communication due to the intrinsic aspects of the signal propagation in the optical and near-optical frequency range. In this paper, secure communication over wireless optical links is examined by studying the secrecy capacity of a direct detection system. For the degraded Poisson wiretap channel, a closed-form expression of the secrecy capacity is given. A complete characterization of the general rate-equivocation region is also presented. For achievability, an optimal code is explicitly constructed by using the structured code designed by Wyner for the Poisson channel. The converse is proved in two dif...

  9. Message Authentication over Noisy Channels

    Directory of Open Access Journals (Sweden)

    Fanfan Zheng


    Full Text Available The essence of authentication is the transmission of unique and irreproducible information. In this paper, the authentication becomes a problem of the secure transmission of the secret key over noisy channels. A general analysis and design framework for message authentication is presented based on the results of Wyner’s wiretap channel. Impersonation and substitution attacks are primarily investigated. Information-theoretic lower and upper bounds on the opponent’s success probability are derived, and the lower bound and the upper bound are shown to match. In general, the fundamental limits on message authentication over noisy channels are fully characterized. Analysis results demonstrate that introducing noisy channels is a reliable way to enhance the security of authentication.

  10. On the Capacity of Memoryless Finite-State Multiple-Access Channels with Asymmetric State Information at the Encoders

    CERN Document Server

    Como, Giacomo


    A single-letter characterization is provided for the capacity region of finite-state multiple-access channels, when the channel state process is an independent and identically distributed sequence, the transmitters have access to partial (quantized) state information, and complete channel state information is available at the receiver. The partial channel state information is assumed to be asymmetric at the encoders. As a main contribution, a tight converse coding theorem is presented. The difficulties associated with the case when the channel state has memory are discussed and connections to decentralized stochastic control theory are presented.

  11. Quantum Emitters near Layered Plasmonic Nanostructures: Decay Rate Contributions

    CERN Document Server

    Pors, Anders


    We introduce a numerical framework for calculating decay rate contributions when excited two-level quantum emitters are located near layered plasmonic nanostructures, particularly emphasizing the case of plasmonic nanostructures atop metal substrates where three decay channels exist: free space radiation, Ohmic losses, and excitation of surface plasmon polaritons (SPPs). The calculation of decay rate contributions is based on Huygen's equivalence principle together with a near-field to far-field transformation of the local electric field, thereby allowing us to discern the part of the electromagnetic field associated with free propagating waves rather than SPPs. The methodology is applied to the case of an emitter inside and near a gap-plasmon resonator, emphasizing strong position and orientation dependencies of the total decay rate, contributions of different decay channels, radiation patterns, and directivity of SPP excitation.

  12. Transient Receptor Potential Cation Channel Subfamily M Member 8 channels mediate the anti-inflammatory effects of eucalyptol. (United States)

    Caceres, Ana I; Liu, Boyi; Jabba, Sairam V; Achanta, Satyanarayana; Morris, John B; Jordt, Sven-Eric


    Eucalyptol (1,8-cineol), the major ingredient in the essential oil of eucalyptus leaves and other medicinal plants, has long been known for its anti-inflammatory properties. Eucalyptol interacts with the TRP cation channels among other targets, but it is unclear which of these mediates its anti-inflammatory effects. Effects of eucalyptol were compared in wild-type and TRPM8 channel-deficient mice in two different models: footpad inflammation elicited by complete Freund's adjuvant (CFA) and pulmonary inflammation following administration of LPS. Oedema formation, behavioural inflammatory pain responses, leukocyte infiltration, enzyme activities and cytokine and chemokine levels were measured. In the CFA model, eucalyptol strongly attenuated oedema and mechanical allodynia and reduced levels of inflammatory cytokines (IL-1β, TNF-α and IL-6), effects comparable with those of ibuprofen. In the LPS model of pulmonary inflammation, eucalyptol treatment diminished leukocyte infiltration, myeloperoxidase activity and production of TNF-α, IL-1β, IFN-γ and IL-6. Genetic deletion of TRPM8 channels abolished the anti-inflammatory effects of eucalyptol in both models. Eucalyptol was at least sixfold more potent on human, than on mouse TRPM8 channels. A metabolite of eucalyptol, 2-hydroxy-1,8-cineol, also activated human TRPM8 channels. Among the pharmacological targets of eucalyptol, TRPM8 channels were essential for its anti-inflammatory effects in mice. Human TRPM8 channels are more sensitive to eucalyptol than rodent TRPM8 channels explaining the higher potency of eucalyptol in humans. Metabolites of eucalyptol could contribute to its anti-inflammatory effects. The development of more potent and selective TRPM8 agonists may yield novel anti-inflammatory agents. © 2017 The British Pharmacological Society.

  13. Ionic Channels as Natural Nanodevices (United States)


    important for ions as transistors are for electrons. The focus of this effort evolved from the development of tools, to the use of those tools to make...control of channels is understood, the opportunity will exist to produce a technology as important for ions as transistors are for electrons. The...introduce the numerical techniques required to simulate charge transport in ion channels. [1] Using Poisson-Nernst-Planck-type ( PNP ) equations

  14. TRP Channels in Human Prostate

    Directory of Open Access Journals (Sweden)

    Carl Van Haute


    Full Text Available This review gives an overview of morphological and functional characteristics in the human prostate. It will focus on the current knowledge about transient receptor potential (TRP channels expressed in the human prostate, and their putative role in normal physiology and prostate carcinogenesis. Controversial data regarding the expression pattern and the potential impact of TRP channels in prostate function, and their involvement in prostate cancer and other prostate diseases, will be discussed.

  15. The Degraded Poisson Wiretap Channel


    Laourine, Amine; Wagner, Aaron B.


    Providing security guarantees for wireless communication is critically important for today's applications. While previous work in this area has concentrated on radio frequency (RF) channels, providing security guarantees for RF channels is inherently difficult because they are prone to rapid variations due small scale fading. Wireless optical communication, on the other hand, is inherently more secure than RF communication due to the intrinsic aspects of the signal propagation in the optical ...

  16. Covert Channel Synthesis for Transducers


    Benattar, Gilles; Bérard, Béatrice; Lime, Didier; Mullins, John; Roux, Olivier Henri; Sassolas, Mathieu


    Research report; Covert channels are a security threat for information systems, since they permit illegal flows, and sometimes leaks, of classified data. Although numerous descriptions have been given at a concrete level, relatively little work has been carried out at a more abstract level, outside probabilistic models. In this paper, we propose a definition of covert channels based on encoding and decoding binary messages with transducers, in a finite transition system. We first compare this...

  17. Eight channel telephone telemetry system (United States)

    Smith, R. E.


    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.

  18. Molecular communication in fluid media: The additive inverse Gaussian noise channel

    CERN Document Server

    Srinivas, K V; Eckford, Andrew W


    We consider molecular communication, with information conveyed in the time of release of molecules. The main contribution of this paper is the development of a theoretical foundation for such a communication system. Specifically, we develop the additive inverse Gaussian (IG) noise channel model: a channel in which the information is corrupted by noise with an inverse Gaussian distribution. We show that such a channel model is appropriate for molecular communication in fluid media - when propagation between transmitter and receiver is governed by Brownian motion and when there is positive drift from transmitter to receiver. Taking advantage of the available literature on the IG distribution, upper and lower bounds on channel capacity are developed, and a maximum likelihood receiver is derived. Theory and simulation results are presented which show that such a channel does not have a single quality measure analogous to signal-to-noise ratio in the AWGN channel. It is also shown that the use of multiple molecule...

  19. Interdependence of ATP signalling and pannexin channels; the servant was really the master all along? (United States)

    Jackson, Michael F


    Pannexin channels are recognized as important conduits for the release of ATP, which contributes to purinergic signalling. Pathologically, ATP release via these channels acts as a find-me signal for apoptotic cell clearance. Accordingly, there is considerable and growing interest in understanding the function and regulation of pannexin channels. In a recent issue of the Biochemical Journal, Boyce et al. provide evidence that the surface expression of pannexin channels is regulated by extracellular ATP. They propose a model in which ATP triggers pannexin channel internalization through a pathway involving clathrin- and caveolin-independent entry into early endosomes. Intriguingly, their evidence suggests that internalization is initiated through the association of ATP with pannexin channels themselves as well as ionotropic purinergic receptor 7 (P2X7) receptors.

  20. Involvement of the S4-S5 linker and the C-linker domain regions to voltage-gating in plant Shaker channels: comparison with animal HCN and Kv channels. (United States)

    Nieves-Cordones, Manuel; Gaillard, Isabelle


    Among the different transport systems present in plant cells, Shaker channels constitute the major pathway for K(+) in the plasma membrane. Plant Shaker channels are members of the 6 transmembrane-1 pore (6TM-1P) cation channel superfamily as the animal Shaker (Kv) and HCN channels. All these channels are voltage-gated K(+) channels: Kv channels are outward-rectifiers, opened at depolarized voltages and HCN channels are inward-rectifiers, opened by membrane hyperpolarization. Among plant Shaker channels, we can find outward-rectifiers, inward-rectifiers and also weak-rectifiers, with weak voltage dependence. Despite the absence of crystal structures of plant Shaker channels, functional analyses coupled to homology modeling, mostly based on Kv and HCN crystals, have permitted the identification of several regions contributing to plant Shaker channel gating. In the present mini-review, we make an update on the voltage-gating mechanism of plant Shaker channels which seem to be comparable to that proposed for HCN channels.

  1. On Cellular MIMO Channel Capacity (United States)

    Adachi, Koichi; Adachi, Fumiyuki; Nakagawa, Masao

    To increase the transmission rate without bandwidth expansion, the multiple-input multiple-output (MIMO) technique has recently been attracting much attention. The MIMO channel capacity in a cellular system is affected by the interference from neighboring co-channel cells. In this paper, we introduce the cellular channel capacity and evaluate its outage capacity, taking into account the frequency-reuse factor, path loss exponent, standard deviation of shadowing loss, and transmission power of a base station (BS). Furthermore, we compare the cellular MIMO downlink channel capacity with those of other multi-antenna transmission techniques such as single-input multiple-output (SIMO) and space-time block coded multiple-input single-output (STBC-MISO). We show that the optimum frequency-reuse factor F that maximizes 10%-outage capacity is 3 and both 50%- and 90%-outage capacities is 1 irrespective of the type of multi-antenna transmission technique, where q%-outage capacity is defined as the channel capacity that gives an outage probability of q%. We also show that the cellular MIMO channel capacity is always higher than those of SIMO and STBC-MISO.

  2. Contribution to contract theory

    Directory of Open Access Journals (Sweden)

    Pantelić Svetlana


    Full Text Available Oliver Hart and Bengt Holmstrom share the Nobel Prize in Economic Sciences for 2016, awarded to them by Sveriges Riksbank. They have been rewarded for their work in enhancing the design of contracts, i.e. arrangements connecting employers with employees or companies with clients, in other words, for their contribution to contract theory in the 1970s and 1980s. Their analysis of optimal contractual arrangements lays an intellectual foundation for designing policies and institutions in many areas, from bankruptcy legislation to political constitutions. Hart is an expert in contract theory, theory of the firm, corporate finance, and law and economics. His contribution to contract theory is exquisite when it comes to designing contracts which cover eventualities that cannot be precisely specified in advance.

  3. Functional Analysis of Orai1 Concatemers Supports a Hexameric Stoichiometry for the CRAC Channel. (United States)

    Yen, Michelle; Lokteva, Ludmila A; Lewis, Richard S


    Store-operated Ca(2+) entry occurs through the binding of the endoplasmic reticulum (ER) Ca(2+) sensor STIM1 to Orai1, the pore-forming subunit of the Ca(2+) release-activated Ca(2+) (CRAC) channel. Although the essential steps leading to channel opening have been described, fundamental questions remain, including the functional stoichiometry of the CRAC channel. The crystal structure of Drosophila Orai indicates a hexameric stoichiometry, while studies of linked Orai1 concatemers and single-molecule photobleaching suggest that channels assemble as tetramers. We assessed CRAC channel stoichiometry by expressing hexameric concatemers of human Orai1 and comparing in detail their ionic currents to those of native CRAC channels and channels generated from monomeric Orai1 constructs. Cell surface biotinylation results indicated that Orai1 channels in the plasma membrane were assembled from intact hexameric polypeptides and not from truncated protein products. In addition, the L273D mutation depressed channel activity equally regardless of which Orai1 subunit in the concatemer carried the mutation. Thus, functional channels were generated from intact Orai1 hexamers in which all subunits contributed equally. These hexameric Orai1 channels displayed the biophysical fingerprint of native CRAC channels, including the distinguishing characteristics of gating (store-dependent activation, Ca(2+)-dependent inactivation, open probability), permeation (ion selectivity, affinity for Ca(2+) block, La(3+) sensitivity, unitary current magnitude), and pharmacology (enhancement and inhibition by 2-aminoethoxydiphenyl borate). Because permeation characteristics depend strongly on pore geometry, it is unlikely that hexameric and tetrameric pores would display identical Ca(2+) affinity, ion selectivity, and unitary current magnitude. Thus, based on the highly similar pore properties of the hexameric Orai1 concatemer and native CRAC channels, we conclude that the CRAC channel functions as a

  4. Abstracts of contributed papers

    Energy Technology Data Exchange (ETDEWEB)


    This volume contains 571 abstracts of contributed papers to be presented during the Twelfth US National Congress of Applied Mechanics. Abstracts are arranged in the order in which they fall in the program -- the main sessions are listed chronologically in the Table of Contents. The Author Index is in alphabetical order and lists each paper number (matching the schedule in the Final Program) with its corresponding page number in the book.

  5. Contributions to statistics

    CERN Document Server

    Mahalanobis, P C


    Contributions to Statistics focuses on the processes, methodologies, and approaches involved in statistics. The book is presented to Professor P. C. Mahalanobis on the occasion of his 70th birthday. The selection first offers information on the recovery of ancillary information and combinatorial properties of partially balanced designs and association schemes. Discussions focus on combinatorial applications of the algebra of association matrices, sample size analogy, association matrices and the algebra of association schemes, and conceptual statistical experiments. The book then examines latt

  6. Contributions to sampling statistics

    CERN Document Server

    Conti, Pier; Ranalli, Maria


    This book contains a selection of the papers presented at the ITACOSM 2013 Conference, held in Milan in June 2013. ITACOSM is the bi-annual meeting of the Survey Sampling Group S2G of the Italian Statistical Society, intended as an international  forum of scientific discussion on the developments of theory and application of survey sampling methodologies and applications in human and natural sciences. The book gathers research papers carefully selected from both invited and contributed sessions of the conference. The whole book appears to be a relevant contribution to various key aspects of sampling methodology and techniques; it deals with some hot topics in sampling theory, such as calibration, quantile-regression and multiple frame surveys, and with innovative methodologies in important topics of both sampling theory and applications. Contributions cut across current sampling methodologies such as interval estimation for complex samples, randomized responses, bootstrap, weighting, modeling, imputati...

  7. Sodium Channels, Mitochondria, and Axonal Degeneration in Peripheral Neuropathy. (United States)

    Persson, Anna-Karin; Hoeijmakers, Janneke G J; Estacion, Mark; Black, Joel A; Waxman, Stephen G


    Peripheral neuropathy results from damage to peripheral nerves and is often accompanied by pain in affected limbs. Treatment represents an unmet medical need and a thorough understanding of the mechanisms underlying axonal injury is needed. Longer nerve fibers tend to degenerate first (length-dependence), and patients carrying pathogenic mutations throughout life usually become symptomatic in mid- or late-life (time-dependence). The activity of voltage-gated sodium channels can contribute to axonal injury and sodium channel gain-of-function mutations have been linked to peripheral neuropathy. Recent studies have implicated sodium channel activity, mitochondrial compromise, and reverse-mode Na(+)/Ca(2+) exchange in time- and length-dependent axonal injury. Elucidation of molecular mechanisms underlying axonal injury in peripheral neuropathy may provide new therapeutic strategies for this painful and debilitating condition.

  8. ATP-dependent potassium channels and type 2 diabetes mellitus. (United States)

    Bonfanti, Dianne Heloisa; Alcazar, Larissa Pontes; Arakaki, Priscila Akemi; Martins, Laysa Toschi; Agustini, Bruna Carla; de Moraes Rego, Fabiane Gomes; Frigeri, Henrique Ravanhol


    Diabetes mellitus is a public health problem, which affects a millions worldwide. Most diabetes cases are classified as type 2 diabetes mellitus, which is highly associated with obesity. Type 2 diabetes is considered a multifactorial disorder, with both environmental and genetic factors contributing to its development. An important issue linked with diabetes development is the failure of the insulin releasing mechanism involving abnormal activity of the ATP-dependent potassium channel, KATP. This channel is a transmembrane protein encoded by the KCNJ11 and ABCC8 genes. Furthermore, polymorphisms in these genes have been linked to type 2 diabetes because of the role of KATP in insulin release. While several genetic variations have been reported to be associated with this disease, the E23K polymorphism is most commonly associated with this pathology, as well as to obesity. Here, we review the molecular genetics of the potassium channel and discusses its most described polymorphisms and their associations with type 2 diabetes mellitus.

  9. Alternative methods for dispoal of low-level radioactive wastes. Task 1. Description of methods and assessment of criteria. [Alternative methods are belowground vaults, aboveground vaults; earth mounded concrete bunkers, mined cavities, augered holes

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, R.D.; Miller, W.O.; Warriner, J.B.; Malone, P.G.; McAneny, C.C.


    The study reported herein contains the results of Task 1 of a four-task study entitled Criteria for Evaluating Engineered Facilities. The overall objective of this study is to ensure that the criteria needed to evaluate five alternative low-level radioactive waste (LLW) disposal methods are available to the Nuclear Regulatory Commission (NRC) and the Agreement States. The alternative methods considered are belowground vaults, aboveground vaults, earth mounded concrete bunkers, mined cavities, and augered holes. Each of these alternatives is either being used by other countries for low-level radioactive waste (LLW) disposal or is being considered by other countries or US agencies. In this report the performance requirements are listed, each alternative is described, the experience gained with its use is discussed, and the performance capabilities of each method are addressed. Next, the existing 10 CFR Part 61 Subpart D criteria with respect to paragraphs 61.50 through 61.53, pertaining to site suitability, design, operations and closure, and monitoring are assessed for applicability to evaluation of each alternative. Preliminary conclusions and recommendations are offered on each method's suitability as an LLW disposal alternative, the applicability of the criteria, and the need for supplemental or modified criteria.

  10. Ion channels on microglia: therapeutic targets for neuroprotection. (United States)

    Skaper, Stephen D


    Under pathological conditions microglia (resident CNS immune cells) become activated, and produce reactive oxygen and nitrogen species and pro-inflammatory cytokines: molecules that can contribute to axon demyelination and neuron death. Because some microglia functions can exacerbate CNS disorders, including stroke, traumatic brain injury, progressive neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis, and several retinal diseases, controlling their activation might ameliorate immune-mediated CNS disorders. A growing body of evidence now points to ion channels on microglia as contributing to the above neuropathologies. For example, the ATP-gated P2X7 purinergic receptor cation channel is up-regulated around amyloid β-peptide plaques in transgenic mouse models of Alzheimer's disease and co-localizes to microglia and astrocytes. Upregulation of the P2X7 receptor subtype on microglia occurs also following spinal cord injury and after ischemia in the cerebral cortex of rats, while P2X7 receptor-like immunoreactivity is increased in activated microglial cells of multiple sclerosis and amyotrophic lateral sclerosis spinal cord. Utilizing neuron/microglia co-cultures as an in vitro model for neuroinflammation, P2X7 receptor activation on microglia appears necessary for microglial cell-mediated injury of neurons. A second example can be found in the chloride intracellular channel 1 (CLIC1), whose expression is related to macrophage activation, undergoes translocation from the cytosol to the plasma membrane (activation) of microglia exposed to amyloid β-peptide, and participates in amyloid β-peptide-induced neurotoxicity through the generation of reactive oxygen species. A final example is the small-conductance Ca2+/calmodulin-activated K+ channel KCNN4/KCa3.1/SK4/IK1, which is highly expressed in rat microglia. Lipopolysaccharide-activated microglia are capable of killing adjacent neurons

  11. Isoform composition of connexin channels determines selectivity among second messengers and uncharged molecules. (United States)

    Bevans, C G; Kordel, M; Rhee, S K; Harris, A L


    Intercellular connexin channels (gap junction channels) have long been thought to mediate molecular signaling between cells, but the nature of the signaling has been unclear. This study shows that connexin channels from native tissue have selective permeabilities, partially based on pore diameter, that discriminate among cytoplasmic second messenger molecules. Permeability was assessed by measurement of selective loss/retention of tracers from liposomes containing reconstituted connexin channels. The tracers employed were tritiated cyclic nucleotides and a series of oligomaltosaccharides derivatized with a small uncharged fluorescent moiety. The data define different size cut-off limits for permeability through homomeric connexin-32 channels and through heteromeric connexin-32/connexin-26 channels. Connexin-26 contributes to a narrowed pore. Both cAMP and cGMP were permeable through the homomeric connexin-32 channels. cAMP was permeable through only a fraction of the heteromeric channels. Surprisingly, cGMP was permeable through a substantially greater fraction of the heteromeric channels than was cAMP. The data suggest that isoform stoichiometry and/or arrangement within a connexin channel determines whether cyclic nucleotides can permeate, and which ones. This is the first evidence for connexin-specific selectivity among biological signaling molecules.

  12. The effect of basal channels on oceanic ice-shelf melting (United States)

    Millgate, Thomas; Holland, Paul R.; Jenkins, Adrian; Johnson, Helen L.


    The presence of ice-shelf basal channels has been noted in a number of Antarctic and Greenland ice shelves, but their impact on basal melting is not fully understood. Here we use the Massachusetts Institute of Technology general circulation model to investigate the effect of ice-shelf basal channels on oceanic melt rate for an idealized ice shelf resembling the floating tongue of Petermann Glacier in Greenland. The introduction of basal channels prevents the formation of a single geostrophically balanced boundary current; instead the flow is diverted up the right-hand (Coriolis-favored) side of each channel, with a return flow in the opposite direction on the left-hand side. As the prescribed number of basal channels is increased the mean basal melt rate decreases, in agreement with previous studies. For a small number of relatively wide channels the subice flow is found to be a largely geostrophic horizontal circulation. The reduction in melt rate is then caused by an increase in the relative contribution of weakly melting channel crests and keels. For a larger number of relatively narrow channels, the subice flow changes to a vertical overturning circulation. This change in circulation results in a weaker sensitivity of melt rates to channel size. The transition between the two regimes is governed by the Rossby radius of deformation. Our results explain why basal channels play an important role in regulating basal melting, increasing the stability of ice shelves.

  13. 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.


    Institute of Scientific and Technical Information of China (English)

    K.H.Sayhood; WuLenan


    A method of coherent detection and channel estimation for punctured convolutional coded binary Quadrature Amplitude Modulation (QAM) signals transmitted over a frequency-flat Rayleigh fading channels used for a digital radio broadcasting transmission is presented.Some known symbols are inserted in the encoded data stream to enhance the channel estimation process.The puilot symbols are used to replace the existing parity symbols so no bandwidth expansion is required.An iterative algorithm that uses decoding information as well as the information contained in the known symbols is used to improve the channel parameter estimate.The scheme complexity grows exponentially with the channel estimation filter length,The performance of the system is compared for a normalized fading rate with both perfect coherent detection(Corresponding to a perfect knowledge of the fading process and noise variance)and differential detection of Differential Amplitude Phase Shift Keying (DAPSK).The tradeoff between simplicity of implementation and bit-error-rate performance of different techniques is also compared.

  15. Capacity of Sparse Wideband Channels with Partial Channel Feedback

    CERN Document Server

    Hariharan, Gautham; Sayeed, Akbar M


    This paper studies the ergodic capacity of wideband multipath channels with limited feedback. Our work builds on recent results that have established the possibility of significant capacity gains in the wideband/low-SNR regime when there is perfect channel state information (CSI) at the transmitter. Furthermore, the perfect CSI benchmark gain can be obtained with the feedback of just one bit per channel coefficient. However, the input signals used in these methods are peaky, that is, they have a large peak-to-average power ratios. Signal peakiness is related to channel coherence and many recent measurement campaigns show that, in contrast to previous assumptions, wideband channels exhibit a sparse multipath structure that naturally leads to coherence in time and frequency. In this work, we first show that even an instantaneous power constraint is sufficient to achieve the benchmark gain when perfect CSI is available at the receiver. In the more realistic non-coherent setting, we study the performance of a tra...

  16. On Robust Covert Channels Inside DNS (United States)

    Nussbaum, Lucas; Neyron, Pierre; Richard, Olivier

    Covert channels inside DNS allow evasion of networks which only provide a restricted access to the Internet. By encapsulating data inside DNS requests and replies exchanged with a server located outside the restricted network, several existing implementations provide either an IP over DNS tunnel, or a socket-like service (TCP over DNS). This paper contributes a detailed overview of the challenges faced by the design of such tunnels, and describes the existing implementations. Then, it introduces TUNS, our prototype of an IP over DNS tunnel, focused on simplicity and protocol compliance. Comparison of TUNS and the other implementations showed that this approach is successful: TUNS works on all the networks we tested, and provides reasonable performance despite its use of less efficient encapsulation techniques, especially when facing degraded network conditions.

  17. Transient receptor potential channels in essential hypertension

    DEFF Research Database (Denmark)

    Liu, Daoyan; Scholze, Alexandra; Zhu, Zhiming


    The role of nonselective cation channels of the transient receptor potential channel (TRPC) family in essential hypertension has not yet been investigated.......The role of nonselective cation channels of the transient receptor potential channel (TRPC) family in essential hypertension has not yet been investigated....

  18. Minimum output entropy of Gaussian channels

    CERN Document Server

    Lloyd, S; Maccone, L; Pirandola, S; Garcia-Patron, R


    We show that the minimum output entropy for all single-mode Gaussian channels is additive and is attained for Gaussian inputs. This allows the derivation of the channel capacity for a number of Gaussian channels, including that of the channel with linear loss, thermal noise, and linear amplification.

  19. Information transfer through quantum channels

    Energy Technology Data Exchange (ETDEWEB)

    Kretschmann, D.


    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

  20. On Termination for Faulty Channel Machines

    CERN Document Server

    Bouyer, Patricia; Ouaknine, Joël; Schnoebelen, Philippe; Worrell, James


    A channel machine consists of a finite controller together with several fifo channels; the controller can read messages from the head of a channel and write messages to the tail of a channel. In this paper, we focus on channel machines with insertion errors, i.e., machines in whose channels messages can spontaneously appear. Such devices have been previously introduced in the study of Metric Temporal Logic. We consider the termination problem: are all the computations of a given insertion channel machine finite? We show that this problem has non-elementary, yet primitive recursive complexity.

  1. Quantum channels with a finite memory

    CERN Document Server

    Bowen, G; Bowen, Garry; Mancini, Stefano


    In this paper we study quantum communication channels with correlated noise effects, i.e., quantum channels with memory. We derive a model for correlated noise channels that includes a channel memory state. We examine the case where the memory is finite, and derive bounds on the classical and quantum capacities. For the entanglement-assisted and unassisted classical capacities it is shown that these bounds are attainable for certain classes of channel. Also, we show that the structure of any finite memory state is unimportant in the asymptotic limit, and specifically, for a perfect finite-memory channel where no information is lost to the environment, the channel is asymptotically noiseless.

  2. Calcium-permeable ion channels in the kidney. (United States)

    Zhou, Yiming; Greka, Anna


    Calcium ions (Ca(2+)) are crucial for a variety of cellular functions. The extracellular and intracellular Ca(2+) concentrations are thus tightly regulated to maintain Ca(2+) homeostasis. The kidney, one of the major organs of the excretory system, regulates Ca(2+) homeostasis by filtration and reabsorption. Approximately 60% of the Ca(2+) in plasma is filtered, and 99% of that is reabsorbed by the kidney tubules. Ca(2+) is also a critical signaling molecule in kidney development, in all kidney cellular functions, and in the emergence of kidney diseases. Recently, studies using genetic and molecular biological approaches have identified several Ca(2+)-permeable ion channel families as important regulators of Ca(2+) homeostasis in kidney. These ion channel families include transient receptor potential channels (TRP), voltage-gated calcium channels, and others. In this review, we provide a brief and systematic summary of the expression, function, and pathological contribution for each of these Ca(2+)-permeable ion channels. Moreover, we discuss their potential as future therapeutic targets.

  3. Propagation and deposition of stony debris flows at channel confluences (United States)

    Stancanelli, L. M.; Lanzoni, S.; Foti, E.


    The fluid dynamics of stony debris flows generated in two small tributaries adjacent to each other and flowing into a main receiving channel was analyzed experimentally at a laboratory scale. The analysis on the propagation along the tributaries and deposition in the main channel provide information about sediment-water mobility, dangerous damming, and potential hazard. Debris flows were generated by releasing a preset water discharge over an erodible layer of saturated gravels material. As a consequence, the debris flow sediment concentration varied accordingly to the entrainment rate which, in turn, was strongly controlled by the tributary slope. The data collected by acoustic level sensors, pore fluid pressure transducers, and a load cell were used to characterize the evolution of bulk density and solid concentration of the sediment-water mixture. These two parameters were relevant to assess the stony debris flow mobility which contributes to determine the shape of sediment deposits in the main channel. The detailed bed topography surveys carried out in the main channel at the end of each experiment provided information on the morphology of these deposits and on the interplay of adjacent confluences. The influences of confluence angle, tributary slopes, and triggering conditions have been investigated, for a total of 18 different configurations. Within the investigated range of parameters, the slope angle was the parameter that mainly influences the stony debris flow mobility while, for adjacent confluences, the degree of obstruction within the receiving channel was strongly influenced by the triggering scenario.

  4. Multi-channel MAC Protocol in Cognitive Radio Networks

    Directory of Open Access Journals (Sweden)

    Yongli Sun


    Full Text Available Since cognitive wireless network (CRN has the characteristic of secondary use, it can enable the device to dynamically access available spectrum without interference to primary users (PUs, which can effectively alleviate contradiction between the lack of spectrum resources and the growing demand for wireless access. However, Medium Access Control (MAC protocol as CRN core components, can achieve competition access of the licensed spectrum and coordination control, which will maximize spectrum utilization efficiency and network throughput. The contribution of this survey is threefold. First, we analyze the characteristics of the existed multi- channel MAC protocol in CRN; Second, according to the different ways of spectrum access in CRNs, the multi-channel MAC protocols are classified into time-slotted based MAC protocol, control channel based MAC protocol and hybrid MAC protocol, and the paper emphatically analyzed the advantages and disadvantages of these multi-channel MAC protocols; Finally, the paper explores the difficulties and the challenges of multi-channel MAC protocols design in cognitive wireless network.

  5. Researches toward potassium channels on tumor progressions. (United States)

    Shen, Zheng; Yang, Qian; You, Qidong


    As trans-membrane proteins located in cytoplasm and organelle membrane, potassium (K(+)) channels are generally divided into four super-families: voltage-gated K(+) channels (K(v)), Ca(2+)-activated K(+) channels (K(Ca)), inwardly rectifying K(+) channels (K(ir)) and two-pore domain K(+) channels (K(2P)). Since dysfunctions of K(+) channels would induce many diseases, various studies toward their functions in physiologic and pathologic process have been extensively launched. This review focuses on the recent advances of K(+) channels in tumor progression, including the brief introduction of K(+) channels, the role of K(+) channels in tumor cells, the possible mechanism of action at cellular level, and the possible application of K(+) channel modulators in cancer chemotherapy.

  6. Turbulent separation in a channel with a curved wall

    CERN Document Server

    Mollicone, Jean-Paul; Gualtieri, Paolo; Casciola, Carlo Massimo


    Flow separation, in both external and internal flows, is the main source of turbulent fluctuations which ultimately results in drag and inefficiency in applications. The basic issue of turbulence self sustainment is still not exhaustively investigated for even mildly complex geometries able to induce separation. In order to provide insightful information on the origin of form drag and related turbulent kinetic energy production and dissipation mechanisms, Direct Numerical Simulations (DNS) of turbulent channel flows with a bump at one of the walls are discussed. The shape of the bump is modified to address the effect of the bluffness on the dynamics of the separation bubble behind the bump. Global quantities reveal that most of the drag is due to the form contribution, whilst the friction contribution does not change appreciably with respect to an equivalent planar channel flow. Beside turbulent kinetic energy, the geometrical complexity of the flow requires the explicit analysis of the energy budget for the ...

  7. Charged and Neutral Particles Channeling Phenomena Channeling 2008 (United States)

    Dabagov, Sultan B.; Palumbo, Luigi


    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

  8. The hitchhiker's guide to the voltage-gated sodium channel galaxy. (United States)

    Ahern, Christopher A; Payandeh, Jian; Bosmans, Frank; Chanda, Baron


    Eukaryotic voltage-gated sodium (Nav) channels contribute to the rising phase of action potentials and served as an early muse for biophysicists laying the foundation for our current understanding of electrical signaling. Given their central role in electrical excitability, it is not surprising that (a) inherited mutations in genes encoding for Nav channels and their accessory subunits have been linked to excitability disorders in brain, muscle, and heart; and (b) Nav channels are targeted by various drugs and naturally occurring toxins. Although the overall architecture and behavior of these channels are likely to be similar to the more well-studied voltage-gated potassium channels, eukaryotic Nav channels lack structural and functional symmetry, a notable difference that has implications for gating and selectivity. Activation of voltage-sensing modules of the first three domains in Nav channels is sufficient to open the channel pore, whereas movement of the domain IV voltage sensor is correlated with inactivation. Also, structure-function studies of eukaryotic Nav channels show that a set of amino acids in the selectivity filter, referred to as DEKA locus, is essential for Na(+) selectivity. Structures of prokaryotic Nav channels have also shed new light on mechanisms of drug block. These structures exhibit lateral fenestrations that are large enough to allow drugs or lipophilic molecules to gain access into the inner vestibule, suggesting that this might be the passage for drug entry into a closed channel. In this Review, we will synthesize our current understanding of Nav channel gating mechanisms, ion selectivity and permeation, and modulation by therapeutics and toxins in light of the new structures of the prokaryotic Nav channels that, for the time being, serve as structural models of their eukaryotic counterparts.

  9. Bubbles, Gating, and Anesthetics in Ion Channels


    Roth, Roland, imp.; Gillespie, Dirk; Nonner, Wolfgang; Eisenberg, Robert E.


    We suggest that bubbles are the bistable hydrophobic gates responsible for the on-off transitions of single channel currents. In this view, many types of channels gate by the same physical mechanism—dewetting by capillary evaporation—but different types of channels use different sensors to modulate hydrophobic properties of the channel wall and thereby trigger and control bubbles and gating. Spontaneous emptying of channels has been seen in many simulations. Because of the physics involved, s...

  10. Information geometry of Gaussian channels

    CERN Document Server

    Monras, Alex


    We define a local Riemannian metric tensor in the manifold of Gaussian channels and the distance that it induces. We adopt an information-geometric approach and define a metric derived from the Bures-Fisher metric for quantum states. The resulting metric inherits several desirable properties from the Bures-Fisher metric and is operationally motivated from distinguishability considerations: It serves as an upper bound to the attainable quantum Fisher information for the channel parameters using Gaussian states, under some restriction on the available resources. We prove that optimal states are always pure and bounded in the number of ancillary modes that are needed. This has experimental and computational advantages: It limits the complexity of optimal experimental setups for channel estimation and reduces the computational requirements for the evaluation of the metric. Indeed, we construct a converging algorithm for computing the metric. We provide explicit formulae for computing the multiparametric quantum F...

  11. Evaluate interference in digital channels (United States)

    Davarian, F.; Sumida, J.


    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.

  12. The First Extracellular Domain Plays an Important Role in Unitary Channel Conductance of Cx50 Gap Junction Channels.

    Directory of Open Access Journals (Sweden)

    Xiaoling Tong

    Full Text Available Gap junction (GJ channels provide direct passage for ions and small molecules to be exchanged between neighbouring cells and are crucial for many physiological processes. GJ channels can be gated by transjunctional voltage (known as Vj-gating and display a wide range of unitary channel conductance (γj, yet the domains responsible for Vj-gating and γj are not fully clear. The first extracellular domain (E1 of several connexins has been shown to line part of their GJ channel pore and play important roles in Vj-gating properties and/or ion permeation selectivity. To test roles of the E1 of Cx50 GJ channels, we generated a chimera, Cx50Cx36E1, where the E1 domain of Cx50 was replaced with that of Cx36, a connexin showing quite distinct Vj-gating and γj from those of Cx50. Detailed characterizations of the chimera and three point mutants in E1 revealed that, although the E1 domain is important in determining γj, the E1 domain of Cx36 is able to effectively function within the context of the Cx50 channel with minor changes in Vj-gating properties, indicating that sequence differences between the E1 domains in Cx36 and Cx50 cannot account for their drastic differences in Vj-gating and γj. Our homology models of the chimera and the E1 mutants revealed that electrostatic properties of the pore-lining residues and their contribution to the electric field in the pore are important factors for the rate of ion permeation of Cx50 and possibly other GJ channels.

  13. Channel incision and water quality (United States)

    Shields, F. D.


    Watershed development often triggers channel incision that leads to radical changes in channel morphology. Although morphologic evolution due to channel incision has been documented and modeled by others, ecological effects, particularly water quality effects, are less well understood. Furthermore, environmental regulatory frameworks for streams frequently focus on stream water quality and underemphasize hydrologic and geomorphic issues. Discharge, basic physical parameters, solids, nutrients (nitrogen and phosphorus), chlorophyll and bacteria were monitored for five years at two sites along a stream in a mixed cover watershed characterized by rapid incision of the entire channel network. Concurrent data were collected from two sites on a nearby stream draining a watershed of similar size and cultivation intensity, but without widespread incision. Data sets describing physical aquatic habitat and fish fauna of each stream were available from other studies. The second stream was impacted by watershed urbanization, but was not incised, so normal channel-floodplain interaction maintained a buffer zone of floodplain wetlands between the study reach and the urban development upstream. The incised stream had mean channel depth and width that were 1.8 and 3.5 times as large as for the nonincised stream, and was characterized by flashier hydrology. The median rise rate for the incised stream was 6.4 times as great as for the nonincised stream. Correlation analyses showed that hydrologic perturbations were associated with water quality degradation, and the incised stream had levels of turbidity and solids that were two to three times higher than the nonincised, urbanizing stream. Total phosphorus, total Kjeldahl N, and chlorophyll a concentrations were significantly higher in the incised stream, while nitrate was significantly greater in the nonincised, urbanizing stream (p Ecological engineering of stream corridors must focus at least as much energy on mediating hydrologic

  14. Ferritin Protein Nanocage Ion Channels (United States)

    Tosha, Takehiko; Behera, Rabindra K.; Ng, Ho-Leung; Bhattasali, Onita; Alber, Tom; Theil, Elizabeth C.


    Ferritin protein nanocages, self-assembled from four-α-helix bundle subunits, use Fe2+ and oxygen to synthesize encapsulated, ferric oxide minerals. Ferritin minerals are iron concentrates stored for cell growth. Ferritins are also antioxidants, scavenging Fenton chemistry reactants. Channels for iron entry and exit consist of helical hairpin segments surrounding the 3-fold symmetry axes of the ferritin nanocages. We now report structural differences caused by amino acid substitutions in the Fe2+ ion entry and exit channels and at the cytoplasmic pores, from high resolution (1.3–1.8 Å) protein crystal structures of the eukaryotic model ferritin, frog M. Mutations that eliminate conserved ionic or hydrophobic interactions between Arg-72 and Asp-122 and between Leu-110 and Leu-134 increase flexibility in the ion channels, cytoplasmic pores, and/or the N-terminal extensions of the helix bundles. Decreased ion binding in the channels and changes in ordered water are also observed. Protein structural changes coincide with increased Fe2+ exit from dissolved, ferric minerals inside ferritin protein cages; Fe2+ exit from ferritin cages depends on a complex, surface-limited process to reduce and dissolve the ferric mineral. High concentrations of bovine serum albumin or lysozyme (protein crowders) to mimic the cytoplasm restored Fe2+ exit in the variants to wild type. The data suggest that fluctuations in pore structure control gating. The newly identified role of the ferritin subunit N-terminal extensions in gating Fe2+ exit from the cytoplasmic pores strengthens the structural and functional analogies between ferritin ion channels in the water-soluble protein assembly and membrane protein ion channels gated by cytoplasmic N-terminal peptides. PMID:22362775

  15. Neurotoxins and their binding areas on voltage-gated sodium channels

    Directory of Open Access Journals (Sweden)

    Marijke eStevens


    Full Text Available Voltage-gated Sodium Channels (VGSCs are large transmembrane proteins that conduct sodium ions across the membrane and by doing so they generate signals of communication between many kinds of tissues. They are responsible for the generation and propagation of action potentials in excitable cells, in close collaboration with other channels like potassium channels. Genetic defects in sodium channel genes therefore can cause a wide variety of diseases, generally called ‘channelopathies’.The first insights into the mechanism of action potentials and the involvement of sodium channels originated from Hodgkin and Huxley for which they were awarded the Nobel Prize in 1963. Until now, these concepts still form the basis for understanding the functioning of VGSCs. When VGSCs sense a sufficient change in membrane potential, they are activated and will generate a massive influx of sodium ions. Immediately after, channels will start inactivating and currents decrease. In the inactivated state channels stay refractory for any new stimulus and they must return to the closed state before being susceptible to any new depolarization. On the other hand, studies with neurotoxins like tetrodotoxin (TTX and saxitoxin (STX also contributed largely to our today’s understanding of the structure and function of ion channels and specifically of VGSCs. Moreover, neurotoxins acting on ion channels turned out to be valuable tools in the development of new drugs for the enormous range of diseases in which ion channels are involved. A recent example of a synthetic neurotoxin that made it to the market is ziconotide (Prialt®, Elan. The original peptide, -MVIIA, is derived from the cone snail Conus magus and now FDA/EMEA-approved for the management of severe chronic pain by blocking the N-type voltage-gated calcium channels in neurons.This review focuses on the current status of research on neurotoxins acting on VGSC, their contribution to further unravel the

  16. Contributing to Functionality

    DEFF Research Database (Denmark)

    Törpel, Bettina


    advocated in this paper, emerges in the specific dynamic interplay of actors, objectives, structures, practices and means. In this view, functionality is the result of creating, harnessing and inhabiting computer supported joint action spaces. The successful creation and further development of a computer......The objective of this paper is the design of computer supported joint action spaces. It is argued against a view of functionality as residing in computer applications. In such a view the creation of functionality is equivalent to the creation of computer applications. Functionality, in the view...... supported joint action space comprises a whole range of appropriate design contributions. The approach is illustrated by the example of the creation of the computer supported joint action space "exchange network of voluntary union educators". As part of the effort a group of participants created...

  17. Contributing from the margins

    DEFF Research Database (Denmark)

    Chimirri, Niklas Alexander

    /herself as a contributor to an investigated practice, as inextricably entangled with the conducts of life of the others in relation to the conditions in practice. Doing research in the kindergarten thus becomes a mutual and collective endeavor, to which pedagogues, parents, children, and the researcher contribute. Even...... empirical study, I focused on kindergarten children’s first-person perspectives on the electronic media technologies they deemed subjectively relevant for conducting everyday life in the practice of their kindergarten. The concept of the children’s perspectives opens possibilities for transcending...... the widespread, one-sided explanations of the relationship between a child and technology, which ascribe agency either to the child or to the technology. However, attempts to access these perspectives raises a number of epistemological and ethical-political challenges, most crucially regarding the concrete role...

  18. adequacy of drainage channels f drainage channels in a small ...

    African Journals Online (AJOL)


    version of Kirpich equation (new equation of time new equation ... that, channels 1, 4, 5, 7, 8, 10, 12 and 13 have flo sediment ... Storm water management syst ..... Qc(m3/s). 0.536. 1.647. 0.141. 0.130. 0.636. Ch length (m). 619. 661. 398. 398.

  19. Lubiprostone: a chloride channel activator. (United States)

    Lacy, Brian E; Levy, L Campbell


    In January 2006 the Food and Drug Administration approved lubiprostone for the treatment of chronic constipation in men and women aged 18 and over. Lubiprostone is categorized as a prostone, a bicyclic fatty acid metabolite of prostaglandin E1. Lubiprostone activates a specific chloride channel (ClC-2) in the gastrointestinal (GI) tract to enhance intestinal fluid secretion, which increases GI transit and improves symptoms of constipation. This article reviews the role of chloride channels in the GI tract, describes the structure, function, and pharmacokinetics of lubiprostone, and discusses clinically important data on this new medication.

  20. Quantum teleportation without classical channel (United States)

    Al Amri, M.; Li, Zheng-Hong; Zubairy, M. Suhail


    For the first time, we show how quantum teleportation can be achieved without the assistance of classical channels. Our protocol does not need any pre-established entangled photon pairs beforehand. Just by utilizing quantum Zeno effect and couterfactual communication idea, we can achieve two goals; entangling a photon and an atom and also disentangling them by non-local interaction. Information is completely transferred from atom to photon with controllable disentanglement processes. More importantly, there is no need to confirm teleportation results via classical channels.

  1. Quantum Markov Channels for Qubits

    CERN Document Server

    Daffer, S; McIver, J K; Daffer, Sonja; Wodkiewicz, Krzysztof; Iver, John K. Mc


    We examine stochastic maps in the context of quantum optics. Making use of the master equation, the damping basis, and the Bloch picture we calculate a non-unital, completely positive, trace-preserving map with unequal damping eigenvalues. This results in what we call the squeezed vacuum channel. A geometrical picture of the effect of stochastic noise on the set of pure state qubit density operators is provided. Finally, we study the capacity of the squeezed vacuum channel to transmit quantum information and to distribute EPR states.

  2. Eight-Channel Continuous Timer (United States)

    Cole, Steven


    A custom laboratory electronic timer circuit measures the durations of successive cycles of nominally highly stable input clock signals in as many as eight channels, for the purpose of statistically quantifying the small instabilities of these signals. The measurement data generated by this timer are sent to a personal computer running software that integrates the measurements to form a phase residual for each channel and uses the phase residuals to compute Allan variances for each channel. (The Allan variance is a standard statistical measure of instability of a clock signal.) Like other laboratory clock-cycle-measuring circuits, this timer utilizes an externally generated reference clock signal having a known frequency (100 MHz) much higher than the frequencies of the input clock signals (between 100 and 120 Hz). It counts the number of reference-clock cycles that occur between successive rising edges of each input clock signal of interest, thereby affording a measurement of the input clock-signal period to within the duration (10 ns) of one reference clock cycle. Unlike typical prior laboratory clock-cycle-measuring circuits, this timer does not skip some cycles of the input clock signals. The non-cycle-skipping feature is an important advantage because in applications that involve integration of measurements over long times for characterizing nominally highly stable clock signals, skipping cycles can degrade accuracy. The timer includes a field-programmable gate array that functions as a 20-bit counter running at the reference clock rate of 100 MHz. The timer also includes eight 20-bit latching circuits - one for each channel - at the output terminals of the counter. Each transition of an input signal from low to high causes the corresponding latching circuit to latch the count at that instant. Each such transition also sets a status flip-flop circuit to indicate the presence of the latched count. A microcontroller reads the values of all eight status flipflops

  3. Interference Decoding for Deterministic Channels

    CERN Document Server

    Bandemer, Bernd


    An inner bound to the capacity region of a class of three user pair deterministic interference channels is presented. The key idea is to simultaneously decode the combined interference signal and the intended message at each receiver. It is shown that this interference decoding inner bound is strictly larger than the inner bound obtained by treating interference as noise, which includes interference alignment for deterministic channels. The gain comes from judicious analysis of the number of combined interference sequences in different regimes of input distributions and message rates.

  4. A Profile of Corporate Contributions. (United States)

    Smith, Hayden W.

    The extent and distribution of charitable contributions by corporations were studied. In addition to a history of giving from 1936 to 1981, information is presented on corporate contributions in 1977 in terms of the distribution of companies (1) by size of contributions, (2) by contributions as percentage of net income, (3) by industry, and (4) by…

  5. Perturbative QCD contributions to inclusive processes

    Energy Technology Data Exchange (ETDEWEB)

    Ritbergen, T. van


    This thesis treats the calculation of quantum corrections to a number of high energy processes that are measured in current and future accelerator experiments. The main objective of these experiments is to accurately verify the generally accepted theory of electro-weak and strong interactions, known as the Standard model, and to look for possible deviations. Most of the processes that are treated in this thesis are of a type for which the final state of of a highly energetic scattering or decay process is measured inclusively. The higher order quantum corrections discussed in this thesis are due to strong interactions. To the inclusive decay rate of Z{sup 0} bosons into all possible final states consisting of hadrons third order QCD contributions have been obtained. Also in the third order QCD an expansion for the inclusive hadronic decay rate of a {tau}-lepton was obtained. Then the top-quark-mass effects on the decay channels of a Higgs boson: Higgs{yields}b-quarks and Higgs{yields}gluons, were investigated. Thereafter the calculation of 3-loop contributions to the deep-inelastic lepton-nucleon scattering process is discussed. Finally the 3-loop contributions to the q{sup 2}-dependence of the lower moments {integral}{sub 0}{sup 1}x{sup N-1}F(x,q{sup 2})dx, N=2,4,6,8 of the structure functions F{sub 2} and F{sub L} were obtained. (orig./HSI).

  6. Role of K(ATP)(+) channels in regulation of systemic, pulmonary, and coronary vasomotor tone in exercising swine

    NARCIS (Netherlands)

    D.J.G.M. Duncker (Dirk); H.H. Oei (Hok-Hay); F. Hu; R. Stubenitsky (René); P.D. Verdouw (Pieter)


    textabstractThe role of ATP-sensitive K(+) (K(ATP)(+)) channels in vasomotor tone regulation during metabolic stimulation is incompletely understood. Consequently, we studied the contribution of K(ATP)(+) channels to vasomotor tone regulation in the systemic, pulmonary,

  7. Differential effects of K(+) channel blockers on frequency-dependent action potential broadening in supraoptic neurons. (United States)

    Hlubek, M D; Cobbett, P


    Recordings were made from magnocellular neuroendocrine cells dissociated from the supraoptic nucleus of the adult guinea pig to determine the role of voltage gated K(+) channels in controlling the duration of action potentials and in mediating frequency-dependent action potential broadening exhibited by these neurons. The K(+) channel blockers charybdotoxin (ChTx), tetraethylammonium (TEA), and 4-aminopyridine (4-AP) increased the duration of individual action potentials indicating that multiple types of K(+) channel are important in controlling action potential duration. The effect of these K(+) channel blockers was almost completely reversed by simultaneous blockade of voltage gated Ca(2+) channels with Cd(2+). Frequency-dependent action potential broadening was exhibited by these neurons during trains of action potentials elicited by membrane depolarizing current pulses presented at 10 Hz but not at 1 Hz. 4-AP but not ChTx or TEA inhibited frequency-dependent action potential broadening indicating that frequency-dependent action potential broadening is dependent on increasing steady-state inactivation of A-type K(+) channels (which are blocked by 4-AP). A model of differential contributions of voltage gated K(+) channels and voltage gated Ca(2+) channels to frequency-dependent action potential broadening, in which an increase of Ca(2+) current during each successive action potential is permitted as a result of the increasing steady-state inactivation of A-type K(+) channels, is presented.

  8. Ion channel expression patterns in glioblastoma stem cells with functional and therapeutic implications for malignancy (United States)

    Pollak, Julia; Rai, Karan G.; Funk, Cory C.; Arora, Sonali; Lee, Eunjee; Zhu, Jun; Price, Nathan D.; Paddison, Patrick J.; Ramirez, Jan-Marino; Rostomily, Robert C.


    Ion channels and transporters have increasingly recognized roles in cancer progression through the regulation of cell proliferation, migration, and death. Glioblastoma stem-like cells (GSCs) are a source of tumor formation and recurrence in glioblastoma multiforme, a highly aggressive brain cancer, suggesting that ion channel expression may be perturbed in this population. However, little is known about the expression and functional relevance of ion channels that may contribute to GSC malignancy. Using RNA sequencing, we assessed the enrichment of ion channels in GSC isolates and non-tumor neural cell types. We identified a unique set of GSC-enriched ion channels using differential expression analysis that is also associated with distinct gene mutation signatures. In support of potential clinical relevance, expression of selected GSC-enriched ion channels evaluated in human glioblastoma databases of The Cancer Genome Atlas and Ivy Glioblastoma Atlas Project correlated with patient survival times. Finally, genetic knockdown as well as pharmacological inhibition of individual or classes of GSC-enriched ion channels constrained growth of GSCs compared to normal neural stem cells. This first-in-kind global examination characterizes ion channels enriched in GSCs and explores their potential clinical relevance to glioblastoma molecular subtypes, gene mutations, survival outcomes, regional tumor expression, and experimental responses to loss-of-function. Together, the data support the potential biological and therapeutic impact of ion channels on GSC malignancy and provide strong rationale for further examination of their mechanistic and therapeutic importance. PMID:28264064

  9. Effects of stochastic channel gating and distribution on the cardiac action potential. (United States)

    Lemay, Mathieu; de Lange, Enno; Kucera, Jan P


    Ion channels exhibit stochastic conformational changes determining their gating behavior. In addition, the process of protein turnover leads to a natural variability of the number of membrane and gap junctional channels. Nevertheless, in computational models, these two aspects are scarcely considered and their impacts are largely unknown. We investigated the effects of stochastic current fluctuations and channel distributions on action potential duration (APD), intercellular conduction delays (ICDs) and conduction blocks using a modified ventricular cell model (Rudy et al.) with Markovian formulations of the principal ion currents (to simulate their stochastic open-close gating behavior) and with channel counts drawn from Poisson distributions (to simulate their natural variability). In single cells, APD variability (coefficient of variation: 1.6% at BCL=1000ms) was essentially caused by stochastic channel gating of I(Ks), persistent I(Na) and I(Ca,L). In cell strands, ICD variability induced by stochastic channel gating and Poissonian channel distributions was low under normal conditions. Nonetheless, at low intercellular coupling levels, Poissonian gap junctional channel distribution resulted in a large ICD variability (coefficient of variation >20%), highly heterogeneous conduction patterns and conduction blocks. Therefore, the stochastic behavior of current fluctuations and channel distributions can contribute to the heterogeneity of conduction patterns and to conduction block, as observed previously in experiments in cardiac tissue with altered intercellular coupling.

  10. Ion channels in development and cancer. (United States)

    Bates, Emily


    Ion channels have emerged as regulators of developmental processes. In model organisms and in people with mutations in ion channels, disruption of ion channel function can affect cell proliferation, cell migration, and craniofacial and limb patterning. Alterations of ion channel function affect morphogenesis in fish, frogs, mammals, and flies, demonstrating that ion channels have conserved roles in developmental processes. One model suggests that ion channels affect proliferation and migration through changes in cell volume. However, ion channels have not explicitly been placed in canonical developmental signaling cascades until recently. This review gives examples of ion channels that influence developmental processes, offers a potential underlying molecular mechanism involving bone morphogenetic protein (BMP) signaling, and finally explores exciting possibilities for manipulating ion channels to influence cell fate for regenerative medicine and to impact disease.

  11. Vascular potassium channels in NVC. (United States)

    Yamada, K


    It has long been proposed that the external potassium ion ([K(+)]0) works as a potent vasodilator in the dynamic regulation of local cerebral blood flow. Astrocytes may play a central role for producing K(+) outflow possibly through calcium-activated potassium channels on the end feet, responding to a rise in the intracellular Ca(2+) concentration, which might well reflect local neuronal activity. A mild elevation of [K(+)]0 in the end feet/vascular smooth muscle space could activate Na(+)/K(+)-ATPase concomitant with inwardly rectifying potassium (Kir) channels in vascular smooth muscle cells, leading to a hyperpolarization of vascular smooth muscle and relaxation of smooth muscle actin-positive vessels. Also proposed notion is endothelial calcium-activated potassium channels and/or inwardly rectifying potassium channel-mediated hyperpolarization of vascular smooth muscle. A larger elevation of [K(+)]0, which may occur pathophysiologically in such as spreading depression or stroke, can trigger a depolarization of vascular smooth muscle cells and vasoconstriction instead.

  12. Store-Operated Calcium Channels. (United States)

    Prakriya, Murali; Lewis, Richard S


    Store-operated calcium channels (SOCs) are a major pathway for calcium signaling in virtually all metozoan cells and serve a wide variety of functions ranging from gene expression, motility, and secretion to tissue and organ development and the immune response. SOCs are activated by the depletion of Ca(2+) from the endoplasmic reticulum (ER), triggered physiologically through stimulation of a diverse set of surface receptors. Over 15 years after the first characterization of SOCs through electrophysiology, the identification of the STIM proteins as ER Ca(2+) sensors and the Orai proteins as store-operated channels has enabled rapid progress in understanding the unique mechanism of store-operate calcium entry (SOCE). Depletion of Ca(2+) from the ER causes STIM to accumulate at ER-plasma membrane (PM) junctions where it traps and activates Orai channels diffusing in the closely apposed PM. Mutagenesis studies combined with recent structural insights about STIM and Orai proteins are now beginning to reveal the molecular underpinnings of these choreographic events. This review describes the major experimental advances underlying our current understanding of how ER Ca(2+) depletion is coupled to the activation of SOCs. Particular emphasis is placed on the molecular mechanisms of STIM and Orai activation, Orai channel properties, modulation of STIM and Orai function, pharmacological inhibitors of SOCE, and the functions of STIM and Orai in physiology and disease.

  13. Higgs in Bosonic channel (CMS)

    CERN Document Server

    Gori, Valentina


    All the investigated properties result to be fully consistent with the SM predictions: the signal strength and the signal strength modifiers are consistent with unity in all the bosonic channels considered; the hypothesis of a scalar particle is strongly favored, ag...

  14. Driven tracers in narrow channels (United States)

    Cividini, J.; Mukamel, D.; Posch, H. A.


    Steady-state properties of a driven tracer moving in a narrow two-dimensional (2D) channel of quiescent medium are studied. The tracer drives the system out of equilibrium, perturbs the density and pressure fields, and gives the bath particles a nonzero average velocity, creating a current in the channel. Three models in which the confining effect of the channel is probed are analyzed and compared in this study: the first is the simple symmetric exclusion process (SSEP), for which the stationary density profile and the pressure on the walls in the frame of the tracer are computed. We show that the tracer acts like a dipolar source in an average velocity field. The spatial structure of this 2D strip is then simplified to a one-dimensional (1D) SSEP, in which exchanges of position between the tracer and the bath particles are allowed. Using a combination of mean-field theory and exact solution in the limit where no exchange is allowed gives good predictions of the velocity of the tracer and the density field. Finally, we show that results obtained for the 1D SSEP with exchanges also apply to a gas of overdamped hard disks in a narrow channel. The correspondence between the parameters of the SSEP and of the gas of hard disks is systematic and follows from simple intuitive arguments. Our analytical results are checked numerically.

  15. Wireless Communication over Dispersive Channels

    NARCIS (Netherlands)

    Fang, K.


    Broadband wireless communication systems require high transmission rates, where the bandwidth of the transmitted signal is larger than the channel coherence bandwidth. This gives rise to time dispersion of the transmitted symbols or frequency-selectivity with different frequency components exhibitin

  16. Sales promotion and channel coordination

    NARCIS (Netherlands)

    Wierenga, B.; Soethoudt, J.M.


    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 c

  17. Improved Ion-Channel Biosensors (United States)

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


    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.

  18. EPICS: Channel Access security design

    Energy Technology Data Exchange (ETDEWEB)

    Kraimer, M.; Hill, J.


    This document presents the design for implementing the requirements specified in: EPICS -- Channel Access Security -- functional requirements, Ned. D. Arnold, 03/09/92. Use of the access security system is described along with a summary of the functional requirements. The programmer`s interface is given. Security protocol is described and finally aids for reading the access security code are provided.

  19. Visualizing multi-channel networks

    DEFF Research Database (Denmark)

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


    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...

  20. Sales promotions and channel coordination

    NARCIS (Netherlands)

    B. Wierenga (Berend); H. Soethoudt (Han)


    textabstractConsumer 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 outco

  1. 500 Channels: Wasteland or Wonderland? (United States)

    Lerner, Eric J.


    Considers the changes that new digital technology will bring to the cable television industry. Topics addressed include the media industry, including telephone companies, television networks, and cable companies; federal regulation; increased channel capacity; costs of mass media; monopolies; education on cable; electronic delivery of newspapers…


    Directory of Open Access Journals (Sweden)

    V. V. Apollonov


    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.

  3. Ergonomics Contribution in Maintainability (United States)

    Teymourian, Kiumars; Seneviratne, Dammika; Galar, Diego


    The objective of this paper is to describe an ergonomics contribution in maintainability. The economical designs, inputs and training helps to increase the maintainability indicators for industrial devices. This analysis can be helpful, among other cases, to compare systems, to achieve a better design regarding maintainability requirements, to improve this maintainability under specific industrial environment and to foresee maintainability problems due to eventual changes in a device operation conditions. With this purpose, this work first introduces the notion of ergonomics and human factors, maintainability and the implementation of assessment of human postures, including some important postures to perform maintenance activities. A simulation approach is used to identify the critical posture of the maintenance personnel and implements the defined postures with minimal loads on the personnel who use the equipment in a practical scenario. The simulation inputs are given to the designers to improve the workplace/equipment in order to high level of maintainability. Finally, the work concludes summarizing the more significant aspects and suggesting future research.

  4. Contribution to postnonclassical psychopathology.

    Directory of Open Access Journals (Sweden)

    Quintino-Aires J.


    Full Text Available Any psychological paradigm needs a psychopathological system that helps professionals to describe and explain the behavioral expressions that deviate from “normal” (whether this term is used with the semantic property of statistical or ideal adaptations. In this work, I seek to present the system that I have been developing since 1998 among the psychologists at the Instituto Vegotsky de Lisboa (Vygotsky Institute of Lisbon, Portugal, to understand psychopathology with regard to the vygotskian approach. It was conceived and designed according to the work of Rita Mendes Leal and her contribution to socioemotional development theory, AR Luria’s systemic and dynamic theory of the human brain, the theory of Activity (dyatel’nost of AN Leont’ev, and the psychopathological German school of E Kraepelin, presented and disseminated in Portugal in the early twentieth century by Professor Sobral Cid. It is intended to be a proposal to colleagues who are interested in postnonclassical psychology and a request for arguments.

  5. Recent advances in therapeutic strategies that focus on the regulation of ion channel expression. (United States)

    Ohya, Susumu; Kito, Hiroaki; Hatano, Noriyuki; Muraki, Katsuhiko


    A number of different ion channel types are involved in cell signaling networks, and homeostatic regulatory mechanisms contribute to the control of ion channel expression. Profiling of global gene expression using microarray technology has recently provided novel insights into the molecular mechanisms underlying the homeostatic and pathological control of ion channel expression. It has demonstrated that the dysregulation of ion channel expression is associated with the pathogenesis of neural, cardiovascular, and immune diseases as well as cancers. In addition to the transcriptional, translational, and post-translational regulation of ion channels, potentially important evidence on the mechanisms controlling ion channel expression has recently been accumulated. The regulation of alternative pre-mRNA splicing is therefore a novel therapeutic strategy for the treatment of dominant-negative splicing disorders. Epigenetic modification plays a key role in various pathological conditions through the regulation of pluripotency genes. Inhibitors of pre-mRNA splicing and histone deacetyalase/methyltransferase have potential as potent therapeutic drugs for cancers and autoimmune and inflammatory diseases. Moreover, membrane-anchoring proteins, lysosomal and proteasomal degradation-related molecules, auxiliary subunits, and pharmacological agents alter the protein folding, membrane trafficking, and post-translational modifications of ion channels, and are linked to expression-defect channelopathies. In this review, we focused on recent insights into the transcriptional, spliceosomal, epigenetic, and proteasomal regulation of ion channel expression: Ca(2+) channels (TRPC/TRPV/TRPM/TRPA/Orai), K(+) channels (voltage-gated, KV/Ca(2+)-activated, KCa/two-pore domain, K2P/inward-rectifier, Kir), and Ca(2+)-activated Cl(-) channels (TMEM16A/TMEM16B). Furthermore, this review highlights expression of these ion channels in expression-defect channelopathies.

  6. Quantum channels and memory effects (United States)

    Caruso, Filippo; Giovannetti, Vittorio; Lupo, Cosmo; Mancini, Stefano


    Any physical process can be represented as a quantum channel mapping an initial state to a final state. Hence it can be characterized from the point of view of communication theory, i.e., in terms of its ability to transfer information. Quantum information provides a theoretical framework and the proper mathematical tools to accomplish this. In this context the notion of codes and communication capacities have been introduced by generalizing them from the classical Shannon theory of information transmission and error correction. The underlying assumption of this approach is to consider the channel not as acting on a single system, but on sequences of systems, which, when properly initialized allow one to overcome the noisy effects induced by the physical process under consideration. While most of the work produced so far has been focused on the case in which a given channel transformation acts identically and independently on the various elements of the sequence (memoryless configuration in jargon), correlated error models appear to be a more realistic way to approach the problem. A slightly different, yet conceptually related, notion of correlated errors applies to a single quantum system which evolves continuously in time under the influence of an external disturbance which acts on it in a non-Markovian fashion. This leads to the study of memory effects in quantum channels: a fertile ground where interesting novel phenomena emerge at the intersection of quantum information theory and other branches of physics. A survey is taken of the field of quantum channels theory while also embracing these specific and complex settings.

  7. Integrated criteria for covert channel auditing

    Institute of Scientific and Technical Information of China (English)

    Chang-da WANG; Shi-guang JU


    A new concept, the security level difference of a covert channel, is presented, which means the security level span from the sender to the receiver of the covert channel. Based on this, the integrated criteria for covert channel auditing are given. Whereas TCSEC (Trusted Computer System Evaluation Criteria) or CC (Common Criteria for Information Technology Security Evaluation) only use the bandwidth to evaluate the threat of covert channels, our new criteria integrate the security level difference, the bandwidth sensitive parameter, bandwidth, duration and instantaneous time of covert channels, so as to give a comprehensive evaluation of the threat of covert channels in a multilevel security system.

  8. Secrecy in Cooperative Relay Broadcast Channels

    CERN Document Server

    Ekrem, E


    We investigate the effects of user cooperation on the secrecy of broadcast channels by considering a cooperative relay broadcast channel. We show that user cooperation can increase the achievable secrecy region. We propose an achievable scheme that combines Marton's coding scheme for broadcast channels and Cover and El Gamal's compress-and-forward scheme for relay channels. We derive outer bounds for the rate-equivocation region using auxiliary random variables for single-letterization. Finally, we consider a Gaussian channel and show that both users can have positive secrecy rates, which is not possible for scalar Gaussian broadcast channels without cooperation.

  9. Hydraulics of combining flow in a right-angled compound open channel junction

    Indian Academy of Sciences (India)

    Sushant K Biswal; Pranab Mohapatra; K Muralidhar


    Although combining flows are common in natural streams, no comprehensive experimental data has been compiled to characterize the three-dimensional flow field within the compound channel confluence. The present study examines the time-averaged flow structure at confluence over a rigid bed. Current knowledge of channel confluence, based on laboratory observation indicates that cross flow interactions exert a significant influence on confluence events. Secondary current and turbulent stresses are reproduced well by the hydraulic model and found greater in the interface region as relative flow ratio decreases. Velocity fields in combining flow region arising from varying discharge ratios are presented. A zone of depression in surface elevation in compound channel junction is observed as well. The flow field in compound channel is seen to be moderately different from that of simple channel junction. This study contributes to a better knowledge of hydraulic key processes into fundamental aspect of combining flow dynamics.

  10. Entrance channel effect with stable and radioactive beams using dynamical cluster decay model

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Raj, E-mail: [Dipartimento di Fisica “Galileo Galilei” and INFN, University of Padova, Padova-35131 (Italy); Jain, Deepika [School of Physics and Material Science, Thapar University, Patiala-147004 (India)


    The decay of hot and rotating {sup 172}Yb*, formed in two entrance channels {sup 124}Sn + {sup 48}Ca and {sup 132}Sn + {sup 40}Ca, is studied using the dynamical cluster-decay model. The effect of entrance channel, deformations (up to β{sub 2}), barrier modification and fusion enhancement are addressed. The decay pattern of compound system, formed in different channels at comparable energy around the barrier, shows change in magnitude with structure remains almost same. There is an increase in the fusion probability with decrease in barrier modification, which leads to fusion enhancement at low energies. The higher ℓ values are contributing for {sup 132}Sn + {sup 40}Ca channel at lower energies as compare to {sup 124}Sn + {sup 48}Ca. It is inferred that with the use of stable and radioactive beam, forming same compound nucleus, the entrance channel dependence changes with the excitation energy.

  11. Double pion photoproduction on the nucleon: study of the isospin channels

    Energy Technology Data Exchange (ETDEWEB)

    Gomez Tejedor, J.A. [Valencia Univ. (Spain). Dept. de Fisica Teorica; Oset, E. [Valencia Univ. (Spain). Dept. de Fisica Teorica


    A model for the {gamma}p{yields}{pi}{sup +}{pi}{sup -}p reaction developed earlier is extended to account for all isospin channels. The model includes N, {Delta}(1232), N{sup *}(1440) and N{sup *}(1520) as intermediate baryonic states and the {rho} meson as an intermediate 2{pi} resonance. Although many terms contribute to the cross section, some channels exhibit particular sensitivity to certain mechanisms of resonance excitation or decay and the reactions provide novel information on such mechanisms. In particular the {gamma}N{yields}N{sup *}(1520){yields}{Delta}{pi} process affects all the channels and is a key ingredient in the interpretation of the data. Comparison is made with all available data and the agreement is good in some channels. The remaining discrepancies in some other channels are discussed. (orig.).

  12. Potential Roles of Amiloride-Sensitive Sodium Channels in Cancer Development

    Directory of Open Access Journals (Sweden)

    Siguang Xu


    Full Text Available The ENaC/degenerin ion channel superfamily includes the amiloride-sensitive epithelial sodium channel (ENaC and acid sensitive ionic channel (ASIC. ENaC is a multimeric ion channel formed by heteromultimeric membrane glycoproteins, which participate in a multitude of biological processes by mediating the transport of sodium (Na+ across epithelial tissues such as the kidney, lungs, bladder, and gut. Aberrant ENaC functions contribute to several human disease states including pseudohypoaldosteronism, Liddle syndrome, cystic fibrosis, and salt-sensitive hypertension. Increasing evidence suggests that ion channels not only regulate ion homeostasis and electric signaling in excitable cells but also play important roles in cancer cell behaviors such as proliferation, apoptosis, invasion, and migration. Indeed, ENaCs/ASICs had been reported to be associated with cancer characteristics. Given their cell surface localization and pharmacology, pharmacological strategies to target ENaC/ASIC family members may be promising cancer therapeutics.

  13. Synchronized network activity in developing rat hippocampus involves regional hyperpolarization-activated cyclic nucleotide-gated (HCN) channel function


    Bender, Roland A.; Galindo, Rafael; Mameli, Manuel; Gonzalez-Vega, Rebeca; Valenzuela, C. Fernando; Tallie Z. Baram


    The principal form of synchronized network activity in neonatal hippocampus consists of low frequency ‘giant depolarizing potentials’ (GDPs). Whereas contribution of both GABA and glutamate to their generation has been demonstrated, full understanding of the mechanisms underlying these synchronized activity bursts remains incomplete. A contribution of the h-current, conducted by HCN channels, to GDPs has been a topic of substantial interest. Here we focus on HCN1, the prevalent HCN channel is...

  14. EMSL Contribution Plan

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, Allison A.


    This Contribution Plan is EMSL’s template for achieving our vision of simultaneous excellence in all aspects of our mission as a national scientific user facility. It reflects our understanding of the long-term stewardship we must work toward to meet the scientific challenges faced by the Department of Energy (DOE) and the nation. During the next decade, we will implement the strategies contained in this Plan, working closely with the scientific community, our advisory committees, DOE’s Office of Biological and Environmental Research, and other key stakeholders. This Plan is fully aligned with the strategic plans of DOE, its Office of Science, and the Pacific Northwest National Laboratory (PNNL). We recognize that shifts in science and technology, national priorities, and resources made available through the Federal budget process create planning uncertainties and, ultimately, a highly dynamic planning environment. Accordingly, this Plan should be viewed as a living document and we continually evaluate the changing needs and opportunities posed by our stakeholders (i.e., DOE, users, staff, advisory committees), work closely with them to understand and respond to those changes, and align our strategy accordingly. This Plan is organized around two sections. Section 1 describes our vision and four strategic outcomes: 1) Scientific Innovation, 2) Capabilities that Transform Science, 3) Outstanding Management and Operations, and Engaged and Proactive Users. These outcomes provide the framework for seven critical actions we must take during the next 3 to 5 years: 1) Establishing leadership in EMSL science themes, 2) building and deploying transformational capabilities, 3) integrating computation with experiment, 4) ensuring EMSL’s workforce meets the scientific challenges of the future, 5) creating partnerships, 6) attracting and engaging users in EMSL’s long-term strategy, and 7) building a research infrastructure that meets emerging scientific needs. Section 2

  15. Linking channel hydrology with riparian wetland accretion in tidal rivers (United States)

    Ensign, Scott H.; Noe, Gregory B.; Hupp, Cliff R.


    hydrologic processes by which tide affects river channel and riparian morphology within the tidal freshwater zone are poorly understood yet are fundamental to predicting the fate of coastal rivers and wetlands as sea level rises. We investigated patterns of sediment accretion in riparian wetlands along the nontidal through oligohaline portion of two coastal plain rivers in Maryland, U.S., and how flow velocity, water level, and suspended sediment concentration (SSC) in the channel may have contributed to those patterns. Sediment accretion was measured over a 1 year period using artificial marker horizons, channel hydrology was measured over a 1 month period using acoustic Doppler current profilers, and SSC was predicted from acoustic backscatter. Riparian sediment accretion was lowest at the nontidal sites (mean and standard deviation = 8 ± 8 mm yr-1), highest at the upstream tidal freshwater forested wetlands (TFFW) (33 ± 28 mm yr-1), low at the midstream TFFW (12 ± 9 mm yr-1), and high at the oligohaline (fresh-to-brackish) marshes (19 ± 8 mm yr-1). Channel maximum flood and ebb velocity was twofold faster at the oligohaline than tidal freshwater zone on both tidal rivers, corresponding with the differences in in-channel SSC: The oligohaline zone's SSC was more than double the tidal freshwater zone's and was greater than historical SSC at the nontidal gages. The tidal wave characteristics differed between rivers, leading to significantly greater in-channel SSC during floodplain inundation in the weakly convergent than the strongly convergent tidal river. High sediment accretion at the upstream TFFW was likely due to high river discharge following a hurricane.

  16. Regulation of CFTR chloride channel macroscopic conductance by extracellular bicarbonate. (United States)

    Li, Man-Song; Holstead, Ryan G; Wang, Wuyang; Linsdell, Paul


    The CFTR contributes to Cl⁻ and HCO₃⁻ transport across epithelial cell apical membranes. The extracellular face of CFTR is exposed to varying concentrations of Cl⁻ and HCO₃⁻ in epithelial tissues, and there is evidence that CFTR is sensitive to changes in extracellular anion concentrations. Here we present functional evidence that extracellular Cl⁻ and HCO₃⁻ regulate anion conduction in open CFTR channels. Using cell-attached and inside-out patch-clamp recordings from constitutively active mutant E1371Q-CFTR channels, we show that voltage-dependent inhibition of CFTR currents in intact cells is significantly stronger when the extracellular solution contains HCO₃⁻ than when it contains Cl⁻. This difference appears to reflect differences in the ability of extracellular HCO₃⁻ and Cl⁻ to interact with and repel intracellular blocking anions from the pore. Strong block by endogenous cytosolic anions leading to reduced CFTR channel currents in intact cells occurs at physiologically relevant HCO₃⁻ concentrations and membrane potentials and can result in up to ∼50% inhibition of current amplitude. We propose that channel block by cytosolic anions is a previously unrecognized, physiologically relevant mechanism of channel regulation that confers on CFTR channels sensitivity to different anions in the extracellular fluid. We further suggest that this anion sensitivity represents a feedback mechanism by which CFTR-dependent anion secretion could be regulated by the composition of the secretions themselves. Implications for the mechanism and regulation of CFTR-dependent secretion in epithelial tissues are discussed.

  17. Sodium channel biophysics, late sodium current and genetic arrhythmic syndromes. (United States)

    Chadda, Karan R; Jeevaratnam, Kamalan; Lei, Ming; Huang, Christopher L-H


    Arrhythmias arise from breakdown of orderly action potential (AP) activation, propagation and recovery driven by interactive opening and closing of successive voltage-gated ion channels, in which one or more Na(+) current components play critical parts. Early peak, Na(+) currents (I Na) reflecting channel activation drive the AP upstroke central to cellular activation and its propagation. Sustained late Na(+) currents (I Na-L) include contributions from a component with a delayed inactivation timecourse influencing AP duration (APD) and refractoriness, potentially causing pro-arrhythmic phenotypes. The magnitude of I Na-L can be analysed through overlaps or otherwise in the overall voltage dependences of the steady-state properties and kinetics of activation and inactivation of the Na(+) conductance. This was useful in analysing repetitive firing associated with paramyotonia congenita in skeletal muscle. Similarly, genetic cardiac Na(+) channel abnormalities increasing I Na-L are implicated in triggering phenomena of automaticity, early and delayed afterdepolarisations and arrhythmic substrate. This review illustrates a wide range of situations that may accentuate I Na-L. These include (1) overlaps between steady-state activation and inactivation increasing window current, (2) kinetic deficiencies in Na(+) channel inactivation leading to bursting phenomena associated with repetitive channel openings and (3) non-equilibrium gating processes causing channel re-opening due to more rapid recoveries from inactivation. All these biophysical possibilities were identified in a selection of abnormal human SCN5A genotypes. The latter presented as a broad range of clinical arrhythmic phenotypes, for which effective therapeutic intervention would require specific identification and targeting of the diverse electrophysiological abnormalities underlying their increased I Na-L.

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

    KAUST Repository

    Chaaban, Anas


    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.

  19. Channel based generating function approach to the stochastic Hodgkin-Huxley neuronal system (United States)

    Ling, Anqi; Huang, Yandong; Shuai, Jianwei; Lan, Yueheng


    Internal and external fluctuations, such as channel noise and synaptic noise, contribute to the generation of spontaneous action potentials in neurons. Many different Langevin approaches have been proposed to speed up the computation but with waning accuracy especially at small channel numbers. We apply a generating function approach to the master equation for the ion channel dynamics and further propose two accelerating algorithms, with an accuracy close to the Gillespie algorithm but with much higher efficiency, opening the door for expedited simulation of noisy action potential propagating along axons or other types of noisy signal transduction.

  20. Mutations in Sodium Channel Gene SCN9A and the Pain Perception Disorders


    Marković, Danica; Janković, Radmilo; Veselinović, Ines


    Voltage-gated sodium channels (NaV) play a crucial role in development and propagation of action potentials in neurons and muscle cells. NaV1.7 channels take a special place in modern science since it is believed that they contribute to nerve hyperexcitability. Mutations of the gene SCN9A, which codes the α subunit of NaV1.7 channels, are associated with pain perception disorders (primary erythermalgia, congenital analgesia, and paroxysmal pain disorder). It is considered that the SCN9A gene ...

  1. Transient Receptor Potential Canonical Type 3 Channels - Their Evolving Role in Hypertension and Its Related Complications

    DEFF Research Database (Denmark)

    Wang, Peijian; Liu, Daoyan; Tepel, Martin


    , and cerebrovascular events. In this review, we summarize the role of TRPC3 channels in the cardiovascular system, we focus on their pathophysiogical role in hypertension and related target organ damages. We provide new insight into the involvement of TRPC3 channels in the development of hypertension and its related......ABSTRACT: Recent studies indicate that transient receptor potential canonical type 3 (TRPC3) channels contribute to the regulation of blood pressure, vascular and renal function. Several studies show that TRPC3 dysfunction is associated with hypertension, atherosclerosis, cardiac hypertrophy...

  2. Spicing up the sensation of stretch: TRPV1 controls mechanosensitive Piezo channels. (United States)

    Altier, Christophe


    Piezo proteins--a family of mammalian cation-selective ion channels that respond to mechanical stretch--are molecular mediators of biological processes, including vascular tone, hearing, touch, and pain. In this issue of Science Signaling, Rohacs and colleagues demonstrate that activation of the heat-sensitive transient receptor potential vanilloid 1 (TRPV1), another cation channel, inhibits Piezo channels through a calcium-induced depletion of phosphoinositides. This regulation could contribute to the cellular mechanisms by which the TRPV1 activator capsaicin mitigates mechanical hypersensitivity.

  3. Distributed Joint Source-Channel Coding on a Multiple Access Channel with Side Information

    CERN Document Server

    Rajesh, R


    We consider the problem of transmission of several distributed sources over a multiple access channel (MAC) with side information at the sources and the decoder. Source-channel separation does not hold for this channel. Sufficient conditions are provided for transmission of sources with a given distortion. The source and/or the channel could have continuous alphabets (thus Gaussian sources and Gaussian MACs are special cases). Various previous results are obtained as special cases. We also provide several good joint source-channel coding schemes for a discrete/continuous source and discrete/continuous alphabet channel. Channels with feedback and fading are also considered. Keywords: Multiple access channel, side information, lossy joint source-channel coding, channels with feedback, fading channels.

  4. Gene transcription and splicing of T-type channels are evolutionarily-conserved strategies for regulating channel expression and gating.

    Directory of Open Access Journals (Sweden)

    Adriano Senatore

    Full Text Available T-type calcium channels operate within tightly regulated biophysical constraints for supporting rhythmic firing in the brain, heart and secretory organs of invertebrates and vertebrates. The snail T-type gene, LCa(v3 from Lymnaea stagnalis, possesses alternative, tandem donor splice sites enabling a choice of a large exon 8b (201 aa or a short exon 25c (9 aa in cytoplasmic linkers, similar to mammalian homologs. Inclusion of optional 25c exons in the III-IV linker of T-type channels speeds up kinetics and causes hyperpolarizing shifts in both activation and steady-state inactivation of macroscopic currents. The abundant variant lacking exon 25c is the workhorse of embryonic Ca(v3 channels, whose high density and right-shifted activation and availability curves are expected to increase pace-making and allow the channels to contribute more significantly to cellular excitation in prenatal tissue. Presence of brain-enriched, optional exon 8b conserved with mammalian Ca(v3.1 and encompassing the proximal half of the I-II linker, imparts a ~50% reduction in total and surface-expressed LCa(v3 channel protein, which accounts for reduced whole-cell calcium currents of +8b variants in HEK cells. Evolutionarily conserved optional exons in cytoplasmic linkers of Ca(v3 channels regulate expression (exon 8b and a battery of biophysical properties (exon 25c for tuning specialized firing patterns in different tissues and throughout development.

  5. Coastal Maintained Channels in US waters (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...

  6. Channel estimation in DCT-based OFDM. (United States)

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


    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.

  7. The quantum capacity with symmetric side channels

    CERN Document Server

    Smith, G; Winter, A; Smith, Graeme; Smolin, John A.; Winter, Andreas


    We present an upper bound for the quantum channel capacity that is both additive and convex. Our bound can be interpreted as the capacity of a channel for high-fidelity communication when assisted by the family of all channels mapping symmetrically to their output and environment. The bound seems to be quite tight, and for degradable quantum channels it coincides with the unassisted channel capacity. Using this symmetric side channel capacity, we find new upper bounds on the capacity of the depolarizing channel. We also briefly indicate an analogous notion for distilling entanglement using the same class of (one-way) channels, yielding one of the few genuinely 1-LOCC monotonic entanglement measures.

  8. Extension of ITU IMT-A Channel Models for Elevation Domains and Line-of-Sight Scenarios

    CERN Document Server

    Zhong, Zhimeng; Li, Xin; Li, Xue


    In this contribution, the 3-dimensional (3D) channel characteristics, particularly in the elevation domains, are extracted through measurements in typical urban macro and micro environments in Xi'an China. Stochastic channel model parameters are obtained based on the high-resolution multi-path parameter estimates. In addition, a modified spatial channel model (SCM) for the line-of-sight (LoS) scenario is proposed where the LoS polarization matrix is parameterized in accordance with the reality. Measurement results justify the reasonability of the proposed model. These works significantly improve the applicability of the ITU SCM models in realistic 3D channel simulations.

  9. Small-conductance Ca2+-activated potassium type 2 channels regulate the formation of contextual fear memory.

    Directory of Open Access Journals (Sweden)

    Saravana R K Murthy

    Full Text Available Small-conductance, Ca2+ activated K+ channels (SK channels are expressed at high levels in brain regions responsible for learning and memory. In the current study we characterized the contribution of SK2 channels to synaptic plasticity and to different phases of hippocampal memory formation. Selective SK2 antisense-treatment facilitated basal synaptic transmission and theta-burst induced LTP in hippocampal brain slices. Using the selective SK2 antagonist Lei-Dab7 or SK2 antisense probes, we found that hippocampal SK2 channels are critical during two different time windows: 1 blockade of SK2 channels before the training impaired fear memory, whereas, 2 blockade of SK2 channels immediately after the training enhanced contextual fear memory. We provided the evidence that the post-training cleavage of the SK2 channels was responsible for the observed bidirectional effect of SK2 channel blockade on memory consolidation. Thus, Lei-Dab7-injection before training impaired the C-terminal cleavage of SK2 channels, while Lei-Dab7 given immediately after training facilitated the C-terminal cleavage. Application of the synthetic peptide comprising a leucine-zipper domain of the C-terminal fragment to Jurkat cells impaired SK2 channel-mediated currents, indicating that the endogenously cleaved fragment might exert its effects on memory formation by blocking SK2 channel-mediated currents. Our present findings suggest that SK2 channel proteins contribute to synaptic plasticity and memory not only as ion channels but also by additionally generating a SK2 C-terminal fragment, involved in both processes. The modulation of fear memory by down-regulating SK2 C-terminal cleavage might have applicability in the treatment of anxiety disorders in which fear conditioning is enhanced.

  10. Degenerate RFID Channel Modeling for Positioning Applications

    Directory of Open Access Journals (Sweden)

    A. Povalac


    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.

  11. Radio propagation measurement and channel modelling

    CERN Document Server

    Salous, Sana


    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

  12. Optimal superdense coding over memory channels

    Energy Technology Data Exchange (ETDEWEB)

    Shadman, Z.; Kampermann, H.; Bruss, D.; Macchiavello, C. [Institute fuer Theoretische Physik III, Heinrich-Heine-Universitaet Duesseldorf, DE-40225 Duesseldorf (Germany); Dipartimento di Fisica ' ' A. Volta' ' and INFM-Unita di Pavia, Via Bassi 6, IT-27100 Pavia (Italy)


    We study the superdense coding capacity in the presence of quantum channels with correlated noise. We investigate both the cases of unitary and nonunitary encoding. Pauli channels for arbitrary dimensions are treated explicitly. The superdense coding capacity for some special channels and resource states is derived for unitary encoding. We also provide an example of a memory channel where nonunitary encoding leads to an improvement in the superdense coding capacity.

  13. Covert channel detection using Information Theory

    CERN Document Server

    Hélouët, Loïc; 10.4204/EPTCS.51.3


    This paper presents an information theory based detection framework for covert channels. We first show that the usual notion of interference does not characterize the notion of deliberate information flow of covert channels. We then show that even an enhanced notion of "iterated multivalued interference" can not capture flows with capacity lower than one bit of information per channel use. We then characterize and compute the capacity of covert channels that use control flows for a class of systems.

  14. Covert channel detection using Information Theory

    Directory of Open Access Journals (Sweden)

    Loïc Hélouët


    Full Text Available This paper presents an information theory based detection framework for covert channels. We first show that the usual notion of interference does not characterize the notion of deliberate information flow of covert channels. We then show that even an enhanced notion of "iterated multivalued interference" can not capture flows with capacity lower than one bit of information per channel use. We then characterize and compute the capacity of covert channels that use control flows for a class of systems.

  15. Walking droplets in linear channels (United States)

    Filoux, Boris; Hubert, Maxime; Schlagheck, Peter; Vandewalle, Nicolas


    When a droplet is placed onto a vertically vibrated bath, it can bounce without coalescing. Upon an increase of the forcing acceleration, the droplet is propelled by the wave it generates and becomes a walker with a well-defined speed. We investigate the confinement of a walker in different rectangular cavities, used as waveguides for the Faraday waves emitted by successive droplet bounces. By studying the walker velocities, we discover that one-dimensional confinement is optimal for narrow channels of width of D ≃1.5 λF . Thereby, the walker follows a quasilinear path. We also propose an analogy with waveguide models based on the observation of the Faraday instability within the channels.

  16. Identity Authentication over Noisy Channels

    Directory of Open Access Journals (Sweden)

    Fanfan Zheng


    Full Text Available Identity authentication is the process of verifying users’ validity. Unlike classical key-based authentications, which are built on noiseless channels, this paper introduces a general analysis and design framework for identity authentication over noisy channels. Specifically, the authentication scenarios of single time and multiple times are investigated. For each scenario, the lower bound on the opponent’s success probability is derived, and it is smaller than the classical identity authentication’s. In addition, it can remain the same, even if the secret key is reused. Remarkably, the Cartesian authentication code proves to be helpful for hiding the secret key to maximize the secrecy performance. Finally, we show a potential application of this authentication technique.

  17. 3D flexible water channel: stretchability of nanoscale water bridge. (United States)

    Chen, Jige; Wang, Chunlei; Wei, Ning; Wan, Rongzheng; Gao, Yi


    Artificial water channels can contribute to a better understanding of natural water channels and offer a highly selective, advanced conductance system. Most studies use nanotubes, however it is difficult to fabricate a flexible structure, and the nanosized diameter brings nanoconfinement effects, and nanotube toxicity arouses biosafety concerns. In this paper, we use an electric field to restrain the water molecules to form a nanoscale water bridge as an artificial water channel to connect a separated solid plate by molecular dynamics simulations. We observe strong 3D flexible stretchability in the water bridge, maintaining a variable length and an arbitrary angle for a considerably long time. The stretching of the water bridge enables it to be polarized at an arbitrary angle and the stretchability is linearly dependent upon the polarization strength. More interestingly, we show the possibility of establishing complex water networks, e.g., triangle, rectangle, hexagon, and tetrahedron-tetrahedron water networks. Our results may help realize structurally flexible and environmentally friendly water channels for lab-on-a-chip applications in nanofluidics.

  18. Groundwater Discharge along a Channelized Coastal Plain Stream

    Energy Technology Data Exchange (ETDEWEB)

    LaSage, Danita M [Ky Dept for natural resources, Div of Mine Permits; Sexton, Joshua L [JL Sexton and Son; Mukherjee, Abhijit [Univ of Tx, Jackson School of Geosciences, Bur of Econ. Geology; Fryar, Alan E [Univ of KY, Dept of Earth and Geoligical Sciences; Greb, Stephen F [Univ of KY, KY Geological Survey


    In the Coastal Plain of the southeastern USA, streams have commonly been artificially channelized for flood control and agricultural drainage. However, groundwater discharge along such streams has received relatively little attention. Using a combination of stream- and spring-flow measurements, spring temperature measurements, temperature profiling along the stream-bed, and geologic mapping, we delineated zones of diffuse and focused discharge along Little Bayou Creek, a channelized, first-order perennial stream in western Kentucky. Seasonal variability in groundwater discharge mimics hydraulic-head fluctuations in a nearby monitoring well and spring-discharge fluctuations elsewhere in the region, and is likely to reflect seasonal variability in recharge. Diffuse discharge occurs where the stream is incised into the semi-confined regional gravel aquifer, which is comprised of the Mounds Gravel. Focused discharge occurs upstream where the channel appears to have intersected preferential pathways within the confining unit. Seasonal fluctuations in discharge from individual springs are repressed where piping results in bank collapse. Thereby, focused discharge can contribute to the morphological evolution of the stream channel.

  19. Landscapes of Santa Rosa Island, Channel Islands National Park, California (United States)

    Schumann, R. Randall; Minor, Scott A.; Muhs, Daniel R.; Pigati, Jeffery S.


    Santa Rosa Island (SRI) is the second-largest of the California Channel Islands. It is one of 4 east–west aligned islands forming the northern Channel Islands chain, and one of the 5 islands in Channel Islands National Park. The landforms, and collections of landforms called landscapes, of Santa Rosa Island have been created by tectonic uplift and faulting, rising and falling sea level, landslides, erosion and deposition, floods, and droughts. Landscape features, and areas delineating groups of related features on Santa Rosa Island, are mapped, classified, and described in this paper. Notable landscapes on the island include beaches, coastal plains formed on marine terraces, sand dunes, and sand sheets. In this study, the inland physiography has been classified into 4 areas based on relief and degree of fluvial dissection. Most of the larger streams on the island occupy broad valleys that have been filled with alluvium and later incised to form steep- to vertical-walled arroyos, or barrancas, leaving a relict floodplain above the present channel. A better understanding of the processes and mechanisms that created these landscapes enhances visitors’ enjoyment of their surroundings and contributes to improving land and resource management strategies in order to optimize and balance the multiple goals of conservation, preservation, restoration, and visitor experience.

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

    Directory of Open Access Journals (Sweden)

    Francisco Andrés Peralta


    Full Text Available 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.