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Sample records for doubly selective channels

  1. Joint Channel Estimation and Signal Detection for the OFDM System Without Cyclic Prefix Over Doubly-Selective Channels

    NASA Astrophysics Data System (ADS)

    Song, Lijun; Lei, Xia; Jin, Maozhu; Lv, Zhihan

    2015-12-01

    In the high-speed railway wireless communication, a joint channel estimation and signal detection algorithm is proposed for the orthogonal frequency division multiplexing (OFDM) system without cyclic prefix in the doubly-selective fading channels. Our proposed method first combines the basis expansion model (BEM) and the inter symbol interference (ISI) cancellation to overcome the situation that exists with the fast time-varying channel and the normalized maximum multipath channel exceeding the length of the cyclic prefix (CP). At first, the channel estimation and signal detection can be approximated without considering the ISI. Then, the channel parameters and signal detection are updated through ISI cancellation and circular convolution reconstruction from the frequency domain. The simulations show the algorithm can improve the performance of channel estimation and signal detection.

  2. Time reversal communication over doubly spread channels.

    PubMed

    Zeng, Wen-Jun; Jiang, Xue

    2012-11-01

    Conventional time reversal can mitigate multipath delay dispersion by temporal focusing. But it is not applicable to time-varying channels with a Doppler spread. Although recently time reversal communication has been adapted to time-variant channels, the modified technique requires frequent channel updates to track channel variations and cannot handle large Doppler spread, which means that it cannot achieve frequency focusing. In this paper, two time reversal receivers for underwater acoustic communications over doubly spread channels are proposed. The proposed approach, which can be interpreted as time-frequency channel matching, is based on the channel spreading function rather than impulse response adopted by the existing techniques; this leads to much less frequent channel updates. Unlike existing methods that only correct a single Doppler shift, the proposed approach uses a rake-like structure to compensate for multiple Doppler shifts and hence can eliminate severe Doppler spread induced by temporal channel variations. Simulation results verify the effectiveness of the proposed approach, indicating that it can simultaneously counteract delay and Doppler spreads, achieving both temporal and frequency focusing.

  3. SINR Analysis of Hexagonal Multicarrier Transmission Systems in the Presence of Insufficient Synchronization for Doubly Dispersive Channel

    NASA Astrophysics Data System (ADS)

    Xu, Kui; Xu, Youyun; Zhang, Dongmei

    2011-07-01

    This paper analyzes the effect of the insufficient synchronization (carrier frequency offset, timing offset) on hexagonal multicarrier transmission (HMT) systems for doubly dispersive channel. Exact SINR and demodulated symbol expressions for HMT systems in the presence of insufficient synchronization transmission conditions over doubly dispersive channel with exponential delay power profile and U-shape Doppler power spectrum and uniform delay power profile and uniform Doppler power spectrum are derived, respectively. Theoretical analysis shows that similar degradations on symbol amplitude and phase caused by insufficient synchronization are incurred as in traditional cyclic-prefix orthogonal frequency division multiplexing (CP-OFDM) transmission. HMT systems outperform traditional OFDM systems with respect to signal to interference-plus-noise-ratio (SINR) against inter-symbol interference (ISI) and inter-carrier interference (ICI) caused by insufficient synchronization and doubly dispersive(DD) channel. The BER performance of the HMT systems using Monte Carlo simulation match with the conclusion given by the proposed exact SINR expression.

  4. Fully Coupled Channel Approach to Doubly Strange s-Shell Hypernuclei

    SciTech Connect

    Nemura, H.; Shinmura, S.; Akaishi, Y.; Myint, Khin Swe

    2005-05-27

    We describe ab initio calculations of doubly strange, S=-2, s-shell hypernuclei ({sub {lambda}}{sub {lambda}}{sup 4}H, {sub {lambda}}{sub {lambda}}{sup 5}H, {sub {lambda}}{sub {lambda}}{sup 5}He, and {sub {lambda}}{sub {lambda}}{sup 6}He) as a first attempt to explore the few-body problem of the full-coupled channel scheme for these systems. The wave function includes {lambda}{lambda}, {lambda}{sigma}, N{xi}, and {sigma}{sigma} channels. Minnesota NN, D2{sup '} YN, and simulated YY potentials based on the Nijmegen hard-core model are used. Bound-state solutions of these systems are obtained. We find that a set of phenomenological B{sub 8}B{sub 8} interactions among the octet baryons in S=0,-1, and -2 sectors, which is consistent with all of the available experimental binding energies of S=0,-1, and -2 s-shell (hyper)nuclei, can predict a particle stable bound state of {sub {lambda}}{sub {lambda}}{sup 4}H. For {sub {lambda}}{sub {lambda}}{sup 5}H and {sub {lambda}}{sub {lambda}}{sup 5}He, {lambda}N-{sigma}N and {xi}N-{lambda}{sigma} potentials significantly affect the net {lambda}{lambda}-N{xi} coupling, and a large {xi} probability is obtained even for a weaker {lambda}{lambda}-N{xi} potential.

  5. Search for doubly-charged Higgs bosons through the diboson decay channel at the ILC

    NASA Astrophysics Data System (ADS)

    Cao, Jun; Liu, Yao-Bei

    2016-09-01

    The doubly-charged Higgs bosons (H5±±) are the typical particles predicted in the Georgi-Machacek (GM) model and their decay modes depend on the magnitude of the triplet vacuum expectation value (VEV) vΔ. In this paper, we focus on the study of their pair production process at the International Linear Collider (ILC): e+e‑→ H 5++H 5‑‑→ W+W+W‑W‑→ ℓ‑ℓ‑jjjjE/ Tmiss, with the subsequent decay of two like-sign W bosons through a pair of like-sign dileptons and the remaining two in their hadronic decays. The 5σ confidence level discovery reach at the ILC is also studied with two collision energies of 1.0 TeV and 1.5 TeV.

  6. Light doubly charged Higgs boson via the WW^* channel at LHC

    NASA Astrophysics Data System (ADS)

    Kang, Zhaofeng; Li, Jinmian; Li, Tianjun; Liu, Yandong; Ning, Guo-Zhu

    2015-12-01

    The doubly charged Higgs bosons H^{± ± } searches at the large hadron collider (LHC) have been studied extensively and strong bound is available for H^{± ± } dominantly decaying into a pair of same-sign di-leptons. In this paper we point out that there is a large cavity in the light H^{± ± } mass region left unexcluded. In particular, H^{± ± } can dominantly decay into WW or WW^* (For instance, in the type-II seesaw mechanism the triplet acquires a vacuum expectation value around 1 GeV), and then it is found that H^{± ± } with mass even below 2m_W remains untouched by the current collider searches. Searching for such a H^{± ± } at the LHC is the topic of this paper. We perform detailed signal and background simulation, especially including the non-prompt tbar{t} background which is the dominant one nevertheless ignored before. We show that such H^{± ± } should be observable at the 14 TeV LHC with 10-30 fb^{-1} integrated luminosity.

  7. Potassium Versus Sodium Selectivity in Monovalent Ion Channel Selectivity Filters.

    PubMed

    Lim, Carmay; Dudev, Todor

    2016-01-01

    Transport of Na(+) and K(+) ions across the cell membrane is carried out by specialized pore-forming ion channel proteins, which exert tight control on electrical signals in cells by regulating the inward/outward flow of the respective cation. As Na(+) and K(+) ions are both present in the body fluids, their respective ion channels should discriminate with high fidelity between the two competing metal ions, conducting the native cation while rejecting its monovalent contender (and other ions present in the cellular/extracellular milieu). Indeed, monovalent ion channels are characterized by remarkable metal selectivity. This striking ion selectivity of monovalent ion channels is astonishing in view of the close similarity between Na(+) and K(+): both are spherical alkali cations with the same charge, analogous chemical and physical properties, and similar ionic radii. The monovalent ion channel selectivity filters (SFs), which dictate the selectivity of the channel, differ in oligomericity, composition, overall charge, pore size, and solvent accessibility. This diversity of SFs raises the following intriguing questions: (1) What factors govern the metal competition in these SFs? (2) Which of these factors are exploited in achieving K(+) or Na(+) selectivity in the different types of monovalent channel SFs? These questions are addressed herein by summarizing results from recent studies. The results show that over billions of years of evolution, the SFs of potassium and sodium ion channels have adapted to the specific physicochemical properties of the cognate ion, using various strategies to enable them to efficiently select the native ion among its contenders.

  8. Ion selectivity strategies of sodium channel selectivity filters.

    PubMed

    Dudev, Todor; Lim, Carmay

    2014-12-16

    CONSPECTUS: Sodium ion channels selectively transport Na(+) cations across the cell membrane. These integral parts of the cell machinery are implicated in regulating the cardiac, skeletal and smooth muscle contraction, nerve impulses, salt and water homeostasis, as well as pain and taste perception. Their malfunction often results in various channelopathies of the heart, brain, skeletal muscles, and lung; thus, sodium channels are key drug targets for various disorders including cardiac arrhythmias, heart attack, stroke, migraine, epilepsy, pain, cancer, and autoimmune disorders. The ability of sodium channels to discriminate the native Na(+) among other competing ions in the surrounding fluids is crucial for proper cellular functions. The selectivity filter (SF), the narrowest part of the channel's open pore, lined with amino acid residues that specifically interact with the permeating ion, plays a major role in determining Na(+) selectivity. Different sodium channels have different SFs, which vary in the symmetry, number, charge, arrangement, and chemical type of the metal-ligating groups and pore size: epithelial/degenerin/acid-sensing ion channels have generally trimeric SFs lined with three conserved neutral serines and/or backbone carbonyls; eukaryotic sodium channels have EKEE, EEKE, DKEA, and DEKA SFs with an invariant positively charged lysine from the second or third domain; and bacterial voltage-gated sodium (Nav) channels exhibit symmetrical EEEE SFs, reminiscent of eukaryotic voltage-gated calcium channels. How do these different sodium channel SFs achieve high selectivity for Na(+) over its key rivals, K(+) and Ca(2+)? What factors govern the metal competition in these SFs and which of these factors are exploited to achieve Na(+) selectivity in the different sodium channel SFs? The free energies for replacing K(+) or Ca(2+) bound inside different model SFs with Na(+), evaluated by a combination of density functional theory and continuum dielectric

  9. The potassium channel: Structure, selectivity and diffusion

    NASA Astrophysics Data System (ADS)

    Allen, T. W.; Bliznyuk, A.; Rendell, A. P.; Kuyucak, S.; Chung, S.-H.

    2000-05-01

    We employ the entire experimentally determined protein structure for the KcsA potassium channel from Streptomyces lividans in molecular dynamics calculations to observe hydrated channel protein structure, ion solvation, selectivity, multiple ion configurations, and diffusion. Free energy perturbation calculations display a significant ion discrimination of ˜9 kT in favor of the larger K+ ion. The protein forming the channel is very flexible yet is unable to fully solvate the Na+ ion because of its smaller size and large solvation energy. There is evidence that acidic and basic sidechains may dissociate in the presence of multiple K+ ions to explain experimental ion density maps. K+ diffusion is found to vary from approximately 10%-90% of bulk, supporting the high channel currents observed experimentally.

  10. Image Discrimination Models With Stochastic Channel Selection

    NASA Technical Reports Server (NTRS)

    Ahumada, Albert J., Jr.; Beard, Bettina L.; Null, Cynthia H. (Technical Monitor)

    1995-01-01

    Many models of human image processing feature a large fixed number of channels representing cortical units varying in spatial position (visual field direction and eccentricity) and spatial frequency (radial frequency and orientation). The values of these parameters are usually sampled at fixed values selected to ensure adequate overlap considering the bandwidth and/or spread parameters, which are usually fixed. Even high levels of overlap does not always ensure that the performance of the model will vary smoothly with image translation or scale changes. Physiological measurements of bandwidth and/or spread parameters result in a broad distribution of estimated parameter values and the prediction of some psychophysical results are facilitated by the assumption that these parameters also take on a range of values. Selecting a sample of channels from a continuum of channels rather than using a fixed set can make model performance vary smoothly with changes in image position, scale, and orientation. It also facilitates the addition of spatial inhomogeneity, nonlinear feature channels, and focus of attention to channel models.

  11. HCN Channels Modulators: The Need for Selectivity.

    PubMed

    Novella Romanelli, Maria; Sartiani, Laura; Masi, Alessio; Mannaioni, Guido; Manetti, Dina; Mugelli, Alessandro; Cerbai, Elisabetta

    2016-01-01

    Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, the molecular correlate of the hyperpolarization-activated current (If/Ih), are membrane proteins which play an important role in several physiological processes and various pathological conditions. In the Sino Atrial Node (SAN) HCN4 is the target of ivabradine, a bradycardic agent that is, at the moment, the only drug which specifically blocks If. Nevertheless, several other pharmacological agents have been shown to modulate HCN channels, a property that may contribute to their therapeutic activity and/or to their side effects. HCN channels are considered potential targets for developing drugs to treat several important pathologies, but a major issue in this field is the discovery of isoform-selective compounds, owing to the wide distribution of these proteins into the central and peripheral nervous systems, heart and other peripheral tissues. This survey is focused on the compounds that have been shown, or have been designed, to interact with HCN channels and on their binding sites, with the aim to summarize current knowledge and possibly to unveil useful information to design new potent and selective modulators. PMID:26975509

  12. Structure and selectivity in bestrophin ion channels

    DOE PAGES

    Yang, Tingting; Liu, Qun; Kloss, Brian; Bruni, Renato; Kalathur, Ravi C.; Guo, Youzhong; Kloppmann, Edda; Rost, Burkhard; Colecraft, Henry M.; Hendrickson, Wayne A.

    2014-09-25

    Human bestrophin 1 (hBest1) is a calcium-activated chloride channel from the retinal pigment epithelium, where it can suffer mutations associated with vitelliform macular degeneration, or Best disease. We describe the structure of a bacterial homolog (KpBest) of hBest1 and functional characterizations of both channels. KpBest is a pentamer that forms a five-helix transmembrane pore, closed by three rings of conserved hydrophobic residues, and has a cytoplasmic cavern with a restricted exit. From electrophysiological analysis of structure-inspired mutations in KpBest and hBest1, we find a subtle control of ion selectivity in the bestrophins, including reversal of anion/cation selectivity, and dramatic activationmore » by mutations at the exit restriction. Lastly, a homology model of hBest1 shows the locations of disease-causing mutations and suggests possible roles in regulation.« less

  13. Structure and selectivity in bestrophin ion channels

    SciTech Connect

    Yang, Tingting; Liu, Qun; Kloss, Brian; Bruni, Renato; Kalathur, Ravi C.; Guo, Youzhong; Kloppmann, Edda; Rost, Burkhard; Colecraft, Henry M.; Hendrickson, Wayne A.

    2014-09-25

    Human bestrophin 1 (hBest1) is a calcium-activated chloride channel from the retinal pigment epithelium, where it can suffer mutations associated with vitelliform macular degeneration, or Best disease. We describe the structure of a bacterial homolog (KpBest) of hBest1 and functional characterizations of both channels. KpBest is a pentamer that forms a five-helix transmembrane pore, closed by three rings of conserved hydrophobic residues, and has a cytoplasmic cavern with a restricted exit. From electrophysiological analysis of structure-inspired mutations in KpBest and hBest1, we find a subtle control of ion selectivity in the bestrophins, including reversal of anion/cation selectivity, and dramatic activation by mutations at the exit restriction. Lastly, a homology model of hBest1 shows the locations of disease-causing mutations and suggests possible roles in regulation.

  14. Highly sensitive and doubly orientated selective molecularly imprinted electrochemical sensor for Cu(2.).

    PubMed

    Li, Jianping; Zhang, Lianming; Wei, Ge; Zhang, Yun; Zeng, Ying

    2015-07-15

    Studies on molecularly imprinted electrochemical sensors for metal ions determination have been widely reported. However, the sensitivity and selectivity of the sensors needs to be improved urgently. In the current work, a novel molecularly imprinted electrochemical sensor was originally developed for selective determination of ultratrace Cu(2+) by combining the metal-ligand chelate orientated recognition with enzyme amplification effect. The detection relied on a competition reaction between Cu(2+)-glycine (Cu-Gly) and horse radish peroxidase (HRP)-labeled Cu-Gly on the imprinted polymer membrane modified electrode. The sensitivity of this sensor was promoted by enzyme amplification. Selectivity was improved by the double-specificity derived from ligand-to-metal ion and metal-ligand chelate orientated recognition of 3D imprinted cavities. This technique was quantitatively sensitive to Cu(2+) concentrations ranging from 0.5nmol/L to 30nmol/L, with a detection limit of 42.4pmol/L. which was lower than those in most of the reported methods. The allowable amounts of interference ions were higher when it compared to other common molecularly imprinted sensors. Moreover, the results of assaying several real samples have proven its feasibility for practical applications. PMID:25771304

  15. Amiloride Selectively Blocks the Low Threshold (T) Calcium Channel

    NASA Astrophysics Data System (ADS)

    Tang, Cha-Min; Presser, Fernando; Morad, Martin

    1988-04-01

    More than one type of voltage-gated calcium channel has been identified in muscle cells and neurons. Many specific organic and inorganic blockers of the conventional, slowly inactivating high threshold (L) calcium channel have been reported. No specific blockers of the low threshold (T) channel have been as yet identified. Amiloride, a potassium sparing diuretic, has now been shown to selectively block the low threshold calcium channel in mouse neuroblastoma and chick dorsal root ganglion neurons. The selective blockade of the T-type calcium channel will allow identification of this channel in different tissues and characterization of its specific physiological role.

  16. Channel selective tunnelling through a nanographene assembly.

    PubMed

    Wong, H S; Feng, X; Müllen, K; Chandrasekhar, N; Durkan, C

    2012-03-01

    We report selective tunnelling through a nanographene intermolecular tunnel junction achieved via scanning tunnelling microscope tip functionalization with hexa-peri-hexabenzocoronene (HBC) molecules. This leads to an offset in the alignment between the energy levels of the tip and the molecular assembly, resulting in the imaging of a variety of distinct charge density patterns in the HBC assembly, not attainable using a bare metallic tip. Different tunnelling channels can be selected by the application of an electric field in the tunnelling junction, which changes the condition of the HBC on the tip. Density functional theory-based calculations relate the imaged HBC patterns to the calculated molecular orbitals at certain energy levels. These patterns bear a close resemblance to the π-orbital states of the HBC molecule calculated at the relevant energy levels, mainly below the Fermi energy of HBC. This correlation demonstrates the ability of an HBC functionalized tip as regards accessing an energy range that is restricted to the usual operating bias range around the Fermi energy with a normal metallic tip at room temperature. Apart from relating to molecular orbitals, some patterns could also be described in association with the Clar aromatic sextet formula. Our observations may help pave the way towards the possibility of controlling charge transport between organic interfaces.

  17. AVHRR channel selection for land cover classification

    USGS Publications Warehouse

    Maxwell, S.K.; Hoffer, R.M.; Chapman, P.L.

    2002-01-01

    Mapping land cover of large regions often requires processing of satellite images collected from several time periods at many spectral wavelength channels. However, manipulating and processing large amounts of image data increases the complexity and time, and hence the cost, that it takes to produce a land cover map. Very few studies have evaluated the importance of individual Advanced Very High Resolution Radiometer (AVHRR) channels for discriminating cover types, especially the thermal channels (channels 3, 4 and 5). Studies rarely perform a multi-year analysis to determine the impact of inter-annual variability on the classification results. We evaluated 5 years of AVHRR data using combinations of the original AVHRR spectral channels (1-5) to determine which channels are most important for cover type discrimination, yet stabilize inter-annual variability. Particular attention was placed on the channels in the thermal portion of the spectrum. Fourteen cover types over the entire state of Colorado were evaluated using a supervised classification approach on all two-, three-, four- and five-channel combinations for seven AVHRR biweekly composite datasets covering the entire growing season for each of 5 years. Results show that all three of the major portions of the electromagnetic spectrum represented by the AVHRR sensor are required to discriminate cover types effectively and stabilize inter-annual variability. Of the two-channel combinations, channels 1 (red visible) and 2 (near-infrared) had, by far, the highest average overall accuracy (72.2%), yet the inter-annual classification accuracies were highly variable. Including a thermal channel (channel 4) significantly increased the average overall classification accuracy by 5.5% and stabilized inter-annual variability. Each of the thermal channels gave similar classification accuracies; however, because of the problems in consistently interpreting channel 3 data, either channel 4 or 5 was found to be a more

  18. A review of channel selection algorithms for EEG signal processing

    NASA Astrophysics Data System (ADS)

    Alotaiby, Turky; El-Samie, Fathi E. Abd; Alshebeili, Saleh A.; Ahmad, Ishtiaq

    2015-12-01

    Digital processing of electroencephalography (EEG) signals has now been popularly used in a wide variety of applications such as seizure detection/prediction, motor imagery classification, mental task classification, emotion classification, sleep state classification, and drug effects diagnosis. With the large number of EEG channels acquired, it has become apparent that efficient channel selection algorithms are needed with varying importance from one application to another. The main purpose of the channel selection process is threefold: (i) to reduce the computational complexity of any processing task performed on EEG signals by selecting the relevant channels and hence extracting the features of major importance, (ii) to reduce the amount of overfitting that may arise due to the utilization of unnecessary channels, for the purpose of improving the performance, and (iii) to reduce the setup time in some applications. Signal processing tools such as time-domain analysis, power spectral estimation, and wavelet transform have been used for feature extraction and hence for channel selection in most of channel selection algorithms. In addition, different evaluation approaches such as filtering, wrapper, embedded, hybrid, and human-based techniques have been widely used for the evaluation of the selected subset of channels. In this paper, we survey the recent developments in the field of EEG channel selection methods along with their applications and classify these methods according to the evaluation approach.

  19. [Model of the selective calcium channel of characean algae].

    PubMed

    Lunevskiĭ, V Z; Zherelova, O M; Aleksandrov, A A; Vinokurov, M G; Berestovskiĭ, G N

    1980-01-01

    The present work was intended to further investigate the selective filter of calcium channel on both a cell membrane and reconstructed channels. For the studies on cell membranes, an inhibitor of chloride channels was chosen (ethacrynic acid) to pass currents only through the calcium channels. On both the cells and reconstructed channels, permeability of ions of different crystal radii and valencies was investigated. The obtained results suggest that the channel represents a wide water pore with a diameter larger than 8 A into which ions go together with the nearest water shell. The values of the maximal currents are given by electrostatic interaction of the ions with the anion center of the channel. A phenomenological two-barrier model of the channel is given which describes the movement of all the ions studied. PMID:6251921

  20. Ion selectivity in the ryanodine receptor and other calcium channels.

    NASA Astrophysics Data System (ADS)

    Gillespie, Dirk

    2006-03-01

    Biological ion channels passively conduct ions across cell membranes, some with great specificity. Calcium channels are selective channels that range in their Ca^2+ affinity depending on the channel's physiological role. For example, the L-type calcium channel has micromolar affinity while the ryanodine receptor (RyR) has millimolar affinity. On the other hand, both of these channels have the chemically-similar EEEE and DDDD amino acid motifs in their selectivity filters. An electrodiffusion model of RyR that reproduces and predicts >50 data curves will be presented. In this model, ions are charged, hard spheres and the chemical potential is computed using density functional theory of fluids. Ion selectivity arises from a competition between the need for cations to screen the negative charges of the channel and the crowding of ions in the tiny space of the channel. Charge/space competition implies that selectivity increases as the channel volume decreases (thereby increasing the protein charge density), something that has recently been experimentally confirmed in mutant channels. Dielectric properties can also increase selectivity. In Monte Carlo simulations, Ca^2+ affinity is much higher when the channel protein has a low dielectric constant. This counterintuitive result occurs because calcium channel selectivity filters are lined with negatively-charged (acidic) amino acids (EEEE or DDDD). These permanent negative charges induce negative polarization charge at the protein/lumen interface. The total negative charge of the protein (polarization plus permanent) is increased, resulting in increased ion densities, increased charge/space competition, and there in increased Ca^2+ affinity. If no negative protein charges were present, cations would induce enough positive polarization charge to prevent flux.

  1. Doubly Selective Multiple Quantum Chemical Shift Imaging and T1 Relaxation Time Measurement of Glutathione (GSH) in the Human Brain In Vivo

    PubMed Central

    Choi, In-Young; Lee, Phil

    2012-01-01

    Mapping of a major antioxidant, glutathione (GSH), was achieved in the human brain in vivo using a doubly selective multiple quantum filtering based chemical shift imaging (CSI) of GSH at 3 T. Both in vivo and phantom tests in CSI and single voxel measurements were consistent with excellent suppression of overlapping signals from creatine, γ-Amino butyric acid (GABA) and macromolecules. The GSH concentration in the fronto-parietal region was 1.20 ± 0.16 µmol/g (mean ± SD, n = 7). The longitudinal relaxation time (T1) of GSH in the human brain was 397 ± 44 ms (mean ± SD, n = 5), which was substantially shorter than those of other metabolites. This GSH CSI method permits us to address regional differences of GSH in the human brain with conditions where oxidative stress has been implicated, including multiple sclerosis, aging and neurodegenerative diseases. PMID:22730142

  2. Initial steps of inactivation at the K+ channel selectivity filter.

    PubMed

    Thomson, Andrew S; Heer, Florian T; Smith, Frank J; Hendron, Eunan; Bernèche, Simon; Rothberg, Brad S

    2014-04-29

    K(+) efflux through K(+) channels can be controlled by C-type inactivation, which is thought to arise from a conformational change near the channel's selectivity filter. Inactivation is modulated by ion binding near the selectivity filter; however, the molecular forces that initiate inactivation remain unclear. We probe these driving forces by electrophysiology and molecular simulation of MthK, a prototypical K(+) channel. Either Mg(2+) or Ca(2+) can reduce K(+) efflux through MthK channels. However, Ca(2+), but not Mg(2+), can enhance entry to the inactivated state. Molecular simulations illustrate that, in the MthK pore, Ca(2+) ions can partially dehydrate, enabling selective accessibility of Ca(2+) to a site at the entry to the selectivity filter. Ca(2+) binding at the site interacts with K(+) ions in the selectivity filter, facilitating a conformational change within the filter and subsequent inactivation. These results support an ionic mechanism that precedes changes in channel conformation to initiate inactivation.

  3. Spectral modeling of channel band shapes in wavelength selective switches.

    PubMed

    Pulikkaseril, Cibby; Stewart, Luke A; Roelens, Michaël A F; Baxter, Glenn W; Poole, Simon; Frisken, Steve

    2011-04-25

    A model for characterizing the spectral response of the passband of Wavelength Selective Switches (WSS) is presented. We demonstrate that, in contrast to the commonly used supergaussian model, the presented model offers a more complete match to measured results, as it is based on the physical operation of the optical system. We also demonstrate that this model is better suited for calculation of WSS channel bandwidths, as well as predicting the final bandwidth of cascaded WSS modules. Finally, we show the utility of this model in predicting channel shapes in flexible bandwidth WSS channel plans.

  4. Ion selectivity and gating mechanisms of FNT channels

    PubMed Central

    Waight, Andrew B.; Czyzewski, Bryan K.; Wang, Da-Neng

    2013-01-01

    The phospholipid bilayer has evolved to be a protective and selective barrier by which the cell maintains high concentrations of life sustaining organic and inorganic material. As gatekeepers responsible for an immense amount of bidirectional chemical traffic between the cytoplasm and extracellular milieu, ion channels have been studied in detail since their postulated existence nearly three-quarters of a century ago. Over the past fifteen years, we have begun to understand how selective permeability can be achieved for both cationic and anionic ions. Our mechanistic knowledge has expanded recently with studies of a large family of anion channels, the Formate Nitrite Transport (FNT) family. This family has proven amenable to structural studies at a resolution high enough to reveal intimate details of ion selectivity and gating. With five representative members having yielded a total of 15 crystal structures, this family represents one of the richest sources of structural information for anion channels. PMID:23773802

  5. Highly Selective Artificial K(+) Channels: An Example of Selectivity-Induced Transmembrane Potential.

    PubMed

    Gilles, Arnaud; Barboiu, Mihail

    2016-01-13

    Natural KcsA K(+) channels conduct at high rates with an extraordinary selectivity for K(+) cations, excluding the Na(+) or other cations. Biomimetic artificial channels have been designed in order to mimick the ionic activity of KcSA channels, but simple artificial systems presenting high K(+)/Na(+) selectivity are rare. Here we report an artificial ion channel of H-bonded hexyl-benzoureido-15-crown-5-ether, where K(+) cations are highly preferred to Na(+) cations. The K(+)-channel conductance is interpreted as arising in the formation of oligomeric highly cooperative channels, resulting in the cation-induced membrane polarization and enhanced transport rates without or under pH-active gradient. These channels are selectively responsive to the presence of K(+) cations, even in the presence of a large excess of Na(+). From the conceptual point of view, these channels express a synergistic adaptive behavior: the addition of the K(+) cation drives the selection and the construction of constitutional polarized ion channels toward the selective conduction of the K(+) cation that promotes their generation in the first place.

  6. Doubly Distributed Transactions

    2014-08-25

    Doubly Distributed Transactions (D2T) offers a technique for managing operations from a set of parallel clients with a collection of distributed services. It detects and manages faults. Example code with a test harness is also provided

  7. Doubly fed induction machine

    DOEpatents

    Skeist, S. Merrill; Baker, Richard H.

    2005-10-11

    An electro-mechanical energy conversion system coupled between an energy source and an energy load including an energy converter device having a doubly fed induction machine coupled between the energy source and the energy load to convert the energy from the energy source and to transfer the converted energy to the energy load and an energy transfer multiplexer coupled to the energy converter device to control the flow of power or energy through the doubly fed induction machine.

  8. Flux, coupling, and selectivity in ionic channels of one conformation.

    PubMed Central

    Chen, D P; Eisenberg, R S

    1993-01-01

    Ions crossing biological membranes are described as a concentration of charge flowing through a selective open channel of one conformation and analyzed by a combination of Poisson and Nernst-Planck equations and boundary conditions, called the PNP theory for short. The ion fluxes in this theory interact much as ion fluxes interact in biological channels and mediated transporters, provided the theoretical channel contains permanent charge and has selectivity created by (electro-chemical) resistance at its ends. Interaction occurs because the flux of different ionic species depends on the same electric field. That electric field is a variable, changing with experimental conditions because the screening (i.e., shielding) of the permanent charge within the channel changes with experimental conditions. For example, the screening of charge and the shape of the electric field depend on the concentration of all ionic species on both sides of the channel. As experimental interventions vary the screening, the electric field varies, and thus the flux of each ionic species varies conjointly, and is, in that sense, coupled. Interdependence and interaction are the rule, independence is the exception, in this channel. PMID:7693003

  9. Modulation of mechanosensitive calcium-selective cation channels by temperature

    NASA Technical Reports Server (NTRS)

    Ding, J. P.; Pickard, B. G.

    1993-01-01

    Gating of associations of mechanosensitive Ca(2+)-selective cation co-channels in the plasmalemma of onion epidermis has a strong and unusual temperature dependence. Tension-dependent activity rises steeply as temperature is lowered from 25 degrees C to about 6 degrees C, but drops to a low level at about 5 degrees C. Under the conditions tested (with Mg2+ and K+ at the cytosolic face of outside-out membrane patches), promotion results both from more bursting at all observed linkage levels and from longer duration of bursts of co-channels linked as quadruplets and quintuplets. Co-channel conductance decreases linearly, but only modestly, with declining temperature. It is proposed that these and related mechanosensitive channels may participate in a variety of responses to temperature, including thermonasty, thermotropism, hydrotropism, and both cold damage and cold acclimation.

  10. Adaptive codebook selection schemes for image classification in correlated channels

    NASA Astrophysics Data System (ADS)

    Hu, Chia Chang; Liu, Xiang Lian; Liu, Kuan-Fu

    2015-09-01

    The multiple-input multiple-output (MIMO) system with the use of transmit and receive antenna arrays achieves diversity and array gains via transmit beamforming. Due to the absence of full channel state information (CSI) at the transmitter, the transmit beamforming vector can be quantized at the receiver and sent back to the transmitter by a low-rate feedback channel, called limited feedback beamforming. One of the key roles of Vector Quantization (VQ) is how to generate a good codebook such that the distortion between the original image and the reconstructed image is the minimized. In this paper, a novel adaptive codebook selection scheme for image classification is proposed with taking both spatial and temporal correlation inherent in the channel into consideration. The new codebook selection algorithm is developed to select two codebooks from the discrete Fourier transform (DFT) codebook, the generalized Lloyd algorithm (GLA) codebook and the Grassmannian codebook to be combined and used as candidates of the original image and the reconstructed image for image transmission. The channel is estimated and divided into four regions based on the spatial and temporal correlation of the channel and an appropriate codebook is assigned to each region. The proposed method can efficiently reduce the required information of feedback under the spatially and temporally correlated channels, where each region is adaptively. Simulation results show that in the case of temporally and spatially correlated channels, the bit-error-rate (BER) performance can be improved substantially by the proposed algorithm compared to the one with only single codebook.

  11. Selective activation of mechanosensitive ion channels using magnetic particles.

    PubMed

    Hughes, Steven; McBain, Stuart; Dobson, Jon; El Haj, Alicia J

    2008-08-01

    This study reports the preliminary development of a novel magnetic particle-based technique that permits the application of highly localized mechanical forces directly to specific regions of an ion-channel structure. We demonstrate that this approach can be used to directly and selectively activate a mechanosensitive ion channel of interest, namely TREK-1. It is shown that manipulation of particles targeted against the extended extracellular loop region of TREK-1 leads to changes in whole-cell currents consistent with changes in TREK-1 activity. Responses were absent when particles were coated with RGD (Arg-Gly-Asp) peptide or when magnetic fields were applied in the absence of magnetic particles. It is concluded that changes in whole-cell current are the result of direct force application to the extracellular loop region of TREK-1 and thus these results implicate this region of the channel structure in mechano-gating. It is hypothesized that the extended loop region of TREK-1 may act as a tension spring that acts to regulate sensitivity to mechanical forces, in a nature similar to that described for MscL. The development of a technique that permits the direct manipulation of mechanosensitive ion channels in real time without the need for pharmacological drugs has huge potential benefits not only for basic biological research of ion-channel gating mechanisms, but also potentially as a tool for the treatment of human diseases caused by ion-channel dysfunction.

  12. Ionic Selectivity and Permeation Properties of Human PIEZO1 Channels

    PubMed Central

    Gnanasambandam, Radhakrishnan; Bae, Chilman; Gottlieb, Philip A.; Sachs, Frederick

    2015-01-01

    Members of the eukaryotic PIEZO family (the human orthologs are noted hPIEZO1 and hPIEZO2) form cation-selective mechanically-gated channels. We characterized the selectivity of human PIEZO1 (hPIEZO1) for alkali ions: K+, Na+, Cs+ and Li+; organic cations: TMA and TEA, and divalents: Ba2+, Ca2+, Mg2+ and Mn2+. All monovalent ions permeated the channel. At a membrane potential of -100 mV, Cs+, Na+ and K+ had chord conductances in the range of 35–55 pS with the exception of Li+, which had a significantly lower conductance of ~ 23 pS. The divalents decreased the single-channel permeability of K+, presumably because the divalents permeated slowly and occupied the open channel for a significant fraction of the time. In cell-attached mode, 90 mM extracellular divalents had a conductance for inward currents carried by the divalents of: 25 pS for Ba2+ and 15 pS for Ca2+ at -80 mV and 10 pS for Mg2+ at -50 mV. The organic cations, TMA and TEA, permeated slowly and attenuated K+ currents much like the divalents. As expected, the channel K+ conductance increased with K+ concentration saturating at ~ 45 pS and the KD of K+ for the channel was 32 mM. Pure divalent ion currents were of lower amplitude than those with alkali ions and the channel opening rate was lower in the presence of divalents than in the presence of monovalents. Exposing cells to the actin disrupting reagent cytochalasin D increased the frequency of openings in cell-attached patches probably by reducing mechanoprotection. PMID:25955826

  13. Gating of a pH-Sensitive K2P Potassium Channel by an Electrostatic Effect of Basic Sensor Residues on the Selectivity Filter

    PubMed Central

    Zúñiga, Leandro; Márquez, Valeria; González-Nilo, Fernando D.; Chipot, Christophe; Cid, L. Pablo; Sepúlveda, Francisco V.; Niemeyer, María Isabel

    2011-01-01

    K+ channels share common selectivity characteristics but exhibit a wide diversity in how they are gated open. Leak K2P K+ channels TASK-2, TALK-1 and TALK-2 are gated open by extracellular alkalinization. The mechanism for this alkalinization-dependent gating has been proposed to be the neutralization of the side chain of a single arginine (lysine in TALK-2) residue near the pore of TASK-2, which occurs with the unusual pKa of 8.0. We now corroborate this hypothesis by transplanting the TASK-2 extracellular pH (pHo) sensor in the background of a pHo-insensitive TASK-3 channel, which leads to the restitution of pHo-gating. Using a concatenated channel approach, we also demonstrate that for TASK-2 to open, pHo sensors must be neutralized in each of the two subunits forming these dimeric channels with no apparent cross-talk between the sensors. These results are consistent with adaptive biasing force analysis of K+ permeation using a model selectivity filter in wild-type and mutated channels. The underlying free-energy profiles confirm that either a doubly or a singly charged pHo sensor is sufficient to abolish ion flow. Atomic detail of the associated mechanism reveals that, rather than a collapse of the pore, as proposed for other K2P channels gated at the selectivity filter, an increased height of the energetic barriers for ion translocation accounts for channel blockade at acid pHo. Our data, therefore, strongly suggest that a cycle of protonation/deprotonation of pHo-sensing arginine 224 side chain gates the TASK-2 channel by electrostatically tuning the conformational stability of its selectivity filter. PMID:21283586

  14. Mechanosensory calcium-selective cation channels in epidermal cells

    NASA Technical Reports Server (NTRS)

    Ding, J. P.; Pickard, B. G.

    1993-01-01

    This paper explores the properties and likely functions of an epidermal Ca(2+)-selective cation channel complex activated by tension. As many as eight or nine linked or linkable equivalent conductance units or co-channels can open together. Open time for co-channel quadruplets and quintuplets tends to be relatively long with millimolar Mg2+ (but not millimolar Ca2+) at the cytosolic face of excised plasma membrane. Sensitivity to tension is regulated by transmembrane voltage and temperature. Under some circumstances channel activity is sychronized in rhythmic pulses. Certain lanthanides and a cytoskeleton-disturbing herbicide that inhibit gravitropic reception act on the channel system at low concentrations. Specifically, ethyl-N-phenylcarbamate promotes tension-dependent activity at micromolar levels. With moderate suction, Gd3+ provided at about 0.5 micromole at the extracellular face of the membrane promotes for several seconds but may then become inhibitory. Provision at 1-2 micromoles promotes and subsequently inhibits more vigorously (often abruptly and totally), and at high levels inhibits immediately. La3+, a poor gravitropic inhibitor, acts similarly but much more gradually and only at much higher concentrations. These properties, particularly these susceptibilities to modulation, indicate that in vivo the mechanosensitive channel must be mechanosensory and mechanoregulatory. It could serve to transduce the shear forces generated in the integrated wall-membrane-cytoskeleton system during turgor changes and cell expansion as well as transducing the stresses induced by gravity, touch and flexure. In so far as such transduction is modulated by voltage and temperature, the channels would also be sensors for these modalities as long as the wall-membrane-cytoskeleton system experiences mechanical stress.

  15. Evolutionary determinants of divergent calcium selectivity of TRPM channels.

    PubMed

    Mederos y Schnitzler, Michael; Wäring, Janine; Gudermann, Thomas; Chubanov, Vladimir

    2008-05-01

    The mammalian TRPM gene family can be subdivided into distinct categories of cation channels that are either highly permeable for Ca(2+) (TRPM3/6/7), nonselective (TRPM2/8), or even Ca(2+) impermeable (TRPM4/5). TRPM6/7 are fused to alpha-kinase domains, whereas TRPM2 is linked to an ADP-ribose phosphohydrolase (Nudix domain). At a molecular level, the evolutionary steps that gave rise to the structural and functional TRPM channel diversity remain elusive. Here, we provide phylogenetic evidence that Nudix-linked channels represent an ancestral type of TRPMs that is present in various phyla, ranging from protists to humans. Surprisingly, the pore-forming segments of invertebrate TRPM2-like proteins display high sequence similarity to those of Ca(2+)-selective TRPMs, while human TRPM2 is characterized by a loss of several conserved residues. Using the patch-clamp technique, Ca(2+) imaging, and site-directed mutagenesis, we demonstrate that restoration of only two "ancient" pore residues in human TRPM2 (Q981E/P983Y) significantly increased (approximately 4-fold) its permeability for Ca(2+). Conversely, introduction of a "modern" sequence motif into mouse TRPM7 (E1047Q/Y1049P) resulted in the loss of Ca(2+) permeation and a linear TRPM2-like current-voltage relationship. Overall, our findings provide an integrative view on the evolution of the domain architecture and the structural basis of the distinct ion permeation profiles of TRPM channels.

  16. Deciphering Subtype-Selective Modulations in TRPA1 Biosensor Channels.

    PubMed

    Kozai, Daisuke; Sakaguchi, Reiko; Ohwada, Tomohiko; Mori, Yasuo

    2015-01-01

    The transient receptor potential (TRP) proteins are a family of ion channels that act as cellular sensors. Several members of the TRP family are sensitive to oxidative stress mediators. Among them, TRPA1 is remarkably susceptible to various oxidants, and is known to mediate neuropathic pain and respiratory, vascular and gastrointestinal functions, making TRPA1 an attractive therapeutic target. Recent studies have revealed a number of modulators (both activators and inhibitors) that act on TRPA1. Endogenous mediators of oxidative stress and exogenous electrophiles activate TRPA1 through oxidative modification of cysteine residues. Non-electrophilic compounds also activate TRPA1. Certain non-electrophilic modulators may act on critical non-cysteine sites in TRPA1. However, a method to achieve selective modulation of TRPA1 by small molecules has not yet been established. More recently, we found that a novel N-nitrosamine compound activates TRPA1 by S-nitrosylation (the addition of a nitric oxide (NO) group to cysteine thiol), and does so with significant selectivity over other NO-sensitive TRP channels. It is proposed that this subtype selectivity is conferred through synergistic effects of electrophilic cysteine transnitrosylation and molecular recognition of the non-electrophilic moiety on the N-nitrosamine. In this review, we describe the molecular pharmacology of these TRPA1 modulators and discuss their modulatory mechanisms. PMID:26411770

  17. Deciphering Subtype-Selective Modulations in TRPA1 Biosensor Channels

    PubMed Central

    Kozai, Daisuke; Sakaguchi, Reiko; Ohwada, Tomohiko; Mori, Yasuo

    2015-01-01

    The transient receptor potential (TRP) proteins are a family of ion channels that act as cellular sensors. Several members of the TRP family are sensitive to oxidative stress mediators. Among them, TRPA1 is remarkably susceptible to various oxidants, and is known to mediate neuropathic pain and respiratory, vascular and gastrointestinal functions, making TRPA1 an attractive therapeutic target. Recent studies have revealed a number of modulators (both activators and inhibitors) that act on TRPA1. Endogenous mediators of oxidative stress and exogenous electrophiles activate TRPA1 through oxidative modification of cysteine residues. Non-electrophilic compounds also activate TRPA1. Certain non-electrophilic modulators may act on critical non-cysteine sites in TRPA1. However, a method to achieve selective modulation of TRPA1 by small molecules has not yet been established. More recently, we found that a novel N-nitrosamine compound activates TRPA1 by S-nitrosylation (the addition of a nitric oxide (NO) group to cysteine thiol), and does so with significant selectivity over other NO-sensitive TRP channels. It is proposed that this subtype selectivity is conferred through synergistic effects of electrophilic cysteine transnitrosylation and molecular recognition of the non-electrophilic moiety on the N-nitrosamine. In this review, we describe the molecular pharmacology of these TRPA1 modulators and discuss their modulatory mechanisms. PMID:26411770

  18. Doubly robust survival trees.

    PubMed

    Steingrimsson, Jon Arni; Diao, Liqun; Molinaro, Annette M; Strawderman, Robert L

    2016-09-10

    Estimating a patient's mortality risk is important in making treatment decisions. Survival trees are a useful tool and employ recursive partitioning to separate patients into different risk groups. Existing 'loss based' recursive partitioning procedures that would be used in the absence of censoring have previously been extended to the setting of right censored outcomes using inverse probability censoring weighted estimators of loss functions. In this paper, we propose new 'doubly robust' extensions of these loss estimators motivated by semiparametric efficiency theory for missing data that better utilize available data. Simulations and a data analysis demonstrate strong performance of the doubly robust survival trees compared with previously used methods. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27037609

  19. Channel selection based on trust and multiarmed bandit in multiuser, multichannel cognitive radio networks.

    PubMed

    Zeng, Fanzi; Shen, Xinwang

    2014-01-01

    This paper proposes a channel selection scheme for the multiuser, multichannel cognitive radio networks. This scheme formulates the channel selection as the multiarmed bandit problem, where cognitive radio users are compared to the players and channels to the arms. By simulation negotiation we can achieve the potential reward on each channel after it is selected for transmission; then the channel with the maximum accumulated rewards is formally chosen. To further improve the performance, the trust model is proposed and combined with multi-armed bandit to address the channel selection problem. Simulation results validate the proposed scheme.

  20. Selection of effective EEG channels in brain computer interfaces based on inconsistencies of classifiers.

    PubMed

    Yang, Huijuan; Guan, Cuntai; Ang, Kai Keng; Phua, Kok Soon; Wang, Chuanchu

    2014-01-01

    This paper proposed a novel method to select the effective Electroencephalography (EEG) channels for the motor imagery tasks based on the inconsistencies from multiple classifiers. The inconsistency criterion for channel selection was designed based on the fluctuation of the classification accuracies among different classifiers when the noisy channels were included. These noisy channels were then identified and removed till a required number of channels was selected or a predefined classification accuracy with reference to baseline was obtained. Experiments conducted on a data set of 13 healthy subjects performing hand grasping and idle revealed that the EEG channels from the motor area were most frequently selected. Furthermore, the mean increases of 4.07%, 3.10% and 1.77% of the averaged accuracies in comparison with the four existing channel selection methods were achieved for the non-feedback, feedback and calibration sessions, respectively, by selecting as low as seven channels. These results further validated the effectiveness of our proposed method.

  1. Design of Nonuniform Filter Bank Transceivers for Frequency Selective Channels

    NASA Astrophysics Data System (ADS)

    Chiang, Han-Ting; Phoong, See-May; Lin, Yuan-Pei

    2006-12-01

    In recent years, there has been considerable interest in the theory and design of filter bank transceivers due to their superior frequency response. In many applications, it is desired to have transceivers that can support multiple services with different incoming data rates and different quality-of-service requirements. To meet these requirements, we can either do resource allocation or design transceivers with a nonuniform bandwidth partition. In this paper, we propose a method for the design of nonuniform filter bank transceivers for frequency selective channels. Both frequency response and signal-to-interference ratio (SIR) can be incorporated in the transceiver design. Moreover, the technique can be extended to the case of nonuniform filter bank transceivers with rational sampling factors. Simulation results show that nonuniform filter bank transceivers with good filter responses as well as high SIR can be obtained by the proposed design method.

  2. Apparatus and method for selectively channeling a fluid

    DOEpatents

    Rightley, Michael Joseph

    2008-01-01

    An apparatus for selectively channeling a high temperature fluid without chemically reacting with the fluid. The apparatus includes an inlet and a membrane positioned adjacent to the inlet, each composed of a chemically inert material. The membrane is formed by compressive preloading techniques. The apparatus further includes a seat disposed on the inlet adjacent to the membrane. The seat is composed of a heat resistant and chemically inert material. Operation of the apparatus requires that the temperature of the fluid remains below the chemical characteristic melting point of the seat. The apparatus further includes an actuator coupled to the membrane for rendering the membrane in an open and a closed position with respect to the seat. Specifically, the actuator supplies a load in the normal direction to the membrane to selectively engage the membrane in a plurality of predetermined configurations. Operatively, the apparatus receives the fluid at the inlet. The fluid is received at a high temperature and is directed from the inlet to the membrane. In the closed position, the actuator engages the membrane to prevent the fluid from flowing from the inlet between the membrane and the seat. Alternatively, in the open position, the actuator engages the membrane to permit fluid flow from the inlet between the membrane and the seat to at least one outlet provided by the apparatus. In one exemplary embodiment, the fluid may be discharged from the at least one outlet to a sensor in fluid communication with the at least one outlet. Accordingly, the sensor may measure the fluid channeled through the heat resistant and chemically inert environment provided by the apparatus.

  3. Calcium ions open a selectivity filter gate during activation of the MthK potassium channel

    NASA Astrophysics Data System (ADS)

    Posson, David J.; Rusinova, Radda; Andersen, Olaf S.; Nimigean, Crina M.

    2015-09-01

    Ion channel opening and closing are fundamental to cellular signalling and homeostasis. Gates that control K+ channel activity were found both at an intracellular pore constriction and within the selectivity filter near the extracellular side but the specific location of the gate that opens Ca2+-activated K+ channels has remained elusive. Using the Methanobacterium thermoautotrophicum homologue (MthK) and a stopped-flow fluorometric assay for fast channel activation, we show that intracellular quaternary ammonium blockers bind to closed MthK channels. Since the blockers are known to bind inside a central channel cavity, past the intracellular entryway, the gate must be within the selectivity filter. Furthermore, the blockers access the closed channel slower than the open channel, suggesting that the intracellular entryway narrows upon pore closure, without preventing access of either the blockers or the smaller K+. Thus, Ca2+-dependent gating in MthK occurs at the selectivity filter with coupled movement of the intracellular helices.

  4. Calcium ions open a selectivity filter gate during activation of the MthK potassium channel.

    PubMed

    Posson, David J; Rusinova, Radda; Andersen, Olaf S; Nimigean, Crina M

    2015-01-01

    Ion channel opening and closing are fundamental to cellular signalling and homeostasis. Gates that control K(+) channel activity were found both at an intracellular pore constriction and within the selectivity filter near the extracellular side but the specific location of the gate that opens Ca(2+)-activated K(+) channels has remained elusive. Using the Methanobacterium thermoautotrophicum homologue (MthK) and a stopped-flow fluorometric assay for fast channel activation, we show that intracellular quaternary ammonium blockers bind to closed MthK channels. Since the blockers are known to bind inside a central channel cavity, past the intracellular entryway, the gate must be within the selectivity filter. Furthermore, the blockers access the closed channel slower than the open channel, suggesting that the intracellular entryway narrows upon pore closure, without preventing access of either the blockers or the smaller K(+). Thus, Ca(2+)-dependent gating in MthK occurs at the selectivity filter with coupled movement of the intracellular helices.

  5. Electrochemical evaluation of chemical selectivity of glutamate receptor ion channel proteins with a multi-channel sensor.

    PubMed

    Sugawara, M; Hirano, A; Rehák, M; Nakanishi, J; Kawai, K; Sato, H; Umezawa, Y

    1997-01-01

    A new method for evaluating chemical selectivity of agonists towards receptor ion channel proteins is proposed by using glutamate receptor (GluR) ion channel proteins and their agonists N-methyl-D-aspartic acid (NMDA), L-glutamate, and (2S, 3R, 4S) isomer of 2-(carboxycyclopropyl)glycine (L-CCG-IV). Integrated multi-channel currents, corresponding to the sum of total amount of ions passed through the multiple open channels, were used as a measure of agonists' selectivity to recognize ion channel proteins and induce channel currents. GluRs isolated from rat synaptic plasma membranes were incorporated into planar bilayer lipid membranes (BLMs) formed by the folding method. The empirical factors that affect the selectivity were demonstrated: (i) the number of GluRs incorporated into BLMs varied from one membrane to another; (ii) each BLM contained different subtypes of GluRs (NMDA and/or non-NMDA subtypes); and (iii) the magnitude of multi-channel responses induced by L-glutamate at negative applied potentials was larger than at positive potentials, while those by NMDA and L-CCG-IV were linearly related to applied potentials. The chemical selectivity among NMDA, L-glutamate and L-CCG-IV for NMDA subtype of GluRs was determined with each single BLM in which only NMDA subtype of GluRs was designed to be active by inhibiting the non-NMDA subtypes using a specific antagonist DNQX. The order of selectivity among the relevant agonists for the NMDA receptor subtype was found to be L-CCG-IV > L-glutamate > NMDA, which is consistent with the order of binding affinity of these agonists towards the same NMDA subtypes. The potential use of this approach for evaluating chemical selectivity towards non-NMDA receptor subtypes of GluRs and other receptor ion channel proteins is discussed.

  6. α-Synuclein forms non-selective cation channels and stimulates ATP-sensitive potassium channels in hippocampal neurons

    PubMed Central

    Mironov, Sergej L

    2015-01-01

    In Parkinson's disease and several other neurodegenerative diseases, the protein α-synuclein (αS) is produced within neurons and accumulates in the extracellular fluid. Several mechanisms of αS action are proposed, one of which is the formation of cation-permeable pores that may mediate toxicity. αS induces non-selective cation channels in lipid bilayers, but whether this occurs in living neurons and which properties the channels possess have not yet been examined. In this study the properties of αS channels in dissociated hippocampal neurons are documented. In cell-attached recordings the incorporation of αS into membranes was driven by applied negative potentials. These channels exhibited multiple levels of conductance (30, 70 and 120 pS at −100 mV) and inward rectification. The persistent activity of αS channels induced local changes in intracellular Na+ and Ca2+, depolarized neurons and augmented bursting activity. αS channels formed by adding αS to the intracellular membrane in inside-out patches exhibited outward rectification. αS channels were equally permeable to Na+, K+ and Ca2+. These channels were also observed in neurons transfected with wild-type or mutant A53T αS, and after extracellular application of wild-type or mutant A53T αS proteins. Opening of αS channels stimulated opening of ATP-sensitive K+ (KATP ) channels and did not interfere with the activity of delayed rectifier K+ channels. The properties of αS channels in neuronal membranes suggest stronger toxicity of extracellularly applied αS than intracellular αS. Enhancement of neuronal excitability and distortions in ion homeostasis may underlie the toxic effects of αS that can be dampened by KATP channels. PMID:25556793

  7. Critical assessment of OmpF channel selectivity: merging information from different experimental protocols

    NASA Astrophysics Data System (ADS)

    López, M. L.; García-Giménez, E.; Aguilella, V. M.; Alcaraz, A.

    2010-11-01

    The ion selectivity of a channel can be quantified in several ways by using different experimental protocols. A wide, mesoscopic channel, the OmpF porin of the outer membrane of E. coli, serves as a case study for comparing and analysing several measures of the channel cation-anion permeability in chlorides of alkali metals (LiCl, NaCl, KCl, CsCl). We show how different insights can be gained and integrated to rationalize the global image of channel selectivity. To this end, reversal potential, channel conductance and bi-ionic potential (two different salts with a common anion on each side of the channel but with the same concentration) experiments are discussed in light of an electrodiffusion model based on the Poisson-Nernst-Planck formalism. Measurements and calculations based on the atomic crystal structure of the channel show that each protocol displays a particular balance between the different sources of selectivity.

  8. Tuning the ion selectivity of tetrameric cation channels by changing the number of ion binding sites

    SciTech Connect

    Derebe, Mehabaw G.; Sauer, David B.; Zeng, Weizhong; Alam, Amer; Shi, Ning; Jiang, Youxing

    2015-11-30

    Selective ion conduction across ion channel pores is central to cellular physiology. To understand the underlying principles of ion selectivity in tetrameric cation channels, we engineered a set of cation channel pores based on the nonselective NaK channel and determined their structures to high resolution. These structures showcase an ensemble of selectivity filters with a various number of contiguous ion binding sites ranging from 2 to 4, with each individual site maintaining a geometry and ligand environment virtually identical to that of equivalent sites in K{sup +} channel selectivity filters. Combined with single channel electrophysiology, we show that only the channel with four ion binding sites is K{sup +} selective, whereas those with two or three are nonselective and permeate Na{sup +} and K{sup +} equally well. These observations strongly suggest that the number of contiguous ion binding sites in a single file is the key determinant of the channel's selectivity properties and the presence of four sites in K{sup +} channels is essential for highly selective and efficient permeation of K{sup +} ions.

  9. Unexpected doubly-magic nucleus.

    SciTech Connect

    Janssens, R. V. F.; Physics

    2009-01-01

    Nuclei with a 'magic' number of both protons and neutrons, dubbed doubly magic, are particularly stable. The oxygen isotope {sup 24}O has been found to be one such nucleus - yet it lies just at the limit of stability.

  10. Doubly-Tagged D

    NASA Astrophysics Data System (ADS)

    Prabhakar, Ernest Navaroop

    1995-01-01

    The D_{s} is a pseudoscalar meson composed of two second generation quarks, the heavy charm and the light strange. The bulk of our knowledge of the D_{s} comes from secondary production via B decays. These experiments have high statistics but are poorly suited to absolute branching fraction or production cross-section measurements. The best way to perform those is to use double-tagging of threshold pair production. Unfortunately, there is no strong resonance near D_{s } threshold, making it difficult to obtain sufficient statistics. This thesis makes use of the {cal L} = 22.8 +/- 0.6 {rm pb}^ {-1} integrated luminosity collected by the Beijing Spectrometer from the Beijing Electron-Positron Collider at 4.03 GeV. This energy was chosen because the coupled-channel model of Eichten et al. predicts an enhancement there of the D_sp{s}{+}D _sp{s}{-} cross section to somewhat below 1 nb. We attempt to fully reconstruct hadronic and semileptonic D_{s} pairs from six-prong events not containing any photons. We combine the chi^2 from kinematic fitting and particle identification to form a single value, the joint confidence level, for each event. Using this in the analysis yields five hadronic events, with multiple combinations per event. Since the D_{s} principally decays to resonant moves, we preferentially select those combinations which lead to resonant two-body masses. This gives us a signal containing 7 resonant decays and 3 non-resonant K^+K^-pi^+ decays. We use Monte Carlo efficiencies and knowledge of the ratio B(D_sp{s}{+} to | K^{*0}K^+)/B(D _sp{s}{+} to K^+K ^-pi^+) to estimate the production rates represented by these tags. We perform a likelihood analysis using those numbers, together with the absolute branching fractions, to obtain a value of sigma(e^+e^- to D_sp{s}{+}D_sp{s }{-}) at 4.03 GeV = 0.53 _sp{-0.20}{+0.28}_sp{ -0.09}{+0.07}nb, one sigma below the coupled channel model. Using only relative branching fractions, we fit to a value for the ratio B(D _sp

  11. [Channel Selection for Multi-class Motor Imagery Based on Common Spatial Pattern].

    PubMed

    Zhou, Bangyan; Wu, Xiaopei; Lu, Zhao; Zhang, Lei; Guo, Xianjing; Zhang, Chao

    2015-06-01

    High-density channels are often used to acquire electroencephalogram (EEG) spatial information in different cortical regions of the brain in brain-computer interface (BCI) systems. However, applying excessive channels is inconvenient for signal acquisition, and it may bring artifacts. To avoid these defects, the common spatial pattern (CSP) algorithm was used for channel selection and a selection criteria based on norm-2 is proposed in this paper. The channels with the highest M scores were selected for the purpose of using fewer channels to acquire similar rate with high density channels. The Dataset III a from BCI competition 2005 were used for comparing the classification accuracies of three motor imagery between whole channels and the selected channels with the present proposed method. The experimental results showed that the classification accuracies of three subjects using the 20 channels selected with the present method were all higher than the classification accuracies using all 60 channels, which convinced that our method could be more effective and useful. PMID:26485971

  12. Electrostatic tuning of permeation and selectivity in aquaporin water channels.

    PubMed

    Jensen, Morten Ø; Tajkhorshid, Emad; Schulten, Klaus

    2003-11-01

    Water permeation and electrostatic interactions between water and channel are investigated in the Escherichia coli glycerol uptake facilitator GlpF, a member of the aquaporin water channel family, by molecular dynamics simulations. A tetrameric model of the channel embedded in a 16:0/18:1c9-palmitoyloleylphosphatidylethanolamine membrane was used for the simulations. During the simulations, water molecules pass through the channel in single file. The movement of the single file water molecules through the channel is concerted, and we show that it can be described by a continuous-time random-walk model. The integrity of the single file remains intact during the permeation, indicating that a disrupted water chain is unlikely to be the mechanism of proton exclusion in aquaporins. Specific hydrogen bonds between permeating water and protein at the channel center (at two conserved Asp-Pro-Ala "NPA" motifs), together with the protein electrostatic fields enforce a bipolar water configuration inside the channel with dipole inversion at the NPA motifs. At the NPA motifs water-protein electrostatic interactions facilitate this inversion. Furthermore, water-water electrostatic interactions are in all regions inside the channel stronger than water-protein interactions, except near a conserved, positively charged Arg residue. We find that variations of the protein electrostatic field through the channel, owing to preserved structural features, completely explain the bipolar orientation of water. This orientation persists despite water translocation in single file and blocks proton transport. Furthermore, we find that for permeation of a cation, ion-protein electrostatic interactions are more unfavorable at the conserved NPA motifs than at the conserved Arg, suggesting that the major barrier against proton transport in aquaporins is faced at the NPA motifs. PMID:14581193

  13. Determination of channel change for selected streams, Maricopa County, Arizona

    USGS Publications Warehouse

    Capesius, Joseph P.; Lehman, Ted W.

    2002-01-01

    In Maricopa County, Arizona, 10 sites on seven streams were studied to determine the lateral and vertical change of the channel. Channel change was studied over time scales ranging from individual floods to decades using cross-section surveys, discharge measurements, changes in the point of zero flow, and repeat photography. All of the channels showed some change in cross-section area or hydraulic radius over the time scales studied, but the direction and mag-nitude of change varied considerably from one flow, or series of flows, to another. The documentation of cross-section geometry for streams in Maricopa County for long-term monitoring was begun in this study.

  14. Comparison of two channel selection criteria for noise suppression in cochlear implants

    PubMed Central

    Hazrati, Oldooz; Loizou, Philipos C.

    2013-01-01

    The performance of current channel selection criteria used in cochlear implant (CI) devices (e.g., maximum selection criterion used in ACE) degrades significantly in the presence of noise. In noisy backgrounds, coding strategies that select the “right” channels for stimulation could potentially produce substantial improvements in intelligibility. In this study, the performance of two alternative channel selection criteria is assessed in terms of intelligibility and subjective quality with CI users in noise. The performance is compared against that of the maximum selection scheme employed in the ACE strategy (comparison is also made with the CIS strategy). Sentences were presented to seven CI users in speech weighted noise (−5, 0, and 5 dB SNR). Both channel selection criteria were implemented under ideal conditions where a priori knowledge of the target and masker was assumed. This was done to assess the full potential benefit of selecting the “right” channels for stimulation in noisy backgrounds. Substantial intelligibility improvement relative to the CI users' daily strategy (i.e., ACE or CIS) was achieved with the two different channel selection criteria under all noisy conditions considered. No significant difference in subjective quality of noisy speech processed by the two channel selection criteria was observed. PMID:23464031

  15. Gating the Selectivity Filter in ClC Chloride Channels

    NASA Astrophysics Data System (ADS)

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

    2003-04-01

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

  16. Channel selection for simultaneous and proportional myoelectric prosthesis control of multiple degrees-of-freedom

    NASA Astrophysics Data System (ADS)

    Hwang, Han-Jeong; Hahne, Janne Mathias; Müller, Klaus-Robert

    2014-10-01

    Objective. Recent studies have shown the possibility of simultaneous and proportional control of electrically powered upper-limb prostheses, but there has been little investigation on optimal channel selection. The objective of this study is to find a robust channel selection method and the channel subsets most suitable for simultaneous and proportional myoelectric prosthesis control of multiple degrees-of-freedom (DoFs). Approach. Ten able-bodied subjects and one person with congenital upper-limb deficiency took part in this study, and performed wrist movements with various combinations of two DoFs (flexion/extension and radial/ulnar deviation). During the experiment, high density electromyographic (EMG) signals and the actual wrist angles were recorded with an 8 × 24 electrode array and a motion tracking system, respectively. The wrist angles were estimated from EMG features with ridge regression using the subsets of channels chosen by three different channel selection methods: (1) least absolute shrinkage and selection operator (LASSO), (2) sequential feature selection (SFS), and (3) uniform selection (UNI). Main results. SFS generally showed higher estimation accuracy than LASSO and UNI, but LASSO always outperformed SFS in terms of robustness, such as noise addition, channel shift and training data reduction. It was also confirmed that about 95% of the original performance obtained using all channels can be retained with only 12 bipolar channels individually selected by LASSO and SFS. Significance. From the analysis results, it can be concluded that LASSO is a promising channel selection method for accurate simultaneous and proportional prosthesis control. We expect that our results will provide a useful guideline to select optimal channel subsets when developing clinical myoelectric prosthesis control systems based on continuous movements with multiple DoFs.

  17. Energetics of divalent selectivity in a calcium channel: the ryanodine receptor case study.

    PubMed

    Gillespie, Dirk

    2008-02-15

    A model of the ryanodine receptor (RyR) calcium channel is used to study the energetics of binding selectivity of Ca(2+) versus monovalent cations. RyR is a calcium-selective channel with a DDDD locus in the selectivity filter, similar to the EEEE locus of the L-type calcium channel. While the affinity of RyR for Ca(2+) is in the millimolar range (as opposed to the micromolar range of the L-type channel), the ease of single-channel measurements compared to L-type and its similar selectivity filter make RyR an excellent candidate for studying calcium selectivity. A Poisson-Nernst-Planck/density functional theory model of RyR is used to calculate the energetics of selectivity. Ca(2+) versus monovalent selectivity is driven by the charge/space competition mechanism in which selectivity arises from a balance of electrostatics and the excluded volume of ions in the crowded selectivity filter. While electrostatic terms dominate the selectivity, the much smaller excluded-volume term also plays a substantial role. In the D4899N and D4938N mutations of RyR that are analyzed, substantial changes in specific components of the chemical potential profiles are found far from the mutation site. These changes result in the significant reduction of Ca(2+) selectivity found in both theory and experiments.

  18. Spatial localization of the K+ channel selectivity filter by mutant cycle-based structure analysis.

    PubMed

    Ranganathan, R; Lewis, J H; MacKinnon, R

    1996-01-01

    The structurally well-characterized scorpion toxin Agitoxin2 inhibits ion permeation through Shaker K+ channels by binding to the external pore entryway. Scanning mutagenesis identified a set of inhibitor residues critical for making energetic contacts with the channel. Using thermodynamic mutant cycle analysis, we have mapped channel residues relative to the known inhibitor structure. This study constrains the position of multiple channel residues within the pore-forming loops; in one stretch, we have been able to map five out of seven contiguous residues to the inhibitor interaction surface, including those involved in ion selectivity. One interaction in particular, that of K27M on the inhibitor with Y445F on the channel, is unique in that it depends on the K+ ion concentration. These results reveal a shallow vestibule formed by the pore loops at the K+ channel entryway. The selectivity filter is located at the center of the vestibule close to (approximately 5 A) the extracellular solution. PMID:8562077

  19. Cation Selectivity in Biological Cation Channels Using Experimental Structural Information and Statistical Mechanical Simulation.

    PubMed

    Finnerty, Justin John; Peyser, Alexander; Carloni, Paolo

    2015-01-01

    Cation selective channels constitute the gate for ion currents through the cell membrane. Here we present an improved statistical mechanical model based on atomistic structural information, cation hydration state and without tuned parameters that reproduces the selectivity of biological Na+ and Ca2+ ion channels. The importance of the inclusion of step-wise cation hydration in these results confirms the essential role partial dehydration plays in the bacterial Na+ channels. The model, proven reliable against experimental data, could be straightforwardly used for designing Na+ and Ca2+ selective nanopores. PMID:26460827

  20. Cation Selectivity in Biological Cation Channels Using Experimental Structural Information and Statistical Mechanical Simulation

    PubMed Central

    Finnerty, Justin John

    2015-01-01

    Cation selective channels constitute the gate for ion currents through the cell membrane. Here we present an improved statistical mechanical model based on atomistic structural information, cation hydration state and without tuned parameters that reproduces the selectivity of biological Na+ and Ca2+ ion channels. The importance of the inclusion of step-wise cation hydration in these results confirms the essential role partial dehydration plays in the bacterial Na+ channels. The model, proven reliable against experimental data, could be straightforwardly used for designing Na+ and Ca2+ selective nanopores. PMID:26460827

  1. The LRRC26 Protein Selectively Alters the Efficacy of BK Channel Activators

    PubMed Central

    Almassy, Janos

    2012-01-01

    Large conductance, Ca2+-activated K channel proteins are involved in a wide range of physiological activities, so there is considerable interest in the pharmacology of large conductance calcium-activated K (BK) channels. One potent activator of BK channels is mallotoxin (MTX), which produces a very large hyperpolarizing shift of the voltage gating of heterologously expressed BK channels and causes a dramatic increase in the activity of BK channels in human smooth muscle cells. However, we found that MTX shifted the steady-state activation of BK channels in native parotid acinar cells by only 6 mV. This was not because the parotid BK isoform (parSlo) is inherently insensitive to MTX as MTX shifted the activation of heterologously expressed parSlo channels by 70 mV. Even though MTX had a minimal effect on steady-state activation of parotid BK channels, it produced an approximate 2-fold speeding of the channel-gating kinetics. The BK channels in parotid acinar cells have a much more hyperpolarized voltage activation range than BK channels in most other cell types. We found that this is probably attributable to an accessory protein, LRRC26, which is expressed in parotid glands: expressed parSlo + LRRC26 channels were resistant to the actions of MTX. Another class of BK activators is the benzimidazalones that includes 1,3-dihydro-1-(2-hydroxy-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-2H-benzimidazol-2-one (NS-1619). Although the LRRC26 accessory protein strongly inhibited the ability of MTX to activate BK channels, we found that it had only a small effect on the action of NS-1619 on BK channels. Thus, the LRRC26 BK channel accessory protein selectively alters the pharmacology of BK channels. PMID:21984254

  2. Use of color-coded sleeve shutters accelerates oscillograph channel selection

    NASA Technical Reports Server (NTRS)

    Bouchlas, T.; Bowden, F. W.

    1967-01-01

    Sleeve-type shutters mechanically adjust individual galvanometer light beams onto or away from selected channels on oscillograph papers. In complex test setups, the sleeve-type shutters are color coded to separately identify each oscillograph channel. This technique could be used on any equipment using tubular galvanometer light sources.

  3. Conductance hysteresis in the voltage dependent anion-selective channel

    PubMed Central

    Hoogerheide, David P.; Rostovtseva, Tatiana K.; Berezhkovskii, Alexander M.; Bezrukov, Sergey M.

    2015-01-01

    When the transmembrane voltage is periodically varied with time, the conductance of voltage-sensitive ion channels shows hysteretic behavior. Although this phenomenon has been used in studies of gating of the voltage-dependent anion channel, VDAC, from the outer mitochondrial membrane for nearly four decades, full hysteresis curves have never been reported, since the focus was only on the channel opening branches of the hysteresis loops. Here we study hysteretic response of a multichannel VDAC system to a triangular voltage ramp whose frequency varies within three orders of magnitude, ranging from 0.5 mHz to 0.2 Hz. We find that in this wide frequency range the area encircled by the hysteresis curves changes by less than a factor of three, thus suggesting a broad distribution of the characteristic times and strongly non-equilibrium behavior. At the same time, hysteresis branches corresponding to VDAC opening show quasi-equilibrium two-state behavior. This allows calculating usual equilibrium gating parameters, the gating charge and voltage of equipartitioning, which turn out to be virtually insensitive to the ramp frequency. To rationalize this peculiarity, we hypothesize that during voltage-induced closure and opening the system explores different regions of the complex free energy landscape, where, in the opening branch, it follows quasi-equilibrium paths. PMID:26094068

  4. Role of protein dynamics in ion selectivity and allosteric coupling in the NaK channel

    PubMed Central

    Brettmann, Joshua B.; Urusova, Darya; Tonelli, Marco; Silva, Jonathan R.; Henzler-Wildman, Katherine A.

    2015-01-01

    Flux-dependent inactivation that arises from functional coupling between the inner gate and the selectivity filter is widespread in ion channels. The structural basis of this coupling has only been well characterized in KcsA. Here we present NMR data demonstrating structural and dynamic coupling between the selectivity filter and intracellular constriction point in the bacterial nonselective cation channel, NaK. This transmembrane allosteric communication must be structurally different from KcsA because the NaK selectivity filter does not collapse under low-cation conditions. Comparison of NMR spectra of the nonselective NaK and potassium-selective NaK2K indicates that the number of ion binding sites in the selectivity filter shifts the equilibrium distribution of structural states throughout the channel. This finding was unexpected given the nearly identical crystal structure of NaK and NaK2K outside the immediate vicinity of the selectivity filter. Our results highlight the tight structural and dynamic coupling between the selectivity filter and the channel scaffold, which has significant implications for channel function. NaK offers a distinct model to study the physiologically essential connection between ion conduction and channel gating. PMID:26621745

  5. Apparent phosphorus availabilities of selected traditional and alternative feedstuffs for channel catfish

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A digestibility trial with channel catfish Ictalurus punctatus was conducted to determine apparent availability coefficients (AACs) of phosphorus for selected common feedstuffs: soybean meal, cottonseed meal, wheat middlings, corn gluten feed (CGF), and corn distillers dried grains with solubles (DD...

  6. Non-selective cation channels in plasma and vacuolar membranes and their contribution to K+ transport.

    PubMed

    Pottosin, Igor; Dobrovinskaya, Oxana

    2014-05-15

    Both in vacuolar and plasma membranes, in addition to truly K(+)-selective channels there is a variety of non-selective channels, which conduct K(+) and other ions with little preference. Many non-selective channels in the plasma membrane are active at depolarized potentials, thus, contributing to K(+) efflux rather than to K(+) uptake. They may play important roles in xylem loading or contribute to a K(+) leak, induced by salt or oxidative stress. Here, three currents, expressed in root cells, are considered: voltage-insensitive cation current, non-selective outwardly rectifying current, and low-selective conductance, activated by reactive oxygen species. The latter two do not only poorly discriminate between different cations (like K(+)vs Na(+)), but also conduct anions. Such solute channels may mediate massive electroneutral transport of salts and might be involved in osmotic adjustment or volume decrease, associated with cell death. In the tonoplast two major currents are mediated by SV (slow) and FV (fast) vacuolar channels, respectively, which are virtually impermeable for anions. SV channels conduct mono- and divalent cations indiscriminately and are activated by high cytosolic Ca(2+) and depolarized voltages. FV channels are inhibited by micromolar cytosolic Ca(2+), Mg(2+), and polyamines, and conduct a variety of monovalent cations, including K(+). Strikingly, both SV and FV channels sense the K(+) content of vacuoles, which modulates their voltage dependence, and in case of SV, also alleviates channel's inhibition by luminal Ca(2+). Therefore, SV and FV channels may operate as K(+)-sensing valves, controlling K(+) distribution between the vacuole and the cytosol.

  7. Computer model for selecting flow measuring structures in open channels

    SciTech Connect

    Hickey, M. J.

    1980-01-01

    Quantifying various pollutants in natural waterways has received increased emphasis with more stringent regulations issued by the Environmental Protection Agency (E.P.A.). Measuring natural stream fows presents a magnitude of problems, the most significant is the type of structure needed to measure the flows at the desired level of accuracy. A computer model designed to select a structure to best fit the engineer's needs is under development. This model, given the pertinent boundary conditions, will pinpoint the structure most suitable, if one exists. This selection process greatly facilitates the old selection process of trial and error.

  8. Study of Internal Channel Surface Roughnesses Manufactured by Selective Laser Melting in Aluminum and Titanium Alloys

    NASA Astrophysics Data System (ADS)

    Pakkanen, Jukka; Calignano, Flaviana; Trevisan, Francesco; Lorusso, Massimo; Ambrosio, Elisa Paola; Manfredi, Diego; Fino, Paolo

    2016-08-01

    Interest in additive manufacturing (AM) has gained considerable impetus over the past decade. One of the driving factors for AM success is the ability to create unique designs with intrinsic characteristics as, e.g., internal channels used for hydraulic components, cooling channels, and heat exchangers. However, a couple of the main problems in internal channels manufactured by AM technologies are the high surface roughness obtained and the distortion of the channel shape. There is still much to understand in these design aspects. In this study, a cylindrical geometry for internal channels to be built with different angles with respect to the building plane in AlSi10Mg and Ti6Al4V alloys by selective laser melting was considered. The internal surfaces of the channels produced in both materials were analyzed by means of a surface roughness tester and by optical and electron microscopy to evaluate the effects of the material and design choices.

  9. Altered ion channel conductance and ionic selectivity induced by large imposed membrane potential pulse.

    PubMed Central

    Chen, W; Lee, R C

    1994-01-01

    The effects of large magnitude transmembrane potential pulses on voltage-gated Na and K channel behavior in frog skeletal muscle membrane were studied using a modified double vaseline-gap voltage clamp. The effects of electroconformational damage to ionic channels were separated from damage to lipid bilayer (electroporation). A 4 ms transmembrane potential pulse of -600 mV resulted in a reduction of both Na and K channel conductivities. The supraphysiologic pulses also reduced ionic selectivity of the K channels against Na+ ions, resulting in a depolarization of the membrane resting potential. However, TTX and TEA binding effects were unaltered. The kinetics of spontaneous reversal of the electroconformational damage of channel proteins was found to be dependent on the magnitude of imposed membrane potential pulse. These results suggest that muscle and nerve dysfunction after electrical shock may be in part caused by electroconformational damage to voltage-gated ion channels. PMID:7948676

  10. On Optimal Input Design and Model Selection for Communication Channels

    SciTech Connect

    Li, Yanyan; Djouadi, Seddik M; Olama, Mohammed M

    2013-01-01

    In this paper, the optimal model (structure) selection and input design which minimize the worst case identification error for communication systems are provided. The problem is formulated using metric complexity theory in a Hilbert space setting. It is pointed out that model selection and input design can be handled independently. Kolmogorov n-width is used to characterize the representation error introduced by model selection, while Gel fand and Time n-widths are used to represent the inherent error introduced by input design. After the model is selected, an optimal input which minimizes the worst case identification error is shown to exist. In particular, it is proven that the optimal model for reducing the representation error is a Finite Impulse Response (FIR) model, and the optimal input is an impulse at the start of the observation interval. FIR models are widely popular in communication systems, such as, in Orthogonal Frequency Division Multiplexing (OFDM) systems.

  11. Grouped Automatic Relevance Determination and Its Application in Channel Selection for P300 BCIs.

    PubMed

    Yu, Tianyou; Yu, Zhuliang; Gu, Zhenghui; Li, Yuanqing

    2015-11-01

    During the development of a brain-computer interface, it is beneficial to exploit information in multiple electrode signals. However, a small channel subset is favored for not only machine learning feasibility, but also practicality in commercial and clinical BCI applications. An embedded channel selection approach based on grouped automatic relevance determination is proposed. The proposed Gaussian conjugate group-sparse prior and the embedded nature of the concerned Bayesian linear model enable simultaneous channel selection and feature classification. Moreover, with the marginal likelihood (evidence) maximization technique, hyper-parameters that determine the sparsity of the model are directly estimated from the training set, avoiding time-consuming cross-validation. Experiments have been conducted on P300 speller BCIs. The results for both public and in-house datasets show that the channels selected by our techniques yield competitive classification performance with the state-of-the-art and are biologically relevant to P300. PMID:25794393

  12. Simulation Studies of Ion Permeation and Selectivity in Voltage-Gated Sodium Channels.

    PubMed

    Ing, C; Pomès, R

    2016-01-01

    Voltage-gated ion channels are responsible for the generation and propagation of action potentials in electrically excitable cells. Molecular dynamics simulations have become a useful tool to study the molecular basis of ion transport in atomistic models of voltage-gated ion channels. The elucidation of several three-dimensional structures of bacterial voltage-gated sodium channels (Nav) in 2011 and 2012 opened the way to detailed computational investigations of this important class of membrane proteins. Here we review the numerous simulation studies of Na(+) permeation and selectivity in bacterial Nav channels published in the past 5years. These studies use a variety of simulation methodologies differing in force field parameters, molecular models, sampling algorithms, and simulation times. Although results disagree on the details of ion permeation mechanisms, they concur in the presence of two primary Na(+) binding sites in the selectivity filter and support a loosely coupled knock-on mechanism of Na(+) permeation. Comparative studies of Na(+), K(+), and Ca(2+) permeation reveal sites within Nav channels that are Na(+) selective, yet a consensus model of selectivity has not been established. We discuss the agreement between simulation and experimental results and propose strategies that may be used to resolve discrepancies between simulation studies in order to improve future computational studies of permeation and selectivity in ion channels. PMID:27586286

  13. OccK Channels from Pseudomonas aeruginosa Exhibit Diverse Single-channel Electrical Signatures, but Conserved Anion Selectivity

    PubMed Central

    Liu, Jiaming; Eren, Elif; Vijayaraghavan, Jagamya; Cheneke, Belete R.; Indic, Mridhu; van den Berg, Bert; Movileanu, Liviu

    2012-01-01

    Pseudomonas aeruginosa is a Gram-negative bacterium that utilizes substrate-specific outer membrane (OM) proteins for the uptake of small, water-soluble nutrients employed in the growth and function of the cell. In this paper, we present for the first time a comprehensive single-channel examination of seven members of the OM carboxylate channel K (OccK) subfamily. Recent biochemical, functional and structural characterization of the OccK proteins revealed their common features, such as a closely related, monomeric, 18-stranded β-barrel conformation with a kidney-shaped transmembrane pore and the presence of a basic ladder within the channel lumen. Here, we report that the OccK proteins exhibited fairly distinct unitary conductance values, in a much broader range than earlier expectations, which includes low (~40–100 pS) and medium (~100–380 pS) conductance. These proteins showed diverse single-channel dynamics of current gating transitions, revealing one (OccK3)-, two (OccK4, OccK5 and OccK6)- and three (OccK1, OccK2 and OccK7)-open sub-state kinetics with functionally distinct conformations. Interestingly, we discovered that anion selectivity is a conserved trait among the members of the OccK subfamily, confirming the presence of a net pool of positively charged residues within their central constriction. Moreover, these results are in accord with an increased specificity and selectivity of these protein channels for negatively charged, carboxylate-containing substrates. Our findings might ignite future functional examinations and full-atomistic computational studies for unraveling a mechanistic understanding of the passage of small molecules across the lumen of substrate-specific, β-barrel OM proteins. PMID:22369314

  14. Selection of the sounding channels for the High Resolution Limb Sounder (HIRDLS)

    SciTech Connect

    Edwards, D.P.; Gille, J.C.; Bailey, P.L.; Barnett, J.J.

    1994-12-31

    In this paper the authors describe the scientific design work behind the selection of the IR spectral passbands for the 21 sounding channels of the High Resolution Dynamics Limb Sounder (HIRDLS) which is scheduled to fly aboard the Earth Observing System (EOS) chemistry platform at the beginning of the next century. At least one radiometer channel must be used for each gas that is being measured. Preferably the interfering contributions to the radiance by other gases in a channel should be small, but the principle requirements are that the desired emission be measured with high signal-to-noise ratio, and that there be separate channels for the measurement of interfering species. However, more than one channel is required to provide full altitude coverage of those target gases such as CO{sub 2}, H{sub 2}O, and O{sub 3}, which have emission bands whose centers become optically thick in the middle atmosphere. Further channels, in which gaseous absorption is low, are required for the characterization of aerosol effects. The authors describe the HIRDLS channels selected for each gas, with emphasis on signal-to-noise considerations and altitude coverage, the elimination of contaminating signal between channels, and non-LTE processes for high altitude sounding and space view definition.

  15. Selection of sounding channels for the High Resolution Dynamics Limb Sounder

    NASA Astrophysics Data System (ADS)

    Barnett, John J.; Edwards, David P.; Gille, John C.; Bailey, Paul L.

    1995-10-01

    We describe the scientific design work behind the selection of the IR spectral passbands for the 21 sounding channels of the High Resolution Dynamics Limb Sounder (HIRDLS), which is scheduled to fly aboard the Earth Observing System chemistry platform at the beginning of the next century. At least one radiometer channel must be used for each gas that is being measured. Preferably the interfering contributions to the radiance by other gases in a channel should be small, but the principal requirements are that the desired emission be measured with high signal-to-noise ratio and that there be separate channels for the measurement of interfering species. However, more than one channel is required for providing full altitude coverage of those target gases such as CO2, H2O, and O3, which have emission bands whose centers become optically thick in the middle atmosphere. Further channels, in which gaseous absorption is low, are required for the characterization of aerosol effects. We describe the HIRDLS channels selected for each gas, with emphasis on signal-to-noise considerations and altitude coverage, the elimination of contaminating signal between channels, and nonlocal thermodynamic equilibrium processes for high-altitude sounding and space view definition.

  16. Selectivity in Exposure to Information Channels during a Gubernatorial Election.

    ERIC Educational Resources Information Center

    Edeani, David O.; Jacoubovitch, M. Daniel

    Data were collected from 93 journalism students before and after the 1978 Ohio gubernatorial election to determine how selectivity in exposure to information was influenced by information utility, fatalism (locus of control), past history of reinforcement, and political party identification. Results showed that past history of reinforcement and…

  17. Lysine and the Na+/K+ Selectivity in Mammalian Voltage-Gated Sodium Channels.

    PubMed

    Li, Yang; Liu, Huihui; Xia, Mengdie; Gong, Haipeng

    2016-01-01

    Voltage-gated sodium (Nav) channels are critical in the generation and transmission of neuronal signals in mammals. The crystal structures of several prokaryotic Nav channels determined in recent years inspire the mechanistic studies on their selection upon the permeable cations (especially between Na+ and K+ ions), a property that is proposed to be mainly determined by residues in the selectivity filter. However, the mechanism of cation selection in mammalian Nav channels lacks direct explanation at atomic level due to the difference in amino acid sequences between mammalian and prokaryotic Nav homologues, especially at the constriction site where the DEKA motif has been identified to determine the Na+/K+ selectivity in mammalian Nav channels but is completely absent in the prokaryotic counterparts. Among the DEKA residues, Lys is of the most importance since its mutation to Arg abolishes the Na+/K+ selectivity. In this work, we modeled the pore domain of mammalian Nav channels by mutating the four residues at the constriction site of a prokaryotic Nav channel (NavRh) to DEKA, and then mechanistically investigated the contribution of Lys in cation selection using molecular dynamics simulations. The DERA mutant was generated as a comparison to understand the loss of ion selectivity caused by the K-to-R mutation. Simulations and free energy calculations on the mutants indicate that Lys facilitates Na+/K+ selection by electrostatically repelling the cation to a highly Na+-selective location sandwiched by the carboxylate groups of Asp and Glu at the constriction site. In contrast, the electrostatic repulsion is substantially weakened when Lys is mutated to Arg, because of two intrinsic properties of the Arg side chain: the planar geometric design and the sparse charge distribution of the guanidine group. PMID:27584582

  18. Lysine and the Na+/K+ Selectivity in Mammalian Voltage-Gated Sodium Channels

    PubMed Central

    Xia, Mengdie

    2016-01-01

    Voltage-gated sodium (Nav) channels are critical in the generation and transmission of neuronal signals in mammals. The crystal structures of several prokaryotic Nav channels determined in recent years inspire the mechanistic studies on their selection upon the permeable cations (especially between Na+ and K+ ions), a property that is proposed to be mainly determined by residues in the selectivity filter. However, the mechanism of cation selection in mammalian Nav channels lacks direct explanation at atomic level due to the difference in amino acid sequences between mammalian and prokaryotic Nav homologues, especially at the constriction site where the DEKA motif has been identified to determine the Na+/K+ selectivity in mammalian Nav channels but is completely absent in the prokaryotic counterparts. Among the DEKA residues, Lys is of the most importance since its mutation to Arg abolishes the Na+/K+ selectivity. In this work, we modeled the pore domain of mammalian Nav channels by mutating the four residues at the constriction site of a prokaryotic Nav channel (NavRh) to DEKA, and then mechanistically investigated the contribution of Lys in cation selection using molecular dynamics simulations. The DERA mutant was generated as a comparison to understand the loss of ion selectivity caused by the K-to-R mutation. Simulations and free energy calculations on the mutants indicate that Lys facilitates Na+/K+ selection by electrostatically repelling the cation to a highly Na+-selective location sandwiched by the carboxylate groups of Asp and Glu at the constriction site. In contrast, the electrostatic repulsion is substantially weakened when Lys is mutated to Arg, because of two intrinsic properties of the Arg side chain: the planar geometric design and the sparse charge distribution of the guanidine group. PMID:27584582

  19. A Wearable Channel Selection-Based Brain-Computer Interface for Motor Imagery Detection

    PubMed Central

    Lo, Chi-Chun; Chien, Tsung-Yi; Chen, Yu-Chun; Tsai, Shang-Ho; Fang, Wai-Chi; Lin, Bor-Shyh

    2016-01-01

    Motor imagery-based brain-computer interface (BCI) is a communication interface between an external machine and the brain. Many kinds of spatial filters are used in BCIs to enhance the electroencephalography (EEG) features related to motor imagery. The approach of channel selection, developed to reserve meaningful EEG channels, is also an important technique for the development of BCIs. However, current BCI systems require a conventional EEG machine and EEG electrodes with conductive gel to acquire multi-channel EEG signals and then transmit these EEG signals to the back-end computer to perform the approach of channel selection. This reduces the convenience of use in daily life and increases the limitations of BCI applications. In order to improve the above issues, a novel wearable channel selection-based brain-computer interface is proposed. Here, retractable comb-shaped active dry electrodes are designed to measure the EEG signals on a hairy site, without conductive gel. By the design of analog CAR spatial filters and the firmware of EEG acquisition module, the function of spatial filters could be performed without any calculation, and channel selection could be performed in the front-end device to improve the practicability of detecting motor imagery in the wearable EEG device directly or in commercial mobile phones or tablets, which may have relatively low system specifications. Finally, the performance of the proposed BCI is investigated, and the experimental results show that the proposed system is a good wearable BCI system prototype. PMID:26861347

  20. A Wearable Channel Selection-Based Brain-Computer Interface for Motor Imagery Detection.

    PubMed

    Lo, Chi-Chun; Chien, Tsung-Yi; Chen, Yu-Chun; Tsai, Shang-Ho; Fang, Wai-Chi; Lin, Bor-Shyh

    2016-02-06

    Motor imagery-based brain-computer interface (BCI) is a communication interface between an external machine and the brain. Many kinds of spatial filters are used in BCIs to enhance the electroencephalography (EEG) features related to motor imagery. The approach of channel selection, developed to reserve meaningful EEG channels, is also an important technique for the development of BCIs. However, current BCI systems require a conventional EEG machine and EEG electrodes with conductive gel to acquire multi-channel EEG signals and then transmit these EEG signals to the back-end computer to perform the approach of channel selection. This reduces the convenience of use in daily life and increases the limitations of BCI applications. In order to improve the above issues, a novel wearable channel selection-based brain-computer interface is proposed. Here, retractable comb-shaped active dry electrodes are designed to measure the EEG signals on a hairy site, without conductive gel. By the design of analog CAR spatial filters and the firmware of EEG acquisition module, the function of spatial filters could be performed without any calculation, and channel selection could be performed in the front-end device to improve the practicability of detecting motor imagery in the wearable EEG device directly or in commercial mobile phones or tablets, which may have relatively low system specifications. Finally, the performance of the proposed BCI is investigated, and the experimental results show that the proposed system is a good wearable BCI system prototype.

  1. The relationship between mean channel selection and the calculated coefficient of variation.

    PubMed

    Schuette, W H; Carducci, E; Marti, G E; Shackney, S E; Eden, M

    1985-09-01

    Calculated coefficients of variation (CV) taken from the quotient of the standard deviation (S.D.) and the mean value of measured distributions are often used as an indicator of system performance in linear flow cytometry (FCM). The ability of the calculated CV to estimate the true CV of the underlying experiment before grouping (channelization) is dependent on the relationship between the width of the data channels and the magnitude of the S.D. of the measured distribution. When the channel width is equal to the S.D. of a distribution, the calculated CV is approximately 20% larger than the true CV of an experiment. By the time the S.D. is only one-half of a channel width, the calculated CV is unreliable. When the distribution S.D. is narrower than a channel's width, small changes in the distribution mean value will cause large variations in the calculated CV. As the true CV decreases, the calculation must be made with higher mean channel values. This dependence of calculated CV accuracy upon the relationship between S.D. and channel width places limitations upon mean channel selection that must be considered when using CV calculations for evaluating system performance, especially when looking for small improvements during optical alignment procedures. When an instrument is assumed to have a constant CV and the data are collected linearly, it is possible to improve the CV estimation accuracy by placing distributions in higher-numbered channels.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Overcharging below the nanoscale: Multivalent cations reverse the ion selectivity of a biological channel

    NASA Astrophysics Data System (ADS)

    García-Giménez, Elena; Alcaraz, Antonio; Aguilella, Vicente M.

    2010-02-01

    We report charge inversion within a nanoscopic biological protein ion channel in salts of multivalent ions. The presence of positive divalent and trivalent counterions reverses the cationic selectivity of the OmpF channel, a general diffusion porin located in the outer membrane of E. coli. We discuss the conditions under which charge inversion can be inferred from the change in sign of the measured quantity, the channel zero current potential. By comparing experimental results in protein channels whose charge has been modified after site-directed mutagenesis, the predictions of current theories of charge inversion are critically examined. It is emphasized that charge inversion does not necessarily increase with the bare surface charge density of the interface and that even this concept of surface charge density may become meaningless in some biological ion channels. Thus, any theory based on electrostatic correlations or chemical binding should explicitly take into account the particular structure of the charged interface.

  3. Second order statistics of selection combining receiver over κ-μ fading channels subject to co-channel interferences

    NASA Astrophysics Data System (ADS)

    Stefanović, Mihajlo; Panić, Stefan R.; Stefanović, DušAn; Nikolić, Bojana; Cvetković, Aleksandra

    2012-12-01

    Radio propagation performances in interference-limited faded environment are studied in this paper. Selection combining (SC) based on signal-to-interference ratio (SIR) overκ-μfading channels is performed. Probability density function (PDF) and cumulative distribution function (CDF) of the received SIR are determined. Based on the results obtained for PDF and CDF, infinite-series expressions are derived for the output level crossing rate (LCR) and average fade duration (AFD). These second order statistical measures are regarded as necessary for supporting technical documentation in every radio communication link design. Influences of various system parameters such as fading severity and the number of co-channel interferences affecting these measures are graphically presented and discussed.

  4. Evoked potential correlates of selective attention with multi-channel auditory inputs

    NASA Technical Reports Server (NTRS)

    Schwent, V. L.; Hillyard, S. A.

    1975-01-01

    Ten subjects were presented with random, rapid sequences of four auditory tones which were separated in pitch and apparent spatial position. The N1 component of the auditory vertex evoked potential (EP) measured relative to a baseline was observed to increase with attention. It was concluded that the N1 enhancement reflects a finely tuned selective attention to one stimulus channel among several concurrent, competing channels. This EP enhancement probably increases with increased information load on the subject.

  5. Discovery of novel tetrahydroisoquinoline derivatives as orally active N-type calcium channel blockers with high selectivity for hERG potassium channels.

    PubMed

    Ogiyama, Takashi; Inoue, Makoto; Honda, Shugo; Yamada, Hiroyoshi; Watanabe, Toshihiro; Gotoh, Takayasu; Kiso, Tetsuo; Koakutsu, Akiko; Kakimoto, Shuichiro; Shishikura, Jun-ichi

    2014-12-15

    N-type calcium channels represent a promising target for the treatment of neuropathic pain. The selective N-type calcium channel blocker ziconotide ameliorates severe chronic pain but has a narrow therapeutic window and requires intrathecal administration. We identified tetrahydroisoquinoline derivative 1a as a novel potent N-type calcium channel blocker. However, this compound also exhibited potent inhibitory activity against hERG channels. Structural optimizations led to identification of (1S)-(1-cyclohexyl-3,4-dihydroisoquinolin-2(1H)-yl)-2-{[(1-hydroxycyclohexyl)methyl]amino}ethanone ((S)-1h), which exhibited high selectivity for hERG channels while retaining potency for N-type calcium channel inhibition. (S)-1h went on to demonstrate in vivo efficacy as an orally available N-type calcium channel blocker in a rat spinal nerve ligation model of neuropathic pain.

  6. The mechanosensory calcium-selective ion channel: key component of a plasmalemmal control centre?

    NASA Technical Reports Server (NTRS)

    Pickard, B. G.; Ding, J. P.

    1993-01-01

    Mechanosensory calcium-selective ion channels probably serve to detect not only mechanical stress but also electrical, thermal, and diverse chemical stimuli. Because all stimuli result in a common output, most notably a shift in second messenger calcium concentration, the channels are presumed to serve as signal integrators. Further, insofar as second messenger calcium in turn gives rise to mechanical, electrical, and diverse chemical changes, the channels are postulated to initiate regulatory feedbacks. It is proposed that the channels and the feedback loops play a wide range of roles in regulating normal plant function, as well as in mediating disturbance of normal function by environmental stressors and various pathogens. In developing evidence for the physiological performance of the channel, a model for a cluster of regulatory plasmalemmal proteins and cytoskeletal elements grouped around a set of wall-to-membrane and transmembrane linkers has proved useful. An illustration of how the model might operate is presented. It is founded on the demonstration that several xenobiotics interfere both with normal channel behaviour and with gravitropic reception. Accordingly, the first part of the illustration deals with how the channels and the control system within which they putatively operate might initiate gravitropism. Assuming that gravitropism is an asymmetric expression of growth, the activities of the channels and the plasmalemmal control system are extrapolated to account for regulation of both rate and allometry of cell expansion. Finally, it is discussed how light, hormones, redox agents and herbicides could in principle affect growth via the putative plasmalemmal control cluster or centre.

  7. Sodium channel selectivity and conduction: prokaryotes have devised their own molecular strategy.

    PubMed

    Finol-Urdaneta, Rocio K; Wang, Yibo; Al-Sabi, Ahmed; Zhao, Chunfeng; Noskov, Sergei Y; French, Robert J

    2014-02-01

    Striking structural differences between voltage-gated sodium (Nav) channels from prokaryotes (homotetramers) and eukaryotes (asymmetric, four-domain proteins) suggest the likelihood of different molecular mechanisms for common functions. For these two channel families, our data show similar selectivity sequences among alkali cations (relative permeability, Pion/PNa) and asymmetric, bi-ionic reversal potentials when the Na/K gradient is reversed. We performed coordinated experimental and computational studies, respectively, on the prokaryotic Nav channels NaChBac and NavAb. NaChBac shows an "anomalous," nonmonotonic mole-fraction dependence in the presence of certain sodium-potassium mixtures; to our knowledge, no comparable observation has been reported for eukaryotic Nav channels. NaChBac's preferential selectivity for sodium is reduced either by partial titration of its highly charged selectivity filter, when extracellular pH is lowered from 7.4 to 5.8, or by perturbation-likely steric-associated with a nominally electro-neutral substitution in the selectivity filter (E191D). Although no single molecular feature or energetic parameter appears to dominate, our atomistic simulations, based on the published NavAb crystal structure, revealed factors that may contribute to the normally observed selectivity for Na over K. These include: (a) a thermodynamic penalty to exchange one K(+) for one Na(+) in the wild-type (WT) channel, increasing the relative likelihood of Na(+) occupying the binding site; (b) a small tendency toward weaker ion binding to the selectivity filter in Na-K mixtures, consistent with the higher conductance observed with both sodium and potassium present; and (c) integrated 1-D potentials of mean force for sodium or potassium movement that show less separation for the less selective E/D mutant than for WT. Overall, tight binding of a single favored ion to the selectivity filter, together with crucial inter-ion interactions within the pore, suggests

  8. Autocrine-Based Selection of Drugs That Target Ion Channels from Combinatorial Venom Peptide Libraries.

    PubMed

    Zhang, Hongkai; Du, Mingjuan; Xie, Jia; Liu, Xiao; Sun, Jingying; Wang, Wei; Xin, Xiu; Possani, Lourival D; Yea, Kyungmoo; Lerner, Richard A

    2016-08-01

    Animal venoms represent a rich source of pharmacologically active peptides that interact with ion channels. However, a challenge to discovering drugs remains because of the slow pace at which venom peptides are discovered and refined. An efficient autocrine-based high-throughput selection system was developed to discover and refine venom peptides that target ion channels. The utility of this system was demonstrated by the discovery of novel Kv1.3 channel blockers from a natural venom peptide library that was formatted for autocrine-based selection. We also engineered a Kv1.3 blocker peptide (ShK) derived from sea anemone to generate a subtype-selective Kv1.3 blocker with a long half-life in vivo. PMID:27197631

  9. High spin spectroscopy near the N=Z line: Channel selection and excitation energy systematics

    SciTech Connect

    Svensson, C.E.; Cameron, J.A.; Flibotte, S.

    1996-12-31

    The total {gamma}-ray and charged-particle energies emitted in fusion-evaporation reactions leading to N=Z compound systems in the A = 50-70 mass region have been measured with the 8{pi} {gamma}-ray spectrometer and the miniball charged-particle detector array. A new method of channel selection has been developed which combines particle identification with these total energy measurements and greatly improves upon the selectivity possible with particle detection alone. In addition, the event by event measurement of total {gamma}-ray energies using the BGO ball of the 8{pi} spectrometer has allowed a determination of excitation energies following particle evaporation for a large number of channels in several different reactions. The new channel selection procedure and excitation energy systematics are illustrated with data from the reaction of {sup 24}Mg on {sup 40}Ca at E{sub lab} = 80MeV.

  10. Simultaneous Channel and Feature Selection of Fused EEG Features Based on Sparse Group Lasso

    PubMed Central

    Wang, Jin-Jia; Xue, Fang; Li, Hui

    2015-01-01

    Feature extraction and classification of EEG signals are core parts of brain computer interfaces (BCIs). Due to the high dimension of the EEG feature vector, an effective feature selection algorithm has become an integral part of research studies. In this paper, we present a new method based on a wrapped Sparse Group Lasso for channel and feature selection of fused EEG signals. The high-dimensional fused features are firstly obtained, which include the power spectrum, time-domain statistics, AR model, and the wavelet coefficient features extracted from the preprocessed EEG signals. The wrapped channel and feature selection method is then applied, which uses the logistical regression model with Sparse Group Lasso penalized function. The model is fitted on the training data, and parameter estimation is obtained by modified blockwise coordinate descent and coordinate gradient descent method. The best parameters and feature subset are selected by using a 10-fold cross-validation. Finally, the test data is classified using the trained model. Compared with existing channel and feature selection methods, results show that the proposed method is more suitable, more stable, and faster for high-dimensional feature fusion. It can simultaneously achieve channel and feature selection with a lower error rate. The test accuracy on the data used from international BCI Competition IV reached 84.72%. PMID:25802861

  11. Selectivity and permeation in calcium release channel of cardiac muscle: alkali metal ions.

    PubMed Central

    Chen, D P; Xu, L; Tripathy, A; Meissner, G; Eisenberg, B

    1999-01-01

    Current was measured from single open channels of the calcium release channel (CRC) of cardiac sarcoplasmic reticulum (over the range +/-180 mV) in pure and mixed solutions (e.g., biionic conditions) of the alkali metal ions Li+, K+, Na+, Rb+, Cs+, ranging in concentration from 25 mM to 2 M. The current-voltage (I-V) relations were analyzed by an extension of the Poisson-Nernst-Planck (PNP) formulation of electrodiffusion, which includes local chemical interaction described by an offset in chemical potential, which likely reflects the difference in dehydration/solvation/rehydration energies in the entry/exit steps of permeation. The theory fits all of the data with few adjustable parameters: the diffusion coefficient of each ion species, the average effective charge distribution on the wall of the pore, and an offset in chemical potential for lithium and sodium ions. In particular, the theory explains the discrepancy between "selectivities" defined by conductance sequence and "selectivities" determined by the permeability ratios (i.e., reversal potentials) in biionic conditions. The extended PNP formulation seems to offer a successful combined treatment of selectivity and permeation. Conductance selectivity in this channel arises mostly from friction: different species of ions have different diffusion coefficients in the channel. Permeability selectivity of an ion is determined by its electrochemical potential gradient and local chemical interaction with the channel. Neither selectivity (in CRC) seems to involve different electrostatic interaction of different ions with the channel protein, even though the ions have widely varying diameters. PMID:10049318

  12. Low-complexity user selection for rate maximization in MIMO broadcast channels with downlink beamforming.

    PubMed

    Castañeda, Eduardo; Silva, Adão; Samano-Robles, Ramiro; Gameiro, Atílio

    2014-01-01

    We present in this work a low-complexity algorithm to solve the sum rate maximization problem in multiuser MIMO broadcast channels with downlink beamforming. Our approach decouples the user selection problem from the resource allocation problem and its main goal is to create a set of quasiorthogonal users. The proposed algorithm exploits physical metrics of the wireless channels that can be easily computed in such a way that a null space projection power can be approximated efficiently. Based on the derived metrics we present a mathematical model that describes the dynamics of the user selection process which renders the user selection problem into an integer linear program. Numerical results show that our approach is highly efficient to form groups of quasiorthogonal users when compared to previously proposed algorithms in the literature. Our user selection algorithm achieves a large portion of the optimum user selection sum rate (90%) for a moderate number of active users.

  13. Steric selectivity in Na channels arising from protein polarization and mobile side chains.

    PubMed

    Boda, Dezso; Nonner, Wolfgang; Valiskó, Mónika; Henderson, Douglas; Eisenberg, Bob; Gillespie, Dirk

    2007-09-15

    Monte Carlo simulations of equilibrium selectivity of Na channels with a DEKA locus are performed over a range of radius R and protein dielectric coefficient epsilon(p). Selectivity arises from the balance of electrostatic forces and steric repulsion by excluded volume of ions and side chains of the channel protein in the highly concentrated and charged (approximately 30 M) selectivity filter resembling an ionic liquid. Ions and structural side chains are described as mobile charged hard spheres that assume positions of minimal free energy. Water is a dielectric continuum. Size selectivity (ratio of Na+ occupancy to K+ occupancy) and charge selectivity (Na+ to Ca2+) are computed in concentrations as low as 10(-5) M Ca2+. In general, small R reduces ion occupancy and favors Na+ over K+ because of steric repulsion. Small epsilon(p) increases occupancy and favors Na+ over Ca2+ because protein polarization amplifies the pore's net charge. Size selectivity depends on R and is independent of epsilon(p); charge selectivity depends on both R and epsilon(p). Thus, small R and epsilon(p) make an efficient Na channel that excludes K+ and Ca2+ while maximizing Na+ occupancy. Selectivity properties depend on interactions that cannot be described by qualitative or verbal models or by quantitative models with a fixed free energy landscape. PMID:17526571

  14. Properties of cyclic nucleotide-gated channels mediating olfactory transduction. Activation, selectivity, and blockage

    PubMed Central

    1992-01-01

    Cyclic nucleotide-gated channels (cng channels) in the sensory membrane of olfactory receptor cells, activated after the odorant-induced increase of cytosolic cAMP concentration, conduct the receptor current that elicits electrical excitation of the receptor neurons. We investigated properties of cng channels from frog and rat using inside- out and outside-out membrane patches excised from isolated olfactory receptor cells. Channels were activated by cAMP and cGMP with activation constants of 2.5-4.0 microM for cAMP and 1.0-1.8 for cGMP. Hill coefficients of dose-response curves were 1.4-1.8, indicating cooperativity of ligand binding. Selectivity for monovalent alkali cations and the Na/Li mole-fraction behavior identified the channel as a nonselective cation channel, having a cation-binding site of high field strength in the pore. Cytosolic pH effects suggest the presence of an additional titratable group which, when protonated, inhibits the cAMP-induced current with an apparent pK of 5.0-5.2. The pH effects were not voltage dependent. Several blockers of Ca2+ channels also blocked olfactory cng channels. Amiloride, D 600, and diltiazem inhibited the cAMP-induced current from the cytosolic side. Inhibition constants were voltage dependent with values of, respectively, 0.1, 0.3, and 1 mM at -60 mV, and 0.03, 0.02, and 0.2 mM at +60 mV. Our results suggest functional similarity between frog and rat cng channels, as well as marked differences to cng channels from photoreceptors and other tissues. PMID:1324972

  15. Comparison of the single channel and multichannel (multivariate) concepts of selectivity in analytical chemistry.

    PubMed

    Dorkó, Zsanett; Verbić, Tatjana; Horvai, George

    2015-07-01

    Different measures of selectivity are in use for single channel and multichannel linear analytical measurements, respectively. It is important to understand that these two measures express related but still distinctly different features of the respective measurements. These relationships are clarified by introducing new arguments. The most widely used selectivity measure of multichannel linear methods (which is based on the net analyte signal, NAS, concept) expresses the sensitivity to random errors of a determination where all bias from interferents is computationally eliminated using pure component spectra. The conventional selectivity measure of single channel linear measurements, on the other hand, helps to estimate the bias caused by an interferent in a biased measurement. In single channel methods expert knowledge about the samples is used to limit the possible range of interferent concentrations. The same kind of expert knowledge allows improved (lower mean squared error, MSE) analyte determinations also in "classical" multichannel measurements if those are intractable due to perfect collinearity or to high noise inflation. To achieve this goal bias variance tradeoff is employed, hence there remains some bias in the results and therefore the concept of single channel selectivity can be extended in a natural way to multichannel measurements. This extended definition and the resulting selectivity measure can also be applied to the so-called inverse multivariate methods like partial least squares regression (PLSR), principal component regression (PCR) and ridge regression (RR). PMID:25882406

  16. Comparison of the single channel and multichannel (multivariate) concepts of selectivity in analytical chemistry.

    PubMed

    Dorkó, Zsanett; Verbić, Tatjana; Horvai, George

    2015-07-01

    Different measures of selectivity are in use for single channel and multichannel linear analytical measurements, respectively. It is important to understand that these two measures express related but still distinctly different features of the respective measurements. These relationships are clarified by introducing new arguments. The most widely used selectivity measure of multichannel linear methods (which is based on the net analyte signal, NAS, concept) expresses the sensitivity to random errors of a determination where all bias from interferents is computationally eliminated using pure component spectra. The conventional selectivity measure of single channel linear measurements, on the other hand, helps to estimate the bias caused by an interferent in a biased measurement. In single channel methods expert knowledge about the samples is used to limit the possible range of interferent concentrations. The same kind of expert knowledge allows improved (lower mean squared error, MSE) analyte determinations also in "classical" multichannel measurements if those are intractable due to perfect collinearity or to high noise inflation. To achieve this goal bias variance tradeoff is employed, hence there remains some bias in the results and therefore the concept of single channel selectivity can be extended in a natural way to multichannel measurements. This extended definition and the resulting selectivity measure can also be applied to the so-called inverse multivariate methods like partial least squares regression (PLSR), principal component regression (PCR) and ridge regression (RR).

  17. The anomalous mole fraction effect in calcium channels: a measure of preferential selectivity.

    PubMed

    Gillespie, Dirk; Boda, Dezso

    2008-09-15

    The cause of the anomalous mole fraction effect (AMFE) in calcium-selective ion channels is studied. An AMFE occurs when the conductance through a channel is lower in a mixture of salts than in the pure salts at the same concentration. The textbook interpretation of the AMFE is that multiple ions move through the pore in coordinated, single-file motion. Instead of this, we find that at its most basic level an AMFE reflects a channel's preferential binding selectivity for one ion species over another. The AMFE is explained by considering the charged and uncharged regions of the pore as electrical resistors in series: the AMFE is produced by these regions of high and low ion concentration changing differently with mole fraction due to the preferential ion selectivity. This is demonstrated with simulations of a model L-type calcium channel and a mathematical analysis of a simplistic point-charge model. The particle simulations reproduce the experimental data of two L-type channel AMFEs. Conditions under which an AMFE may be found experimentally are discussed. The resistors-in-series model provides a fundamentally different explanation of the AMFE than the traditional theory and does not require single filing, multiple occupancy, or momentum-correlated ion motion.

  18. Aluminium and hydrogen ions inhibit a mechanosensory calcium-selective cation channel

    NASA Technical Reports Server (NTRS)

    Ding, J. P.; Pickard, B. G.

    1993-01-01

    The tension-dependent activity of mechanosensory calcium-selective cation channels in excised plasmalemmal patches from onion bulb scale epidermis is modulated by pH in the physiologically meaningful range between 4.5 and 7.2. It is rapidly lowered by lowering pH and rapidly raised by raising pH. Channel activity is effectively inhibited by low levels of aluminium ions and activity can be partially restored by washing for a few minutes. We suggest that under normal conditions the sensitivity of the mechanosensory channels to pH of the wall free space plays important roles in regulation of plant activities such as growth. We further suggest that, when levels of acid and aluminium ions in the soil solution are high, they might inhibit similar sensory channels in cells of the root tip, thus contributing critically to the acid soil syndrome.

  19. Zn(2+) modulation of neuronal transient K(+) current: fast and selective binding to the deactivated channels

    PubMed Central

    Kuo, CC; Chen, FP

    1999-01-01

    Modulation of voltage-dependent transient K(+) currents (A type K(+) or K(A) current) by Zn(2+) was studied in rat hippocampal neurons by the whole-cell patch-clamp technique. It is found that Zn(2+) selectively binds to the resting (deactivated or closed) K(A) channels with a dissociation constant (K(d)) of approximately 3 &mgr;M, whereas the affinity between Zn(2+) and the inactivated K(A) channels is 1000-fold lower. Zn(2+) therefore produces a concentration-dependent shift of the K(A) channel inactivation curve and enhances the K(A) current elicited from relatively positive holding potentials. It is also found that the kinetics of Zn(2+) action are fast enough to compete with the transition rates between different gating states of the channel. The rapid and selective binding of Zn(2+) to the closed K(A) channels keeps the channel in the closed state and explains the ion's concentration-dependent slowing effect on the activation of K(A) current. This in turn accounts for the inhibitory effect of Zn(2+) on the K(A) current elicited from hyperpolarized holding potentials. Because the molecular mechanisms underlying these gating changes are kinetic interactions between the binding-unbinding of Zn(2+) and the intrinsic gating processes of the channel, the shift of the inactivation curve and slowing of K(A) channel activation are quantitatively correlated with ambient Zn(2+) over a wide concentration range without "saturation"; i.e., The effects are already manifest in micromolar Zn(2+), yet are not saturated even in millimolar Zn(2+). Because the physiological concentration of Zn(2+) could vary over a similarly wide range according to neural activities, Zn(2+) may be a faithful physiological "fine tuner," controlling and controlled by neural activities through its effect on the K(A) current. PMID:10545356

  20. (De)constructing the ryanodine receptor: modeling ion permeation and selectivity of the calcium release channel.

    PubMed

    Gillespie, Dirk; Xu, Le; Wang, Ying; Meissner, Gerhard

    2005-08-18

    Biological ion channels are proteins that passively conduct ions across membranes that are otherwise impermeable to ions. Here, we present a model of ion permeation and selectivity through a single, open ryanodine receptor (RyR) ion channel. Combining recent mutation data with electrodiffusion of finite-sized ions, the model reproduces the current/voltage curves of cardiac RyR (RyR2) in KCl, LiCl, NaCl, RbCl, CsCl, CaCl(2), MgCl(2), and their mixtures over large concentrations and applied voltage ranges. It also reproduces the reduced K(+) conductances and Ca(2+) selectivity of two skeletal muscle RyR (RyR1) mutants (D4899N and E4900Q). The model suggests that the selectivity filter of RyR contains the negatively charged residue D4899 that dominates the permeation and selectivity properties and gives RyR a DDDD locus similar to the EEEE locus of the L-type calcium channel. In contrast to previously applied barrier models, the current model describes RyR as a multi-ion channel with approximately three monovalent cations in the selectivity filter at all times. Reasons for the contradicting occupancy predictions are discussed. In addition, the model predicted an anomalous mole fraction effect for Na(+)/Cs(+) mixtures, which was later verified by experiment. Combining these results, the binding selectivity of RyR appears to be driven by the same charge/space competition mechanism of other highly charged channels.

  1. Local anesthetic anchoring to cardiac sodium channels. Implications into tissue-selective drug targeting.

    PubMed

    Li, R A; Tsushima, R G; Himmeldirk, K; Dime, D S; Backx, P H

    1999-07-01

    Local anesthetics inhibit Na+ channels in a variety of tissues, leading to potentially serious side effects when used clinically. We have created a series of novel local anesthetics by connecting benzocaine (BZ) to the sulfhydryl-reactive group methanethiosulfonate (MTS) via variable-length polyethylether linkers (L) (MTS-LX-BZ [X represents 0, 3, 6, or 9]). The application of MTS-LX-BZ agents modified native rat cardiac as well as heterologously expressed human heart (hH1) and rat skeletal muscle (rSkM1) Na+ channels in a manner resembling that of free BZ. Like BZ, the effects of MTS-LX-BZ on rSkM1 channels were completely reversible. In contrast, MTS-LX-BZ modification of heart and mutant rSkM1 channels, containing a pore cysteine at the equivalent location as cardiac Na+ channels (ie, Y401C), persisted after drug washout unless treated with DTT, which suggests anchoring to the pore via a disulfide bond. Anchored MTS-LX-BZ competitively reduced the affinity of cardiac Na+ channels for lidocaine but had minimal effects on mutant channels with disrupted local anesthetic modification properties. These results establish that anchored MTS-LX-BZ compounds interact with the local anesthetic binding site (LABS). Variation in the linker length altered the potency of channel modification by the anchored drugs, thus providing information on the spatial relationship between the anchoring site and the LABS. Our observations demonstrate that local anesthetics can be anchored to the extracellular pore cysteine in cardiac Na+ channels and dynamically interact with the intracellular LABS. These results suggest that nonselective agents, such as local anesthetics, might be made more selective by linking these agents to target-specific anchors.

  2. Coulomb blockade model of permeation and selectivity in biological ion channels

    NASA Astrophysics Data System (ADS)

    Kaufman, I. Kh; McClintock, P. V. E.; Eisenberg, R. S.

    2015-08-01

    Biological ion channels are protein nanotubes embedded in, and passing through, the bilipid membranes of cells. Physiologically, they are of crucial importance in that they allow ions to pass into and out of cells, fast and efficiently, though in a highly selective way. Here we show that the conduction and selectivity of calcium/sodium ion channels can be described in terms of ionic Coulomb blockade in a simplified electrostatic and Brownian dynamics model of the channel. The Coulomb blockade phenomenon arises from the discreteness of electrical charge, the strong electrostatic interaction, and an electrostatic exclusion principle. The model predicts a periodic pattern of Ca2+ conduction versus the fixed charge Qf at the selectivity filter (conduction bands) with a period equal to the ionic charge. It thus provides provisional explanations of some observed and modelled conduction and valence selectivity phenomena, including the anomalous mole fraction effect and the calcium conduction bands. Ionic Coulomb blockade and resonant conduction are similar to electronic Coulomb blockade and resonant tunnelling in quantum dots. The same considerations may also be applicable to other kinds of channel, as well as to charged artificial nanopores.

  3. Simultaneous multi-channel OSNR monitoring with a wavelength selective switch.

    PubMed

    Schröder, Jochen; Brasier, Owen; Vo, Trung D; Roelens, Michaël A F; Frisken, Steve; Eggleton, Benjamin J

    2010-10-11

    We show the first simultaneous OSNR monitoring of two 40 Gb/s OOK and DPSK channels, using only a wavelength selective switch and two slow photodetectors. Our approach is modulation format and bit-rate independent and can easily be included in existing reconfigurable networks.

  4. Structural plasticity and dynamic selectivity of acid-sensing ion channel-spider toxin complexes

    SciTech Connect

    Baconguis, Isabelle; Gouaux, Eric

    2012-07-29

    Acid-sensing ion channels (ASICs) are voltage-independent, amiloride-sensitive channels involved in diverse physiological processes ranging from nociception to taste. Despite the importance of ASICs in physiology, we know little about the mechanism of channel activation. Here we show that psalmotoxin activates non-selective and Na+-selective currents in chicken ASIC1a at pH7.25 and 5.5, respectively. Crystal structures of ASIC1a–psalmotoxin complexes map the toxin binding site to the extracellular domain and show how toxin binding triggers an expansion of the extracellular vestibule and stabilization of the open channel pore. At pH7.25 the pore is approximately 10Å in diameter, whereas at pH5.5 the pore is largely hydrophobic and elliptical in cross-section with dimensions of approximately 5 by 7Å, consistent with a barrier mechanism for ion selectivity. These studies define mechanisms for activation of ASICs, illuminate the basis for dynamic ion selectivity and provide the blueprints for new therapeutic agents.

  5. Porphyrin derivatives as potent and selective blockers of neuronal Kv1 channels.

    PubMed

    Daly, D; Al-Sabi, A; Kinsella, G K; Nolan, K; Dolly, J O

    2015-01-21

    Selective inhibitors of voltage-activated K(+) channels are needed for the treatment of multiple sclerosis. In this work it was discovered that porphyrins bearing 2-4 carbon alkyl ammonium side chains predominantly blocked the Kv1.1 current whilst Kv1.2 was susceptible to a porphyrin bearing polyamine side chains.

  6. Theoretical analysis of selectivity mechanisms in molecular transport through channels and nanopores

    SciTech Connect

    Agah, Shaghayegh; Pasquali, Matteo; Kolomeisky, Anatoly B.

    2015-01-28

    Selectivity is one of the most fundamental concepts in natural sciences, and it is also critically important in various technological, industrial, and medical applications. Although there are many experimental methods that allow to separate molecules, frequently they are expensive and not efficient. Recently, a new method of separation of chemical mixtures based on utilization of channels and nanopores has been proposed and successfully tested in several systems. However, mechanisms of selectivity in the molecular transport during the translocation are still not well understood. Here, we develop a simple theoretical approach to explain the origin of selectivity in molecular fluxes through channels. Our method utilizes discrete-state stochastic models that take into account all relevant chemical transitions and can be solved analytically. More specifically, we analyze channels with one and two binding sites employed for separating mixtures of two types of molecules. The effects of the symmetry and the strength of the molecular-pore interactions are examined. It is found that for one-site binding channels, the differences in the strength of interactions for two species drive the separation. At the same time, in more realistic two-site systems, the symmetry of interaction potential becomes also important. The most efficient separation is predicted when the specific binding site is located near the entrance to the nanopore. In addition, the selectivity is higher for large entrance rates into the channel. It is also found that the molecular transport is more selective for repulsive interactions than for attractive interactions. The physical-chemical origin of the observed phenomena is discussed.

  7. Unraveling the mechanism of selective ion transport in hydrophobic subnanometer channels

    PubMed Central

    Li, Hui; Francisco, Joseph S.; Zeng, Xiao Cheng

    2015-01-01

    Recently reported synthetic organic nanopore (SONP) can mimic a key feature of natural ion channels, i.e., selective ion transport. However, the physical mechanism underlying the K+/Na+ selectivity for the SONPs is dramatically different from that of natural ion channels. To achieve a better understanding of the selective ion transport in hydrophobic subnanometer channels in general and SONPs in particular, we perform a series of ab initio molecular dynamics simulations to investigate the diffusivity of aqua Na+ and K+ ions in two prototype hydrophobic nanochannels: (i) an SONP with radius of 3.2 Å, and (ii) single-walled carbon nanotubes (CNTs) with radii of 3–5 Å (these radii are comparable to those of the biological potassium K+ channels). We find that the hydration shell of aqua Na+ ion is smaller than that of aqua K+ ion but notably more structured and less yielding. The aqua ions do not lower the diffusivity of water molecules in CNTs, but in SONP the diffusivity of aqua ions (Na+ in particular) is strongly suppressed due to the rugged inner surface. Moreover, the aqua Na+ ion requires higher formation energy than aqua K+ ion in the hydrophobic nanochannels. As such, we find that the ion (K+ vs. Na+) selectivity of the (8, 8) CNT is ∼20× higher than that of SONP. Hence, the (8, 8) CNT is likely the most efficient artificial K+ channel due in part to its special interior environment in which Na+ can be fully solvated, whereas K+ cannot. This work provides deeper insights into the physical chemistry behind selective ion transport in nanochannels. PMID:26283377

  8. Energetics of discrete selectivity bands and mutation-induced transitions in the calcium-sodium ion channels family

    NASA Astrophysics Data System (ADS)

    Kaufman, I.; Luchinsky, D. G.; Tindjong, R.; McClintock, P. V. E.; Eisenberg, R. S.

    2013-11-01

    We use Brownian dynamics (BD) simulations to study the ionic conduction and valence selectivity of a generic electrostatic model of a biological ion channel as functions of the fixed charge Qf at its selectivity filter. We are thus able to reconcile the discrete calcium conduction bands recently revealed in our BD simulations, M0 (Qf=1e), M1 (3e), M2 (5e), with a set of sodium conduction bands L0 (0.5e), L1 (1.5e), thereby obtaining a completed pattern of conduction and selectivity bands vs Qf for the sodium-calcium channels family. An increase of Qf leads to an increase of calcium selectivity: L0 (sodium-selective, nonblocking channel) → M0 (nonselective channel) → L1 (sodium-selective channel with divalent block) → M1 (calcium-selective channel exhibiting the anomalous mole fraction effect). We create a consistent identification scheme where the L0 band is putatively identified with the eukaryotic sodium channel The scheme created is able to account for the experimentally observed mutation-induced transformations between nonselective channels, sodium-selective channels, and calcium-selective channels, which we interpret as transitions between different rows of the identification table. By considering the potential energy changes during permeation, we show explicitly that the multi-ion conduction bands of calcium and sodium channels arise as the result of resonant barrierless conduction. The pattern of periodic conduction bands is explained on the basis of sequential neutralization taking account of self-energy, as Qf(z,i)=ze(1/2+i), where i is the order of the band and z is the valence of the ion. Our results confirm the crucial influence of electrostatic interactions on conduction and on the Ca2+/Na+ valence selectivity of calcium and sodium ion channels. The model and results could be also applicable to biomimetic nanopores with charged walls.

  9. Energetics of discrete selectivity bands and mutation-induced transitions in the calcium-sodium ion channels family.

    PubMed

    Kaufman, I; Luchinsky, D G; Tindjong, R; McClintock, P V E; Eisenberg, R S

    2013-11-01

    We use Brownian dynamics (BD) simulations to study the ionic conduction and valence selectivity of a generic electrostatic model of a biological ion channel as functions of the fixed charge Q(f) at its selectivity filter. We are thus able to reconcile the discrete calcium conduction bands recently revealed in our BD simulations, M0 (Q(f)=1e), M1 (3e), M2 (5e), with a set of sodium conduction bands L0 (0.5e), L1 (1.5e), thereby obtaining a completed pattern of conduction and selectivity bands vs Q(f) for the sodium-calcium channels family. An increase of Q(f) leads to an increase of calcium selectivity: L0 (sodium-selective, nonblocking channel) → M0 (nonselective channel) → L1 (sodium-selective channel with divalent block) → M1 (calcium-selective channel exhibiting the anomalous mole fraction effect). We create a consistent identification scheme where the L0 band is putatively identified with the eukaryotic sodium channel The scheme created is able to account for the experimentally observed mutation-induced transformations between nonselective channels, sodium-selective channels, and calcium-selective channels, which we interpret as transitions between different rows of the identification table. By considering the potential energy changes during permeation, we show explicitly that the multi-ion conduction bands of calcium and sodium channels arise as the result of resonant barrierless conduction. The pattern of periodic conduction bands is explained on the basis of sequential neutralization taking account of self-energy, as Q(f)(z,i)=ze(1/2+i), where i is the order of the band and z is the valence of the ion. Our results confirm the crucial influence of electrostatic interactions on conduction and on the Ca(2+)/Na(+) valence selectivity of calcium and sodium ion channels. The model and results could be also applicable to biomimetic nanopores with charged walls. PMID:24329301

  10. The Doubly Exceptional Child: A Principal's Dilemma.

    ERIC Educational Resources Information Center

    Kesner, Rebecca J., Ed.

    2002-01-01

    This document contains two articles concerned with doubly exceptional children and gifted education. In "The Doubly Exceptional Child: A Principal's Dilemma," (Carol J. Mills and Linda E. Brody), such children do not fit into the usual categories for sorting children because their gifts and disabilities often mask each other. Suggestions are…

  11. Ion Selectivity Mechanism in a Bacterial Pentameric Ligand-Gated Ion Channel

    SciTech Connect

    Fritsch, Sebastian; Ivanov, Ivaylo; Wang, Hailong; Cheng, Xiaolin

    2010-01-01

    The proton-gated ion channel from Gloeobacter violaceus (GLIC) is a prokaryotic homolog of the eukaryotic nicotinic acetylcholine receptor that responds to the binding of neurotransmitter acetylcholine and mediates fast signal transmission. Recent emergence of a high-resolution crystal structure of GLIC captured in a potentially open state allowed detailed, atomic-level insight into ion conduction and selectivity mechanisms in these channels. Herein, we have examined the barriers to ion conduction and origins of ion selectivity in the GLIC channel by the construction of potential-of-mean-force profiles for sodium and chloride ions inside the transmembrane region. Our calculations reveal that the GLIC channel is open for a sodium ion to transport, but presents a 11 kcal/mol free energy barrier for a chloride ion. Our collective findings identify three distinct contributions to the observed preference for the permeant ions. First, there is a substantial contribution due to a ring of negatively charged glutamate residues (E-2 ) at the narrow intracellular end of the channel. The negative electrostatics of this region and the ability of the glutamate side chains to directly bind cations would strongly favor the passage of sodium ions while hindering translocation of chloride ions. Second, our results imply a significant hydrophobic contribution to selectivity linked to differences in the desolvation penalty for the sodium versus chloride ions in the central hydrophobic region of the pore. This hydrophobic contribution is evidenced by the large free energy barriers experienced by Cl in the middle of the pore for both GLIC and the E-2 A mutant. Finally, there is a distinct contribution arising from the overall negative electrostatics of the channel.

  12. Selectivity Mechanism of the Voltage-gated Proton Channel, HV1

    PubMed Central

    Dudev, Todor; Musset, Boris; Morgan, Deri; Cherny, Vladimir V.; Smith, Susan M. E.; Mazmanian, Karine; DeCoursey, Thomas E.; Lim, Carmay

    2015-01-01

    Voltage-gated proton channels, HV1, trigger bioluminescence in dinoflagellates, enable calcification in coccolithophores, and play multifarious roles in human health. Because the proton concentration is minuscule, exquisite selectivity for protons over other ions is critical to HV1 function. The selectivity of the open HV1 channel requires an aspartate near an arginine in the selectivity filter (SF), a narrow region that dictates proton selectivity, but the mechanism of proton selectivity is unknown. Here we use a reduced quantum model to elucidate how the Asp–Arg SF selects protons but excludes other ions. Attached to a ring scaffold, the Asp and Arg side chains formed bidentate hydrogen bonds that occlude the pore. Introducing H3O+ protonated the SF, breaking the Asp–Arg linkage and opening the conduction pathway, whereas Na+ or Cl– was trapped by the SF residue of opposite charge, leaving the linkage intact, thus preventing permeation. An Asp–Lys SF behaved like the Asp–Arg one and was experimentally verified to be proton-selective, as predicted. Hence, interacting acidic and basic residues form favorable AspH0–H2O0–Arg+ interactions with hydronium but unfavorable Asp––X–/X+–Arg+ interactions with anions/cations. This proposed mechanism may apply to other proton-selective molecules engaged in bioenergetics, homeostasis, and signaling. PMID:25955978

  13. Selectivity Mechanism of the Voltage-gated Proton Channel, HV1.

    PubMed

    Dudev, Todor; Musset, Boris; Morgan, Deri; Cherny, Vladimir V; Smith, Susan M E; Mazmanian, Karine; DeCoursey, Thomas E; Lim, Carmay

    2015-05-08

    Voltage-gated proton channels, HV1, trigger bioluminescence in dinoflagellates, enable calcification in coccolithophores, and play multifarious roles in human health. Because the proton concentration is minuscule, exquisite selectivity for protons over other ions is critical to HV1 function. The selectivity of the open HV1 channel requires an aspartate near an arginine in the selectivity filter (SF), a narrow region that dictates proton selectivity, but the mechanism of proton selectivity is unknown. Here we use a reduced quantum model to elucidate how the Asp-Arg SF selects protons but excludes other ions. Attached to a ring scaffold, the Asp and Arg side chains formed bidentate hydrogen bonds that occlude the pore. Introducing H3O(+) protonated the SF, breaking the Asp-Arg linkage and opening the conduction pathway, whereas Na(+) or Cl(-) was trapped by the SF residue of opposite charge, leaving the linkage intact, thus preventing permeation. An Asp-Lys SF behaved like the Asp-Arg one and was experimentally verified to be proton-selective, as predicted. Hence, interacting acidic and basic residues form favorable AspH(0)-H2O(0)-Arg(+) interactions with hydronium but unfavorable Asp(-)-X(-)/X(+)-Arg(+) interactions with anions/cations. This proposed mechanism may apply to other proton-selective molecules engaged in bioenergetics, homeostasis, and signaling.

  14. Selectivity Mechanism of the Voltage-gated Proton Channel, HV1

    NASA Astrophysics Data System (ADS)

    Dudev, Todor; Musset, Boris; Morgan, Deri; Cherny, Vladimir V.; Smith, Susan M. E.; Mazmanian, Karine; Decoursey, Thomas E.; Lim, Carmay

    2015-05-01

    Voltage-gated proton channels, HV1, trigger bioluminescence in dinoflagellates, enable calcification in coccolithophores, and play multifarious roles in human health. Because the proton concentration is minuscule, exquisite selectivity for protons over other ions is critical to HV1 function. The selectivity of the open HV1 channel requires an aspartate near an arginine in the selectivity filter (SF), a narrow region that dictates proton selectivity, but the mechanism of proton selectivity is unknown. Here we use a reduced quantum model to elucidate how the Asp-Arg SF selects protons but excludes other ions. Attached to a ring scaffold, the Asp and Arg side chains formed bidentate hydrogen bonds that occlude the pore. Introducing H3O+ protonated the SF, breaking the Asp-Arg linkage and opening the conduction pathway, whereas Na+ or Cl- was trapped by the SF residue of opposite charge, leaving the linkage intact, thus preventing permeation. An Asp-Lys SF behaved like the Asp-Arg one and was experimentally verified to be proton-selective, as predicted. Hence, interacting acidic and basic residues form favorable AspH0-H2O0-Arg+ interactions with hydronium but unfavorable Asp--X-/X+-Arg+ interactions with anions/cations. This proposed mechanism may apply to other proton-selective molecules engaged in bioenergetics, homeostasis, and signaling.

  15. Channel-morphology data for the Tongue River and selected tributaries, southeastern Montana, 2001-02

    USGS Publications Warehouse

    Chase, Katherine J.

    2004-01-01

    Coal-bed methane exploration and production have begun within the Tongue River watershed in southeastern Montana. The development of coal-bed methane requires production of large volumes of ground water, some of which may be discharged to streams, potentially increasing stream discharge and sediment load. Changes in stream discharge or sediment load may result in changes to channel morphology through changes in erosion and vegetation. These changes might be subtle and difficult to detect without baseline data that indicate stream-channel conditions before extensive coal-bed methane development began. In order to provide this baseline channel-morphology data, the U.S. Geological Survey, in cooperation with the Bureau of Land Management, collected channel-morphology data in 2001-02 to document baseline conditions for several reaches along the Tongue River and selected tributaries. This report presents channel-morphology data for five sites on the mainstem Tongue River and four sites on its tributaries. Bankfull, water-surface, and thalweg elevations, channel sections, and streambed-particle sizes were measured along reaches near streamflow-gaging stations. At each site, the channel was classified using methods described by Rosgen. For six sites, bankfull discharge was determined from the stage- discharge relation at the gage for the stage corresponding to the bankfull elevation. For three sites, the step-backwater computer model HEC-RAS was used to estimate bankfull discharge. Recurrence intervals for the bankfull discharge also were estimated for eight of the nine sites. Channel-morphology data for each site are presented in maps, tables, graphs, and photographs.

  16. Evaluating State Dependence and Subtype Selectivity of Calcium Channel Modulators in Automated Electrophysiology Assays

    PubMed Central

    Kuryshev, Yuri A.; Brown, Arthur M.; Duzic, Emir

    2014-01-01

    Abstract Voltage-gated Ca2+ channels play essential roles in control of neurosecretion and muscle contraction. The pharmacological significance of Cav channels stem from their identification as the molecular targets of calcium blockers used in the treatment of cardiovascular diseases, such as hypertension, angina, and arrhythmia, and neurologic diseases, such as pain and seizure. It has been proposed that state-dependent Cav inhibitors, that is, those that preferentially bind to channels in open or inactivated states, may improve the therapeutic window over relatively state-independent Cav inhibitors. High-throughput fluorescent-based functional assays have been useful in screening chemical libraries to identify Cav inhibitors. However, hit confirmation, mechanism of action, and subtype selectivity are better suited to automated patch clamp assays that have sufficient capacity to handle the volume of compounds identified during screening, even of modest sized libraries (≤500,000 compounds), and the flexible voltage control that allows evaluation of state-dependent drug blocks. IonWorks™ Barracuda (IWB), the newest generation of IonWorks instruments, provides the opportunity to accelerate the Cav drug discovery studies in an automated patch clamp platform in 384-well format capable of medium throughput screening and profiling studies. We have validated hCav1.2, hCav2.1, hCav2.2, and hCav3.2 channels assays on the IWB platform (population patch clamp mode) and demonstrated that the biophysical characteristics of the channels (activation, inactivation, and steady-state inactivation) obtained with the IWB system are consistent with known subtype-specific characteristics. Using standard reference compounds (nifedipine, BAY K8644, verapamil, mibefradil, and pimozide), we demonstrated subtype-selective and state- and use-dependent characteristics of drug–channel interactions. Here we describe the design and validation of novel robust high-throughput Cav channel

  17. Possible roles of exceptionally conserved residues around the selectivity filters of sodium and calcium channels.

    PubMed

    Tikhonov, Denis B; Zhorov, Boris S

    2011-01-28

    In the absence of x-ray structures of sodium and calcium channels their homology models are used to rationalize experimental data and design new experiments. A challenge is to model the outer-pore region that folds differently from potassium channels. Here we report a new model of the outer-pore region of the NaV1.4 channel, which suggests roles of highly conserved residues around the selectivity filter. The model takes from our previous study (Tikhonov, D. B., and Zhorov, B. S. (2005) Biophys. J. 88, 184-197) the general disposition of the P-helices, selectivity filter residues, and the outer carboxylates, but proposes new intra- and inter-domain contacts that support structural stability of the outer pore. Glycine residues downstream from the selectivity filter are proposed to participate in knob-into-hole contacts with the P-helices and S6s. These contacts explain the adapted tetrodotoxin resistance of snakes that feed on toxic prey through valine substitution of isoleucine in the P-helix of repeat IV. Polar residues five positions upstream from the selectivity filter residues form H-bonds with the ascending-limb backbones. Exceptionally conserved tryptophans are engaged in inter-repeat H-bonds to form a ring whose π-electrons would facilitate passage of ions from the outer carboxylates to the selectivity filter. The outer-pore model of CaV1.2 derived from the NaV1.4 model is also stabilized by the ring of exceptionally conservative tryptophans and H-bonds between the P-helices and ascending limbs. In this model, the exceptionally conserved aspartate downstream from the selectivity-filter glutamate in repeat II facilitates passage of calcium ions to the selectivity-filter ring through the tryptophan ring. Available experimental data are discussed in view of the models.

  18. Ionic selectivity and thermal adaptations within the voltage-gated sodium channel family of alkaliphilic Bacillus.

    PubMed

    DeCaen, Paul G; Takahashi, Yuka; Krulwich, Terry A; Ito, Masahiro; Clapham, David E

    2014-01-01

    Entry and extrusion of cations are essential processes in living cells. In alkaliphilic prokaryotes, high external pH activates voltage-gated sodium channels (Nav), which allows Na(+) to enter and be used as substrate for cation/proton antiporters responsible for cytoplasmic pH homeostasis. Here, we describe a new member of the prokaryotic voltage-gated Na(+) channel family (NsvBa; Non-selective voltage-gated, Bacillus alcalophilus) that is nonselective among Na(+), Ca(2+) and K(+) ions. Mutations in NsvBa can convert the nonselective filter into one that discriminates for Na(+) or divalent cations. Gain-of-function experiments demonstrate the portability of ion selectivity with filter mutations to other Bacillus Nav channels. Increasing pH and temperature shifts their activation threshold towards their native resting membrane potential. Furthermore, we find drugs that target Bacillus Nav channels also block the growth of the bacteria. This work identifies some of the adaptations to achieve ion discrimination and gating in Bacillus Nav channels. PMID:25385530

  19. Non-selective cation channels mediate chloroquine-induced relaxation in precontracted mouse airway smooth muscle.

    PubMed

    Zhang, Ting; Luo, Xiao-Jing; Sai, Wen-Bo; Yu, Meng-Fei; Li, Wen-Er; Ma, Yun-Fei; Chen, Weiwei; Zhai, Kui; Qin, Gangjian; Guo, Donglin; Zheng, Yun-Min; Wang, Yong-Xiao; Shen, Jin-Hua; Ji, Guangju; Liu, Qing-Hua

    2014-01-01

    Bitter tastants can induce relaxation in precontracted airway smooth muscle by activating big-conductance potassium channels (BKs) or by inactivating voltage-dependent L-type Ca2+ channels (VDLCCs). In this study, a new pathway for bitter tastant-induced relaxation was defined and investigated. We found nifedipine-insensitive and bitter tastant chloroquine-sensitive relaxation in epithelium-denuded mouse tracheal rings (TRs) precontracted with acetylcholine (ACH). In the presence of nifedipine (10 µM), ACH induced cytosolic Ca2+ elevation and cell shortening in single airway smooth muscle cells (ASMCs), and these changes were inhibited by chloroquine. In TRs, ACH triggered a transient contraction under Ca2+-free conditions, and, following a restoration of Ca2+, a strong contraction occurred, which was inhibited by chloroquine. Moreover, the ACH-activated whole-cell and single channel currents of non-selective cation channels (NSCCs) were blocked by chloroquine. Pyrazole 3 (Pyr3), an inhibitor of transient receptor potential C3 (TRPC3) channels, partially inhibited ACH-induced contraction, intracellular Ca2+ elevation, and NSCC currents. These results demonstrate that NSCCs play a role in bitter tastant-induced relaxation in precontracted airway smooth muscle.

  20. M-type channels selectively control bursting in rat dopaminergic neurons

    PubMed Central

    Drion, Guillaume; Bonjean, Maxime; Waroux, Olivier; Scuvée-Moreau, Jacqueline; Liégeois, Jean-François; Sejnowski, Terrence J; Sepulchre, Rodolphe; Seutin, Vincent

    2010-01-01

    Midbrain dopaminergic neurons in the substantia nigra, pars compacta and ventral tegmental area are critically important in many physiological functions. These neurons exhibit firing patterns that include tonic slow pacemaking, irregular firing and bursting, and the amount of dopamine that is present in the synaptic cleft is much increased during bursting. The mechanisms responsible for the switch between these spiking patterns remain unclear. Using both in-vivo recordings combined with microiontophoretic or intraperitoneal drug applications and in-vitro experiments, we have found that M-type channels, which are present in midbrain dopaminergic cells, modulate the firing during bursting without affecting the background low-frequency pacemaker firing. Thus, a selective blocker of these channels, 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone dihydrochloride, specifically potentiated burst firing. Computer modeling of the dopamine neuron confirmed the possibility of a differential influence of M-type channels on excitability during various firing patterns. Therefore, these channels may provide a novel target for the treatment of dopamine-related diseases, including Parkinson’s disease and drug addiction. Moreover, our results demonstrate that the influence of M-type channels on the excitability of these slow pacemaker neurons is conditional upon their firing pattern. PMID:20180842

  1. Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain.

    PubMed

    Osteen, Jeremiah D; Herzig, Volker; Gilchrist, John; Emrick, Joshua J; Zhang, Chuchu; Wang, Xidao; Castro, Joel; Garcia-Caraballo, Sonia; Grundy, Luke; Rychkov, Grigori Y; Weyer, Andy D; Dekan, Zoltan; Undheim, Eivind A B; Alewood, Paul; Stucky, Cheryl L; Brierley, Stuart M; Basbaum, Allan I; Bosmans, Frank; King, Glenn F; Julius, David

    2016-06-23

    Voltage-gated sodium (Nav) channels initiate action potentials in most neurons, including primary afferent nerve fibres of the pain pathway. Local anaesthetics block pain through non-specific actions at all Nav channels, but the discovery of selective modulators would facilitate the analysis of individual subtypes of these channels and their contributions to chemical, mechanical, or thermal pain. Here we identify and characterize spider (Heteroscodra maculata) toxins that selectively activate the Nav1.1 subtype, the role of which in nociception and pain has not been elucidated. We use these probes to show that Nav1.1-expressing fibres are modality-specific nociceptors: their activation elicits robust pain behaviours without neurogenic inflammation and produces profound hypersensitivity to mechanical, but not thermal, stimuli. In the gut, high-threshold mechanosensitive fibres also express Nav1.1 and show enhanced toxin sensitivity in a mouse model of irritable bowel syndrome. Together, these findings establish an unexpected role for Nav1.1 channels in regulating the excitability of sensory nerve fibres that mediate mechanical pain. PMID:27281198

  2. Determinants of ligand selectivity in a cyclic nucleotide-regulated potassium channel.

    PubMed

    Pessoa, João; Fonseca, Fátima; Furini, Simone; Morais-Cabral, João H

    2014-07-01

    Cyclic nucleotide-binding (CNB) domains regulate the activity of channels, kinases, exchange factors, and transcription factors. These proteins are highly variable in their ligand selectivity; some are highly selective for either cAMP or cGMP, whereas others are not. Several molecular determinants of ligand selectivity in CNB domains have been defined, but these do not provide a complete view of the selectivity mechanism. We performed a thorough analysis of the ligand-binding properties of mutants of the CNB domain from the MlotiK1 potassium channel. In particular, we defined which residues specifically favor cGMP or cAMP. Inversion of ligand selectivity, from favoring cAMP to favoring cGMP, was only achieved through a combination of three mutations in the ligand-binding pocket. We determined the x-ray structure of the triple mutant bound to cGMP and performed molecular dynamics simulations and a biochemical analysis of the effect of the mutations. We concluded that the increase in cGMP affinity and selectivity does not result simply from direct interactions between the nucleotide base and the amino acids introduced in the ligand-binding pocket residues. Rather, tighter cGMP binding over cAMP results from the polar chemical character of the mutations, from greater accessibility of water molecules to the ligand in the bound state, and from an increase in the structural flexibility of the mutated binding pocket.

  3. A general method for selecting quantum channel for bidirectional controlled state teleportation and other schemes of controlled quantum communication

    NASA Astrophysics Data System (ADS)

    Thapliyal, Kishore; Verma, Amit; Pathak, Anirban

    2015-12-01

    Recently, a large number of protocols for bidirectional controlled state teleportation (BCST) have been proposed using n-qubit entangled states (nin {5,6,7}) as quantum channel. Here, we propose a general method of selecting multiqubit (n>4) quantum channels suitable for BCST and show that all the channels used in the existing protocols of BCST can be obtained using the proposed method. Further, it is shown that the quantum channels used in the existing protocols of BCST form only a negligibly small subset of the set of all the quantum channels that can be constructed using the proposed method to implement BCST. It is also noted that all these quantum channels are also suitable for controlled bidirectional remote state preparation. Following the same logic, methods for selecting quantum channels for other controlled quantum communication tasks, such as controlled bidirectional joint remote state preparation and controlled quantum dialogue, are also provided.

  4. Chemical and genetic engineering of selective ligand-ion channel interactions

    PubMed Central

    Magnus, Christopher J.; Lee, Peter H.; Atasoy, Deniz; Su, Helen H.; Looger, Loren L.; Sternson, Scott M.

    2011-01-01

    Ionic flux in defined cell populations mediates essential physiological and behavioral functions. Cell type-specific activators of diverse ionic conductances are needed for probing these relationships. We combined chemistry and protein engineering to enable systematic creation of a toolbox of ligand-gated ion channels (LGICs) with orthogonal pharmacologic selectivity and divergent functional properties. The LGICs and their small molecule effectors can activate a range of ionic conductances in genetically-specified cell types. LGICs constructed for neuronal perturbation can be used to selectively manipulate neuron activity in mammalian brains in vivo. The diversity of ion channel tools accessible from this approach will be useful for examining the relationship between neuronal activity and animal behavior, as well as for cell biological and physiological applications requiring chemical control of ion conductance. PMID:21885782

  5. An Efficient P300-based BCI Using Wavelet Features and IBPSO-based Channel Selection

    PubMed Central

    Perseh, Bahram; Sharafat, Ahmad R.

    2012-01-01

    We present a novel and efficient scheme that selects a minimal set of effective features and channels for detecting the P300 component of the event-related potential in the brain–computer interface (BCI) paradigm. For obtaining a minimal set of effective features, we take the truncated coefficients of discrete Daubechies 4 wavelet, and for selecting the effective electroencephalogram channels, we utilize an improved binary particle swarm optimization algorithm together with the Bhattacharyya criterion. We tested our proposed scheme on dataset IIb of BCI competition 2005 and achieved 97.5% and 74.5% accuracy in 15 and 5 trials, respectively, using a simple classification algorithm based on Bayesian linear discriminant analysis. We also tested our proposed scheme on Hoffmann's dataset for eight subjects, and achieved similar results. PMID:23717804

  6. Selection and design of the secondary electron channel of the time-of-flight mass spectrometer

    NASA Astrophysics Data System (ADS)

    Fishkova, T. Ya.; Basalaev, A. A.; Kuz'michev, V. V.

    2016-03-01

    Computer simulation is carried out for selecting a compact electron-optical system of the channel for detecting secondary electrons formed during the interaction of xenon atoms or ions with energy of 1-30 keV with Xe atoms. The solid angle of passage of secondary electron beams in a wide range of their initial energies is calculated. The energy spectrum of secondary electrons with various energies is determined by constructing their deceleration curve.

  7. Ion Selectivity Mechanism in a Bacterial Pentameric Ligand-Gated Ion Channel

    SciTech Connect

    Fritsch, Sebastian M; Ivanov, Ivaylo N; Wang, Hailong; Cheng, Xiaolin

    2011-01-01

    The proton-gated ion channel from Gloeobacter violaceus (GLIC) is a prokaryotic homolog of the eukaryotic nicotinic acetylcholine receptor (nAChR) that responds to the binding of neurotransmitter acetylcholine and mediates fast signal transmission. Recent emergence of a high resolution crystal structure of GLIC captured in a potentially open state allowed detailed, atomic-level insight into ion conduction and selectivity mechanisms in these channels. Herein, we have examined the barriers to ion conduction and origins of ion selectivity in the GLIC channel by the construction of potential of mean force (PMF) profiles for sodium and chloride ions inside the transmembrane region. Our calculations reveal that the GLIC channel is open for a sodium ion to transport, but presents a ~10 kcal/mol free energy barrier for a chloride ion, which arises primarily from the unfavorable interactions with a ring of negatively charged glutamate residues (E-2 ) at the intracellular end and a ring of hydrophobic residues (I9 ) in the middle of the transmembrane domain. Our collective findings further suggest that the charge selection mechanism can, to a large extent, be attributed to the narrow intracellular end and a ring of glutamate residues in this position their strong negative electrostatics and ability to bind cations. By contrast, E19 at the extracellular entrance only plays a minor role in ion selectivity of GLIC. In addition to electrostatics, both ion hydration and protein dynamics are found to be crucial for ion conduction as well, which explains why a chloride ion experiences a much greater barrier than a sodium ion in the hydrophobic region of the pore.

  8. Doubly Excited States in Be III

    NASA Astrophysics Data System (ADS)

    Andersen, T.; Bentzen, S. M.; Poulsen, O.

    1980-01-01

    The triplet spectrum of doubly excited Be III has been studied in the wavelength region of 75-5000 Å in order to test the validity of the theoretical term values reported by Lipsky et al. The beam-foil excitation technique was applied to effectively populate the doubly excited states. The identified lower-lying, doubly excited states 2p2 3P, 2pnp 3P, or 3D, and 2pnd 3P, or 3D (n = 3, 4) show that the theoretical term values should be slightly modified.

  9. Receptor model for the molecular basis of tissue selectivity of 1, 4-dihydropyridine calcium channel drugs.

    PubMed

    Langs, D A; Strong, P D; Triggle, D J

    1990-09-01

    Our analysis of the solid state conformations of nifedipine [dimethyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinecarboxylate ] and its 1,4-dihydropyridine (1,4-DHP) analogues produced a cartoon description of the important interactions between these drugs and their voltage-dependent calcium channel receptor. In the present study a molecular-level detailed model of the 1,4-DHP receptor binding site has been built from the published amino acid sequence of the alpha 1 subunit of the voltage-dependent calcium channel isolated from rabbit skeletal muscle transverse tubule membranes. The voltage-sensing component of the channel described in this work differs from other reported for the homologous sodium channel in that it incorporates a water structure and a staggered, rather than eclipsed, hydrogen bonded S4 helix conformation. The major recognition surfaces of the receptor lie in helical grooves on the S4 or voltage-sensing alpha-helix that is positioned in the center of the bundle of transmembrane helices that define each of the four calcium channel domains. Multiple binding clefts defined by Arg-X-X-Arg-P-X-X-S 'reading frames' exist on the S4 strand. The tissue selectivity of nifedipine and its analogues may arise, in part, from conservative changes in the amino acid residues at the P and S positions of the reading frame that define the ester-binding regions of receptors from different tissues. The crystal structures of two tissue-selective nifedipine analogues, nimodipine [isopropyl (2-methoxyethyl) 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinecarboxylate ] and nitrendipine [ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3, 5-pyridinecarboxylate] are reported. Nimodipine was observed to have an unusual ester side chain conformation that enhances the fit to the proposed ester-sensing region of the receptor.

  10. Selectivity of Cx43 channels is regulated through PKC-dependent phosphorylation

    PubMed Central

    Ek-Vitorin, Jose F.; King, Timothy J.; Heyman, Nathanael S.; Lampe, Paul D.; Burt, Janis M.

    2006-01-01

    Coordinated contractile activation of the heart and resistance to ischemic injury depend, in part, on the intercellular communication mediated by Cx43-composed gap junctions. The function of these junctions is regulated at multiple levels (assembly to degradation) through phosphorylation at specific sites in the carboxyl terminus (CT) of the Cx43 protein. We show here that the selective permeability of Cx43 junctions is regulated through PKC-dependent phosphorylation at serine 368 (S368). Selective permeability was measured in several Cx43-expressing cell lines as the rate constant for intercellular dye diffusion relative to junctional conductance. The selective permeability of Cx43 junctions under control conditions was quite variable, as was the open state behavior of the comprising channels. Co-expression of the CT of Cx43 as a distinct protein, treatment with a PKC inhibitor, or mutation of S368 to alanine all reduced (or eliminated) phosphorylation at S368, reduced the incidence of 55–70pS channels, and reduced by ten fold the selective permeability of the junctions for a small cationic dye. Since PKC activation during pre-ischemic conditioning is cardio-protective during subsequent ischemic episodes, we examined no-flow, ischemic hearts for Cx43 phosphorylated at S368 (pS368). Consistent with early activation of PKC, pS368-Cx43 was increased in ischemic hearts; despite extensive lateralization of total Cx43, pS368-Cx43 remained predominantly at intercalated disks. Our data suggest that the selectivity of gap junction channels at intercalated disks is increased early in ischemia. PMID:16709897

  11. Mechanism for phosphoinositide selectivity and activation of TRPV1 ion channels

    PubMed Central

    Ufret-Vincenty, Carmen A.; Klein, Rebecca M.; Collins, Marcus D.; Rosasco, Mario G.; Martinez, Gilbert Q.

    2015-01-01

    Although PI(4,5)P2 is believed to play an essential role in regulating the activity of numerous ion channels and transporters, the mechanisms by which it does so are unknown. Here, we used the ability of the TRPV1 ion channel to discriminate between PI(4,5)P2 and PI(4)P to localize the region of TRPV1 sequence that interacts directly with the phosphoinositide. We identified a point mutation in the proximal C-terminal region after the TRP box, R721A, that inverted the selectivity of TRPV1. Although the R721A mutation produced only a 30% increase in the EC50 for activation by PI(4,5)P2, it decreased the EC50 for activation by PI(4)P by more than two orders of magnitude. We used chemically induced and voltage-activated phosphatases to determine that PI(4)P continued to support TRPV1 activity even after depletion of PI(4,5)P2 from the plasma membrane. Our data cannot be explained by a purely electrostatic mechanism for interaction between the phosphoinositide and the protein, similar to that of the MARCKS (myristoylated alanine-rich C kinase substrate) effector domain or the EGF receptor. Rather, conversion of a PI(4,5)P2-selective channel to a PI(4)P-selective channel indicates that a structured phosphoinositide-binding site mediates the regulation of TRPV1 activity and that the amino acid at position 721 likely interacts directly with the moiety at the 5′ position of the phosphoinositide. PMID:25918361

  12. A Novel Variable Selection Method Based on a Partial KL Information Measure and Its Application to Channel Selection for Bioelectric Signal Classification

    NASA Astrophysics Data System (ADS)

    Shibanoki, Taro; Shima, Keisuke; Tsuji, Toshio; Takaki, Takeshi; Otsuka, Akira; Chin, Takaaki

    This paper proposes a novel variable selection method based on the KL information measure, and applies it to optimal channel selection for bioelectric signal classification. Generally, the accuracy of classifcation for bioelectric signals is greatly influenced by measuring positions of the signals as well as individual physical abilities of a user. Therefore, it is effective for classification to select optimal positions for each user in advance. In the proposed method, the probability density functions (pdfs) of measured data are estimated through learning of a multidimensional probabilistic neural network (PNN) based on the KL information theory. Then, a partial KL information measure is newly defined to evaluate contribution of each dimension in the data. The effective dimensions can be selected eliminating ineffective ones based on the partial KL information in a one-by-one manner. In the experiments, the proposed method was applied to EMG electrode selection with six subjects (including an amputee), and the effective channels were selected from all channels attached to each subject's forearm. Experimental results showed that the number of channels was reduced with 36.1±12.5 [%], and the average classification rate using selected channels by the proposed method was 98.99±1.31 [%]. These results indicated that the proposed method is capable to select effective channels (optimal or semi-optimal) for accurate classification.

  13. Recent (circa 1998 to 2011) channel-migration rates of selected streams in Indiana

    USGS Publications Warehouse

    Robinson, Bret A.

    2013-01-01

    An investigation was completed to document recent (circa 1998 to 2011) channel-migration rates at 970 meander bends along 38 of the largest streams in Indiana. Data collection was completed by using the Google Earth™ platform and, for each selected site, identifying two images with capture dates separated by multiple years. Within each image, the position of the meander-bend cutbank was measured relative to a fixed local landscape feature visible in both images, and an average channel-migration rate was calculated at the point of maximum cutbank displacement. From these data it was determined that 65 percent of the measured sites have recently been migrating at a rate less than 1 ft/yr, 75 percent of the sites have been migrating at a rate less than 10 ft/yr, and while some sites are migrating in excess of 20 ft/yr, these occurrences are rare. In addition, it is shown that recent channel-migration activity is not evenly distributed across Indiana. For the stream reaches studied, far northern and much of far southern Indiana are drained by streams that recently have been relatively stationary. At the same time, this study shows that most of the largest streams in west-central Indiana and many of the largest streams in east-central Indiana have shown significant channel-migration activity during the recent past. It is anticipated that these results will support several fluvial-erosion-hazard mitigation activities currently being undertaken in Indiana.

  14. The Vpu protein of human immunodeficiency virus type 1 forms cation-selective ion channels.

    PubMed Central

    Ewart, G D; Sutherland, T; Gage, P W; Cox, G B

    1996-01-01

    Vpu is a small phosphorylated integral membrane protein encoded by the human immunodeficiency virus type 1 genome and found in the endoplasmic reticulum and Golgi membranes of infected cells. It has been linked to roles in virus particle budding and degradation of CD4 in the endoplasmic reticulum. However, the molecular mechanisms employed by Vpu in performance of these functions are unknown. Structural similarities between Vpu and the M2 protein of influenza A virus have raised the question of whether the two proteins are functionally analogous: M2 has been demonstrated to form cation-selective ion channels in phospholipid membranes. In this paper we provide evidence that Vpu, purified after expression in Escherichia coli, also forms ion channels in planar lipid bilayers. The channels are approximately five- to sixfold more permeable to sodium and potassium cations than to chloride or phosphate anions. A bacterial cross-feeding assay was used to demonstrate that Vpu can also form sodium-permeable channels in vivo in the E. coli plasma membrane. PMID:8794357

  15. Dimethyl sulfoxide at high concentrations inhibits non-selective cation channels in human erythrocytes.

    PubMed

    Nardid, Oleg A; Schetinskey, Miroslav I; Kucherenko, Yuliya V

    2013-03-01

    Dimethyl sulfoxide (DMSO), a by-product of the pulping industry, is widely used in biological research, cryobiology and medicine. On cellular level DMSO was shown to suppress NMDA-AMPA channels activation, blocks Na+ channel activation and attenuates Ca2+ influx (Lu and Mattson 2001). In the present study we explored the whole-cell patch-clamp to examine the acute effect of high concentrations of DMSO (0.1-2 mol/l) on cation channels activity in human erythrocytes. Acute application of DMSO (0.1-2 mol/l) dissolved in Cl--containing saline buffer solution significantly inhibited cation conductance in human erythrocytes. Inhibition was concentration-dependent and had an exponential decay profile. DMSO (2 mol/l) induced cation inhibition in Cl-- containing saline solutions of: 40.3 ± 3.9% for K+, 35.4 ± 3.1% for Ca2+ and 47.4 ± 1.9% for NMDG+. Substitution of Cl- with gluconate- increased the inhibitory effect of DMSO on the Na+ current. Inhibitory effect of DMSO was neither due to high permeability of erythrocytes to DMSO nor to an increased tonicity of the bath media since no effect was observed in 2 mol/l glycerol solution. In conclusion, we have shown that high concentrations of DMSO inhibit the non-selective cation channels in human erythrocytes and thus protect the cells against Na+ and Ca2+ overload. Possible mechanisms of DMSO effect on cation conductance are discussed. PMID:23531832

  16. Regulatory evolution and voltage-gated ion channel expression in squid axon: selection-mutation balance and fitness cliffs.

    PubMed

    Kim, Min; McKinnon, Don; MacCarthy, Thomas; Rosati, Barbara; McKinnon, David

    2015-01-01

    It has been suggested that optimization of either axonal conduction velocity or the energy efficiency of action potential conduction predominates in the selection of voltage-gated sodium conductance levels in the squid axon. A population genetics model of channel gene regulatory function was used to examine the role of these and other evolutionary forces on the selection of both sodium and potassium channel expression levels. In this model, the accumulating effects of mutations result in degradation of gene regulatory function, causing channel gene expression to fall to near-zero in the absence of positive selection. In the presence of positive selection, channel expression levels fall to the lowest values consistent with the selection criteria, thereby establishing a selection-mutation balance. Within the parameter space of sodium and potassium conductance values, the physiological performance of the squid axon model showed marked discontinuities associated with conduction failure and excitability. These discontinuities in physiological function may produce fitness cliffs. A fitness cliff associated with conduction failure, combined with the effects of phenotypic noise, can account for the selection of sodium conductance levels, without considering either conduction velocity or metabolic cost. A fitness cliff associated with a transition in axonal excitability, combined with phenotypic noise, can explain the selection of potassium channel expression levels. The results suggest that voltage-gated ion channel expression will fall to low levels, consistent with key functional constraints, even in the absence of positive selection for energy efficiency. Channel expression levels and individual variation in channel expression within the population can be explained by regulatory evolution in combination with genetic variation in regulatory function and phenotypic noise, without resorting to more complex mechanisms, such as activity-dependent homeostasis. Only a

  17. Engineering Highly Potent and Selective Microproteins against Nav1.7 Sodium Channel for Treatment of Pain.

    PubMed

    Shcherbatko, Anatoly; Rossi, Andrea; Foletti, Davide; Zhu, Guoyun; Bogin, Oren; Galindo Casas, Meritxell; Rickert, Mathias; Hasa-Moreno, Adela; Bartsevich, Victor; Crameri, Andreas; Steiner, Alexander R; Henningsen, Robert; Gill, Avinash; Pons, Jaume; Shelton, David L; Rajpal, Arvind; Strop, Pavel

    2016-07-01

    The prominent role of voltage-gated sodium channel 1.7 (Nav1.7) in nociception was revealed by remarkable human clinical and genetic evidence. Development of potent and subtype-selective inhibitors of this ion channel is crucial for obtaining therapeutically useful analgesic compounds. Microproteins isolated from animal venoms have been identified as promising therapeutic leads for ion channels, because they naturally evolved to be potent ion channel blockers. Here, we report the engineering of highly potent and selective inhibitors of the Nav1.7 channel based on tarantula ceratotoxin-1 (CcoTx1). We utilized a combination of directed evolution, saturation mutagenesis, chemical modification, and rational drug design to obtain higher potency and selectivity to the Nav1.7 channel. The resulting microproteins are highly potent (IC50 to Nav1.7 of 2.5 nm) and selective. We achieved 80- and 20-fold selectivity over the closely related Nav1.2 and Nav1.6 channels, respectively, and the IC50 on skeletal (Nav1.4) and cardiac (Nav1.5) sodium channels is above 3000 nm The lead molecules have the potential for future clinical development as novel therapeutics in the treatment of pain. PMID:27129258

  18. Channel

    NASA Technical Reports Server (NTRS)

    2006-01-01

    [figure removed for brevity, see original site] Context image for PIA03693 Channel

    This channel is located south of Iani Chaos.

    Image information: VIS instrument. Latitude -10.9N, Longitude 345.5E. 17 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.

  19. Protein interactions central to stabilizing the K[superscript +] channel selectivity filter in a four-sited configuration for selective K[superscript +] permeation

    SciTech Connect

    Sauer, David B.; Zeng, Weizhong; Raghunathan, Srinivasan; Jiang, Youxing

    2011-11-18

    The structural and functional conversion of the nonselective NaK channel to a K{sup +} selective channel (NaK2K) allows us to identify two key residues, Tyr and Asp in the filter sequence of TVGYGD, that participate in interactions central to stabilizing the K{sup +} channel selectivity filter. By using protein crystallography and channel electrophysiology, we demonstrate that the K{sup +} channel filter exists as an energetically strained structure and requires these key protein interactions working in concert to hold the filter in the precisely defined four-sited configuration that is essential for selective K{sup +} permeation. Disruption of either interaction, as tested on both the NaK2K and eukaryotic K{sub v}1.6 channels, can reduce or completely abolish K{sup +} selectivity and in some cases may also lead to channel inactivation due to conformational changes at the filter. Additionally, on the scaffold of NaK we recapitulate the protein interactions found in the filter of the Kir channel family, which uses a distinct interaction network to achieve similar stabilization of the filter.

  20. Two conserved arginine residues from the SK3 potassium channel outer vestibule control selectivity of recognition by scorpion toxins.

    PubMed

    Feng, Jing; Hu, Youtian; Yi, Hong; Yin, Shijin; Han, Song; Hu, Jun; Chen, Zongyun; Yang, Weishan; Cao, Zhijian; De Waard, Michel; Sabatier, Jean-Marc; Li, Wenxin; Wu, Yingliang

    2013-05-01

    Potassium channel functions are often deciphered by using selective and potent scorpion toxins. Among these toxins, only a limited subset is capable of selectively blocking small conductance Ca(2+)-activated K(+) (SK) channels. The structural bases of this selective SK channel recognition remain unclear. In this work, we demonstrate the key role of the electric charges of two conserved arginine residues (Arg-485 and Arg-489) from the SK3 channel outer vestibule in the selective recognition by the SK3-blocking BmP05 toxin. Indeed, individually substituting these residues with histidyl or lysyl (maintaining the positive electric charge partially or fully), although decreasing BmP05 affinity, still preserved the toxin sensitivity profile of the SK3 channel (as evidenced by the lack of recognition by many other types of potassium channel-sensitive charybdotoxin). In contrast, when Arg-485 or Arg-489 of the SK3 channel was mutated to an acidic (Glu) or alcoholic (Ser) amino acid residue, the channel lost its sensitivity to BmP05 and became susceptible to the "new" blocking activity by charybdotoxin. In addition to these SK3 channel basic residues important for sensitivity, two acidic residues, Asp-492 and Asp-518, also located in the SK3 channel outer vestibule, were identified as being critical for toxin affinity. Furthermore, molecular modeling data indicate the existence of a compact SK3 channel turret conformation (like a peptide screener), where the basic rings of Arg-485 and Arg-489 are stabilized by strong ionic interactions with Asp-492 and Asp-518. In conclusion, the unique properties of Arg-485 and Arg-489 (spatial orientations and molecular interactions) in the SK3 channel account for its toxin sensitivity profile. PMID:23511633

  1. Dimensions and ion selectivity of recombinant AMPA and kainate receptor channels and their dependence on Q/R site residues.

    PubMed Central

    Burnashev, N; Villarroel, A; Sakmann, B

    1996-01-01

    1. Recombinant alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPAR) subunits (GluR-A or GluR-B) and kainate receptor (KAR) subunit (GluR-6) in their unedited (Q)- and edited (R)-forms were expressed in HEK 293 cells. To estimate the dimensions of the narrow portion of these channels, biionic reversal potentials for organic cations of different mean diameters were determined with Cs+ as the internal reference ion. 2. Homomeric channels assembled from Q-form subunits were cation selective. The relation between the relative permeability and the mean size of different organic cations suggests that the diameter of the narrow portion of Q-form channels is approximately 0.78 nm for AMPAR and 0.75 nm for KAR channels. 3. Homomeric channels assembled from R-form subunits were permeant for anions and cations. When probed with CsC1 gradients the relative chloride permeability (PC1/PCs) was estimated as 0.14 for GluR-B(R) and 0.74 for GluR-6(R)-subunit channels. The permeability versus mean size relation for large cations measured with the weakly permeant F- as anion, indicates that for the R-form KAR channels the apparent pore diameter is close to 0.76 nm. 4. Heteromeric AMPAR and KAR channels co-assembled from Q- and R-form subunits were cation selective. The diameter of the narrow portion of these channels is estimated to be in the range between 0.70 and 0.74 nm. 5. The results indicated that the diameters of the narrow portion of AMPAR and KAR channels of different subunit composition and of widely different ion selectivity are comparable. Therefore, the differences in the anion versus cation selectivity, in Ca2+ permeability and in channel conductance are likely to be determined by the difference in charge density of the channel. PMID:8910205

  2. Discrimination of correlated and entangling quantum channels with selective process tomography

    NASA Astrophysics Data System (ADS)

    Dumitrescu, Eugene; Humble, Travis S.

    2016-10-01

    The accurate and reliable characterization of quantum dynamical processes underlies efforts to validate quantum technologies, where discrimination between competing models of observed behaviors inform efforts to fabricate and operate qubit devices. We present a protocol for quantum channel discrimination that leverages advances in direct characterization of quantum dynamics (DCQD) codes. We demonstrate that DCQD codes enable selective process tomography to improve discrimination between entangling and correlated quantum dynamics. Numerical simulations show selective process tomography requires only a few measurement configurations to achieve a low false alarm rate and that the DCQD encoding improves the resilience of the protocol to hidden sources of noise. Our results show that selective process tomography with DCQD codes is useful for efficiently distinguishing sources of correlated crosstalk from uncorrelated noise in current and future experimental platforms.

  3. Discrimination of correlated and entangling quantum channels with selective process tomography

    DOE PAGES

    Dumitrescu, Eugene; Humble, Travis S.

    2016-10-10

    The accurate and reliable characterization of quantum dynamical processes underlies efforts to validate quantum technologies, where discrimination between competing models of observed behaviors inform efforts to fabricate and operate qubit devices. We present a protocol for quantum channel discrimination that leverages advances in direct characterization of quantum dynamics (DCQD) codes. We demonstrate that DCQD codes enable selective process tomography to improve discrimination between entangling and correlated quantum dynamics. Numerical simulations show selective process tomography requires only a few measurement configurations to achieve a low false alarm rate and that the DCQD encoding improves the resilience of the protocol to hiddenmore » sources of noise. Lastly, our results show that selective process tomography with DCQD codes is useful for efficiently distinguishing sources of correlated crosstalk from uncorrelated noise in current and future experimental platforms.« less

  4. Robust fetal QRS detection from noninvasive abdominal electrocardiogram based on channel selection and simultaneous multichannel processing.

    PubMed

    Ghaffari, Ali; Mollakazemi, Mohammad Javad; Atyabi, Seyyed Abbas; Niknazar, Mohammad

    2015-12-01

    The purpose of this study is to provide a new method for detecting fetal QRS complexes from non-invasive fetal electrocardiogram (fECG) signal. Despite most of the current fECG processing methods which are based on separation of fECG from maternal ECG (mECG), in this study, fetal heart rate (FHR) can be extracted with high accuracy without separation of fECG from mECG. Furthermore, in this new approach thoracic channels are not necessary. These two aspects have reduced the required computational operations. Consequently, the proposed approach can be efficiently applied to different real-time healthcare and medical devices. In this work, a new method is presented for selecting the best channel which carries strongest fECG. Each channel is scored based on two criteria of noise distribution and good fetal heartbeat visibility. Another important aspect of this study is the simultaneous and combinatorial use of available fECG channels via the priority given by their scores. A combination of geometric features and wavelet-based techniques was adopted to extract FHR. Based on fetal geometric features, fECG signals were divided into three categories, and different strategies were employed to analyze each category. The method was validated using three datasets including Noninvasive fetal ECG database, DaISy and PhysioNet/Computing in Cardiology Challenge 2013. Finally, the obtained results were compared with other studies. The adopted strategies such as multi-resolution analysis, not separating fECG and mECG, intelligent channels scoring and using them simultaneously are the factors that caused the promising performance of the method. PMID:26462679

  5. Enhancement of the NMSU Channel Error Simulator to Provide User-Selectable Link Delays

    NASA Technical Reports Server (NTRS)

    Horan, Stephen; Wang, Ru-Hai

    2000-01-01

    This is the third in a continuing series of reports describing the development of the Space-to-Ground Link Simulator (SGLS) to be used for testing data transfers under simulated space channel conditions. The SGLS is based upon Virtual Instrument (VI) software techniques for managing the error generation, link data rate configuration, and, now, selection of the link delay value. In this report we detail the changes that needed to be made to the SGLS VI configuration to permit link delays to be added to the basic error generation and link data rate control capabilities. This was accomplished by modifying the rate-splitting VIs to include a buffer the hold the incoming data for the duration selected by the user to emulate the channel link delay. In sample tests of this configuration, the TCP/IP(sub ftp) service and the SCPS(sub fp) service were used to transmit 10-KB data files using both symmetric (both forward and return links set to 115200 bps) and unsymmetric (forward link set at 2400 bps and a return link set at 115200 bps) link configurations. Transmission times were recorded at bit error rates of 0 through 10(exp -5) to give an indication of the link performance. In these tests. we noted separate timings for the protocol setup time to initiate the file transfer and the variation in the actual file transfer time caused by channel errors. Both protocols showed similar performance to that seen earlier for the symmetric and unsymmetric channels. This time, the delays in establishing the file protocol also showed that these delays could double the transmission time and need to be accounted for in mission planning. Both protocols also showed a difficulty in transmitting large data files over large link delays. In these tests, there was no clear favorite between the TCP/IP(sub ftp) and the SCPS(sub fp). Based upon these tests, further testing is recommended to extend the results to different file transfer configurations.

  6. New positive Ca2+-activated K+ channel gating modulators with selectivity for KCa3.1.

    PubMed

    Coleman, Nichole; Brown, Brandon M; Oliván-Viguera, Aida; Singh, Vikrant; Olmstead, Marilyn M; Valero, Marta Sofia; Köhler, Ralf; Wulff, Heike

    2014-09-01

    Small-conductance (KCa2) and intermediate-conductance (KCa3.1) calcium-activated K(+) channels are voltage-independent and share a common calcium/calmodulin-mediated gating mechanism. Existing positive gating modulators like EBIO, NS309, or SKA-31 activate both KCa2 and KCa3.1 channels with similar potency or, as in the case of CyPPA and NS13001, selectively activate KCa2.2 and KCa2.3 channels. We performed a structure-activity relationship (SAR) study with the aim of optimizing the benzothiazole pharmacophore of SKA-31 toward KCa3.1 selectivity. We identified SKA-111 (5-methylnaphtho[1,2-d]thiazol-2-amine), which displays 123-fold selectivity for KCa3.1 (EC50 111 ± 27 nM) over KCa2.3 (EC50 13.7 ± 6.9 μM), and SKA-121 (5-methylnaphtho[2,1-d]oxazol-2-amine), which displays 41-fold selectivity for KCa3.1 (EC50 109 nM ± 14 nM) over KCa2.3 (EC50 4.4 ± 1.6 μM). Both compounds are 200- to 400-fold selective over representative KV (KV1.3, KV2.1, KV3.1, and KV11.1), NaV (NaV1.2, NaV1.4, NaV1.5, and NaV1.7), as well as CaV1.2 channels. SKA-121 is a typical positive-gating modulator and shifts the calcium-concentration response curve of KCa3.1 to the left. In blood pressure telemetry experiments, SKA-121 (100 mg/kg i.p.) significantly lowered mean arterial blood pressure in normotensive and hypertensive wild-type but not in KCa3.1(-/-) mice. SKA-111, which was found in pharmacokinetic experiments to have a much longer half-life and to be much more brain penetrant than SKA-121, not only lowered blood pressure but also drastically reduced heart rate, presumably through cardiac and neuronal KCa2 activation when dosed at 100 mg/kg. In conclusion, with SKA-121, we generated a KCa3.1-specific positive gating modulator suitable for further exploring the therapeutical potential of KCa3.1 activation.

  7. New Positive Ca2+-Activated K+ Channel Gating Modulators with Selectivity for KCa3.1

    PubMed Central

    Coleman, Nichole; Brown, Brandon M.; Oliván-Viguera, Aida; Singh, Vikrant; Olmstead, Marilyn M.; Valero, Marta Sofia; Köhler, Ralf

    2014-01-01

    Small-conductance (KCa2) and intermediate-conductance (KCa3.1) calcium-activated K+ channels are voltage-independent and share a common calcium/calmodulin-mediated gating mechanism. Existing positive gating modulators like EBIO, NS309, or SKA-31 activate both KCa2 and KCa3.1 channels with similar potency or, as in the case of CyPPA and NS13001, selectively activate KCa2.2 and KCa2.3 channels. We performed a structure-activity relationship (SAR) study with the aim of optimizing the benzothiazole pharmacophore of SKA-31 toward KCa3.1 selectivity. We identified SKA-111 (5-methylnaphtho[1,2-d]thiazol-2-amine), which displays 123-fold selectivity for KCa3.1 (EC50 111 ± 27 nM) over KCa2.3 (EC50 13.7 ± 6.9 μM), and SKA-121 (5-methylnaphtho[2,1-d]oxazol-2-amine), which displays 41-fold selectivity for KCa3.1 (EC50 109 nM ± 14 nM) over KCa2.3 (EC50 4.4 ± 1.6 μM). Both compounds are 200- to 400-fold selective over representative KV (KV1.3, KV2.1, KV3.1, and KV11.1), NaV (NaV1.2, NaV1.4, NaV1.5, and NaV1.7), as well as CaV1.2 channels. SKA-121 is a typical positive-gating modulator and shifts the calcium-concentration response curve of KCa3.1 to the left. In blood pressure telemetry experiments, SKA-121 (100 mg/kg i.p.) significantly lowered mean arterial blood pressure in normotensive and hypertensive wild-type but not in KCa3.1−/− mice. SKA-111, which was found in pharmacokinetic experiments to have a much longer half-life and to be much more brain penetrant than SKA-121, not only lowered blood pressure but also drastically reduced heart rate, presumably through cardiac and neuronal KCa2 activation when dosed at 100 mg/kg. In conclusion, with SKA-121, we generated a KCa3.1-specific positive gating modulator suitable for further exploring the therapeutical potential of KCa3.1 activation. PMID:24958817

  8. Phosphatidylinositol 4,5-bisphosphate alters pharmacological selectivity for epilepsy-causing KCNQ potassium channels.

    PubMed

    Zhou, Pingzheng; Yu, Haibo; Gu, Min; Nan, Fa-jun; Gao, Zhaobing; Li, Min

    2013-05-21

    Pharmacological augmentation of neuronal KCNQ muscarinic (M) currents by drugs such as retigabine (RTG) represents a first-in-class therapeutic to treat certain hyperexcitatory diseases by dampening neuronal firing. Whereas all five potassium channel subtypes (KCNQ1-KCNQ5) are found in the nervous system, KCNQ2 and KCNQ3 are the primary players that mediate M currents. We investigated the plasticity of subtype selectivity by two M current effective drugs, retigabine and zinc pyrithione (ZnPy). Retigabine is more effective on KCNQ3 than KCNQ2, whereas ZnPy is more effective on KCNQ2 with no detectable effect on KCNQ3. In neurons, activation of muscarinic receptor signaling desensitizes effects by retigabine but not ZnPy. Importantly, reduction of phosphatidylinositol 4,5-bisphosphate (PIP2) causes KCNQ3 to become sensitive to ZnPy but lose sensitivity to retigabine. The dynamic shift of pharmacological selectivity caused by PIP2 may be induced orthogonally by voltage-sensitive phosphatase, or conversely, abolished by mutating a PIP2 site within the S4-S5 linker of KCNQ3. Therefore, whereas drug-channel binding is a prerequisite, the drug selectivity on M current is dynamic and may be regulated by receptor signaling pathways via PIP2. PMID:23650395

  9. High-order derivative spectroscopy for selecting spectral regions and channels for remote sensing algorithm development

    NASA Astrophysics Data System (ADS)

    Bostater, Charles R., Jr.

    1999-12-01

    A remote sensing reflectance model, which describes the transfer of irradiant light within a plant canopy or water column has previously been used to simulate the nadir viewing reflectance of vegetation canopies and leaves under solar induced or an artificial light source and the water surface reflectance. Wavelength dependent features such as canopy reflectance leaf absorption and canopy bottom reflectance as well as water absorption and water bottom reflectance have been used to simulate or generate synthetic canopy and water surface reflectance signatures. This paper describes how derivative spectroscopy can be utilized to invert the synthetic or modeled as well as measured reflectance signatures with the goal of selecting the optimal spectral channels or regions of these environmental media. Specifically, in this paper synthetic and measured reflectance signatures are used for selecting vegetative dysfunction variables for different plant species. The measured reflectance signatures as well as model derived or synthetic signatures are processed using extremely fast higher order derivative processing techniques which filter the synthetic/modeled or measured spectra and automatically selects the optimal channels for automatic and direct algorithm application. The higher order derivative filtering technique makes use of a translating and dilating, derivative spectroscopy signal processing (TDDS-SPR) approach based upon remote sensing science and radiative transfer theory. Thus the technique described, unlike other signal processing techniques being developed for hyperspectral signatures and associated imagery, is based upon radiative transfer theory instead of statistical or purely mathematical operational techniques such as wavelets.

  10. Multi-ion free energy landscapes underscore the microscopic mechanism of ion selectivity in the KcsA channel

    PubMed Central

    Medovoy, David; Perozo, Eduardo; Roux, Benoît

    2016-01-01

    Potassium (K+) channels are transmembrane proteins that passively and selectively allow K+ ions to flow through them, after opening in response to an external stimulus. One of the most critical functional aspects of their function is their ability to remain very selective for K+ over Na+ while allowing high-throughput ion conduction at a rate close to the diffusion limit. Classically, it is assumed that the free energy difference between K+ and Na+ in the pore relative to the bulk solution is the critical quantity at the origin of selectivity. This is the thermodynamic view of ion selectivity. An alternative view assumes that kinetic factor play the dominant role. Recent results from a number of studies have also highlighted the great importance of the multi-ion single file on the selectivity of K+ channels. The data indicate that having multiple K+ ions bound simultaneously is required for selective K+ conduction, and that a reduction in the number of bound K+ ions destroys the multi-ion selectivity mechanism utilized by K+ channels. In the present study, multi-ion potential of mean force molecular dynamics computations are carried out to clarify the mechanism of ion selectivity in the KcsA channel. The computations show that the multi-ion character of the permeation process is a critical element for establishing the selective ion conductivity through K+-channels. PMID:26896693

  11. Putative resolution of the EEEE selectivity paradox in L-type Ca2+ and bacterial Na+ biological ion channels

    NASA Astrophysics Data System (ADS)

    Kaufman, I. Kh; Luchinsky, D. G.; Gibby, W. A. T.; McClintock, P. V. E.; Eisenberg, R. S.

    2016-05-01

    The highly selective permeation of ions through biological ion channels can be described and explained in terms of fluctuational dynamics under the influence of powerful electrostatic forces. Hence valence selectivity, e.g. between Ca2+ and Na+ in calcium and sodium channels, can be described in terms of ionic Coulomb blockade, which gives rise to distinct conduction bands and stop-bands as the fixed negative charge Q f at the selectivity filter of the channel is varied. This picture accounts successfully for a wide range of conduction phenomena in a diversity of ion channels. A disturbing anomaly, however, is that what appears to be the same electrostatic charge and structure (the so-called EEEE motif) seems to select Na+ conduction in bacterial channels but Ca2+ conduction in mammalian channels. As a possible resolution of this paradox it is hypothesised that an additional charged protein residue on the permeation path of the mammalian channel increases |{{Q}f}| by e, thereby altering the selectivity from Na+ to Ca2+. Experiments are proposed that will enable the hypothesis to be tested.

  12. Cooperation of Hydrophobic Gating, Knock-on Effect, and Ion Binding Determines Ion Selectivity in the p7 Channel.

    PubMed

    Padhi, Siladitya; Priyakumar, U Deva

    2016-05-19

    Ion channels selectively allow certain ions to pass through at much higher rates than others, and thereby modulate ionic concentrations across cell membranes. The current molecular dynamics study elucidates the intricate mechanisms that render ion selectivity to the viral channel p7 by employing free energy calculations. Free energy barriers of 5.4 and 19.4 kcal mol(-1) for K(+) and Ca(2+), respectively, explain the selectivity of the channel reported in experiments. Initially, the permeating ions encounter a hydrophobic barrier followed by stabilization in an ion-binding site. Electrostatic repulsion between the permeating ions propels one of the ions out of the binding site to complete the process of permeation. K(+) and Ca(2+) are seen to exhibit different modes of binding toward a ring of asparagine residues, which serves as the binding site. The findings illustrate how the overall selectivity of a channel can be achieved by a combination of subtle differences. PMID:27111292

  13. Fragmentation of singly, doubly, and triply charged hydrogen deficient peptide radical cations in infrared multiphoton dissociation and electron induced dissociation.

    PubMed

    Kalli, Anastasia; Hess, Sonja

    2012-02-01

    Gas phase fragmentation of hydrogen deficient peptide radical cations continues to be an active area of research. While collision induced dissociation (CID) of singly charged species is widely examined, dissociation channels of singly and multiply charged radical cations in infrared multiphoton dissociation (IRMPD) and electron induced dissociation (EID) have not been, so far, investigated. Here, we report on the gas phase dissociation of singly, doubly and triply charged hydrogen deficient peptide radicals, [M + nH]((n+1)+·) (n=0, 1, 2), in MS(3) IRMPD and EID and compare the observed fragmentation pathways to those obtained in MS(3) CID. Backbone fragmentation in MS(3) IRMPD and EID was highly dependent on the charge state of the radical precursor ions, whereas amino acid side chain cleavages were largely independent of the charge state selected for fragmentation. Cleavages at aromatic amino acids, either through side chain loss or backbone fragmentation, were significantly enhanced over other dissociation channels. For singly charged species, the MS(3) IRMPD and EID spectra were mainly governed by radical-driven dissociation. Fragmentation of doubly and triply charged radical cations proceeded through both radical- and charge-driven processes, resulting in the formation of a wide range of backbone product ions including, a-, b-, c-, y-, x-, and z-type. While similarities existed between MS(3) CID, IRMPD, and EID of the same species, several backbone product ions and side chain losses were unique for each activation method. Furthermore, dominant dissociation pathways in each spectrum were dependent on ion activation method, amino acid composition, and charge state selected for fragmentation.

  14. Discovery and Characterization of a Potent and Selective Inhibitor of Aedes aegypti Inward Rectifier Potassium Channels

    PubMed Central

    Raphemot, Rene; Rouhier, Matthew F.; Swale, Daniel R.; Days, Emily; Weaver, C. David; Lovell, Kimberly M.; Konkel, Leah C.; Engers, Darren W.; Bollinger, Sean F.; Hopkins, Corey; Piermarini, Peter M.; Denton, Jerod S.

    2014-01-01

    Vector-borne diseases such as dengue fever and malaria, which are transmitted by infected female mosquitoes, affect nearly half of the world's population. The emergence of insecticide-resistant mosquito populations is reducing the effectiveness of conventional insecticides and threatening current vector control strategies, which has created an urgent need to identify new molecular targets against which novel classes of insecticides can be developed. We previously demonstrated that small molecule inhibitors of mammalian Kir channels represent promising chemicals for new mosquitocide development. In this study, high-throughput screening of approximately 30,000 chemically diverse small-molecules was employed to discover potent and selective inhibitors of Aedes aegypti Kir1 (AeKir1) channels heterologously expressed in HEK293 cells. Of 283 confirmed screening ‘hits’, the small-molecule inhibitor VU625 was selected for lead optimization and in vivo studies based on its potency and selectivity toward AeKir1, and tractability for medicinal chemistry. In patch clamp electrophysiology experiments of HEK293 cells, VU625 inhibits AeKir1 with an IC50 value of 96.8 nM, making VU625 the most potent inhibitor of AeKir1 described to date. Furthermore, electrophysiology experiments in Xenopus oocytes revealed that VU625 is a weak inhibitor of AeKir2B. Surprisingly, injection of VU625 failed to elicit significant effects on mosquito behavior, urine excretion, or survival. However, when co-injected with probenecid, VU625 inhibited the excretory capacity of mosquitoes and was toxic, suggesting that the compound is a substrate of organic anion and/or ATP-binding cassette (ABC) transporters. The dose-toxicity relationship of VU625 (when co-injected with probenecid) is biphasic, which is consistent with the molecule inhibiting both AeKir1 and AeKir2B with different potencies. This study demonstrates proof-of-concept that potent and highly selective inhibitors of mosquito Kir channels

  15. Discovery and characterization of a potent and selective inhibitor of Aedes aegypti inward rectifier potassium channels.

    PubMed

    Raphemot, Rene; Rouhier, Matthew F; Swale, Daniel R; Days, Emily; Weaver, C David; Lovell, Kimberly M; Konkel, Leah C; Engers, Darren W; Bollinger, Sean R; Bollinger, Sean F; Hopkins, Corey; Piermarini, Peter M; Denton, Jerod S

    2014-01-01

    Vector-borne diseases such as dengue fever and malaria, which are transmitted by infected female mosquitoes, affect nearly half of the world's population. The emergence of insecticide-resistant mosquito populations is reducing the effectiveness of conventional insecticides and threatening current vector control strategies, which has created an urgent need to identify new molecular targets against which novel classes of insecticides can be developed. We previously demonstrated that small molecule inhibitors of mammalian Kir channels represent promising chemicals for new mosquitocide development. In this study, high-throughput screening of approximately 30,000 chemically diverse small-molecules was employed to discover potent and selective inhibitors of Aedes aegypti Kir1 (AeKir1) channels heterologously expressed in HEK293 cells. Of 283 confirmed screening 'hits', the small-molecule inhibitor VU625 was selected for lead optimization and in vivo studies based on its potency and selectivity toward AeKir1, and tractability for medicinal chemistry. In patch clamp electrophysiology experiments of HEK293 cells, VU625 inhibits AeKir1 with an IC50 value of 96.8 nM, making VU625 the most potent inhibitor of AeKir1 described to date. Furthermore, electrophysiology experiments in Xenopus oocytes revealed that VU625 is a weak inhibitor of AeKir2B. Surprisingly, injection of VU625 failed to elicit significant effects on mosquito behavior, urine excretion, or survival. However, when co-injected with probenecid, VU625 inhibited the excretory capacity of mosquitoes and was toxic, suggesting that the compound is a substrate of organic anion and/or ATP-binding cassette (ABC) transporters. The dose-toxicity relationship of VU625 (when co-injected with probenecid) is biphasic, which is consistent with the molecule inhibiting both AeKir1 and AeKir2B with different potencies. This study demonstrates proof-of-concept that potent and highly selective inhibitors of mosquito Kir channels can

  16. Wavenumber selection for small-wavelength Goertler vortices in curved channel flows

    NASA Technical Reports Server (NTRS)

    Dando, Andrew; Hall, Philip

    1995-01-01

    The problem of wavenumber selection for fully nonlinear, small-wavelength Goertler vortices in a curved channel flow is considered. These types of Goertler vortices were first considered by Hall & Lakin (1988) for an external boundary layer flow. They proved particularly amenable to asymptotic description, it was possible to consider vortices large enough so that the mean flow correction driven by them is as large as the basic state, and this prompted the authors to consider them in a curved channel flow as an initial application of the phase-equation approach to Goertler vortices. This involves the assumption that the phase variable of these Goertler vortices varies on slow spanwise and time scales, then an analysis of both inside and outside the core region, to which vortex activity is restricted, leads to a system of partial differential equations which can be solved numerically for the wavenumber. The authors consider in particular the effect on the wavenumber of the outer channel wall varying on the same slow spanwise scale as the phase variable.

  17. Wavenumber selection for small-wavelength Goertler vortices in curved channel flows

    NASA Astrophysics Data System (ADS)

    Dando, Andrew; Hall, Philip

    1995-04-01

    The problem of wavenumber selection for fully nonlinear, small-wavelength Goertler vortices in a curved channel flow is considered. These types of Goertler vortices were first considered by Hall & Lakin (1988) for an external boundary layer flow. They proved particularly amenable to asymptotic description, it was possible to consider vortices large enough so that the mean flow correction driven by them is as large as the basic state, and this prompted the authors to consider them in a curved channel flow as an initial application of the phase-equation approach to Goertler vortices. This involves the assumption that the phase variable of these Goertler vortices varies on slow spanwise and time scales, then an analysis of both inside and outside the core region, to which vortex activity is restricted, leads to a system of partial differential equations which can be solved numerically for the wavenumber. The authors consider in particular the effect on the wavenumber of the outer channel wall varying on the same slow spanwise scale as the phase variable.

  18. Recombinant expression and functional characterization of martentoxin: a selective inhibitor for BK channel (α + β4).

    PubMed

    Tao, Jie; Zhou, Zhi Lei; Wu, Bin; Shi, Jian; Chen, Xiao Ming; Ji, Yong Hua

    2014-04-01

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

  19. Selectivity filters and cysteine-rich extracellular loops in voltage-gated sodium, calcium, and NALCN channels

    PubMed Central

    Stephens, Robert F.; Guan, W.; Zhorov, Boris S.; Spafford, J. David

    2015-01-01

    How nature discriminates sodium from calcium ions in eukaryotic channels has been difficult to resolve because they contain four homologous, but markedly different repeat domains. We glean clues from analyzing the changing pore region in sodium, calcium and NALCN channels, from single-cell eukaryotes to mammals. Alternative splicing in invertebrate homologs provides insights into different structural features underlying calcium and sodium selectivity. NALCN generates alternative ion selectivity with splicing that changes the high field strength (HFS) site at the narrowest level of the hourglass shaped pore where the selectivity filter is located. Alternative splicing creates NALCN isoforms, in which the HFS site has a ring of glutamates contributed by all four repeat domains (EEEE), or three glutamates and a lysine residue in the third (EEKE) or second (EKEE) position. Alternative splicing provides sodium and/or calcium selectivity in T-type channels with extracellular loops between S5 and P-helices (S5P) of different lengths that contain three or five cysteines. All eukaryotic channels have a set of eight core cysteines in extracellular regions, but the T-type channels have an infusion of 4–12 extra cysteines in extracellular regions. The pattern of conservation suggests a possible pairing of long loops in Domains I and III, which are bridged with core cysteines in NALCN, Cav, and Nav channels, and pairing of shorter loops in Domains II and IV in T-type channel through disulfide bonds involving T-type specific cysteines. Extracellular turrets of increasing lengths in potassium channels (Kir2.2, hERG, and K2P1) contribute to a changing landscape above the pore selectivity filter that can limit drug access and serve as an ion pre-filter before ions reach the pore selectivity filter below. Pairing of extended loops likely contributes to the large extracellular appendage as seen in single particle electron cryo-microscopy images of the eel Nav1 channel. PMID

  20. Ion selectivity from local configurations of ligands in solutions and ion channels

    PubMed Central

    Asthagiri, D.; Dixit, P.D.; Merchant, S.; Paulaitis, M.E.; Pratt, L.R.; Rempe, S.B.; Varma, S.

    2010-01-01

    Probabilities of numbers of ligands proximal to an ion lead to simple, general formulae for the free energy of ion selectivity between different media. That free energy does not depend on the definition of an inner shell for ligand-counting, but other quantities of mechanistic interest do. If analysis is restricted to a specific coordination number, then two distinct probabilities are required to obtain the free energy in addition. The normalizations of those distributions produce partition function formulae for the free energy. Quasi-chemical theory introduces concepts of chemical equilibrium, then seeks the probability that is simplest to estimate, that of the most probable coordination number. Quasi-chemical theory establishes the utility of distributions of ligand-number, and sharpens our understanding of quasi-chemical calculations based on electronic structure methods. This development identifies contributions with clear physical interpretations, and shows that evaluation of those contributions can establish a mechanistic understanding of the selectivity in ion channels. PMID:23750043

  1. Isospin Splittings of Doubly Heavy Baryons

    SciTech Connect

    Brodsky, Stanley J.; Guo, Feng-Kun; Hanhart, Christoph; Meissner, Ulf-G.; /Julich, Forschungszentrum /JCHP, Julich /IAS, Julich /Bonn U., HISKP /Bonn U.

    2011-08-18

    The SELEX Collaboration has reported a very large isospin splitting of doubly charmed baryons. We show that this effect would imply that the doubly charmed baryons are very compact. One intriguing possibility is that such baryons have a linear geometry Q-q-Q where the light quark q oscillates between the two heavy quarks Q, analogous to a linear molecule such as carbon dioxide. However, using conventional arguments, the size of a heavy-light hadron is expected to be around 0.5 fm, much larger than the size needed to explain the observed large isospin splitting. Assuming the distance between two heavy quarks is much smaller than that between the light quark and a heavy one, the doubly heavy baryons are related to the heavy mesons via heavy quark-diquark symmetry. Based on this symmetry, we predict the isospin splittings for doubly heavy baryons including {Xi}{sub cc}, {Xi}{sub bb} and {Xi}{sub bc}. The prediction for the {Xi}{sub cc} is much smaller than the SELEX value. On the other hand, the {Xi}{sub bb} baryons are predicted to have an isospin splitting as large as (6.3 {+-} 1.7) MeV. An experimental study of doubly bottomed baryons is therefore very important to better understand the structure of baryons with heavy quarks.

  2. Diversity technique for DAPSK signal over the frequency-selective fading channel

    NASA Astrophysics Data System (ADS)

    Lee, Jong Y.; Chung, Young M.; Lee, Sang U.

    2001-10-01

    In this paper, a maximal ratio combining (MRC) and weighted maximal ratio combining (WMRC) diversity receiver are proposed. The MRC receiver makes a decision at each branch based on the minimum distance criterion. The performance of the MRC receiver is analyzed on the frequency-selective Rayleigh and Rician fading channels, in terms of the union bound for bit error probability. In addition, the WMRC receiver, which assigns weighting factors to the decision variable at each branch, based on the optimum decision boundaries, is proposed. The performance of the WMRC is investigated through the computer simulation and compared with those of MRC and equal gain combining (EGC). From the results, it is found that the performances of the WMRC and MRC are better than those of EGC on both the frequency-selective Rayleigh and Rician fading channels and performance improvements over the EGC are noticeable when the number of diversity branches is large as long as the root mean square (rms) delay is smaller than or equal to 10% of the symbol period.

  3. An embryo of protocells: The capsule of graphene with selective ion channels

    SciTech Connect

    Li, Zhan; Wang, Chunmei; Tian, Longlong; Bai, Jing; Yao, Huijun; Zhao, Yang; Zhang, Xin; Cao, Shiwei; Qi, Wei; Wang, Suomin; Shi, Keliang; Xu, Youwen; Mingliang, Zhang; Liu, Bo; Qiu, Hongdeng; Liu, Jie; Wu, Wangsuo; Wang, Xiaoli; Wenzhen, An

    2015-05-19

    In this study, the synthesis of artificial cell is a route for searching the origin of protocell. Here, we create a novel cell model of graphene capsules with selective ion channels, indicating that graphene might be an embryo of protocell membrane. Firstly, we found that the highly oxidized graphene and phospholipid-graphene oxide composite would curl into capsules under a strongly acidic saturated solution of heavy metallic salt solution at low temperature. Secondly, L-amino acids exhibited higher reactivity than D-amino acids on graphene oxides to form peptides, and the formed peptides in the influence of graphene would be transformed into a secondary structure, promoting the formation of left-handed proteins. Lastly, monolayer nanoporous graphene, prepared by unfocused 84Kr25+, has a high selectivity for permeation of the monovalent metal ions ( Rb+ > K+ > Cs+ > Na+ > Li+, based on permeation concentration), but does not allow Cl- go through. It is similar to K+ channels, which would cause an influx of K+ into capsule of graphene with the increase of pH in the primitive ocean, creating a suitable inner condition for the origin of life. Therefore, we built a model cell of graphene, which would provide a route for reproducing the origin of life.

  4. Thiram and ziram stimulate non-selective cation channel and induce apoptosis in PC12 cells.

    PubMed

    Sook Han, Myoung; Shin, Kum Joo; Kim, Yun Hee; Kim, Sun Hee; Lee, Taehoon; Kim, Euikyung; Ho Ryu, Sung; Suh, Pann Ghill

    2003-06-01

    The neurotoxicity of dithiocarbamates has been previously reported, however, the detailed mechanism underlying the neurotoxicity is still not fully understood. Among the dithiocarbamates, we investigated thiram and ziram in a neuronal-like pheochromocytoma (PC12) cells. Thiram and ziram strongly induced cell death in both dose- and time-dependent manners with the LC(50) of 0.3 and 2 microM, respectively. The cell death showed typical apoptotic features, such as DNA fragmentation and an increase of subdiploidy nuclei. Interestingly, both thiram and ziram induced rapid and sustained increases of intracellular Ca(2+) in PC12 cells, which were almost completely blocked by flufenamic acid (FFA), an inhibitor of non-selective cation channel. BAPTA-AM, an intracellular Ca(2+) chelator, inhibited the thiram- and ziram-induced apoptotic cell death. These results suggest that thiram and ziram induce apoptotic neuronal cell death by Ca(2+) influx through non-selective cation channels. The present study may provide a clue for understanding the mechanism of neurotoxicity of thiram and ziram.

  5. An embryo of protocells: The capsule of graphene with selective ion channels.

    PubMed

    Li, Zhan; Wang, Chunmei; Tian, Longlong; Bai, Jing; Yao, Huijun; Zhao, Yang; Zhang, Xin; Cao, Shiwei; Qi, Wei; Wang, Suomin; Shi, Keliang; Xu, Youwen; Mingliang, Zhang; Liu, Bo; Qiu, Hongdeng; Liu, Jie; Wu, Wangsuo; Wang, Xiaoli; Wenzhen, An

    2015-01-01

    The synthesis of artificial cell is a route for searching the origin of protocell. Here, we create a novel cell model of graphene capsules with selective ion channels, indicating that graphene might be an embryo of protocell membrane. Firstly, we found that the highly oxidized graphene and phospholipid-graphene oxide composite would curl into capsules under a strongly acidic saturated solution of heavy metallic salt solution at low temperature. Secondly, L-amino acids exhibited higher reactivity than D-amino acids on graphene oxides to form peptides, and the formed peptides in the influence of graphene would be transformed into a secondary structure, promoting the formation of left-handed proteins. Lastly, monolayer nanoporous graphene, prepared by unfocused (84)Kr(25+), has a high selectivity for permeation of the monovalent metal ions ( Rb(+) > K(+) > Cs(+) > Na(+) > Li(+), based on permeation concentration), but does not allow Cl(-) go through. It is similar to K(+) channels, which would cause an influx of K(+) into capsule of graphene with the increase of pH in the primitive ocean, creating a suitable inner condition for the origin of life. Therefore, we built a model cell of graphene, which would provide a route for reproducing the origin of life. PMID:25989440

  6. An embryo of protocells: The capsule of graphene with selective ion channels

    DOE PAGES

    Li, Zhan; Wang, Chunmei; Tian, Longlong; Bai, Jing; Yao, Huijun; Zhao, Yang; Zhang, Xin; Cao, Shiwei; Qi, Wei; Wang, Suomin; et al

    2015-05-19

    In this study, the synthesis of artificial cell is a route for searching the origin of protocell. Here, we create a novel cell model of graphene capsules with selective ion channels, indicating that graphene might be an embryo of protocell membrane. Firstly, we found that the highly oxidized graphene and phospholipid-graphene oxide composite would curl into capsules under a strongly acidic saturated solution of heavy metallic salt solution at low temperature. Secondly, L-amino acids exhibited higher reactivity than D-amino acids on graphene oxides to form peptides, and the formed peptides in the influence of graphene would be transformed into amore » secondary structure, promoting the formation of left-handed proteins. Lastly, monolayer nanoporous graphene, prepared by unfocused 84Kr25+, has a high selectivity for permeation of the monovalent metal ions ( Rb+ > K+ > Cs+ > Na+ > Li+, based on permeation concentration), but does not allow Cl- go through. It is similar to K+ channels, which would cause an influx of K+ into capsule of graphene with the increase of pH in the primitive ocean, creating a suitable inner condition for the origin of life. Therefore, we built a model cell of graphene, which would provide a route for reproducing the origin of life.« less

  7. An embryo of protocells: The capsule of graphene with selective ion channels

    PubMed Central

    Li, Zhan; Wang, Chunmei; Tian, Longlong; Bai, Jing; Yao, Huijun; Zhao, Yang; Zhang, Xin; Cao, Shiwei; Qi, Wei; Wang, Suomin; Shi, Keliang; Xu, Youwen; Mingliang, Zhang; Liu, Bo; Qiu, Hongdeng; Liu, Jie; Wu, Wangsuo; Wang, Xiaoli; Wenzhen, An

    2015-01-01

    The synthesis of artificial cell is a route for searching the origin of protocell. Here, we create a novel cell model of graphene capsules with selective ion channels, indicating that graphene might be an embryo of protocell membrane. Firstly, we found that the highly oxidized graphene and phospholipid-graphene oxide composite would curl into capsules under a strongly acidic saturated solution of heavy metallic salt solution at low temperature. Secondly, L-amino acids exhibited higher reactivity than D-amino acids on graphene oxides to form peptides, and the formed peptides in the influence of graphene would be transformed into a secondary structure, promoting the formation of left-handed proteins. Lastly, monolayer nanoporous graphene, prepared by unfocused 84Kr25+, has a high selectivity for permeation of the monovalent metal ions ( Rb+ > K+ > Cs+ > Na+ > Li+, based on permeation concentration), but does not allow Cl- go through. It is similar to K+ channels, which would cause an influx of K+ into capsule of graphene with the increase of pH in the primitive ocean, creating a suitable inner condition for the origin of life. Therefore, we built a model cell of graphene, which would provide a route for reproducing the origin of life. PMID:25989440

  8. Channel selection in the modulation domain for improved speech intelligibility in noise

    PubMed Central

    Wójcicki, Kamil K.; Loizou, Philipos C.

    2012-01-01

    Background noise reduces the depth of the low-frequency envelope modulations known to be important for speech intelligibility. The relative strength of the target and masker envelope modulations can be quantified using a modulation signal-to-noise ratio, (S/N)mod, measure. Such a measure can be used in noise-suppression algorithms to extract target-relevant modulations from the corrupted (target + masker) envelopes for potential improvement in speech intelligibility. In the present study, envelopes are decomposed in the modulation spectral domain into a number of channels spanning the range of 0–30 Hz. Target-dominant modulations are identified and retained in each channel based on the (S/N)mod selection criterion, while modulations which potentially interfere with perception of the target (i.e., those dominated by the masker) are discarded. The impact of modulation-selective processing on the speech-reception threshold for sentences in noise is assessed with normal-hearing listeners. Results indicate that the intelligibility of noise-masked speech can be improved by as much as 13 dB when preserving target-dominant modulations, present up to a modulation frequency of 18 Hz, while discarding masker-dominant modulations from the mixture envelopes. PMID:22501068

  9. An embryo of protocells: The capsule of graphene with selective ion channels

    NASA Astrophysics Data System (ADS)

    Li, Zhan; Wang, Chunmei; Tian, Longlong; Bai, Jing; Yao, Huijun; Zhao, Yang; Zhang, Xin; Cao, Shiwei; Qi, Wei; Wang, Suomin; Shi, Keliang; Xu, Youwen; Mingliang, Zhang; Liu, Bo; Qiu, Hongdeng; Liu, Jie; Wu, Wangsuo; Wang, Xiaoli; Wenzhen, An

    2015-05-01

    The synthesis of artificial cell is a route for searching the origin of protocell. Here, we create a novel cell model of graphene capsules with selective ion channels, indicating that graphene might be an embryo of protocell membrane. Firstly, we found that the highly oxidized graphene and phospholipid-graphene oxide composite would curl into capsules under a strongly acidic saturated solution of heavy metallic salt solution at low temperature. Secondly, L-amino acids exhibited higher reactivity than D-amino acids on graphene oxides to form peptides, and the formed peptides in the influence of graphene would be transformed into a secondary structure, promoting the formation of left-handed proteins. Lastly, monolayer nanoporous graphene, prepared by unfocused 84Kr25+, has a high selectivity for permeation of the monovalent metal ions ( Rb+ > K+ > Cs+ > Na+ > Li+, based on permeation concentration), but does not allow Cl- go through. It is similar to K+ channels, which would cause an influx of K+ into capsule of graphene with the increase of pH in the primitive ocean, creating a suitable inner condition for the origin of life. Therefore, we built a model cell of graphene, which would provide a route for reproducing the origin of life.

  10. Thermodynamic and kinetic studies of the gating behavior of a K+- selective channel from the sarcoplasmic reticulum membrane

    PubMed Central

    1980-01-01

    A voltage-dependent, K+-selective ionic channel from sarcoplasmic reticulum of rabbit skeletal muscle has been studied in a planar phospholipid bilayer membrane. The puppose of this work is to study the mechanism by which the channel undergoes transitions between its conducting and nonconducting states. Thermodynamic studies show that the "open" and "closed" states of the channel exist in a voltage- dependent equilibrium, and that the channel displays only a single open state; the channel conductance is 120 pmho in 0.1 M K+. The channel's gating process follows single exponential kinetics at all voltages tested, and the individual opening and closing rate constants are exponentially dependent on voltage. The individual rate constants may also be determined from a stochastic analysis of channel fluctuations among multiple conductance levels. Neither the thermodynamic nor the kinetic parameters of gating depend on the absolute concentration of channels in the bilayer. The results are taken as evidence that the channel gates by an unusually simple two-state conformational mechanism in which the equivalent of 1.1 net charges are moved across the membrane during the formation of the open channel. PMID:6255061

  11. A structural, functional, and computational analysis suggests pore flexibility as the base for the poor selectivity of CNG channels

    PubMed Central

    Napolitano, Luisa Maria Rosaria; Bisha, Ina; De March, Matteo; Marchesi, Arin; Arcangeletti, Manuel; Demitri, Nicola; Mazzolini, Monica; Rodriguez, Alex; Magistrato, Alessandra; Onesti, Silvia; Laio, Alessandro; Torre, Vincent

    2015-01-01

    Cyclic nucleotide-gated (CNG) ion channels, despite a significant homology with the highly selective K+ channels, do not discriminate among monovalent alkali cations and are permeable also to several organic cations. We combined electrophysiology, molecular dynamics (MD) simulations, and X-ray crystallography to demonstrate that the pore of CNG channels is highly flexible. When a CNG mimic is crystallized in the presence of a variety of monovalent cations, including Na+, Cs+, and dimethylammonium (DMA+), the side chain of Glu66 in the selectivity filter shows multiple conformations and the diameter of the pore changes significantly. MD simulations indicate that Glu66 and the prolines in the outer vestibule undergo large fluctuations, which are modulated by the ionic species and the voltage. This flexibility underlies the coupling between gating and permeation and the poor ionic selectivity of CNG channels. PMID:26100907

  12. Myrsinane, Premyrsinane, and Cyclomyrsinane Diterpenes from Euphorbia falcata as Potassium Ion Channel Inhibitors with Selective G Protein-Activated Inwardly Rectifying Ion Channel (GIRK) Blocking Effects.

    PubMed

    Vasas, Andrea; Forgo, Peter; Orvos, Péter; Tálosi, László; Csorba, Attila; Pinke, Gyula; Hohmann, Judit

    2016-08-26

    GIRK channels are activated by a large number of G protein-coupled receptors and regulate the electrical activity of neurons, cardiac atrial myocytes, and β-pancreatic cells. Abnormalities in GIRK channel function have been implicated in the pathophysiology of neuropathic pain, drug addiction, and cardiac arrhythmias. In the heart, GIRK channels are selectively expressed in the atrium, and their activation inhibits pacemaker activity, thereby slowing the heart rate. In the present study, 19 new diterpenes, falcatins A-S (1-19), and the known euphorprolitherin D (20) were isolated from Euphorbia falcata. The compounds were assayed on stable transfected HEK-hERG (Kv11.1) and HEK-GIRK1/4 (Kir3.1 and Kir3.4) cells. Blocking activity on GIRK channels was exerted by 13 compounds (61-83% at 10 μM), and, among them, five possessed low potency on the hERG channel (4-20% at 10 μM). These selective activities suggest that myrsinane-related diterpenes are potential lead compounds for the treatment of atrial fibrillation. PMID:27441737

  13. Menthol derivative WS-12 selectively activates transient receptor potential melastatin-8 (TRPM8) ion channels.

    PubMed

    Ma, Sherkheli; G, Gisselmann; Ak, Vogt-Eisele; Jf, Doerner; H, Hatt

    2008-10-01

    Transient receptor potential melastatin-8 (TRPM8), a cationic ion channel is involved in detection of normal cooling-sensation in mammals. TRPM8 activation by cooling or chemical agonists have been shown to produce profound, mechanistically novel analgesia in chronic pain states such as neuropathic pain in rodents. Known TRPM8 agonists such as menthol and icilin have a relatively low potency and cross-activate nociceptors like TRPA1; thus bearing a limited therapeutic usefulness. For that reason, characterising ligands, which selectively activate TRPM8, presents a clinical need. Using Xenopus laevis oocytes as expression system, we evaluated WS-12, a menthol derivative, for its potential interaction with all six thermo-sensitive TRP ion channels. Oocytes were injected with cRNA of gene of interest and incubated for 3-5 days (at 16 degrees C) before testing for functional characterisation of the recombinant ion channels. Oocytes were superfused with the test and standard substances respectively. Responses were measured by two-electrode voltage clamp technique and the amplitudes of evoked currents were compared with baseline values. WS-12 robustly activated TRPM8 in low micromolar concentrations (EC50 12+/-5 microM) thereby displaying a higher potency and efficacy compared to menthol (EC50 196+/-22 microM). Any of the other described thermo-sensitive TRP ion channel including TRPV1, TRPV2, TRPV3, TRPV4 and TRPA1 were not activated at a concentration (1 mM) optimally effective for TRPM8 responses; a characteristic which is in sharp contrast to menthol as it activates TRPA1 and TRPV3 in addition to TRPM8. Unlike icilin (75% reduction; p<0.001, n=6), WS-12 does not induce tachyphylaxis (4+/-2.3% increase in responses; p<0.08, n=6) of TRPM8 mediated currents to repeated exposure of 1 mM doses. In addition, acidosis or variations in extracellular calcium have no influence on potency/efficacy of WS-12 for TRPM8. The selectivity profile of WS-12, its several-fold higher

  14. α-SNAP regulates dynamic, on-site assembly and calcium selectivity of Orai1 channels

    PubMed Central

    Li, Peiyao; Miao, Yong; Dani, Adish; Vig, Monika

    2016-01-01

    Orai1 forms a highly calcium-selective pore of the calcium release activated channel, and α-SNAP is necessary for its function. Here we show that α-SNAP regulates on-site assembly of Orai1 dimers into calcium-selective multimers. We find that Orai1 is a dimer in resting primary mouse embryonic fibroblasts but displays variable stoichiometry in the plasma membrane of store-depleted cells. Remarkably, α-SNAP depletion induces formation of higher-order Orai1 oligomers, which permeate significant levels of sodium via Orai1 channels. Sodium permeation in α-SNAP–deficient cells cannot be corrected by tethering multiple Stim1 domains to Orai1 C-terminal tail, demonstrating that α-SNAP regulates functional assembly and calcium selectivity of Orai1 multimers independently of Stim1 levels. Fluorescence nanoscopy reveals sustained coassociation of α-SNAP with Stim1 and Orai1, and α-SNAP–depleted cells show faster and less constrained mobility of Orai1 within ER-PM junctions, suggesting Orai1 and Stim1 coentrapment without stable contacts. Furthermore, α-SNAP depletion significantly reduces fluorescence resonance energy transfer between Stim1 and Orai1 N-terminus but not C-terminus. Taken together, these data reveal a unique role of α-SNAP in the on-site functional assembly of Orai1 subunits and suggest that this process may, in part, involve enabling crucial low-affinity interactions between Orai1 N-terminus and Stim1. PMID:27335124

  15. α-SNAP regulates dynamic, on-site assembly and calcium selectivity of Orai1 channels.

    PubMed

    Li, Peiyao; Miao, Yong; Dani, Adish; Vig, Monika

    2016-08-15

    Orai1 forms a highly calcium-selective pore of the calcium release activated channel, and α-SNAP is necessary for its function. Here we show that α-SNAP regulates on-site assembly of Orai1 dimers into calcium-selective multimers. We find that Orai1 is a dimer in resting primary mouse embryonic fibroblasts but displays variable stoichiometry in the plasma membrane of store-depleted cells. Remarkably, α-SNAP depletion induces formation of higher-order Orai1 oligomers, which permeate significant levels of sodium via Orai1 channels. Sodium permeation in α-SNAP-deficient cells cannot be corrected by tethering multiple Stim1 domains to Orai1 C-terminal tail, demonstrating that α-SNAP regulates functional assembly and calcium selectivity of Orai1 multimers independently of Stim1 levels. Fluorescence nanoscopy reveals sustained coassociation of α-SNAP with Stim1 and Orai1, and α-SNAP-depleted cells show faster and less constrained mobility of Orai1 within ER-PM junctions, suggesting Orai1 and Stim1 coentrapment without stable contacts. Furthermore, α-SNAP depletion significantly reduces fluorescence resonance energy transfer between Stim1 and Orai1 N-terminus but not C-terminus. Taken together, these data reveal a unique role of α-SNAP in the on-site functional assembly of Orai1 subunits and suggest that this process may, in part, involve enabling crucial low-affinity interactions between Orai1 N-terminus and Stim1.

  16. Doubly fed machine review: agenda. Conference report, Washington, DC

    SciTech Connect

    Not Available

    1982-09-01

    The visual aids presented at the doubly fed machine review are presented. The doubly fed machine is a generating system either for wind turbines or hydro systems. Conceptual design and trade-offs are included, as well as testing. (LEW)

  17. On the classical vibrational coherence of carbonyl groups in the selectivity filter backbone of the KcsA ion channel.

    PubMed

    Salari, V; Sajadi, M; Bassereh, H; Rezania, V; Alaei, M; Tuszynski, J A

    2015-06-01

    It has been suggested that quantum coherence in the selectivity filter of ion channel may play a key role in fast conduction and selectivity of ions. However, it has not been clearly elucidated yet why classical coherence is not sufficient for this purpose. In this paper, we investigate the classical vibrational coherence between carbonyl groups oscillations in the selectivity filter of KcsA ion channels based on the data obtained from molecular dynamics simulations. Our results show that classical coherence plays no effective role in fast ionic conduction. PMID:25990939

  18. Tackling the combined effects of reverberation and masking noise using ideal channel selection

    PubMed Central

    Hazrati, Oldooz

    2012-01-01

    Purpose A new signal processing algorithm is proposed and evaluated in this study for the suppression of the combined effects of reverberation and noise. Method The proposed algorithm decomposes, on a short-term basis (every 20 ms), the reverberant stimuli into a number of channels and retains only a subset of the channels satisfying a signal-to-reverberant ratio (SRR) criterion. The construction of this criterion assumes access to a priori knowledge of the target (anechoic) signal and the aim of the present study is to assess the full potential of the proposed channel-selection algorithm assuming that this criterion can be estimated accurately. Listening tests were conducted with normal-hearing listeners to assess the performance of the proposed algorithm in highly reverberant conditions (T60 = 1.0 s) which included additive noise at 0 and 5 dB SNR. Results A substantial gain in intelligibility was obtained in both reverberant and combined reverberant and noise conditions. The mean intelligibility scores improved by 44 and 33 percentage points at 0 and 5 dB SNR reverberant+noise conditions. Feature analysis of the consonant confusion matrices revealed that the transmission of voicing information was most negatively affected, followed by manner and place of articulation. Conclusions The proposed algorithm was found to produce substantial gains in intelligibility, and this benefit was attributed to the ability of the proposed SRR criterion to accurately detect voiced/unvoiced boundaries. Detection of those boundaries is postulated to be critical for better perception of voicing information and manner of articulation. PMID:22232411

  19. Osteoinduction of porous Ti implants with a channel structure fabricated by selective laser melting.

    PubMed

    Fukuda, A; Takemoto, M; Saito, T; Fujibayashi, S; Neo, M; Pattanayak, Deepak K; Matsushita, T; Sasaki, K; Nishida, N; Kokubo, T; Nakamura, T

    2011-05-01

    Many studies have shown that certain biomaterials with specific porous structures can induce bone formation in non-osseous sites without the need for osteoinductive biomolecules, however, the mechanisms responsible for this phenomenon (intrinsic osteoinduction of biomaterials) remain unclear. In particular, to our knowledge the type of pore structure suitable for osteoinduction has not been reported in detail. In the present study we investigated the effects of interconnective pore size on osteoinductivity and the bone formation processes during osteoinduction. Selective laser melting was employed to fabricate porous Ti implants (diameter 3.3mm, length 15 mm) with a channel structure comprising four longitudinal square channels, representing pores, of different diagonal widths, 500, 600, 900, and 1200 μm (termed p500, p600, p900, and p1200, respectively). These were then subjected to chemical and heat treatments to induce bioactivity. Significant osteoinduction was observed in p500 and p600, with the highest observed osteoinduction occurring at 5mm from the end of the implants. A distance of 5mm probably provides a favorable balance between blood circulation and fluid movement. Thus, the simple architecture of the implants allowed effective investigation of the influence of the interconnective pore size on osteoinduction, as well as the relationship between bone quantity and its location for different pore sizes.

  20. Selective trapping and concentration of nanoparticles and viruses in dual-height nanofluidic channels.

    PubMed

    Hamblin, Mark N; Xuan, Jie; Maynes, Daniel; Tolley, H Dennis; Belnap, David M; Woolley, Adam T; Lee, Milton L; Hawkins, Aaron R

    2010-01-21

    Nanofluidic systems offer advantages for chemical analysis, including small sample volumes, size-selective particle trapping, sample concentration and the ability to separate and detect single molecules. Such systems can be fabricated using planar nanochannels, which rely on standard photolithographic techniques. Nanochannel fluid flow can be driven by capillary action, which benefits from simple injection and reasonably high flow rates. We demonstrate an analysis chip fabricated with planar nanochannels that consist of two adjoining segments of different heights. When nano-analytes elute through the channel, they become physically trapped when the channel dimensions shrink below the size of the particles. We demonstrate the capability of these devices to trap and concentrate by using the following: 120-nm polymer beads, 30-nm polymer beads, Herpes simplex virus 1 capsids, and hepatitis B virus capsids. Each species was fluorescently labeled and its resulting fluorescent signal was detected using a cooled CCD camera. We show how the signal-to-noise ratio of trapped analyte intensity varies linearly with analyte concentration. The goal of this work is to eventually perform size-based fractionation of a variety of nanoparticles, including biomolecules such as proteins.

  1. Cultured giant fiber lobe of squid expresses three distinct potassium channel activities in selective combinations.

    PubMed

    Griggs, W D; Hanyu, Y; Matsumoto, G

    1996-07-01

    Neurons from the giant fiber lobe (GFL) of squid Loligo bleekeri were dissociated and cultured. The ionic currents were recorded using whole-cell patch clamp methods. The sodium current and the noninactivating potassium current like those elicited by the giant axon were among the currents expressed in axonal bulbs and bulblike structures upon dissociation. Meanwhile axonless cell bodies did not elicit such currents. Axonless cell bodies and some bulblike structures elicited two kinds of inactivating potassium currents, the slow- and the fast-inactivating current, which differed in their inactivation kinetics and pharmacology. Within 24 hr of plating, the current composition remained the same. While the noninactivating current was not sensitive to 4-aminopyridine, the two inactivating currents were sensitive, the slow-inactivating current being more sensitive. Selective combinations of the sodium current and the three potassium currents expressed in different structures of the acutely dissociated GFL could have resulted from cellular control of synthesis and transportation of the channel proteins to the somatic and the axonal membrane. The sodium current and the noninactivating potassium current could be recorded from some axonless cell bodies maintained in culture for over three days, indicating that the separation of the giant axon from its somata could result in the transportation of the channels normally expressed on the giant axon membrane to the somatic membrane.

  2. Serum factor induces selective increase in Na-channel expression in cultured skeletal muscle

    SciTech Connect

    Brodie, C.; Sampson, S.R. )

    1991-07-01

    The authors have examined effects of horse serum (HS) and various fractions (1 million-1M, 300K, 100K, and 30K nominal molecular weight limit) obtained by ultrafiltration on expression of TTX-sensitive Na-channels and on activities of the Na-K pump and glucose transport systems in cultured myotubes obtained from 1-2-day-old neonatal rat pups. Five-day-old cells were transferred to serum-free medium with no hormone or growth factor supplements (DMEM) for 24 hr and then treated with the various serum fractions for 48 hr. Measurements were made of specific (3H)-saxitoxin (STX) binding, action potential properties, 86Rb-uptake and 2-deoxyglucose (2-DG) uptake. HS significantly increased all parameters compared to DMEM (increases in STX-binding, 69%; Rb-uptake, 65%; 2-DG uptake, 93%). Results of treatment with the separate fractions showed that the 300K fraction caused a significantly greater increase in STX-binding than either HS or the other fractions. In contrast, the increases in Rb and 2-DG uptakes induced by the different fractions were not different from that obtained with HS. They conclude that serum contains a factor that selectively increases expression of TTX-sensitive Na-channels in skeletal muscle.

  3. Osteoinduction of porous Ti implants with a channel structure fabricated by selective laser melting.

    PubMed

    Fukuda, A; Takemoto, M; Saito, T; Fujibayashi, S; Neo, M; Pattanayak, Deepak K; Matsushita, T; Sasaki, K; Nishida, N; Kokubo, T; Nakamura, T

    2011-05-01

    Many studies have shown that certain biomaterials with specific porous structures can induce bone formation in non-osseous sites without the need for osteoinductive biomolecules, however, the mechanisms responsible for this phenomenon (intrinsic osteoinduction of biomaterials) remain unclear. In particular, to our knowledge the type of pore structure suitable for osteoinduction has not been reported in detail. In the present study we investigated the effects of interconnective pore size on osteoinductivity and the bone formation processes during osteoinduction. Selective laser melting was employed to fabricate porous Ti implants (diameter 3.3mm, length 15 mm) with a channel structure comprising four longitudinal square channels, representing pores, of different diagonal widths, 500, 600, 900, and 1200 μm (termed p500, p600, p900, and p1200, respectively). These were then subjected to chemical and heat treatments to induce bioactivity. Significant osteoinduction was observed in p500 and p600, with the highest observed osteoinduction occurring at 5mm from the end of the implants. A distance of 5mm probably provides a favorable balance between blood circulation and fluid movement. Thus, the simple architecture of the implants allowed effective investigation of the influence of the interconnective pore size on osteoinduction, as well as the relationship between bone quantity and its location for different pore sizes. PMID:21295166

  4. X-ray structure of acid-sensing ion channel 1-snake toxin complex reveals open state of a Na(+)-selective channel.

    PubMed

    Baconguis, Isabelle; Bohlen, Christopher J; Goehring, April; Julius, David; Gouaux, Eric

    2014-02-13

    Acid-sensing ion channels (ASICs) detect extracellular protons produced during inflammation or ischemic injury and belong to the superfamily of degenerin/epithelial sodium channels. Here, we determine the cocrystal structure of chicken ASIC1a with MitTx, a pain-inducing toxin from the Texas coral snake, to define the structure of the open state of ASIC1a. In the MitTx-bound open state and in the previously determined low-pH desensitized state, TM2 is a discontinuous α helix in which the Gly-Ala-Ser selectivity filter adopts an extended, belt-like conformation, swapping the cytoplasmic one-third of TM2 with an adjacent subunit. Gly 443 residues of the selectivity filter provide a ring of three carbonyl oxygen atoms with a radius of ∼3.6 Å, presenting an energetic barrier for hydrated ions. The ASIC1a-MitTx complex illuminates the mechanism of MitTx action, defines the structure of the selectivity filter of voltage-independent, sodium-selective ion channels, and captures the open state of an ASIC.

  5. X-ray structure of acid-sensing ion channel 1–snake toxin complex reveals open state of a Na+-selective channel

    PubMed Central

    Baconguis, Isabelle; Bohlen, Christopher J.; Goehring, April; Julius, David; Gouaux, Eric

    2014-01-01

    Summary Acid sensing ion channels (ASICs) detect extracellular protons produced during inflammation or ischemic injury and belong to the super family of degenerin/epithelial sodium channels. Here, we determine the cocrystal structure of chicken ASIC1a with MitTx, a pain-inducing toxin from the Texas coral snake, to define the structure of the open state of ASIC1a. In the MitTx-bound open state and in the previously determined low pH desensitized state, TM2 is a discontinuous α-helix in which the Gly-Ala-Ser selectivity filter adopts an extended, belt-like conformation, swapping the cytoplasmic one-third of TM2 with an adjacent subunit. Gly 443 residues of the selectivity filter provide a ring of 3 carbonyl oxygen atoms with a radius of ~3.6 Å, presenting an energetic barrier for hydrated ions. The ASIC1a-MitTx complex illuminates the mechanism of MitTx action, defines the structure of the selectivity filter of voltage-independent, sodium-selective ion channels and captures the open state of an ASIC. PMID:24507937

  6. Multilevel Concatenated Block Modulation Codes for the Frequency Non-selective Rayleigh Fading Channel

    NASA Technical Reports Server (NTRS)

    Lin, Shu; Rhee, Dojun

    1996-01-01

    This paper is concerned with construction of multilevel concatenated block modulation codes using a multi-level concatenation scheme for the frequency non-selective Rayleigh fading channel. In the construction of multilevel concatenated modulation code, block modulation codes are used as the inner codes. Various types of codes (block or convolutional, binary or nonbinary) are being considered as the outer codes. In particular, we focus on the special case for which Reed-Solomon (RS) codes are used as the outer codes. For this special case, a systematic algebraic technique for constructing q-level concatenated block modulation codes is proposed. Codes have been constructed for certain specific values of q and compared with the single-level concatenated block modulation codes using the same inner codes. A multilevel closest coset decoding scheme for these codes is proposed.

  7. Channel Selection and Feature Projection for Cognitive Load Estimation Using Ambulatory EEG

    PubMed Central

    Lan, Tian; Erdogmus, Deniz; Adami, Andre; Mathan, Santosh; Pavel, Misha

    2007-01-01

    We present an ambulatory cognitive state classification system to assess the subject's mental load based on EEG measurements. The ambulatory cognitive state estimator is utilized in the context of a real-time augmented cognition (AugCog) system that aims to enhance the cognitive performance of a human user through computer-mediated assistance based on assessments of cognitive states using physiological signals including, but not limited to, EEG. This paper focuses particularly on the offline channel selection and feature projection phases of the design and aims to present mutual-information-based techniques that use a simple sample estimator for this quantity. Analyses conducted on data collected from 3 subjects performing 2 tasks (n-back/Larson) at 2 difficulty levels (low/high) demonstrate that the proposed mutual-information-based dimensionality reduction scheme can achieve up to 94% cognitive load estimation accuracy. PMID:18364990

  8. A novel selective and orally bioavailable Nav1.8 channel blocker, PF-01247324, attenuates nociception and sensory neuron excitability

    PubMed Central

    Payne, Claire Elizabeth; Brown, Adam R; Theile, Jonathon W; Loucif, Alexandre J C; Alexandrou, Aristos J; Fuller, Mathew D; Mahoney, John H; Antonio, Brett M; Gerlach, Aaron C; Printzenhoff, David M; Prime, Rebecca L; Stockbridge, Gillian; Kirkup, Anthony J; Bannon, Anthony W; England, Steve; Chapman, Mark L; Bagal, Sharan; Roeloffs, Rosemarie; Anand, Uma; Anand, Praveen; Bungay, Peter J; Kemp, Mark; Butt, Richard P; Stevens, Edward B

    2015-01-01

    Background and Purpose NaV1.8 ion channels have been highlighted as important molecular targets for the design of low MW blockers for the treatment of chronic pain. Here, we describe the effects of PF-01247324, a new generation, selective, orally bioavailable Nav1.8 channel blocker of novel chemotype. Experimental Approach The inhibition of Nav1.8 channels by PF-01247324 was studied using in vitro patch-clamp electrophysiology and the oral bioavailability and antinociceptive effects demonstrated using in vivo rodent models of inflammatory and neuropathic pain. Key Results PF-01247324 inhibited native tetrodotoxin-resistant (TTX-R) currents in human dorsal root ganglion (DRG) neurons (IC50: 331 nM) and in recombinantly expressed h Nav1.8 channels (IC50: 196 nM), with 50-fold selectivity over recombinantly expressed TTX-R hNav1.5 channels (IC50: ∼10 μM) and 65–100-fold selectivity over TTX-sensitive (TTX-S) channels (IC50: ∼10–18 μM). Native TTX-R currents in small-diameter rodent DRG neurons were inhibited with an IC50 448 nM, and the block of both human recombinant Nav1.8 channels and TTX-R from rat DRG neurons was both frequency and state dependent. In vitro current clamp showed that PF-01247324 reduced excitability in both rat and human DRG neurons and also altered the waveform of the action potential. In vivo experiments n rodents demonstrated efficacy in both inflammatory and neuropathic pain models. Conclusions and Implications Using PF-01247324, we have confirmed a role for Nav1.8 channels in both inflammatory and neuropathic pain. We have also demonstrated a key role for Nav1.8 channels in action potential upstroke and repetitive firing of rat and human DRG neurons. PMID:25625641

  9. Gating-pore currents demonstrate selective and specific modulation of individual sodium channel voltage-sensors by biological toxins.

    PubMed

    Xiao, Yucheng; Blumenthal, Kenneth; Cummins, Theodore R

    2014-08-01

    Voltage-gated sodium channels are critical determinants of nerve and muscle excitability. Although numerous toxins and small molecules target sodium channels, identifying the mechanisms of action is challenging. Here we used gating-pore currents selectively generated in each of the voltage-sensors from the four α-subunit domains (DI-DIV) to monitor the activity of individual voltage-sensors and to investigate the molecular determinants of sodium channel pharmacology. The tarantula toxin huwentoxin-IV (HWTX-IV), which inhibits sodium channel current, exclusively enhanced inward gating-pore currents through the DII voltage-sensor. By contrast, the tarantula toxin ProTx-II, which also inhibits sodium channel currents, altered the gating-pore currents in multiple voltage-sensors in a complex manner. Thus, whereas HWTX-IV inhibits central-pore currents by selectively trapping the DII voltage-sensor in the resting configuration, ProTx-II seems to inhibit central-pore currents by differentially altering the configuration of multiple voltage-sensors. The sea anemone toxin anthopleurin B, which impairs open-channel inactivation, exclusively enhanced inward gating-pore currents through the DIV voltage-sensor. This indicates that trapping the DIV voltage-sensor in the resting configuration selectively impairs open-channel inactivation. Furthermore, these data indicate that although activation of all four voltage-sensors is not required for central-pore current generation, activation of the DII voltage-sensor is crucial. Overall, our data demonstrate that gating-pore currents can determine the mechanism of action for sodium channel gating modifiers with high precision. We propose this approach could be adapted to identify the molecular mechanisms of action for gating modifiers of various voltage-gated ion channels.

  10. Gating-Pore Currents Demonstrate Selective and Specific Modulation of Individual Sodium Channel Voltage-Sensors by Biological Toxins

    PubMed Central

    Xiao, Yucheng; Blumenthal, Kenneth

    2014-01-01

    Voltage-gated sodium channels are critical determinants of nerve and muscle excitability. Although numerous toxins and small molecules target sodium channels, identifying the mechanisms of action is challenging. Here we used gating-pore currents selectively generated in each of the voltage-sensors from the four α-subunit domains (DI–DIV) to monitor the activity of individual voltage-sensors and to investigate the molecular determinants of sodium channel pharmacology. The tarantula toxin huwentoxin-IV (HWTX-IV), which inhibits sodium channel current, exclusively enhanced inward gating-pore currents through the DII voltage-sensor. By contrast, the tarantula toxin ProTx-II, which also inhibits sodium channel currents, altered the gating-pore currents in multiple voltage-sensors in a complex manner. Thus, whereas HWTX-IV inhibits central-pore currents by selectively trapping the DII voltage-sensor in the resting configuration, ProTx-II seems to inhibit central-pore currents by differentially altering the configuration of multiple voltage-sensors. The sea anemone toxin anthopleurin B, which impairs open-channel inactivation, exclusively enhanced inward gating-pore currents through the DIV voltage-sensor. This indicates that trapping the DIV voltage-sensor in the resting configuration selectively impairs open-channel inactivation. Furthermore, these data indicate that although activation of all four voltage-sensors is not required for central-pore current generation, activation of the DII voltage-sensor is crucial. Overall, our data demonstrate that gating-pore currents can determine the mechanism of action for sodium channel gating modifiers with high precision. We propose this approach could be adapted to identify the molecular mechanisms of action for gating modifiers of various voltage-gated ion channels. PMID:24898004

  11. Gating-pore currents demonstrate selective and specific modulation of individual sodium channel voltage-sensors by biological toxins.

    PubMed

    Xiao, Yucheng; Blumenthal, Kenneth; Cummins, Theodore R

    2014-08-01

    Voltage-gated sodium channels are critical determinants of nerve and muscle excitability. Although numerous toxins and small molecules target sodium channels, identifying the mechanisms of action is challenging. Here we used gating-pore currents selectively generated in each of the voltage-sensors from the four α-subunit domains (DI-DIV) to monitor the activity of individual voltage-sensors and to investigate the molecular determinants of sodium channel pharmacology. The tarantula toxin huwentoxin-IV (HWTX-IV), which inhibits sodium channel current, exclusively enhanced inward gating-pore currents through the DII voltage-sensor. By contrast, the tarantula toxin ProTx-II, which also inhibits sodium channel currents, altered the gating-pore currents in multiple voltage-sensors in a complex manner. Thus, whereas HWTX-IV inhibits central-pore currents by selectively trapping the DII voltage-sensor in the resting configuration, ProTx-II seems to inhibit central-pore currents by differentially altering the configuration of multiple voltage-sensors. The sea anemone toxin anthopleurin B, which impairs open-channel inactivation, exclusively enhanced inward gating-pore currents through the DIV voltage-sensor. This indicates that trapping the DIV voltage-sensor in the resting configuration selectively impairs open-channel inactivation. Furthermore, these data indicate that although activation of all four voltage-sensors is not required for central-pore current generation, activation of the DII voltage-sensor is crucial. Overall, our data demonstrate that gating-pore currents can determine the mechanism of action for sodium channel gating modifiers with high precision. We propose this approach could be adapted to identify the molecular mechanisms of action for gating modifiers of various voltage-gated ion channels. PMID:24898004

  12. Observation of the doubly strange b baryon Omegab-.

    PubMed

    Abazov, V M; Abbott, B; Abolins, M; Acharya, B S; Adams, M; Adams, T; Aguilo, E; Ahsan, M; Alexeev, G D; Alkhazov, G; Alton, A; Alverson, G; Alves, G A; Anastasoaie, M; Ancu, L S; Andeen, T; Andrieu, B; Anzelc, M S; Aoki, M; Arnoud, Y; Arov, M; Arthaud, M; Askew, A; Asman, B; Assis Jesus, A C S; Atramentov, O; Avila, C; Badaud, F; Bagby, L; Baldin, B; Bandurin, D V; Banerjee, P; Banerjee, S; Barberis, E; Barfuss, A-F; Bargassa, P; Baringer, P; Barreto, J; Bartlett, J F; Bassler, U; Bauer, D; Beale, S; Bean, A; Begalli, M; Begel, M; Belanger-Champagne, C; Bellantoni, L; Bellavance, A; Benitez, J A; Beri, S B; Bernardi, G; Bernhard, R; Bertram, I; Besançon, M; Beuselinck, R; Bezzubov, V A; Bhat, P C; Bhatnagar, V; Biscarat, C; Blazey, G; Blekman, F; Blessing, S; Bloom, K; Boehnlein, A; Boline, D; Bolton, T A; Boos, E E; Borissov, G; Bose, T; Brandt, A; Brock, R; Brooijmans, G; Bross, A; Brown, D; Bu, X B; Buchanan, N J; Buchholz, D; Buehler, M; Buescher, V; Bunichev, V; Burdin, S; Burnett, T H; Buszello, C P; Butler, J M; Calfayan, P; Calvet, S; Cammin, J; Carrera, E; Carvalho, W; Casey, B C K; Castilla-Valdez, H; Chakrabarti, S; Chakraborty, D; Chan, K M; Chandra, A; Cheu, E; Chevallier, F; Cho, D K; Choi, S; Choudhary, B; Christofek, L; Christoudias, T; Cihangir, S; Claes, D; Clutter, J; Cooke, M; Cooper, W E; Corcoran, M; Couderc, F; Cousinou, M-C; Crépé-Renaudin, S; Cuplov, V; Cutts, D; Cwiok, M; da Motta, H; Das, A; Davies, G; De, K; de Jong, S J; De La Cruz-Burelo, E; De Oliveira Martins, C; DeVaughan, K; Degenhardt, J D; Déliot, F; Demarteau, M; Demina, R; Denisov, D; Denisov, S P; Desai, S; Diehl, H T; Diesburg, M; Dominguez, A; Dong, H; Dorland, T; Dubey, A; Dudko, L V; Duflot, L; Dugad, S R; Duggan, D; Duperrin, A; Dyer, J; Dyshkant, A; Eads, M; Edmunds, D; Ellison, J; Elvira, V D; Enari, Y; Eno, S; Ermolov, P; Evans, H; Evdokimov, A; Evdokimov, V N; Ferapontov, A V; Ferbel, T; Fiedler, F; Filthaut, F; Fisher, W; Fisk, H E; Fortner, M; Fox, H; Fu, S; Fuess, S; Gadfort, T; Galea, C F; Garcia, C; Garcia-Bellido, A; Gavrilov, V; Gay, P; Geist, W; Geng, W; Gerber, C E; Gershtein, Y; Gillberg, D; Ginther, G; Gollub, N; Gómez, B; Goussiou, A; Grannis, P D; Greenlee, H; Greenwood, Z D; Gregores, E M; Grenier, G; Gris, Ph; Grivaz, J-F; Grohsjean, A; Grünendahl, S; Grünewald, M W; Guo, F; Guo, J; Gutierrez, G; Gutierrez, P; Haas, A; Hadley, N J; Haefner, P; Hagopian, S; Haley, J; Hall, I; Hall, R E; Han, L; Harder, K; Harel, A; Hauptman, J M; Hays, J; Hebbeker, T; Hedin, D; Hegeman, J G; Heinson, A P; Heintz, U; Hensel, C; Herner, K; Hesketh, G; Hildreth, M D; Hirosky, R; Hobbs, J D; Hoeneisen, B; Hoeth, H; Hohlfeld, M; Hossain, S; Houben, P; Hu, Y; Hubacek, Z; Hynek, V; Iashvili, I; Illingworth, R; Ito, A S; Jabeen, S; Jaffré, M; Jain, S; Jakobs, K; Jarvis, C; Jesik, R; Johns, K; Johnson, C; Johnson, M; Johnston, D; Jonckheere, A; Jonsson, P; Juste, A; Kajfasz, E; Kalk, J M; Karmanov, D; Kasper, P A; Katsanos, I; Kau, D; Kaushik, V; Kehoe, R; Kermiche, S; Khalatyan, N; Khanov, A; Kharchilava, A; Kharzheev, Y M; Khatidze, D; Kim, T J; Kirby, M H; Kirsch, M; Klima, B; Kohli, J M; Komissarov, E V; Konrath, J-P; Kozelov, A V; Kraus, J; Kuhl, T; Kumar, A; Kupco, A; Kurca, T; Kuzmin, V A; Kvita, J; Lacroix, F; Lam, D; Lammers, S; Landsberg, G; Lebrun, P; Lee, W M; Leflat, A; Lellouch, J; Li, J; Li, L; Li, Q Z; Lietti, S M; Lim, J K; Lima, J G R; Lincoln, D; Linnemann, J; Lipaev, V V; Lipton, R; Liu, Y; Liu, Z; Lobodenko, A; Lokajicek, M; Love, P; Lubatti, H J; Luna, R; Lyon, A L; Maciel, A K A; Mackin, D; Madaras, R J; Mättig, P; Magass, C; Magerkurth, A; Mal, P K; Malbouisson, H B; Malik, S; Malyshev, V L; Maravin, Y; Martin, B; McCarthy, R; Melnitchouk, A; Mendoza, L; Mercadante, P G; Merekov, Y P; Merkin, M; Merritt, K W; Meyer, A; Meyer, J; Mitrevski, J; Mommsen, R K; Mondal, N K; Moore, R W; Moulik, T; Muanza, G S; Mulhearn, M; Mundal, O; Mundim, L; Nagy, E; Naimuddin, M; Narain, M; Naumann, N A; Neal, H A; Negret, J P; Neustroev, P; Nilsen, H; Nogima, H; Novaes, S F; Nunnemann, T; O'Dell, V; O'Neil, D C; Obrant, G; Ochando, C; Onoprienko, D; Orduna, J; Oshima, N; Osman, N; Osta, J; Otec, R; Otero y Garzón, G J; Owen, M; Padley, P; Pangilinan, M; Parashar, N; Park, S-J; Park, S K; Parsons, J; Partridge, R; Parua, N; Patwa, A; Pawloski, G; Penning, B; Perfilov, M; Peters, K; Peters, Y; Pétroff, P; Petteni, M; Piegaia, R; Piper, J; Pleier, M-A; Podesta-Lerma, P L M; Podstavkov, V M; Pogorelov, Y; Pol, M-E; Polozov, P; Pope, B G; Popov, A V; Potter, C; Prado da Silva, W L; Prosper, H B; Protopopescu, S; Qian, J; Quadt, A; Quinn, B; Rakitine, A; Rangel, M S; Ranjan, K; Ratoff, P N; Renkel, P; Rich, P; Rieger, J; Rijssenbeek, M; Ripp-Baudot, I; Rizatdinova, F; Robinson, S; Rodrigues, R F; Rominsky, M; Royon, C; Rozhdestvenski, A; Rubinov, P; Ruchti, R; Safronov, G; Sajot, G; Sánchez-Hernández, A; Sanders, M P; Sanghi, B; Savage, G; Sawyer, L; Scanlon, T; Schaile, D; Schamberger, R D; Scheglov, Y; Schellman, H; Schliephake, T; Schlobohm, S; Schwanenberger, C; Schwartzman, A; Schwienhorst, R; Sekaric, J; Severini, H; Shabalina, E; Shamim, M; Shary, V; Shchukin, A A; Shivpuri, R K; Siccardi, V; Simak, V; Sirotenko, V; Skubic, P; Slattery, P; Smirnov, D; Snow, G R; Snow, J; Snyder, S; Söldner-Rembold, S; Sonnenschein, L; Sopczak, A; Sosebee, M; Soustruznik, K; Spurlock, B; Stark, J; Steele, J; Stolin, V; Stoyanova, D A; Strandberg, J; Strandberg, S; Strang, M A; Strauss, E; Strauss, M; Ströhmer, R; Strom, D; Stutte, L; Sumowidagdo, S; Svoisky, P; Sznajder, A; Tamburello, P; Tanasijczuk, A; Taylor, W; Tiller, B; Tissandier, F; Titov, M; Tokmenin, V V; Torchiani, I; Tsybychev, D; Tuchming, B; Tully, C; Tuts, P M; Unalan, R; Uvarov, L; Uvarov, S; Uzunyan, S; Vachon, B; van den Berg, P J; Van Kooten, R; van Leeuwen, W M; Varelas, N; Varnes, E W; Vasilyev, I A; Verdier, P; Vertogradov, L S; Vertogradova, Y; Verzocchi, M; Vilanova, D; Villeneuve-Seguier, F; Vint, P; Vokac, P; Voutilainen, M; Wagner, R; Wahl, H D; Wang, M H L S; Warchol, J; Watts, G; Wayne, M; Weber, G; Weber, M; Welty-Rieger, L; Wenger, A; Wermes, N; Wetstein, M; White, A; Wicke, D; Williams, M; Wilson, G W; Wimpenny, S J; Wobisch, M; Wood, D R; Wyatt, T R; Xie, Y; Yacoob, S; Yamada, R; Yang, W-C; Yasuda, T; Yatsunenko, Y A; Yin, H; Yip, K; Yoo, H D; Youn, S W; Yu, J; Zeitnitz, C; Zelitch, S; Zhao, T; Zhou, B; Zhu, J; Zielinski, M; Zieminska, D; Zieminski, A; Zivkovic, L; Zutshi, V; Zverev, E G

    2008-12-01

    We report the observation of the doubly strange b baryon Omegab- in the decay channel Omegab(-)-->J/psiOmega-, with J/psi-->mu+mu(-) and Omega(-)-->LambdaK(-)-->(ppi-)K-, in pp collisions at sqrt[s]=1.96 TeV. Using approximately 1.3 fb(-1) of data collected with the D0 detector at the Fermilab Tevatron Collider, we observe 17.8+/-4.9(stat)+/-0.8(syst) Omegab- signal events at a mass of 6.165+/-0.010(stat)+/-0.013(syst) GeV. The significance of the observed signal is 5.4sigma, corresponding to a probability of 6.7 x 10(-8) of it arising from a background fluctuation. PMID:19113541

  13. Charged residues distribution modulates selectivity of the open state of human isoforms of the voltage dependent anion-selective channel.

    PubMed

    Amodeo, Giuseppe Federico; Scorciapino, Mariano Andrea; Messina, Angela; De Pinto, Vito; Ceccarelli, Matteo

    2014-01-01

    Voltage Dependent Anion-selective Channels (VDACs) are pore-forming proteins located in the outer mitochondrial membrane. They are responsible for the access of ions and energetic metabolites into the inner membrane transport systems. Three VDAC isoforms exist in mammalian, but their specific role is unknown. In this work we have performed extensive (overall ∼5 µs) Molecular Dynamics (MD) simulations of the human VDAC isoforms to detect structural and conformational variations among them, possibly related to specific functional roles of these proteins. Secondary structure analysis of the N-terminal domain shows a high similarity among the three human isoforms of VDAC but with a different plasticity. In particular, the N-terminal domain of the hVDAC1 is characterized by a higher plasticity, with a ∼20% occurrence for the 'unstructured' conformation throughout the folded segment, while hVDAC2, containing a peculiar extension of 11 amino acids at the N-terminal end, presents an additional 310-helical folded portion comprising residues 10' to 3, adhering to the barrel wall. The N-terminal sequences of hVDAC isoforms are predicted to have a low flexibility, with possible consequences in the dynamics of the human VDACs. Clear differences were found between hVDAC1 and hVDAC3 against hVDAC2: a significantly modified dynamics with possible important consequence on the voltage-gating mechanism. Charge distribution inside and at the mouth of the pore is responsible for a different preferential localization of ions with opposite charge and provide a valuable rationale for hVDAC1 and hVDAC3 having a Cl-/K+ selectivity ratio of 1.8, whereas hVDAC2 of 1.4. Our conclusion is that hVDAC isoforms, despite sharing a similar scaffold, have modified working features and a biological work is now requested to give evidence to the described dissimilarities. PMID:25084457

  14. The food dye FD&C Blue No. 1 is a selective inhibitor of the ATP release channel Panx1.

    PubMed

    Wang, Junjie; Jackson, David George; Dahl, Gerhard

    2013-05-01

    The food dye FD&C Blue No. 1 (Brilliant Blue FCF [BB FCF]) is structurally similar to the purinergic receptor antagonist Brilliant Blue G (BBG), which is a well-known inhibitor of the ionotropic P2X7 receptor (P2X7R). The P2X7R functionally interacts with the membrane channel protein pannexin 1 (Panx1) in inflammasome signaling. Intriguingly, ligands to the P2X7R, regardless of whether they are acting as agonists or antagonists at the receptor, inhibit Panx1 channels. Thus, because both P2X7R and Panx1 are inhibited by BBG, the diagnostic value of the drug is limited. Here, we show that the food dye BB FCF is a selective inhibitor of Panx1 channels, with an IC50 of 0.27 µM. No significant effect was observed with concentrations as high as 100 µM of BB FCF on P2X7R. Differing by just one hydroxyl group from BB FCF, the food dye FD&C Green No. 3 exhibited similar selective inhibition of Panx1 channels. A reverse selectivity was observed for the P2X7R antagonist, oxidized ATP, which in contrast to other P2X7R antagonists had no significant inhibitory effect on Panx1 channels. Based on its selective action, BB FCF can be added to the repertoire of drugs to study the physiology of Panx1 channels. Furthermore, because Panx1 channels appear to be involved directly or indirectly through P2X7Rs in several disorders, BB FCF and derivatives of this "safe" food dye should be given serious consideration for pharmacological intervention of conditions such as acute Crohn's disease, stroke, and injuries to the central nervous system.

  15. Meroterpenoid Chrodrimanins Are Selective and Potent Blockers of Insect GABA-Gated Chloride Channels.

    PubMed

    Xu, Yan; Furutani, Shogo; Ihara, Makoto; Ling, Yun; Yang, Xinling; Kai, Kenji; Hayashi, Hideo; Matsuda, Kazuhiko

    2015-01-01

    Meroterpenoid chrodrimanins, produced from Talaromyces sp. YO-2, are known to paralyze silkworm (Bombyx mori) larvae, but their target is unknown. We have investigated the actions of chrodrimanin B on ligand-gated ion channels of silkworm larval neurons using patch-clamp electrophysiology. Chrodrimanin B had no effect on membrane currents when tested alone at 1 μM. However, it completely blocked the γ-aminobutyric acid (GABA)-induced current and showed less pronounced actions on acetylcholine- and L-glutamate-induced currents, when delivered at 1 μM for 1 min prior to co-application with transmitter GABA. Thus, chrodrimanins were also tested on a wild-type isoform of the B. mori GABA receptor (GABAR) RDL using two-electrode voltage-clamp electrophysiology. Chrodrimanin B attenuated the peak current amplitude of the GABA response of RDL with an IC50 of 1.66 nM. The order of the GABAR-blocking potency of chrodrimanins B > D > A was in accordance with their reported insecticidal potency. Chrodrimanin B had no open channel blocking action when tested at 3 nM on the GABA response of RDL. Co-application with 3 nM chrodrimanin B shifted the GABA concentration response curve to a higher concentration and further increase of chrodrimanin B concentration to 10 nM; it reduced maximum current amplitude of the GABA response, pointing to a high-affinity competitive action and a lower affinity non-competitive action. The A282S;T286V double mutation of RDL, which impairs the actions of fipronil, hardly affected the blocking action of chrodrimanin B, indicating a binding site of chrodrimanin B distinct from that of fipronil. Chrodrimanin B showed approximately 1,000-fold lower blocking action on human α1β2γ2 GABAR compared to RDL and thus is a selective blocker of insect GABARs.

  16. Evaluation of agonist selectivity for the NMDA receptor ion channel in bilayer lipid membranes based on integrated single-channel currents.

    PubMed

    Hirano, A; Sugawara, M; Umezawa, Y; Uchino, S; Nakajima-Iijima, S

    2000-06-01

    A new method for evaluating chemical selectivity of agonists to activate the N-methyl-D-aspartate (NMDA) receptor was presented by using typical agonists NMDA, L-glutamate and (2S, 3R, 4S)-2-(carboxycyclopropyl)glycine (L-CCG-IV) and the mouse epsilon1/zeta1 NMDA receptor incorporated in bilayer lipid membranes (BLMs) as an illustrative example. The method was based on the magnitude of an agonist-induced integrated single-channel current corresponding to the number of total ions passed through the open channel. The very magnitudes of the integrated single-channel currents were compared with the different BLMs as a new measure of agonist selectivity. The epsilon1/zeta1 NMDA receptor was partially purified from Chinese hamster ovary (CHO) cells expressing the epsilon1/zeta1 NMDA receptor and incorporated in BLMs formed by the tip-dip method. The agonist-induced integrated single-channel currents were obtained at 50 microM agonist concentration, where the integrated current for NMDA was shown to reach its saturated value. The obtained integrated currents were found to be (4.5 +/- 0.55) x 10(-13) C/s for NMDA, (5.8 +/- 0.72) x 10(-13) C/s for L-glutamate and (6.6 +/- 0.61) x 10(-13) C/s for L-CCG-IV, respectively. These results suggest that the agonist selectivity in terms of the total ion flux through the single epsilon1/zeta1 NMDA receptor is in the order of L-CCG-IV approximately = L-glutamate > NMDA.

  17. Pre-synaptic BK channels selectively control glutamate versus GABA release from cortical and hippocampal nerve terminals.

    PubMed

    Martire, Maria; Barrese, Vincenzo; D'Amico, Monia; Iannotti, Fabio Arturo; Pizzarelli, Rocco; Samengo, Irene; Viggiano, Davide; Ruth, Peter; Cherubini, Enrico; Taglialatela, Maurizio

    2010-10-01

    In the present study, by means of genetic, biochemical, morphological, and electrophysiological approaches, the role of large-conductance voltage- and Ca(2+)-dependent K(+) channels (BK channels) in the release of excitatory and non-excitatory neurotransmitters at hippocampal and non-hippocampal sites has been investigated. The results obtained show that the pharmacological modulation of pre-synaptic BK channels selectively regulates [(3)H]D-aspartate release from cortical and hippocampal rat synaptosomes, but it fails to influence the release of excitatory neurotransmitters from cerebellar nerve endings or that of [(3)H]GABA, [(3)H]Noradrenaline, or [(3)H]Dopamine from any of the brain regions investigated. Confocal immunofluorescence experiments in hippocampal or cerebrocortical nerve terminals revealed that the main pore-forming BK α subunit was more abundantly expressed in glutamatergic (vGLUT1(+)) versus GABAergic (GAD(65-67)(+)) nerve terminals. Double patch recordings in monosynaptically connected hippocampal neurons in culture confirmed a preferential control exerted by BK channels on glutamate over GABA release. Altogether, the present results highlight a high degree of specificity in the regulation of the release of various neurotransmitters from distinct brain regions by BK channels, supporting the concept that BK channel modulators can be used to selectively limit excessive excitatory amino acid release, a major pathogenetic mechanism in several neuropsychiatric disorders.

  18. Main-channel slopes of selected streams in Iowa for estimation of flood-frequency discharges

    USGS Publications Warehouse

    Eash, David A.

    2003-01-01

    This report describes a statewide study conducted to develop main-channel slope (MCS) curves for 138 selected streams in Iowa with drainage areas greater than 100 square miles. MCS values determined from the curves can be used in regression equations for estimating floodfrequency discharges. Multivariable regression equations previously developed for two of the three hydrologic regions defined for Iowa require the measurement of MCS. Main-channel slope is a difficult measurement to obtain for large streams using 1:24,000-scale topographic maps. The curves developed in this report provide a simplified method for determining MCS values for sites located along large streams in Iowa within hydrologic Regions 2 and 3. The curves were developed using MCS values quantified for 2,058 selected sites along 138 selected streams in Iowa. A geographic information system (GIS) technique and 1:24,000-scale topographic data were used to quantify MCS values for the stream sites. The sites were selected at about 5-mile intervals along the streams. River miles were quantified for each stream site using a GIS program. Data points for river-mile and MCS values were plotted and a best-fit curve was developed for each stream. An adjustment was applied to all 138 curves to compensate for differences in MCS values between manual measurements and GIS quantifications. The multivariable equations for Regions 2 and 3 were developed using manual measurements of MCS. A comparison of manual measurements and GIS quantifications of MCS indicates that manual measurements typically produce greater values of MCS compared to GIS quantifications. Median differences between manual measurements and GIS quantifications of MCS are 14.8 and 17.7 percent for Regions 2 and 3, respectively. Comparisons of percentage differences between flood-frequency discharges calculated using MCS values of manual measurements and GIS quantifications indicate that use of GIS values of MCS for Region 3 substantially

  19. Keeping active channels in their place: membrane phosphoinositides regulate TRPM channel activity in a compartment-selective manner.

    PubMed

    Braun, Andrew P

    2012-01-01

    We have long appreciated that the controlled movement of ions and solutes across the cell surface or plasma membrane affects every aspect of cell function, ranging from membrane excitability to metabolism to secretion, and is also critical for the long-term maintenance of cell viability. Studies examining these physiological transport processes have revealed a vast array of ion channels, transporters and ATPase-driven pumps that underlie these transmembrane ionic movements and how acquired or genetic disruption of these processes are linked to disease. More recently, it has become evident that the ongoing function of intracellular organelles and subcellular compartments also depends heavily on the controlled movement of ions to establish distinct pH or ionic environments. However, limited experimental access to these subcellular domains/structures has hampered scientific progress in this area, due in large part to the difficulty of applying proven functional assays, such as patch clamp and radiotracer methodologies, to these specialized membrane locations. Using both functional and immune-labeling assays, we now know that the types and complement of channels, transporters and pumps located within intracellular membranes and organelles often differ from those present on the plasma membrane. Moreover, it appears that this differential distribution is due to the presence of discrete tags/signals present within these transport proteins that dictate their sorting/trafficking to spatially discrete membrane compartments, where they may also interact with scaffolding proteins that help maintain their localization. Such targeting signals may thus operate in a manner analogous to the way a postal code is used to direct the delivery of a letter. PMID:23151432

  20. Urinary bladder instability induced by selective suppression of the murine small conductance calcium-activated potassium (SK3) channel

    PubMed Central

    Herrera, Gerald M; Pozo, Maria J; Zvara, Peter; Petkov, Georgi V; Bond, Chris T; Adelman, John P; Nelson, Mark T

    2003-01-01

    Small conductance, calcium-activated potassium (SK) channels have an important role in determining the excitability and contractility of urinary bladder smooth muscle. Here, the role of the SK isoform SK3 was examined by altering expression levels of the SK3 gene using a mouse model that conditionally overexpresses SK3 channels (SK3T/T). Prominent SK3 immunostaining was found in both the smooth muscle (detrusor) and urothelium layers of the urinary bladder. SK currents were elevated 2.4-fold in isolated myocytes from SK3T/T mice. Selective suppression of SK3 expression by dietary doxycycline (DOX) decreased SK current density in isolated myocytes, increased phasic contractions of isolated urinary bladder smooth muscle strips and exposed high affinity effects of the blocker apamin of the SK isoforms (SK1–3), suggesting an additional participation from SK2 channels. The role of SK3 channels in urinary bladder function was assessed using cystometry in conscious, freely moving mice. The urinary bladders of SK3T/T had significantly greater bladder capacity, and urine output exceeded the infused saline volume. Suppression of SK3 channel expression did not alter filling pressure, threshold pressure or bladder capacity, but micturition pressure was elevated compared to control mice. However, SK3 suppression did eliminate excess urine production and caused a marked increase in non-voiding contractions. The ability to examine bladder function in mice in which SK3 channel expression is selectively altered reveals that these channels have a significant role in the control of non-voiding contractions in vivo. Activation of these channels may be a therapeutic approach for management of non-voiding contractions, a condition which characterizes many types of urinary bladder dysfunctions including urinary incontinence. PMID:12813145

  1. Isolation and characterization of an amino acid-selective channel protein present in the chloroplastic outer envelope membrane

    PubMed Central

    Pohlmeyer, Kai; Soll, Jürgen; Steinkamp, Thomas; Hinnah, Silke; Wagner, Richard

    1997-01-01

    The reconstituted pea chloroplastic outer envelope protein of 16 kDa (OEP16) forms a slightly cation-selective, high-conductance channel with a conductance of Λ = 1,2 nS (in 1 M KCl). The open probability of OEP16 channel is highest at 0 mV (Popen = 0.8), decreasing exponentially with higher potentials. Transport studies using reconstituted recombinant OEP16 protein show that the OEP16 channel is selective for amino acids but excludes triosephosphates or uncharged sugars. Crosslinking indicates that OEP16 forms a homodimer in the membrane. According to its primary sequence and predicted secondary structure, OEP16 shows neither sequence nor structural homologies to classical porins. The results indicate that the intermembrane space between the two envelope membranes might not be as freely accessible as previously thought. PMID:9256512

  2. Human HDAC isoform selectivity achieved via exploitation of the acetate release channel with structurally unique small molecule inhibitors

    SciTech Connect

    Whitehead, Lewis; Dobler, Markus R.; Radetich, Branko; Zhu, Yanyi; Atadja, Peter W.; Claiborne, Tavina; Grob, Jonathan E.; McRiner, Andrew; Pancost, Margaret R.; Patnaik, Anup; Shao, Wenlin; Shultz, Michael; Tichkule, Ritesh; Tommasi, Ruben A.; Vash, Brian; Wang, Ping; Stams, Travis

    2013-11-20

    Herein we report the discovery of a family of novel yet simple, amino-acid derived class I HDAC inhibitors that demonstrate isoform selectivity via access to the internal acetate release channel. Isoform selectivity criteria is discussed on the basis of X-ray crystallography and molecular modeling of these novel inhibitors bound to HDAC8, potentially revealing insights into the mechanism of enzymatic function through novel structural features revealed at the atomic level.

  3. Targeting the ion channel Kv1.3 with scorpion venom peptides engineered for potency, selectivity, and half-life.

    PubMed

    Edwards, Wilson; Fung-Leung, Wai-Ping; Huang, Chichi; Chi, Ellen; Wu, Nancy; Liu, Yi; Maher, Michael P; Bonesteel, Rachelle; Connor, Judith; Fellows, Ross; Garcia, Elena; Lee, Jerry; Lu, Lu; Ngo, Karen; Scott, Brian; Zhou, Hong; Swanson, Ronald V; Wickenden, Alan D

    2014-08-15

    Ion channels are an attractive class of drug targets, but progress in developing inhibitors for therapeutic use has been limited largely due to challenges in identifying subtype selective small molecules. Animal venoms provide an alternative source of ion channel modulators, and the venoms of several species, such as scorpions, spiders and snails, are known to be rich sources of ion channel modulating peptides. Importantly, these peptides often bind to hyper-variable extracellular loops, creating the potential for subtype selectivity rarely achieved with small molecules. We have engineered scorpion venom peptides and incorporated them in fusion proteins to generate highly potent and selective Kv1.3 inhibitors with long in vivo half-lives. Kv1.3 has been reported to play a role in human T cell activation, and therefore, these Kv1.3 inhibitor fusion proteins may have potential for the treatment of autoimmune diseases. Our results support an emerging approach to generating subtype selective therapeutic ion channel inhibitors.

  4. Selective blockade of TRPA1 channel attenuates pathological pain without altering noxious cold sensation or body temperature regulation.

    PubMed

    Chen, Jun; Joshi, Shailen K; DiDomenico, Stanley; Perner, Richard J; Mikusa, Joe P; Gauvin, Donna M; Segreti, Jason A; Han, Ping; Zhang, Xu-Feng; Niforatos, Wende; Bianchi, Bruce R; Baker, Scott J; Zhong, Chengmin; Simler, Gricelda H; McDonald, Heath A; Schmidt, Robert G; McGaraughty, Steve P; Chu, Katharine L; Faltynek, Connie R; Kort, Michael E; Reilly, Regina M; Kym, Philip R

    2011-05-01

    Despite the increasing interest in TRPA1 channel as a pain target, its role in cold sensation and body temperature regulation is not clear; the efficacy and particularly side effects resulting from channel blockade remain poorly understood. Here we use a potent, selective, and bioavailable antagonist to address these issues. A-967079 potently blocks human (IC(50): 51 nmol/L, electrophysiology, 67 nmol/L, Ca(2+) assay) and rat TRPA1 (IC(50): 101 nmol/L, electrophysiology, 289 nmol/L, Ca(2+) assay). It is >1000-fold selective over other TRP channels, and is >150-fold selective over 75 other ion channels, enzymes, and G-protein-coupled receptors. Oral dosing of A-967079 produces robust drug exposure in rodents, and exhibits analgesic efficacy in allyl isothiocyanate-induced nocifensive response and osteoarthritic pain in rats (ED(50): 23.2 mg/kg, p.o.). A-967079 attenuates cold allodynia produced by nerve injury but does not alter noxious cold sensation in naive animals, suggesting distinct roles of TRPA1 in physiological and pathological states. Unlike TRPV1 antagonists, A-967079 does not alter body temperature. It also does not produce locomotor or cardiovascular side effects. Collectively, these data provide novel insights into TRPA1 function and suggest that the selective TRPA1 blockade may present a viable strategy for alleviating pain without untoward side effects.

  5. Search for doubly charged Higgs bosons through vector boson fusion at the LHC and beyond

    NASA Astrophysics Data System (ADS)

    Bambhaniya, G.; Chakrabortty, J.; Gluza, J.; Jeliński, T.; Szafron, R.

    2015-07-01

    Production and decays of doubly charged Higgs bosons at the LHC and future hadron colliders triggered by a vector boson fusion mechanism are discussed in the context of the minimal left-right symmetric model. Our analysis is based on the Higgs boson mass spectrum compatible with available constraints which include flavor changing neutral current (FCNC) effects and vacuum stability of the scalar potential. Though the parity breaking scale vR is large (˜ few TeV) and scalar masses which contribute to FCNC effects are even larger, a consistent Higgs boson mass spectrum still allows us to keep doubly charged scalar masses below 1 TeV which is an interesting situation for LHC and future circular collider (FCC). We have shown that the allowed Higgs boson mass spectrum constrains the splittings (MH1±±-MH1± ), closing the possibility of H1±±→W1±H1± decays. Assuming that doubly charged Higgs bosons decay predominantly into a pair of same-sign charged leptons through the process p p →H1/2 ±±H1/2 ∓∓j j →ℓ±ℓ±ℓ∓ℓ∓j j , we find that for the LHC operating at √{s }=14 TeV with an integrated luminosity at the level of 3000 fb-1 (HL-LHC), there is practically no chance to detect such particles at the reasonable significance level through this channel. However, at 33 TeV HE-LHC and (or) 100 TeV FCC-hh, a wide region opens up for exploring the doubly charged Higgs boson mass spectrum. In FCC-hh, the doubly charged Higgs bosons mass up to 1 TeV can be easily probed.

  6. Frequency-selective fading statistics of shallow-water acoustic communication channel with a few multipaths

    NASA Astrophysics Data System (ADS)

    Bae, Minja; Park, Jihyun; Kim, Jongju; Xue, Dandan; Park, Kyu-Chil; Yoon, Jong Rak

    2016-07-01

    The bit error rate of an underwater acoustic communication system is related to multipath fading statistics, which determine the signal-to-noise ratio. The amplitude and delay of each path depend on sea surface roughness, propagation medium properties, and source-to-receiver range as a function of frequency. Therefore, received signals will show frequency-dependent fading. A shallow-water acoustic communication channel generally shows a few strong multipaths that interfere with each other and the resulting interference affects the fading statistics model. In this study, frequency-selective fading statistics are modeled on the basis of the phasor representation of the complex path amplitude. The fading statistics distribution is parameterized by the frequency-dependent constructive or destructive interference of multipaths. At a 16 m depth with a muddy bottom, a wave height of 0.2 m, and source-to-receiver ranges of 100 and 400 m, fading statistics tend to show a Rayleigh distribution at a destructive interference frequency, but a Rice distribution at a constructive interference frequency. The theoretical fading statistics well matched the experimental ones.

  7. Doubly excited states in some light atoms

    SciTech Connect

    Berry, H.G.; Brooks, R.L.; Hardis, J.E.; Ray, W.J.

    1981-01-01

    We have identified a singlet transition in doubly excited helium: 2p/sup 2/ /sup 1/D - 2p3d /sup 1/D, at 3298 +- 2A with a full width of 54A or 0.061 +- 0.005 eV. This width is in good agreement with a previous measurement and theory for the width of the 2p/sup 2/ /sup 1/D/sub 2/ state. We have remeasured the decay rate of 1s/sup 2/2p/sup 2/P - 1s2p/sup 2/ /sup 2/P in Li I and find it is in good agreement with theory. Several transitions in doubly excited Li II have been identified in the 1000A region. No evidence was found for doubly excited quartet transitions in Li I in the vacuum ultraviolet. We present measurements of wavelengths and fine structure of the 1s2s2p/sup 2/ /sup 5/P - 1s2p/sup 3/ /sup 5/S transitions in C III, N IV and O V.

  8. Selective disruption of high sensitivity heat activation but not capsaicin activation of TRPV1 channels by pore turret mutations.

    PubMed

    Cui, Yuanyuan; Yang, Fan; Cao, Xu; Yarov-Yarovoy, Vladimir; Wang, KeWei; Zheng, Jie

    2012-04-01

    The capsaicin receptor transient receptor potential vanilloid (TRPV)1 is a highly heat-sensitive ion channel. Although chemical activation and heat activation of TRPV1 elicit similar pungent, painful sensation, the molecular mechanism underlying synergistic activation remains mysterious. In particular, where the temperature sensor is located and whether heat and capsaicin share a common activation pathway are debated. To address these fundamental issues, we searched for channel mutations that selectively affected one form of activation. We found that deletion of the first 10 amino acids of the pore turret significantly reduced the heat response amplitude and shifted the heat activation threshold, whereas capsaicin activation remained unchanged. Removing larger portions of the turret disrupted channel function. Introducing an artificial sequence to replace the deleted region restored sensitive capsaicin activation in these nonfunctional channels. The heat activation, however, remained significantly impaired, with the current exhibiting diminishing heat sensitivity to a level indistinguishable from that of a voltage-gated potassium channel, Kv7.4. Our results demonstrate that heat and capsaicin activation of TRPV1 are structurally and mechanistically distinct processes, and the pore turret is an indispensible channel structure involved in the heat activation process but is not part of the capsaicin activation pathway. Synergistic effect of heat and capsaicin on TRPV1 activation may originate from convergence of the two pathways on a common activation gate.

  9. Outage Performance of Cooperative Relay Selection with Multiple Source and Destination Antennas over Dissimilar Nakagami-m Fading Channels

    NASA Astrophysics Data System (ADS)

    Lee, Wooju; Yoon, Dongweon

    Cooperative relay selection, in which one of multiple relays is selected to retransmit the source signal to the destination, has received considerable attention in recent years, because it is a simple way to obtain cooperative diversity in wireless networks. The exact expression of outage probability for a decode-and-forward cooperative relay selection with multiple source and destination antennas over Rayleigh fading channels was recently derived in [9]. In this letter, we derive the exact expressions of outage probability and diversity-multiplexing tradeoff over independent and non-identically distributed Nakagami-m fading channels as an extension of [9]. We then analyze the effects of various parameters such as fading conditions, number of relays, and number of source and destination antennas on the outage probability.

  10. K+ Channel density increases selectively in the endfoot of retinal glial cells during development of Rana catesbiana.

    PubMed

    Rojas, L; Orkand, R K

    1999-01-15

    The radial glial cells that span the retina, described by Müller in 1851, have a remarkable distribution of ion channels in adult amphibia that mediate extracellular K+ spatial buffering. 94% of the total membrane conductance of these cells resides in inward rectifier K+ channels in the endfoot processes apposed to the vitreous humour. We now report that this regional specialization is found in Müller cells isolated from adult (>120 day old) bullfrogs but to a far less extent in those from 10-20 day old tadpoles (stages 34-36). Using the cell attached configuration of the patch-clamp technique, we found, in agreement with previous studies in salamanders, that the endfoot of adult cells had 19.2+/-2.4 (mean +/- S.E., n = 81) channels/patch, whereas the soma had 1.81+/-0.28 (n = 21) channels/patch. In the tadpole, the respective values were 4.29+/-0.26 (n = 79) for the endfoot and 2.26+/-0.24 (n = 27) for the soma. The slope conductance of the inward rectifier K+ channel in 115 mM K+, 19.2+/-0.25 pS (n = 205), channel kinetics and the resting membrane potential (-69+/-2.7 mV, n = 224) were similar at both the endfoot and soma of both adults and embryos. We conclude that during development, the K+ conductance of the Müller cell endfoot, but not of the soma, increases due to a selective clustering of inwardly rectifying K+ channels in that specific region of the cell membrane. The properties of the channels change little during the transformation from tadpole to adult bullfrog. PMID:9890634

  11. Selective deposition response to aeolian-fluvial sediment supply in the desert braided channel of the upper Yellow River, China

    NASA Astrophysics Data System (ADS)

    Wang, H.; Jia, X.; Li, Y.; Peng, W.

    2015-09-01

    Rivers flow across aeolian dunes and develop braided stream channels. Both aeolian and fluvial sediment supplies regulate sediment transport and deposition in such cross-dune braided rivers. Here we show a significant selective deposition in response to both aeolian and fluvial sediment supplies in the Ulan Buh desert braided channel. The Ulan Buh desert is the main coarse sediment source for this desert braided channel, and the mean percentage of the coarser (> 0.08 mm) grains on the aeolian dunes surface is 95.34 %. The lateral selective deposition process is developed by the interaction between the flows and the aeolian-fluvial sediment supplies, causing the coarser sediments (> 0.08 mm) from aeolian sand supply and bank erosion to accumulate in the channel centre and the finer fluvial sediments (< 0.08 mm) to be deposited on the bar and floodplain surfaces, forming a coarser-grained thalweg bed bounded by finer-grained floodplain surfaces. This lateral selective deposition reduces the downstream sediment transport and is a primary reason for the formation of an "above-ground" river in the braided reach of the upper Yellow River in response to aeolian and fluvial sediment supplies.

  12. Tackling the Combined Effects of Reverberation and Masking Noise Using Ideal Channel Selection

    ERIC Educational Resources Information Center

    Hazrati, Oldooz; Loizou, Philipos C.

    2012-01-01

    Purpose: In this article, a new signal-processing algorithm is proposed and evaluated for the suppression of the combined effects of reverberation and noise. Method: The proposed algorithm decomposes, on a short-term basis (every 20 ms), the reverberant stimuli into a number of channels and retains only a subset of the channels satisfying a…

  13. Structural and Functional Consequences of an Amide-to-Ester Substitution in the Selectivity Filter of a Potassium Channel

    SciTech Connect

    Valiyaveetil,F.; Sekedat, M.; MacKinnon, R.; Muir, T.

    2006-01-01

    The selectivity filter of K{sup +} channels comprises four contiguous ion binding sites, S1 through S4. Structural and functional data indicate that the filter contains on average two K{sup +} ions at any given time and that these ions reside primarily in two configurations, namely to sites S1 and S3 or to sites S2 and S4. Maximum ion flux through the channel is expected to occur when the energy difference between these two binding configurations is zero. In this study, we have used protein semisynthesis to selectively perturb site 1 within the filter of the KcsA channel through use of an amide-to-ester substitution. The modification alters K{sup +} conduction properties. The structure of the selectivity filter is largely unperturbed by the modification, despite the loss of an ordered water molecule normally located just behind the filter. Introduction of the ester moiety was found to alter the distribution of K{sup +}, Rb{sup +}, and Cs{sup +} within the filter, with the most dramatic change found for Rb{sup +}. The redistribution of ions is associated with the appearance of a partially hydrated ion just external to the filter, at a position where no ion is observed in the wild-type channel. The appearance of this new ion-binding site creates a change in the distance between a pair of K{sup +} ions some fraction of the time, apparently leading to a reduction in the ion conduction rate. Importantly, this finding suggests that the selectivity filter of a potassium channel is optimized both in terms of absolute ion occupancy and in terms of the separation in distance between the conducting ions.

  14. Doubly Sparse Relevance Vector Machine for Continuous Facial Behavior Estimation.

    PubMed

    Kaltwang, Sebastian; Todorovic, Sinisa; Pantic, Maja

    2016-09-01

    Certain inner feelings and physiological states like pain are subjective states that cannot be directly measured, but can be estimated from spontaneous facial expressions. Since they are typically characterized by subtle movements of facial parts, analysis of the facial details is required. To this end, we formulate a new regression method for continuous estimation of the intensity of facial behavior interpretation, called Doubly Sparse Relevance Vector Machine (DSRVM). DSRVM enforces double sparsity by jointly selecting the most relevant training examples (a.k.a. relevance vectors) and the most important kernels associated with facial parts relevant for interpretation of observed facial expressions. This advances prior work on multi-kernel learning, where sparsity of relevant kernels is typically ignored. Empirical evaluation on challenging Shoulder Pain videos, and the benchmark DISFA and SEMAINE datasets demonstrate that DSRVM outperforms competing approaches with a multi-fold reduction of running times in training and testing. PMID:26595911

  15. Selective modulation of cellular voltage-dependent calcium channels by hyperbaric pressure—a suggested HPNS partial mechanism

    PubMed Central

    Aviner, Ben; Gradwohl, Gideon; Mor Aviner, Merav; Levy, Shiri; Grossman, Yoram

    2014-01-01

    Professional deep sea divers experience motor and cognitive impairment, known as High Pressure Neurological Syndrome (HPNS), when exposed to pressures of 100 msw (1.1 MPa) and above, considered to be the result of synaptic transmission alteration. Previous studies have indicated modulation of presynaptic Ca2+ currents at high pressure. We directly measured for the first time pressure effects on the currents of voltage dependent Ca2+ channels (VDCCs) expressed in Xenopus oocytes. Pressure selectivity augmented the current in CaV1.2 and depressed it in CaV3.2 channels. Pressure application also affected the channels' kinetics, such as ƮRise, ƮDecay. Pressure modulation of VDCCs seems to play an important role in generation of HPNS signs and symptoms. PMID:24904281

  16. Examining the Relationship Between Flexible Resources and Health Information Channel Selection.

    PubMed

    Manierre, Matthew

    2016-01-01

    This study examines how variations in flexible resources influence where individuals begin their search for health information. Access to flexible resources such as money, power, and knowledge can alter the accessibility of channels for health information, such as doctors, the Internet, and print media. Using the HINTS 3 sample, whether information channel utilization is predicted by the same factors in two groups with distinct levels of access to flexible resources, as approximated by high and low levels of education, is investigated. Differences in access to flexible resources are hypothesized to produce variations in channel utilization in bivariate analyses, as well as changes in coefficient strength and statistical significance in multivariate models. Multinomial logit models were used to assess how a number of variables influence the probability of using a specific information channel first in either flexible resource group. Results suggest that individuals with higher levels of education, a proxy for flexible resources, are more likely to report seeking information from the Internet first, which is consistent with research on the digital divide. It appears that diminished access to flexible resources is also associated with heightened utilization of offline channels, including doctors. A handful of differences in predictors were found between the low and high flexible resource groups when multivariate models were compared. Future research should take into account the distinctions between different offline channels while also seeking to further understand how social inequality relates to the utilization of different channels and corresponding health outcomes.

  17. Examining the Relationship Between Flexible Resources and Health Information Channel Selection.

    PubMed

    Manierre, Matthew

    2016-01-01

    This study examines how variations in flexible resources influence where individuals begin their search for health information. Access to flexible resources such as money, power, and knowledge can alter the accessibility of channels for health information, such as doctors, the Internet, and print media. Using the HINTS 3 sample, whether information channel utilization is predicted by the same factors in two groups with distinct levels of access to flexible resources, as approximated by high and low levels of education, is investigated. Differences in access to flexible resources are hypothesized to produce variations in channel utilization in bivariate analyses, as well as changes in coefficient strength and statistical significance in multivariate models. Multinomial logit models were used to assess how a number of variables influence the probability of using a specific information channel first in either flexible resource group. Results suggest that individuals with higher levels of education, a proxy for flexible resources, are more likely to report seeking information from the Internet first, which is consistent with research on the digital divide. It appears that diminished access to flexible resources is also associated with heightened utilization of offline channels, including doctors. A handful of differences in predictors were found between the low and high flexible resource groups when multivariate models were compared. Future research should take into account the distinctions between different offline channels while also seeking to further understand how social inequality relates to the utilization of different channels and corresponding health outcomes. PMID:25616853

  18. Fragmentation of doubly charged HDO, H{sub 2}O, and D{sub 2}O molecules induced by proton and monocharged fluorine beam impact at 3 keV

    SciTech Connect

    Martin, S.; Chen, L.; Brédy, R.; Bernard, J.; Cassimi, A.

    2015-03-07

    Doubly charged ions HDO{sup 2+}, H{sub 2}O{sup 2+}, and D{sub 2}O{sup 2+} were prepared selectively to triplet or singlet excited states in collisions with F{sup +} or H{sup +} projectiles at 3 keV. Excitation energies of dications following two-body or three-body dissociation channels were measured and compared with recent calculations using ab initio multi-reference configuration interaction method [Gervais et al., J. Chem. Phys. 131, 024302 (2009)]. For HDO{sup 2+}, preferential cleavage of O–H rather than O–D bond has been observed and the ratio between the populations of the fragmentation channels OD{sup +}-H{sup +} and OH{sup +}-D{sup +} were measured. The kinetic energy release has been measured and compared with previous experiments.

  19. Riparian vegetation patterns in relation to fluvial landforms and channel evolution along selected rivers of Tuscany (Central Italy)

    USGS Publications Warehouse

    Hupp, C.R.; Rinaldi, M.

    2007-01-01

    Riparian vegetation distribution patterns and diversity relative to various fluvial geomorphic channel patterns, landforms, and processes are described and interpreted for selected rivers of Tuscany, Central Italy; with emphasis on channel evolution following human impacts. Field surveys were conducted along thirteen gauged reaches for species presence, fluvial landforms, and the type and amount of channel/riparian zone change. Inundation frequency of different geomorphic surfaces was determined, and vegetation data were analyzed using BDA (binary discriminate analysis) and DCA (detrended correspondence analysis) and related to hydrogeomorphology. Multivariate analyses revealed distinct quantitative vegetation patterns relative to six major fluvial geomorphic surfaces. DCA of the vegetation data also showed distinct associations of plants to processes of adjustment that are related to stage of channel evolution, and clearly separated plants along disturbance/landform/soil moisture gradients. Species richness increases from the channel bed to the terrace and on heterogeneous riparian areas, whereas species richness decreases from moderate to intense incision and from low to intense narrowing. ?? 2007 by Association of American Geographers.

  20. Reduction of the pectoral spine and girdle in domesticated Channel catfish is likely caused by changes in selection pressure.

    PubMed

    Fine, Michael L; Lahiri, Shweta; Sullivan, Amanda D H; Mayo, Mark; Newton, Scott H; Sismour, Edward N

    2014-07-01

    Locked pectoral spines of the Channel Catfish Ictalurus punctatus more than double the fish's width and complicate ingestion by gape-limited predators. The spine mates with the pectoral girdle, a robust structure that anchors the spine. This study demonstrates that both spine and girdle exhibit negative allometric growth and that pectoral spines and girdles are lighter in domesticated than in wild Channel Catfish. This finding could be explained by changes in selection pressure for spine growth during domestication or by an epigenetic effect in which exposure to predators in wild fish stimulates pectoral growth. We tested the epigenetic hypothesis by exposing domesticated Channel Catfish fingerlings to Largemouth Bass Micropterus salmoides predators for 13 weeks. Spines and girdles grow isometrically in the fingerlings, and regression analysis indicates no difference in proportional pectoral growth between control and predator-exposed fish. Therefore a change in selection pressure likely accounts for smaller pectoral growth in domesticated Channel Catfish. Decreasing spine growth in older fish suggests anti-predator functions are most important in smaller fish. Additionally, growth of the appendicular and axial skeleton is controlled differentially, and mechanical properties of the spine and not just its length are an important component of this defensive adaptation.

  1. Reduction of the pectoral spine and girdle in domesticated Channel catfish is likely caused by changes in selection pressure.

    PubMed

    Fine, Michael L; Lahiri, Shweta; Sullivan, Amanda D H; Mayo, Mark; Newton, Scott H; Sismour, Edward N

    2014-07-01

    Locked pectoral spines of the Channel Catfish Ictalurus punctatus more than double the fish's width and complicate ingestion by gape-limited predators. The spine mates with the pectoral girdle, a robust structure that anchors the spine. This study demonstrates that both spine and girdle exhibit negative allometric growth and that pectoral spines and girdles are lighter in domesticated than in wild Channel Catfish. This finding could be explained by changes in selection pressure for spine growth during domestication or by an epigenetic effect in which exposure to predators in wild fish stimulates pectoral growth. We tested the epigenetic hypothesis by exposing domesticated Channel Catfish fingerlings to Largemouth Bass Micropterus salmoides predators for 13 weeks. Spines and girdles grow isometrically in the fingerlings, and regression analysis indicates no difference in proportional pectoral growth between control and predator-exposed fish. Therefore a change in selection pressure likely accounts for smaller pectoral growth in domesticated Channel Catfish. Decreasing spine growth in older fish suggests anti-predator functions are most important in smaller fish. Additionally, growth of the appendicular and axial skeleton is controlled differentially, and mechanical properties of the spine and not just its length are an important component of this defensive adaptation. PMID:24673385

  2. Bordetella pertussis major outer membrane porin protein forms small, anion-selective channels in lipid bilayer membranes.

    PubMed Central

    Armstrong, S K; Parr, T R; Parker, C D; Hancock, R E

    1986-01-01

    The major outer membrane protein of molecular weight 40,000 (the 40K protein) of a virulent isolate of Bordetella pertussis was purified to apparent homogeneity. The purified protein formed an oligomer band (of apparent molecular weight 90,000) on sodium dodecyl sulfate-polyacrylamide gels after solubilization at low temperatures. The porin function of this protein was characterized by the black lipid bilayer method. The 40K protein formed channels smaller than all other constitutive major outer membrane porins studied to date. The average single-channel conductance in 1 M KCl was 0.56 nS. This was less than a third of the conductance previously observed for Escherichia coli porins. Zero-current potential measurements made of the porin to determine its ion selectivity revealed the porin to be more than 100-fold selective for anions over cations. The single-channel conductance was measured as a function of salt concentration. The data could be fitted to a Lineweaver-Burk plot suggesting an anion binding site with a Kd of 1.17 M Cl- and a maximum possible conductance through the channel of 1.28 nS. Images PMID:2420780

  3. (-)-Englerin A is a potent and selective activator of TRPC4 and TRPC5 calcium channels.

    PubMed

    Akbulut, Yasemin; Gaunt, Hannah J; Muraki, Katsuhiko; Ludlow, Melanie J; Amer, Mohamed S; Bruns, Alexander; Vasudev, Naveen S; Radtke, Lea; Willot, Matthieu; Hahn, Sven; Seitz, Tobias; Ziegler, Slava; Christmann, Mathias; Beech, David J; Waldmann, Herbert

    2015-03-16

    Current therapies for common types of cancer such as renal cell cancer are often ineffective and unspecific, and novel pharmacological targets and approaches are in high demand. Here we show the unexpected possibility for the rapid and selective killing of renal cancer cells through activation of calcium-permeable nonselective transient receptor potential canonical (TRPC) calcium channels by the sesquiterpene (-)-englerin A. This compound was found to be a highly efficient, fast-acting, potent, selective, and direct stimulator of TRPC4 and TRPC5 channels. TRPC4/5 activation through a high-affinity extracellular (-)-englerin A binding site may open up novel opportunities for drug discovery aimed at renal cancer.

  4. Peregrination of the selectivity filter delineates the pore of the human voltage-gated proton channel hHV1

    PubMed Central

    Morgan, Deri; Musset, Boris; Kulleperuma, Kethika; Smith, Susan M.E.; Rajan, Sindhu; Cherny, Vladimir V.; Pomès, Régis

    2013-01-01

    Extraordinary selectivity is crucial to all proton-conducting molecules, including the human voltage-gated proton channel (hHV1), because the proton concentration is >106 times lower than that of other cations. Here we use “selectivity filter scanning” to elucidate the molecular requirements for proton-specific conduction in hHV1. Asp112, in the middle of the S1 transmembrane helix, is an essential part of the selectivity filter in wild-type (WT) channels. After neutralizing Asp112 by mutating it to Ala (D112A), we introduced Asp at each position along S1 from 108 to 118, searching for “second site suppressor” activity. Surprisingly, most mutants lacked even the anion conduction exhibited by D112A. Proton-specific conduction was restored only with Asp or Glu at position 116. The D112V/V116D channel strikingly resembled WT in selectivity, kinetics, and ΔpH-dependent gating. The S4 segment of this mutant has similar accessibility to WT in open channels, because R211H/D112V/V116D was inhibited by internally applied Zn2+. Asp at position 109 allowed anion permeation in combination with D112A but did not rescue function in the nonconducting D112V mutant, indicating that selectivity is established externally to the constriction at F150. The three positions that permitted conduction all line the pore in our homology model, clearly delineating the conduction pathway. Evidently, a carboxyl group must face the pore directly to enable conduction. Molecular dynamics simulations indicate reorganization of hydrogen bond networks in the external vestibule in D112V/V116D. At both positions where it produces proton selectivity, Asp frequently engages in salt linkage with one or more Arg residues from S4. Surprisingly, mean hydration profiles were similar in proton-selective, anion-permeable, and nonconducting constructs. That the selectivity filter functions in a new location helps to define local environmental features required to produce proton-selective conduction. PMID

  5. Evidence for a doubly magic 24O

    NASA Astrophysics Data System (ADS)

    Hoffman, C. R.; Baumann, T.; Bazin, D.; Brown, J.; Christian, G.; Denby, D. H.; DeYoung, P. A.; Finck, J. E.; Frank, N.; Hinnefeld, J.; Mosby, S.; Peters, W. A.; Rogers, W. F.; Schiller, A.; Spyrou, A.; Scott, M. J.; Tabor, S. L.; Thoennessen, M.; Voss, P.

    2009-02-01

    The decay energy spectrum for neutron unbound states in 24O ( Z=8, N=16) has been observed for the first time. The resonance energy of the lowest lying state, interpreted as the 2 level, has been observed at a decay energy above 600 keV. The resulting excitation energy of the 2 level above 4.7 MeV, supplies strong evidence that 24O is a doubly magic nucleus. The data is also consistent with the presence of a second excited state around 5.33 MeV which can be interpreted as the 1 level.

  6. Evaluation of habitat quality for selected wildlife species associated with back channels.

    USGS Publications Warehouse

    Anderson, James T.; Zadnik, Andrew K.; Wood, Petra Bohall; Bledsoe, Kerry

    2013-01-01

    The islands and associated back channels on the Ohio River, USA, are believed to provide critical habitat features for several wildlife species. However, few studies have quantitatively evaluated habitat quality in these areas. Our main objective was to evaluate the habitat quality of back and main channel areas for several species using habitat suitability index (HSI) models. To test the effectiveness of these models, we attempted to relate HSI scores and the variables measured for each model with measures of relative abundance for the model species. The mean belted kingfisher (Ceryle alcyon) HSI was greater on the main than back channel. However, the model failed to predict kingfisher abundance. The mean reproduction component of the great blue heron (Ardea herodias) HSI, total common muskrat (Ondatra zibethicus) HSI, winter cover component of the snapping turtle (Chelydra serpentina) HSI, and brood-rearing component of the wood duck (Aix sponsa) HSI were all greater on the back than main channel, and were positively related with the relative abundance of each species. We found that island back channels provide characteristics not found elsewhere on the Ohio River and warrant conservation as important riparian wildlife habitat. The effectiveness of using HSI models to predict species abundance on the river was mixed. Modifications to several of the models are needed to improve their use on the Ohio River and, likely, other large rivers.

  7. Selective potentiation of 2-APB-induced activation of TRPV1–3 channels by acid

    PubMed Central

    Gao, Luna; Yang, Pu; Qin, Peizhong; Lu, Yungang; Li, Xinxin; Tian, Quan; Li, Yang; Xie, Chang; Tian, Jin-bin; Zhang, Chengwei; Tian, Changlin; Zhu, Michael X.; Yao, Jing

    2016-01-01

    Temperature-sensitive TRP channels are important for responses to pain and inflammation, to both of which tissue acidosis is a major contributing factor. However, except for TRPV1, acid-sensing by other ThermoTRP channels remains mysterious. We show here that unique among TRPV1–3 channels, TRPV3 is directly activated by protons from cytoplasmic side. This effect is very weak and involves key cytoplasmic residues L508, D512, S518, or A520. However, mutations of these residues did not affect a strong proton induced potentiation of TRPV3 currents elicited by the TRPV1–3 common agonist, 2-aminoethoxydiphenyl borate (2-APB), no matter if the ligand was applied from extracellular or cytoplasmic side. The acid potentiation was common among TRPV1–3 and only seen with 2-APB-related ligands. Using 1H-nuclear magnetic resonance to examine the solution structures of 2-APB and its analogs, we observed striking structural differences of the boron-containing compounds at neutral/basic as compared to acidic pH, suggesting that a pH-dependent configuration switch of 2-APB-based drugs may underlie their functionality. Supporting this notion, protons also enhanced the inhibitory action of 2-APB on TRPM8. Collectively, our findings reveal novel insights into 2-APB action on TRP channels, which should facilitate the design of new drugs for these channels. PMID:26876731

  8. In pursuit of small molecule chemistry for calcium-permeable non-selective TRPC channels -- mirage or pot of gold?

    PubMed

    Bon, Robin S; Beech, David J

    2013-10-01

    The primary purpose of this review is to address the progress towards small molecule modulators of human Transient Receptor Potential Canonical proteins (TRPC1, TRPC3, TRPC4, TRPC5, TRPC6 and TRPC7). These proteins generate channels for calcium and sodium ion entry. They are relevant to many mammalian cell types including acinar gland cells, adipocytes, astrocytes, cardiac myocytes, cochlea hair cells, endothelial cells, epithelial cells, fibroblasts, hepatocytes, keratinocytes, leukocytes, mast cells, mesangial cells, neurones, osteoblasts, osteoclasts, platelets, podocytes, smooth muscle cells, skeletal muscle and tumour cells. There are broad-ranging positive roles of the channels in cell adhesion, migration, proliferation, survival and turning, vascular permeability, hypertrophy, wound-healing, hypo-adiponectinaemia, angiogenesis, neointimal hyperplasia, oedema, thrombosis, muscle endurance, lung hyper-responsiveness, glomerular filtration, gastrointestinal motility, pancreatitis, seizure, innate fear, motor coordination, saliva secretion, mast cell degranulation, cancer cell drug resistance, survival after myocardial infarction, efferocytosis, hypo-matrix metalloproteinase, vasoconstriction and vasodilatation. Known small molecule stimulators of the channels include hyperforin, genistein and rosiglitazone, but there is more progress with inhibitors, some of which have promising potency and selectivity. The inhibitors include 2-aminoethoxydiphenyl borate, 2-aminoquinolines, 2-aminothiazoles, fatty acids, isothiourea derivatives, naphthalene sulfonamides, N-phenylanthranilic acids, phenylethylimidazoles, piperazine/piperidine analogues, polyphenols, pyrazoles and steroids. A few of these agents are starting to be useful as tools for determining the physiological and pathophysiological functions of TRPC channels. We suggest that the pursuit of small molecule modulators for TRPC channels is important but that it requires substantial additional effort and

  9. Designing and modeling doubly porous polymeric materials

    NASA Astrophysics Data System (ADS)

    Ly, H.-B.; Le Droumaguet, B.; Monchiet, V.; Grande, D.

    2015-07-01

    Doubly porous organic materials based on poly(2-hydroxyethyl methacrylate) are synthetized through the use of two distinct types of porogen templates, namely a macroporogen and a nanoporogen. Two complementary strategies are implemented by using either sodium chloride particles or fused poly(methyl methacrylate) beads as macroporogens, in conjunction with ethanol as a porogenic solvent. The porogen removal respectively allows for the generation of either non-interconnected or interconnected macropores with an average diameter of about 100-200 μm and nanopores with sizes lying within the 100 nm order of magnitude, as evidenced by mercury intrusion porosimetry and scanning electron microscopy. Nitrogen sorption measurements evidence the formation of materials with rather high specific surface areas, i.e. higher than 140 m2.g-1. This paper also addresses the development of numerical tools for computing the permeability of such doubly porous materials. Due to the coexistence of well separated scales between nanopores and macropores, a consecutive double homogenization approach is proposed. A nanoscopic scale and a mesoscopic scale are introduced, and the flow is evaluated by means of the Finite Element Method to determine the macroscopic permeability. At the nanoscopic scale, the flow is described by the Stokes equations with an adherence condition at the solid surface. At the mesoscopic scale, the flow obeys the Stokes equations in the macropores and the Darcy equation in the permeable polymer in order to account for the presence of the nanopores.

  10. Double photoionization of doubly-excited lithium

    NASA Astrophysics Data System (ADS)

    Armstrong, G.; Pindzola, M. S.; Kheifets, A.; Schuricke, M.; Veeravalli, G.; Dornes, Ch.; Zhu, G.; Joachimsmeyer, K.; Treusch, R.; Dorn, A.; Colgan, J.

    2012-06-01

    We present triple differential cross sections and recoil ion momentum distributions for double photoionization of the 1s2s2p state of lithium. Double ionization of lithium may be treated as a two-active-electron process, where the ``active'' 2s and 2p electrons move in the field of the ``frozen-core'' Li^2+ 1s state.The time-dependent close-coupling (TDCC) method is used to solve the two-electron time-dependent Schr"odinger equation in full dimensionality. This work is motivated by recent FLASH experiments, which have obtained recoil-ion momentum distributions at a photon energy of 59 eV, where the 1s2s2p state is first reached via a 1s-2p photoexcitation from the initial ground state, and may then be doubly-ionized after the absorption of a second photon. The TDCC calculations in this work treat the subsequent photoionization of this doubly-excited state. The results are compared to those obtained by the convergent close-coupling method and to measurement, and provide a first comparison between theory and experiment in this fundamental few-photon few-body problem.

  11. Adaptive Zero-Padding OFDM over Frequency-Selective Multipath Channels

    NASA Astrophysics Data System (ADS)

    Wang, Neng; Blostein, Steven D.

    2004-12-01

    We present a novel bandwidth (BW) efficient orthogonal frequency division multiplexing (OFDM) scheme with adaptive zero-padding (AZP-OFDM) for wireless transmission. Redundancy issues in OFDM based on cyclic prefix (CP), zero-padding (ZP), as well as no guard interval (NGI) systems are analyzed. A novel system design criterion based on the channel matrix condition is studied and applied to the design of an AZP-OFDM system. Simulation results have shown that the proposed AZP-OFDM offers performance similar to that of CP-OFDM, complexity similar to that of ZP-OFDM, with BW efficiency higher than that of both CP- and ZP-OFDM in channels with small to moderate delay spread. In channels with large delay spread, AZP scheme adaptively maintains high performance at the expense of BW efficiency. Essentially, AZP-OFDM offers a more flexible tradeoff between symbol recovery, BW efficiency, and complexity.

  12. Baseline Channel Geometry and Aquatic Habitat Data for Selected Streams in the Matanuska-Susitna Valley, Alaska

    USGS Publications Warehouse

    Curran, Janet H.; Rice, William J.

    2009-01-01

    Small streams in the rapidly developing Matanuska-Susitna Valley in south-central Alaska are known to support anadromous and resident fish but little is known about their hydrologic and riparian conditions, or their sensitivity to the rapid development of the area or climate variability. To help address this need, channel geometry and aquatic habitat data were collected in 2005 as a baseline of stream conditions for selected streams. Three streams were selected as representative of various stream types, and one drainage network, the Big Lake drainage basin, was selected for a systematic assessment. Streams in the Big Lake basin were drawn in a Geographic Information System (GIS), and 55 reaches along 16 miles of Meadow Creek and its primary tributary Little Meadow Creek were identified from orthoimagery and field observations on the basis of distinctive physical and habitat parameters, most commonly gradient, substrate, and vegetation. Data-collection methods for sites at the three representative reaches and the 55 systematically studied reaches consisted of a field survey of channel and flood-plain geometry and collection of 14 habitat attributes using published protocols or slight modifications. Width/depth and entrenchment ratios along the Meadow-Little Meadow Creek corridor were large and highly variable upstream of Parks Highway and lower and more consistent downstream of Parks Highway. Channel width was strongly correlated with distance, increasing downstream in a log-linear relation. Runs formed the most common habitat type, and instream vegetation dominated the habitat cover types, which collectively covered 53 percent of the channel. Gravel suitable for spawning covered isolated areas along Meadow Creek and about 29 percent of Little Meadow Creek. Broad wetlands were common along both streams. For a comprehensive assessment of small streams in the Mat-Su Valley, critical additional data needs include hydrologic, geologic and geomorphic, and biologic data

  13. Guide for selecting Manning's roughness coefficients for natural channels and flood plains

    USGS Publications Warehouse

    Arcement, George J.; Schneider, Verne R.

    1989-01-01

    Although much research has been done on Manning's roughness coefficient, n, for stream channels, very little has been done concerning the roughness values for densely vegetated flood plains. The n value is determined from the values of the factors that affect the roughness of channels and flood plains. In densely vegetated flood plains, the major roughness is caused by trees, vines, and brush. The n value for this type of flood plain can be determined by measuring the vegetation density of the flood plain. Photographs of flood-plain segments where n values have been verified can be used as a comparison standard to aid in assigning n values to similar flood plains.

  14. Divalent cation permeability and blockade of Ca2+-permeant non-selective cation channels in rat adrenal zona glomerulosa cells

    PubMed Central

    Lotshaw, David P; Sheehan, Katherine A

    1999-01-01

    The effects of the divalent cations Ca2+, Mg2+ and Ni2+ on unitary Na+ currents through receptor-regulated non-selective cation channels were studied in inside-out and cell-attached patches from rat adrenal zona glomerulosa cells.External Ca2+ caused a concentration-dependent and voltage-independent inhibition of inward Na+ current, exhibiting an IC50 of 1.4 mm. The channel was also Ca2+ permeant and external Ca2+ shifted the reversal potential as expected for a channel exhibiting a constant Ca2+:Na+ permeability ratio near to 4.External and internal 2 mm Mg2+ caused voltage-dependent inhibition of inward and outward Na+ current, respectively. Modelling Mg2+ as an impermeant fast open channel blocker indicated that external Mg2+ blocked the pore at a single site exhibiting a zero voltage Kd of 5.1 mm for Mg2+ and located 19% of the distance through the transmembrane electric field from the external surface. Internal Mg2+ blocked the pore at a second site exhibiting a Kd of 1.7 mm for Mg2+ and located 36% of the distance through the transmembrane electric field from the cytosolic surface.External Ni2+ caused a voltage- and concentration-dependent slow blockade of inward Na+ current. Modelling Ni2+ as an impermeant slow open channel blocker indicated that Ni2+ blocked the pore at a single site exhibiting a Kd of 1.09 mm for Ni2+ and located 13.7% of the distance through the transmembrane electric field from the external surface.External 2 mm Mg2+ increased the Kd for external Ni2+ binding to 1.27 mm, consistent with competition for a single binding site. Changing ionic strength did not substantially affect Ni2+ blockade indicating the absence of surface potential under physiological ionic conditions.It is concluded that at least two divalent cation binding sites, separated by a high free energy barrier (the selectivity filter), are located in the pore and contribute to Ca2+ selectivity and permeability of the channel. PMID:9852322

  15. A distinct sodium channel voltage-sensor locus determines insect selectivity of the spider toxin Dc1a.

    PubMed

    Bende, Niraj S; Dziemborowicz, Sławomir; Mobli, Mehdi; Herzig, Volker; Gilchrist, John; Wagner, Jordan; Nicholson, Graham M; King, Glenn F; Bosmans, Frank

    2014-07-11

    β-Diguetoxin-Dc1a (Dc1a) is a toxin from the desert bush spider Diguetia canities that incapacitates insects at concentrations that are non-toxic to mammals. Dc1a promotes opening of German cockroach voltage-gated sodium (Nav) channels (BgNav1), whereas human Nav channels are insensitive. Here, by transplanting commonly targeted S3b-S4 paddle motifs within BgNav1 voltage sensors into Kv2.1, we find that Dc1a interacts with the domain II voltage sensor. In contrast, Dc1a has little effect on sodium currents mediated by PaNav1 channels from the American cockroach even though their domain II paddle motifs are identical. When exploring regions responsible for PaNav1 resistance to Dc1a, we identified two residues within the BgNav1 domain II S1-S2 loop that when mutated to their PaNav1 counterparts drastically reduce toxin susceptibility. Overall, our results reveal a distinct region within insect Nav channels that helps determine Dc1a sensitivity, a concept that will be valuable for the design of insect-selective insecticides.

  16. A distinct sodium channel voltage-sensor locus determines insect selectivity of the spider toxin Dc1a

    NASA Astrophysics Data System (ADS)

    Bende, Niraj S.; Dziemborowicz, Sławomir; Mobli, Mehdi; Herzig, Volker; Gilchrist, John; Wagner, Jordan; Nicholson, Graham M.; King, Glenn F.; Bosmans, Frank

    2014-07-01

    β-Diguetoxin-Dc1a (Dc1a) is a toxin from the desert bush spider Diguetia canities that incapacitates insects at concentrations that are non-toxic to mammals. Dc1a promotes opening of German cockroach voltage-gated sodium (Nav) channels (BgNav1), whereas human Nav channels are insensitive. Here, by transplanting commonly targeted S3b-S4 paddle motifs within BgNav1 voltage sensors into Kv2.1, we find that Dc1a interacts with the domain II voltage sensor. In contrast, Dc1a has little effect on sodium currents mediated by PaNav1 channels from the American cockroach even though their domain II paddle motifs are identical. When exploring regions responsible for PaNav1 resistance to Dc1a, we identified two residues within the BgNav1 domain II S1-S2 loop that when mutated to their PaNav1 counterparts drastically reduce toxin susceptibility. Overall, our results reveal a distinct region within insect Nav channels that helps determine Dc1a sensitivity, a concept that will be valuable for the design of insect-selective insecticides.

  17. A distinct sodium channel voltage-sensor locus determines insect selectivity of the spider toxin Dc1a

    PubMed Central

    Bende, Niraj S; Dziemborowicz, Slawomir; Mobli, Mehdi; Herzig, Volker; Gilchrist, John; Wagner, Jordan; Nicholson, Graham M; King, Glenn F; Bosmans, Frank

    2014-01-01

    β-Diguetoxin-Dc1a (Dc1a) is a toxin from the desert bush spider Diguetia canities that incapacitates insects at concentrations that are non-toxic to mammals. Dc1a promotes opening of German cockroach voltage-gated sodium (Nav) channels (BgNav1), whereas human Nav channels are insensitive. Here, by transplanting commonly targeted S3b-S4 paddle motifs within BgNav1 voltage sensors into Kv2.1, we find that Dc1a interacts with the domain II voltage sensor. In contrast, Dc1a has little effect on sodium currents mediated by PaNav1 channels from the American cockroach even though their domain II paddle motifs are identical. When exploring regions responsible for PaNav1 resistance to Dc1a, we identified two residues within the BgNav1 domain II S1–S2 loop that when mutated to their PaNav1 counterparts drastically reduce toxin susceptibility. Overall, our results reveal a distinct region within insect Nav channels that helps determine Dc1a sensitivity, aconcept that will be valuable for the design of insect-selective insecticides. PMID:25014760

  18. Differential inhibition of cardiac and neuronal Na(+) channels by the selective serotonin-norepinephrine reuptake inhibitors duloxetine and venlafaxine.

    PubMed

    Stoetzer, Carsten; Papenberg, Bastian; Doll, Thorben; Völker, Marc; Heineke, Joerg; Stoetzer, Marcus; Wegner, Florian; Leffler, Andreas

    2016-07-15

    Duloxetine and venlafaxine are selective serotonin-norepinephrine-reuptake-inhibitors used as antidepressants and co-analgesics. While venlafaxine rather than duloxetine induce cardiovascular side-effects, neither of the substances are regarded cardiotoxic. Inhibition of cardiac Na(+)-channels can be associated with cardiotoxicity, and duloxetine was demonstrated to block neuronal Na(+)-channels. The aim of this study was to investigate if the non-life threatening cardiotoxicities of duloxetine and venlafaxine correlate with a weak inhibition of cardiac Na(+)-channels. Effects of duloxetine, venlafaxine and amitriptyline were examined on endogenous Na(+)-channels in neuroblastoma ND7/23 cells and on the α-subunits Nav1.5, Nav1.7 and Nav1.8 with whole-cell patch clamp recordings. Tonic block of the cardiac Na(+)-channel Nav1.5 and rat-cardiomyocytes (CM) revealed a higher potency for duloxetine (Nav 1.5 IC50 14±1µM, CM IC50 27±3µM) as compared to venlafaxine (Nav 1.5 IC50 671±26µM, CM IC50 452±34µM). Duloxetine was as potent as the cardiotoxic antidepressant amitriptyline (IC50 13±1µM). While venlafaxine almost failed to induce use-dependent block on Nav1.5 and cardiomyocytes, low concentrations of duloxetine (1, 10µM) induced prominent use-dependent block similar to amitriptyline. Duloxetine, but not venlafaxine stabilized fast and slow inactivation and delayed recovery from inactivation. Duloxetine induced an unselective inhibition of neuronal Na(+)-channels (IC50 ND7/23 23±1µM, Nav1.7 19±2µM, Nav1.8 29±2). Duloxetine, but not venlafaxine inhibits cardiac Na(+)-channels with a potency similar to amitriptyline. These data indicate that an inhibition of Na(+)-channels does not predict a clinically relevant cardiotoxicity. PMID:27130441

  19. Verification of roughness coefficients for selected natural and constructed stream channels in Arizona

    USGS Publications Warehouse

    Phillips, Jeff V.; Ingersoll, Todd L.

    1998-01-01

    Physical and hydraulic characteristics are presented for 14 river and canal reaches in Arizona for which 37 roughness coefficients have been determined. The verified roughness coefficients which ranged from 0.017 to 0.067, were computed from discharges, channel geometry, and water-surface profiles measured at each of the sites. The information given for each stream segment includes bed and bank descriptions, data tables showing hydraulic components, a plan view, cross-section plots, and color photographs that can be used as a comparison aid in determining roughness coefficients for similarly channeled streams. Relations derived from the data presented relate Manning's roughness coefficient (n) to various hydraulic components. For gravel-bed streams, verified roughness coefficients are related to median grain size of the bed material and hydraulic radius resulting in an equation that can be used to transfer results to similar dry-land channels. The equation developed for base values of n for gravel-bed channels in Arizona is significantly different from similarly derived equations for other regions of the United States and the world.

  20. Control of the Selectivity of the Aquaporin Water Channel Family by Global Orientational Tuning

    NASA Astrophysics Data System (ADS)

    Tajkhorshid, Emad; Nollert, Peter; Jensen, Morten Ø.; Miercke, Larry J. W.; O'Connell, Joseph; Stroud, Robert M.; Schulten, Klaus

    2002-04-01

    Aquaporins are transmembrane channels found in cell membranes of all life forms. We examine their apparently paradoxical property, facilitation of efficient permeation of water while excluding protons, which is of critical importance to preserving the electrochemical potential across the cell membrane. We have determined the structure of the Escherichia coli aquaglyceroporin GlpF with bound water, in native (2.7 angstroms) and in W48F/F200T mutant (2.1 angstroms) forms, and carried out 12-nanosecond molecular dynamics simulations that define the spatial and temporal probability distribution and orientation of a single file of seven to nine water molecules inside the channel. Two conserved asparagines force a central water molecule to serve strictly as a hydrogen bond donor to its neighboring water molecules. Assisted by the electrostatic potential generated by two half-membrane spanning loops, this dictates opposite orientations of water molecules in the two halves of the channel, and thus prevents the formation of a ``proton wire,'' while permitting rapid water diffusion. Both simulations and observations revealed a more regular distribution of channel water and an increased water permeability for the W48F/F200T mutant.

  1. Immunosuppressive Interactions among Calcium Channel Antagonists and Selected Corticosteroids and Macrolides Using Human whole Blood Lymphocytes

    PubMed Central

    Chow, Fung-Sing; Jusko, William J.

    2014-01-01

    Summary The immunosuppressive interactions of calcium channel antagonists [diltiazem (Dil), verapamil (Ver) and nifedipine (Nif)], with corticosteroids [methylprednisolone (Mpl), prednisolone (Prd)], and macrolides [tacrolimus (Tac) and sirolnnus (Sir)] were examined in human whole blood lymphocyte cultures. Gender-related differences in responses in the interactions between these drug classes were studied using blood from 6 males and 6 females. The nature and intensity of interactions were determined using an extended Loewe additivity model. All immunosuppressants exhibited higher potency than the calcium channel antagonists with mean IC50 values of: Dil (mM)Ver (mM)Nif (mM)Mpl (nM)Prd (nM)Tac (nM)Sir (nM)Male13541.921312.118.6150327Female11431.847.44.68.8111106 Gender-related differences in responses to Mpl and Prd were observed while the others were not significant. Additive interactions were found among calcium channel antagonists and corticosteroids. Significant synergistic interactions were observed between calcium channel antagonists and tacrolimus and sirolimus, although these are unlikely to be of clinical importance. These studies demonstrate diverse drug interactions in the examination of an important array of immunosuppressant drug combinations. PMID:15681895

  2. Analysis of channel confined selective area growth in evolutionary growth of GaN on SiO2

    NASA Astrophysics Data System (ADS)

    Leung, Benjamin; Tsai, Miao-Chan; Song, Jie; Zhang, Yu; Xiong, Kanglin; Yuan, Ge; Coltrin, Michael E.; Han, Jung

    2015-09-01

    Here, we analyze the chemical vapor deposition of semiconductor crystals by selective area growth in a non-planar geometry. Specifically, the growth process in laterally and vertically confined masks forming single-crystal GaN on SiO2 by metal-organic chemical vapor deposition is considered in detail. A textured AlN seed is used to initiate growth of oriented GaN selectively through the mask, allowing the reduction of degrees of freedom by the evolutionary grain selection process. As shown by measurements of growth rates within the mask, the sub micron length scale of the channel opening is comparable to the mean free path of precursors in the gas phase, resulting in transport characteristics that can be described by an intermediate flow regime between continuum and free-molecular. Mass transport is modeled through kinetic theory to explain the growth rate enhancements of more than a factor of two by changes in reactor pressure. The growth conditions that enable the modification of nucleation density within the channel are then discussed, and are measured by electron-back scatter diffraction of the nucleated grains on the AlN seed. Finally, the selectivity behavior using the low fill factor masks needed in these configurations has been optimized by control of precursor flow rates and the H2 enhanced etching of the polycrystalline GaN nuclei.

  3. Inhibition of collagen synthesis by select calcium and sodium channel blockers can be mitigated by ascorbic acid and ascorbyl palmitate.

    PubMed

    Ivanov, Vadim; Ivanova, Svetlana; Kalinovsky, Tatiana; Niedzwiecki, Aleksandra; Rath, Matthias

    2016-01-01

    Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction. In addition to the side effects mentioned above by different channel blockers, these drugs can cause arterial wall damage, thereby contributing to vascular wall structure destabilization and promoting events facilitating rupture of plaques. Collagen synthesis is regulated by ascorbic acid, which is also essential for its optimum structure as a cofactor in lysine and proline hydroxylation, a precondition for optimum crosslinking of collagen and elastin. Therefore, the main objective in this study was to evaluate effects of various types of channel blockers on intracellular accumulation and cellular functions of ascorbate, specifically in relation to formation and extracellular deposition of major collagen types relevant for vascular function. Effects of select Na- and Ca- channel blockers on collagen synthesis and deposition were evaluated in cultured human dermal fibroblasts and aortic smooth muscle cells by immunoassay. All channel blockers tested demonstrated inhibitory effects on collagen type I deposition to the ECM by fibroblasts, each to a different degree. Ascorbic acid significantly increased collagen I ECM deposition. Nifedipine (50 µM), a representative of channel blockers tested, significantly reduced ascorbic acid and ascorbyl palmitate-dependent ECM deposition of collagen type l and collagen type lV by cultured aortic smooth muscle cells. In addition, nifedipine (50 µM) significantly reduced ascorbate-dependent collagen type l and type lV synthesis by cultured aortic smooth

  4. Inhibition of collagen synthesis by select calcium and sodium channel blockers can be mitigated by ascorbic acid and ascorbyl palmitate.

    PubMed

    Ivanov, Vadim; Ivanova, Svetlana; Kalinovsky, Tatiana; Niedzwiecki, Aleksandra; Rath, Matthias

    2016-01-01

    Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction. In addition to the side effects mentioned above by different channel blockers, these drugs can cause arterial wall damage, thereby contributing to vascular wall structure destabilization and promoting events facilitating rupture of plaques. Collagen synthesis is regulated by ascorbic acid, which is also essential for its optimum structure as a cofactor in lysine and proline hydroxylation, a precondition for optimum crosslinking of collagen and elastin. Therefore, the main objective in this study was to evaluate effects of various types of channel blockers on intracellular accumulation and cellular functions of ascorbate, specifically in relation to formation and extracellular deposition of major collagen types relevant for vascular function. Effects of select Na- and Ca- channel blockers on collagen synthesis and deposition were evaluated in cultured human dermal fibroblasts and aortic smooth muscle cells by immunoassay. All channel blockers tested demonstrated inhibitory effects on collagen type I deposition to the ECM by fibroblasts, each to a different degree. Ascorbic acid significantly increased collagen I ECM deposition. Nifedipine (50 µM), a representative of channel blockers tested, significantly reduced ascorbic acid and ascorbyl palmitate-dependent ECM deposition of collagen type l and collagen type lV by cultured aortic smooth muscle cells. In addition, nifedipine (50 µM) significantly reduced ascorbate-dependent collagen type l and type lV synthesis by cultured aortic smooth

  5. Inhibition of collagen synthesis by select calcium and sodium channel blockers can be mitigated by ascorbic acid and ascorbyl palmitate

    PubMed Central

    Ivanov, Vadim; Ivanova, Svetlana; Kalinovsky, Tatiana; Niedzwiecki, Aleksandra; Rath, Matthias

    2016-01-01

    Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction. In addition to the side effects mentioned above by different channel blockers, these drugs can cause arterial wall damage, thereby contributing to vascular wall structure destabilization and promoting events facilitating rupture of plaques. Collagen synthesis is regulated by ascorbic acid, which is also essential for its optimum structure as a cofactor in lysine and proline hydroxylation, a precondition for optimum crosslinking of collagen and elastin. Therefore, the main objective in this study was to evaluate effects of various types of channel blockers on intracellular accumulation and cellular functions of ascorbate, specifically in relation to formation and extracellular deposition of major collagen types relevant for vascular function. Effects of select Na- and Ca- channel blockers on collagen synthesis and deposition were evaluated in cultured human dermal fibroblasts and aortic smooth muscle cells by immunoassay. All channel blockers tested demonstrated inhibitory effects on collagen type I deposition to the ECM by fibroblasts, each to a different degree. Ascorbic acid significantly increased collagen I ECM deposition. Nifedipine (50 µM), a representative of channel blockers tested, significantly reduced ascorbic acid and ascorbyl palmitate-dependent ECM deposition of collagen type l and collagen type lV by cultured aortic smooth muscle cells. In addition, nifedipine (50 µM) significantly reduced ascorbate-dependent collagen type l and type lV synthesis by cultured aortic smooth

  6. A doubly cross-linked nano-adhesive for the reliable sealing of flexible microfluidic devices.

    PubMed

    You, Jae Bem; Min, Kyoung-Ik; Lee, Bora; Kim, Dong-Pyo; Im, Sung Gap

    2013-04-01

    Along with the expansion of microfluidics into many areas of applications such as sensors, microreactors and analytical tools, many other materials besides poly(dimethylsiloxane) (PDMS) have been suggested such as poly(imide) (PI) or poly(ethylene terephthalate) (PET). However, the sealing methods for these materials are not reliable in that many of the methods are specific to the substrate materials. Here, we report a novel robust doubly cross-linked nano-adhesive (DCNA) for bonding of various heterogeneous substrates. By depositing 200 nm of epoxy-containing polymer, poly(glycidyl methacrylate), via initiated chemical vapour deposition (iCVD) onto various substrates and cross-linking them with ethylenediamine, a strong adhesion was obtained between the substrates. This adhesive system was not only able to bond various difficult-to-bond substrates, such as PET or PI, but it could also preserve the complicated morphology of the surfaces owing to the thin nature of the DCNA system. The DCNA allowed fabrication of microfluidic devices using both rigid substrates, such as silicon wafer and glass, and flexible substrates, such as PDMS, PET and PI. The burst pressure of the devices sealed with DCNA exceeded 2.5 MPa, with a maximum burst pressure of 11.7 MPa. Furthermore, the adhesive system demonstrated an exceptional chemical and thermal resistance. The adhesion strength of the adhesive sandwiched between glass substrates remained the same even after a 10 day exposure to strong organic solvents such as toluene, acetone, and tetrahydrofuran (THF). Also, exposure to 200 °C for 15 h was not able to damage the adhesion strength. Using the high adhesive strength and flexibility of DCNA, flexible microfluidic devices that can be completely folded or rolled without any delamination during the operation were fabricated. The DCNA bonding is highly versatile in the sealing of microfluidic systems, and is compatible with a wide selection of materials, including flexible and

  7. Gas-phase reactions of doubly charged actinide cations with alkanes and alkenes--probing the chemical activity of 5f electrons from Th to Cm.

    PubMed

    Marçalo, Joaquim; Santos, Marta; Gibson, John K

    2011-11-01

    Small alkanes (methane, ethane, propane, n-butane) and alkenes (ethene, propene, 1-butene) were used to probe the gas-phase reactivity of doubly charged actinide cations, An(2+) (An = Th, Pa, U, Np, Pu, Am, Cm), by means of Fourier transform ion cyclotron resonance mass spectrometry. Different combinations of doubly and singly charged ions were observed as reaction products, comprising species formed via metal-ion induced eliminations of small molecules, simple adducts and ions resulting from electron, hydride or methide transfer channels. Th(2+), Pa(2+), U(2+) and Np(2+) preferentially yielded doubly charged products of hydrocarbon activation, while Pu(2+), Am(2+) and Cm(2+) reacted mainly through transfer channels. Cm(2+) was also capable of forming doubly charged products with some of the hydrocarbons whereas Pu(2+) and Am(2+) were not, these latter two ions conversely being the only for which adduct formation was observed. The product distributions and the reaction efficiencies are discussed in relation to the electronic configurations of the metal ions, the energetics of the reactions and similar studies previously performed with doubly charged lanthanide and transition metal cations. The conditions for hydrocarbon activation to occur as related to the accessibility of electronic configurations with one or two 5f and/or 6d unpaired electrons are examined and the possible chemical activity of the 5f electrons in these early actinide ions, particularly Pa(2+), is considered.

  8. Selective Modulation of Histaminergic Inputs on Projection Neurons of Cerebellum Rapidly Promotes Motor Coordination via HCN Channels.

    PubMed

    Zhang, Jun; Zhuang, Qian-Xing; Li, Bin; Wu, Guan-Yi; Yung, Wing-Ho; Zhu, Jing-Ning; Wang, Jian-Jun

    2016-03-01

    Insights into function of central histaminergic system, a general modulator originating from the hypothalamus for whole brain activity, in motor control are critical for understanding the mechanism underlying somatic-nonsomatic integration. Here, we show a novel selective role of histamine in the cerebellar nuclei, the final integrative center and output of the cerebellum. Histamine depolarizes projection neurons but not interneurons in the cerebellar nuclei via the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels coupled to histamine H2 receptors, which are exclusively expressed on glutamatergic and glycinergic projection neurons. Furthermore, blockage of HCN channels to block endogenous histaminergic afferent inputs in the cerebellar nuclei significantly attenuates motor balance and coordination. Therefore, through directly and quickly modulation on projection neurons but not interneurons in the cerebellar nuclei, central histaminergic system may act as a critical biasing force to not only promptly regulate ongoing movement but also realize a rapid integration of somatic and nonsomatic response.

  9. ML418: The First Selective, Sub-Micromolar Pore Blocker of Kir7.1 Potassium Channels.

    PubMed

    Swale, Daniel R; Kurata, Haruto; Kharade, Sujay V; Sheehan, Jonathan; Raphemot, Rene; Voigtritter, Karl R; Figueroa, Eric E; Meiler, Jens; Blobaum, Anna L; Lindsley, Craig W; Hopkins, Corey R; Denton, Jerod S

    2016-07-20

    The inward rectifier potassium (Kir) channel Kir7.1 (KCNJ13) has recently emerged as a key regulator of melanocortin signaling in the brain, electrolyte homeostasis in the eye, and uterine muscle contractility during pregnancy. The pharmacological tools available for exploring the physiology and therapeutic potential of Kir7.1 have been limited to relatively weak and nonselective small-molecule inhibitors. Here, we report the discovery in a fluorescence-based high-throughput screen of a novel Kir7.1 channel inhibitor, VU714. Site-directed mutagenesis of pore-lining amino acid residues identified glutamate 149 and alanine 150 as essential determinants of VU714 activity. Lead optimization with medicinal chemistry generated ML418, which exhibits sub-micromolar activity (IC50 = 310 nM) and superior selectivity over other Kir channels (at least 17-fold selective over Kir1.1, Kir2.1, Kir2.2, Kir2.3, Kir3.1/3.2, and Kir4.1) except for Kir6.2/SUR1 (equally potent). Evaluation in the EuroFins Lead Profiling panel of 64 GPCRs, ion-channels, and transporters for off-target activity of ML418 revealed a relatively clean ancillary pharmacology. While ML418 exhibited low CLHEP in human microsomes which could be modulated with lipophilicity adjustments, it showed high CLHEP in rat microsomes regardless of lipophilicity. A subsequent in vivo PK study of ML418 by intraperitoneal (IP) administration (30 mg/kg dosage) revealed a suitable PK profile (Cmax = 0.20 μM and Tmax = 3 h) and favorable CNS distribution (mouse brain/plasma Kp of 10.9 to support in vivo studies. ML418, which represents the current state-of-the-art in Kir7.1 inhibitors, should be useful for exploring the physiology of Kir7.1 in vitro and in vivo. PMID:27184474

  10. Identification of a Peptide Toxin from Grammostola spatulata Spider Venom That Blocks Cation-Selective Stretch-Activated Channels

    PubMed Central

    Suchyna, Thomas M.; Johnson, Janice H.; Hamer, Katherine; Leykam, Joseph F.; Gage, Douglas A.; Clemo, Henry F.; Baumgarten, Clive M.; Sachs, Frederick

    2000-01-01

    We have identified a 35 amino acid peptide toxin of the inhibitor cysteine knot family that blocks cationic stretch-activated ion channels. The toxin, denoted GsMTx-4, was isolated from the venom of the spider Grammostola spatulata and has <50% homology to other neuroactive peptides. It was isolated by fractionating whole venom using reverse phase HPLC, and then assaying fractions on stretch-activated channels (SACs) in outside-out patches from adult rat astrocytes. Although the channel gating kinetics were different between cell-attached and outside-out patches, the properties associated with the channel pore, such as selectivity for alkali cations, conductance (∼45 pS at −100 mV) and a mild rectification were unaffected by outside-out formation. GsMTx-4 produced a complete block of SACs in outside-out patches and appeared specific since it had no effect on whole-cell voltage-sensitive currents. The equilibrium dissociation constant of ∼630 nM was calculated from the ratio of association and dissociation rate constants. In hypotonically swollen astrocytes, GsMTx-4 produces ∼40% reduction in swelling-activated whole-cell current. Similarly, in isolated ventricular cells from a rabbit dilated cardiomyopathy model, GsMTx-4 produced a near complete block of the volume-sensitive cation-selective current, but did not affect the anion current. In the myopathic heart cells, where the swell-induced current is tonically active, GsMTx-4 also reduced the cell size. This is the first report of a peptide toxin that specifically blocks stretch-activated currents. The toxin affect on swelling-activated whole-cell currents implicates SACs in volume regulation. PMID:10779316

  11. Search for the doubly charmed baryon

    NASA Astrophysics Data System (ADS)

    Aaij, R.; Adeva, B.; Adinolfi, M.; Adrover, C.; Affolder, A.; Ajaltouni, Z.; Albrecht, J.; Alessio, F.; Alexander, M.; Ali, S.; Alkhazov, G.; Alvarez Cartelle, P.; Alves, A. A.; Amato, S.; Amerio, S.; Amhis, Y.; Anderlini, L.; Anderson, J.; Andreassen, R.; Andrews, J. E.; Appleby, R. B.; Aquines Gutierrez, O.; Archilli, F.; Artamonov, A.; Artuso, M.; Aslanides, E.; Auriemma, G.; Baalouch, M.; Bachmann, S.; Back, J. J.; Badalov, A.; Baesso, C.; Balagura, V.; Baldini, W.; Barlow, R. J.; Barschel, C.; Barsuk, S.; Barter, W.; Bauer, Th.; Bay, A.; Beddow, J.; Bedeschi, F.; Bediaga, I.; Belogurov, S.; Belous, K.; Belyaev, I.; Ben-Haim, E.; Bencivenni, G.; Benson, S.; Benton, J.; Berezhnoy, A.; Bernet, R.; Bettler, M.-O.; van Beuzekom, M.; Bien, A.; Bifani, S.; Bird, T.; Bizzeti, A.; Bjørnstad, P. M.; Blake, T.; Blanc, F.; Blouw, J.; Blusk, S.; Bocci, V.; Bondar, A.; Bondar, N.; Bonivento, W.; Borghi, S.; Borgia, A.; Bowcock, T. J. V.; Bowen, E.; Bozzi, C.; Brambach, T.; van den Brand, J.; Bressieux, J.; Brett, D.; Britsch, M.; Britton, T.; Brook, N. H.; Brown, H.; Bursche, A.; Busetto, G.; Buytaert, J.; Cadeddu, S.; Callot, O.; Calvi, M.; Calvo Gomez, M.; Camboni, A.; Campana, P.; Campora Perez, D.; Carbone, A.; Carboni, G.; Cardinale, R.; Cardini, A.; Carranza-Mejia, H.; Carson, L.; Carvalho Akiba, K.; Casse, G.; Castillo Garcia, L.; Cattaneo, M.; Cauet, Ch.; Cenci, R.; Charles, M.; Charpentier, Ph.; Cheung, S.-F.; Chiapolini, N.; Chrzaszcz, M.; Ciba, K.; Cid Vidal, X.; Ciezarek, G.; Clarke, P. E. L.; Clemencic, M.; Cliff, H. V.; Closier, J.; Coca, C.; Coco, V.; Cogan, J.; Cogneras, E.; Collins, P.; Comerma-Montells, A.; Contu, A.; Cook, A.; Coombes, M.; Coquereau, S.; Corti, G.; Couturier, B.; Cowan, G. A.; Craik, D. C.; Cruz Torres, M.; Cunliffe, S.; Currie, R.; D'Ambrosio, C.; David, P.; David, P. N. Y.; Davis, A.; De Bonis, I.; De Bruyn, K.; De Capua, S.; De Cian, M.; De Miranda, J. M.; De Paula, L.; De Silva, W.; De Simone, P.; Decamp, D.; Deckenhoff, M.; Del Buono, L.; Déléage, N.; Derkach, D.; Deschamps, O.; Dettori, F.; Di Canto, A.; Dijkstra, H.; Dogaru, M.; Donleavy, S.; Dordei, F.; Dosil Suárez, A.; Dossett, D.; Dovbnya, A.; Dupertuis, F.; Durante, P.; Dzhelyadin, R.; Dziurda, A.; Dzyuba, A.; Easo, S.; Egede, U.; Egorychev, V.; Eidelman, S.; van Eijk, D.; Eisenhardt, S.; Eitschberger, U.; Ekelhof, R.; Eklund, L.; El Rifai, I.; Elsasser, Ch.; Falabella, A.; Färber, C.; Farinelli, C.; Farry, S.; Ferguson, D.; Fernandez Albor, V.; Ferreira Rodrigues, F.; Ferro-Luzzi, M.; Filippov, S.; Fiore, M.; Fitzpatrick, C.; Fontana, M.; Fontanelli, F.; Forty, R.; Francisco, O.; Frank, M.; Frei, C.; Frosini, M.; Furfaro, E.; Gallas Torreira, A.; Galli, D.; Gandelman, M.; Gandini, P.; Gao, Y.; Garofoli, J.; Garosi, P.; Garra Tico, J.; Garrido, L.; Gaspar, C.; Gauld, R.; Gersabeck, E.; Gersabeck, M.; Gershon, T.; Ghez, Ph.; Gibson, V.; Giubega, L.; Gligorov, V. V.; Göbel, C.; Golubkov, D.; Golutvin, A.; Gomes, A.; Gorbounov, P.; Gordon, H.; Grabalosa Gándara, M.; Graciani Diaz, R.; Granado Cardoso, L. A.; Graugés, E.; Graziani, G.; Grecu, A.; Greening, E.; Gregson, S.; Griffith, P.; Grillo, L.; Grünberg, O.; Gui, B.; Gushchin, E.; Guz, Yu.; Gys, T.; Hadjivasiliou, C.; Haefeli, G.; Haen, C.; Haines, S. C.; Hall, S.; Hamilton, B.; Hampson, T.; Hansmann-Menzemer, S.; Harnew, N.; Harnew, S. T.; Harrison, J.; Hartmann, T.; He, J.; Head, T.; Heijne, V.; Hennessy, K.; Henrard, P.; Hernando Morata, J. A.; van Herwijnen, E.; Heß, M.; Hicheur, A.; Hicks, E.; Hill, D.; Hoballah, M.; Hombach, C.; Hulsbergen, W.; Hunt, P.; Huse, T.; Hussain, N.; Hutchcroft, D.; Hynds, D.; Iakovenko, V.; Idzik, M.; Ilten, P.; Jacobsson, R.; Jaeger, A.; Jans, E.; Jaton, P.; Jawahery, A.; Jing, F.; John, M.; Johnson, D.; Jones, C. R.; Joram, C.; Jost, B.; Kaballo, M.; Kandybei, S.; Kanso, W.; Karacson, M.; Karbach, T. M.; Kenyon, I. R.; Ketel, T.; Khanji, B.; Kochebina, O.; Komarov, I.; Koopman, R. F.; Koppenburg, P.; Korolev, M.; Kozlinskiy, A.; Kravchuk, L.; Kreplin, K.; Kreps, M.; Krocker, G.; Krokovny, P.; Kruse, F.; Kucharczyk, M.; Kudryavtsev, V.; Kurek, K.; Kvaratskheliya, T.; La Thi, V. N.; Lacarrere, D.; Lafferty, G.; Lai, A.; Lambert, D.; Lambert, R. W.; Lanciotti, E.; Lanfranchi, G.; Langenbruch, C.; Latham, T.; Lazzeroni, C.; Le Gac, R.; van Leerdam, J.; Lees, J.-P.; Lefèvre, R.; Leflat, A.; Lefrançois, J.; Leo, S.; Leroy, O.; Lesiak, T.; Leverington, B.; Li, Y.; Li Gioi, L.; Liles, M.; Lindner, R.; Linn, C.; Liu, B.; Liu, G.; Lohn, S.; Longstaff, I.; Lopes, J. H.; Lopez-March, N.; Lu, H.; Lucchesi, D.; Luisier, J.; Luo, H.; Lupton, O.; Machefert, F.; Machikhiliyan, I. V.; Maciuc, F.; Maev, O.; Malde, S.; Manca, G.; Mancinelli, G.; Maratas, J.; Marconi, U.; Marino, P.; Märki, R.; Marks, J.; Martellotti, G.; Martens, A.; Martín Sánchez, A.; Martinelli, M.; Martinez Santos, D.; Martins Tostes, D.; Martynov, A.; Massafferri, A.; Matev, R.; Mathe, Z.; Matteuzzi, C.; Maurice, E.; Mazurov, A.; McCarthy, J.; McNab, A.; McNulty, R.; McSkelly, B.; Meadows, B.; Meier, F.; Meissner, M.; Merk, M.; Milanes, D. A.; Minard, M.-N.; Molina Rodriguez, J.; Monteil, S.; Moran, D.; Morawski, P.; Mordà, A.; Morello, M. J.; Mountain, R.; Mous, I.; Muheim, F.; Müller, K.; Muresan, R.; Muryn, B.; Muster, B.; Naik, P.; Nakada, T.; Nandakumar, R.; Nasteva, I.; Needham, M.; Neubert, S.; Neufeld, N.; Nguyen, A. D.; Nguyen, T. D.; Nguyen-Mau, C.; Nicol, M.; Niess, V.; Niet, R.; Nikitin, N.; Nikodem, T.; Nomerotski, A.; Novoselov, A.; Oblakowska-Mucha, A.; Obraztsov, V.; Oggero, S.; Ogilvy, S.; Okhrimenko, O.; Oldeman, R.; Orlandea, M.; Otalora Goicochea, J. M.; Owen, P.; Oyanguren, A.; Pal, B. K.; Palano, A.; Palutan, M.; Panman, J.; Papanestis, A.; Pappagallo, M.; Parkes, C.; Parkinson, C. J.; Passaleva, G.; Patel, G. D.; Patel, M.; Patrick, G. N.; Patrignani, C.; Pavel-Nicorescu, C.; Pazos Alvarez, A.; Pearce, A.; Pellegrino, A.; Penso, G.; Pepe Altarelli, M.; Perazzini, S.; Perez Trigo, E.; Pérez-Calero Yzquierdo, A.; Perret, P.; Perrin-Terrin, M.; Pescatore, L.; Pesen, E.; Pessina, G.; Petridis, K.; Petrolini, A.; Phan, A.; Picatoste Olloqui, E.; Pietrzyk, B.; Pilař, T.; Pinci, D.; Playfer, S.; Plo Casasus, M.; Polci, F.; Polok, G.; Poluektov, A.; Polycarpo, E.; Popov, A.; Popov, D.; Popovici, B.; Potterat, C.; Powell, A.; Prisciandaro, J.; Pritchard, A.; Prouve, C.; Pugatch, V.; Puig Navarro, A.; Punzi, G.; Qian, W.; Rachwal, B.; Rademacker, J. H.; Rakotomiaramanana, B.; Rangel, M. S.; Raniuk, I.; Rauschmayr, N.; Raven, G.; Redford, S.; Reichert, S.; Reid, M. M.; dos Reis, A. C.; Ricciardi, S.; Richards, A.; Rinnert, K.; Rives Molina, V.; Roa Romero, D. A.; Robbe, P.; Roberts, D. A.; Rodrigues, A. B.; Rodrigues, E.; Rodriguez Perez, P.; Roiser, S.; Romanovsky, V.; Romero Vidal, A.; Rotondo, M.; Rouvinet, J.; Ruf, T.; Ruffini, F.; Ruiz, H.; Ruiz Valls, P.; Sabatino, G.; Saborido Silva, J. J.; Sagidova, N.; Sail, P.; Saitta, B.; Salustino Guimaraes, V.; Sanmartin Sedes, B.; Santacesaria, R.; Santamarina Rios, C.; Santovetti, E.; Sapunov, M.; Sarti, A.; Satriano, C.; Satta, A.; Savrie, M.; Savrina, D.; Schiller, M.; Schindler, H.; Schlupp, M.; Schmelling, M.; Schmidt, B.; Schneider, O.; Schopper, A.; Schune, M.-H.; Schwemmer, R.; Sciascia, B.; Sciubba, A.; Seco, M.; Semennikov, A.; Senderowska, K.; Sepp, I.; Serra, N.; Serrano, J.; Seyfert, P.; Shapkin, M.; Shapoval, I.; Shcheglov, Y.; Shears, T.; Shekhtman, L.; Shevchenko, O.; Shevchenko, V.; Shires, A.; Silva Coutinho, R.; Sirendi, M.; Skidmore, N.; Skwarnicki, T.; Smith, N. A.; Smith, E.; Smith, E.; Smith, J.; Smith, M.; Sokoloff, M. D.; Soler, F. J. P.; Soomro, F.; Souza, D.; Souza De Paula, B.; Spaan, B.; Sparkes, A.; Spradlin, P.; Stagni, F.; Stahl, S.; Steinkamp, O.; Stevenson, S.; Stoica, S.; Stone, S.; Storaci, B.; Straticiuc, M.; Straumann, U.; Subbiah, V. K.; Sun, L.; Sutcliffe, W.; Swientek, S.; Syropoulos, V.; Szczekowski, M.; Szczypka, P.; Szilard, D.; Szumlak, T.; T'Jampens, S.; Teklishyn, M.; Teodorescu, E.; Teubert, F.; Thomas, C.; Thomas, E.; van Tilburg, J.; Tisserand, V.; Tobin, M.; Tolk, S.; Tonelli, D.; Topp-Joergensen, S.; Torr, N.; Tournefier, E.; Tourneur, S.; Tran, M. T.; Tresch, M.; Tsaregorodtsev, A.; Tsopelas, P.; Tuning, N.; Ubeda Garcia, M.; Ukleja, A.; Ustyuzhanin, A.; Uwer, U.; Vagnoni, V.; Valenti, G.; Vallier, A.; Vazquez Gomez, R.; Vazquez Regueiro, P.; Vázquez Sierra, C.; Vecchi, S.; Velthuis, J. J.; Veltri, M.; Veneziano, G.; Vesterinen, M.; Viaud, B.; Vieira, D.; Vilasis-Cardona, X.; Vollhardt, A.; Volyanskyy, D.; Voong, D.; Vorobyev, A.; Vorobyev, V.; Voß, C.; Voss, H.; Waldi, R.; Wallace, C.; Wallace, R.; Wandernoth, S.; Wang, J.; Ward, D. R.; Watson, N. K.; Webber, A. D.; Websdale, D.; Whitehead, M.; Wicht, J.; Wiechczynski, J.; Wiedner, D.; Wiggers, L.; Wilkinson, G.; Williams, M. P.; Williams, M.; Wilson, F. F.; Wimberley, J.; Wishahi, J.; Wislicki, W.; Witek, M.; Wormser, G.; Wotton, S. A.; Wright, S.; Wu, S.; Wyllie, K.; Xie, Y.; Xing, Z.; Yang, Z.; Yuan, X.; Yushchenko, O.; Zangoli, M.; Zavertyaev, M.; Zhang, F.; Zhang, L.; Zhang, W. C.; Zhang, Y.; Zhelezov, A.; Zhokhov, A.; Zhong, L.; Zvyagin, A.

    2013-12-01

    A search for the doubly charmed baryon in the decay mode is performed with a data sample, corresponding to an integrated luminosity of 0.65 fb-1, of pp collisions recorded at a centre-of-mass energy of 7 TeV. No significant signal is found in the mass range 3300-3800 MeV /c 2. Upper limits at the 95% confidence level on the ratio of the production cross-section times branching fraction to that of the , R, are given as a function of the mass and lifetime. The largest upper limits range from R < 1.5 × 10-2 for a lifetime of 100 fs to R < 3 .9 × 10-4 for a lifetime of 400 fs. [Figure not available: see fulltext.

  12. Brushless generation with cascaded doubly fed machines

    NASA Astrophysics Data System (ADS)

    Ortmeyer, T. H.; Borger, W. U.

    The solid state converter used by the system operates at a fraction of the system power and frequency. What is more, the system operates without hydraulics. The fundamental characteristics of operation are discussed. Attention is given to the choice of optimum speeds and pole numbers for a given speed range. It is shown that two discrete operating modes exist for this type of system, namely subsynchronous and supersynchronous. System analysis is treated, and particular power, var, and frequency requirements for a 1.5:1 speed range system are presented. Cascaded doubly fed machines are seen as forming a viable basis for a generator system that holds considerable promise for operation that is high in reliability and low in cost.

  13. Data selection criteria in star-based monitoring of GOES imager visible-channel responsivities

    NASA Astrophysics Data System (ADS)

    Chang, I.-Lok; Crosby, David; Dean, Charles; Weinreb, Michael; Baltimore, Perry; Baucom, Jeanette; Han, Dejiang

    2004-10-01

    Monitoring the responsivities of the visible channels of the operational Geostationary Operational Environmental Satellites (GOES) is an on-going effort at NOAA. Various techniques are being used. In this paper we describe the technique based on the analysis of star signals that are used in the GOES Orbit and Attitude Tracking System (OATS) for satellite attitude and orbit determination. Time series of OATS star observations give information on the degradation of the detectors of a visible channel. Investigations of star data from the past three years have led to several modifications of the method we initially used to calculate the exponential degradation coefficient of a star-signal time series. First we observed that different patterns of detector output versus time result when star images drift across the detector array along different trajectories. We found that certain trajectories should be rejected in the data analysis. We found also that some detector-dependent weighting coefficients used in the OATS analysis tend to scatter the star signals measured by different detectors. We present a set of modifications to our star monitoring algorithms for resolving such problems. Other simple enhancements on the algorithms will also be described. With these modifications, the time series of the star signals show less scatter. This allows for more confidence in the estimated degradation rates and a more realistic statistical analysis on the extent of uncertainty in those rates. The resulting time series and estimated degradation rates for the visible channels of GOES-8 and GOES-10 Imagers will be presented.

  14. A K+-selective CNG channel orchestrates Ca2+ signalling in zebrafish sperm

    PubMed Central

    Fechner, Sylvia; Alvarez, Luis; Bönigk, Wolfgang; Müller, Astrid; Berger, Thomas K; Pascal, Rene; Trötschel, Christian; Poetsch, Ansgar; Stölting, Gabriel; Siegfried, Kellee R; Kremmer, Elisabeth; Seifert, Reinhard; Kaupp, U Benjamin

    2015-01-01

    Calcium in the flagellum controls sperm navigation. In sperm of marine invertebrates and mammals, Ca2+ signalling has been intensely studied, whereas for fish little is known. In sea urchin sperm, a cyclic nucleotide-gated K+ channel (CNGK) mediates a cGMP-induced hyperpolarization that evokes Ca2+ influx. Here, we identify in sperm of the freshwater fish Danio rerio a novel CNGK family member featuring non-canonical properties. It is located in the sperm head rather than the flagellum and is controlled by intracellular pH, but not cyclic nucleotides. Alkalization hyperpolarizes sperm and produces Ca2+ entry. Ca2+ induces spinning-like swimming, different from swimming of sperm from other species. The “spinning” mode probably guides sperm into the micropyle, a narrow entrance on the surface of fish eggs. A picture is emerging of sperm channel orthologues that employ different activation mechanisms and serve different functions. The channel inventories probably reflect adaptations to species-specific challenges during fertilization. DOI: http://dx.doi.org/10.7554/eLife.07624.001 PMID:26650356

  15. Developing a comparative docking protocol for the prediction of peptide selectivity profiles: investigation of potassium channel toxins.

    PubMed

    Chen, Po-Chia; Kuyucak, Serdar

    2012-02-01

    During the development of selective peptides against highly homologous targets, a reliable tool is sought that can predict information on both mechanisms of binding and relative affinities. These tools must first be tested on known profiles before application on novel therapeutic candidates. We therefore present a comparative docking protocol in HADDOCK using critical motifs, and use it to "predict" the various selectivity profiles of several major αKTX scorpion toxin families versus K(v)1.1, K(v)1.2 and K(v)1.3. By correlating results across toxins of similar profiles, a comprehensive set of functional residues can be identified. Reasonable models of channel-toxin interactions can be then drawn that are consistent with known affinity and mutagenesis. Without biological information on the interaction, HADDOCK reproduces mechanisms underlying the universal binding of αKTX-2 toxins, and K(v)1.3 selectivity of αKTX-3 toxins. The addition of constraints encouraging the critical lysine insertion confirms these findings, and gives analogous explanations for other families, including models of partial pore-block in αKTX-6. While qualitatively informative, the HADDOCK scoring function is not yet sufficient for accurate affinity-ranking. False minima in low-affinity complexes often resemble true binding in high-affinity complexes, despite steric/conformational penalties apparent from visual inspection. This contamination significantly complicates energetic analysis, although it is usually possible to obtain correct ranking via careful interpretation of binding-well characteristics and elimination of false positives. Aside from adaptations to the broader potassium channel family, we suggest that this strategy of comparative docking can be extended to other channels of interest with known structure, especially in cases where a critical motif exists to improve docking effectiveness.

  16. Doubly Magic Optical Trapping for Cs Atom Hyperfine Clock Transitions

    NASA Astrophysics Data System (ADS)

    Carr, A. W.; Saffman, M.

    2016-10-01

    We analyze doubly magic trapping of Cs hyperfine transitions including previously neglected contributions from the ground state hyperpolarizability and the interaction of the laser light and a static magnetic field. Extensive numerical searches do not reveal any doubly magic trapping conditions for any pair of hyperfine states. However, including the hyperpolarizability reveals light intensity insensitive traps for a wide range of wavelengths at specific intensities. We then investigate the use of bichromatic trapping light fields. Deploying a bichromatic scheme, we demonstrate doubly magic red and blue detuned traps for pairs of states separated by one or two single photon transitions.

  17. Analyzing the components of the free-energy landscape in a calcium selective ion channel by Widom's particle insertion method

    NASA Astrophysics Data System (ADS)

    Boda, Dezső; Giri, Janhavi; Henderson, Douglas; Eisenberg, Bob; Gillespie, Dirk

    2011-02-01

    The selectivity filter of the L-type calcium channel works as a Ca2 + binding site with a very large affinity for Ca2 + versus Na+. Ca2 + replaces half of the Na+ ions in the filter even when these ions are present in 1 μM and 30 mM concentrations in the bath, respectively. The energetics of this strong selectivity is analyzed in this paper. We use Widom's particle insertion method to compute the space-dependent profiles of excess chemical potential in our grand canonical Monte Carlo simulations. These profiles define the free-energy landscape for the various ions. Following Gillespie [Biophys. J. 94, 1169 (2008)], the difference of the excess chemical potentials for the two competing ions defines the advantage that one of the ions has over the other in the competition for space in the crowded selectivity filter. These advantages depend on ionic bath concentrations: the ion that is present in the bath in larger quantity (Na+) has the "number" advantage which is balanced by the free-energy advantage of the other ion (Ca2 +). The excess chemical potentials are decomposed into hard sphere exclusion and electrostatic components. The electrostatic terms correspond to interactions with the mean electric field produced by ions and induced charges as well to ionic correlations beyond the mean field description. Dielectrics are needed to produce micromolar Ca2 + versus Na+ selectivity in the L-type channel. We study the behavior of these terms with changes in bath concentrations of ions, charges, and diameters of ions, as well as geometrical parameters such as radius of the pore and the dielectric constant of the protein. Ion selectivity in calcium binding proteins probably has a similar mechanism.

  18. Affinity purification of the voltage-sensitive sodium channel from electroplax with resins selective for sialic acid

    SciTech Connect

    James, W.M.; Emerick, M.C.; Agnew, W.S. )

    1989-07-11

    The voltage-sensitive sodium channel present in the eel (Electrophorus electricus) has an unusually high content of sialic acid, including {alpha}-(2{yields}8)-linked polysialic acid, not found in other electroplax membrane glycopeptides. Lectins from Limax flavus (LFA) and wheat germ (WGA) proved the most effective of 11 lectin resins tried. The most selective resin was prepared from IgM antibodies against Neisseria meningitidis {alpha}-(2{yields}8)-polysialic acid which were affinity purified and coupled to Sepharose 4B. The sodium channel was found to bind to WGA, LFA, and IgM resins and was readily eluted with the appropriate soluble carbohydrates. Experiments with LFA and IgM resins demonstrated binding and unbinding rates and displacement kinetics, which suggest highly specific binding at multiple sites on the sodium channel protein. In preparative-scale purification of protein previously fractionated by anion-exchange chromatography, without stabilizing TTX, high yields were reproducibly obtained. Further, when detergent extracts were prepared from electroplax membranes fractionated by low-speed sedimentation, a single step over the IgM resin provided a 70-fold purification, yielding specific activities of 3,200 pmol of ({sup 3}H)TTX-binding sites/mg of protein and a single polypeptide of {approximately}285,000 Da on SDS-acrylamide gels. No small peptides were observed after this 5-h isolation. The authors describe a cation-dependent stabilization with millimolar levels of monovalent and micromolar levels of divalent species.

  19. MDIMP, a novel cardiac Ca(2+) channel blocker with atrial selectivity.

    PubMed

    Santamaria-Herrera, Mireille Aline; Ríos-Pérez, Erick Benjamín; de la Rosa, Juan Antonio Manuel; García-Castañeda, Maricela; Osornio-Garduño, Diana Stephanie; Ramos-Mondragón, Roberto; Mancilla-Percino, Teresa; Avila, Guillermo

    2016-06-15

    In cardiac muscle cells both T-and L-type Ca(2+) channels (TTCCs and LTCCs, respectively) are expressed, and the latter are relevant to a process known as excitation-contraction coupling (ECC). Evidence obtained from docking studies suggests that isoindolines derived from α-amino acids bind to the LTCC CaV1.2. In the present study, we investigated whether methyl (S)-2-(1,3-dihydroisoindol-2-yl)-4-methylpentanoate (MDIMP), which is derived from L-leucine, modulates both Ca(2+) channels and ECC. To this end, mechanical properties, as well as Ca(2+) transients and currents, were all investigated in isolated cardiac myocytes. The effects of MDIMP on CaV1.2 (transiently expressed in 293T/17 cells) were also studied. In this system, evidence was found for an inhibitory action that develops and recovers in min, with an IC50 of 450µM. With respect to myocytes: atrial-TTCCs, atrial-LTCCs, and ventricular-LTCCs were also inhibited, in that order of potency. Accordingly, Ca(2+) transients, contractions, and window currents of LTCCs were all reduced more strongly in atrial cells. Interestingly, while the modulation of LTCCs was state-independent in these cells, it was state-dependent, and dual, on the ventricular ones. Furthermore, practically all of the ventricular LTCCs were closed at resting membrane potentials. This could explain their resistance to MDIMP, as they were affected in only open or inactivated states. All these features in turn explain the preferential down-regulation of the atrial ECC. Thus, our results support the view that isoindolines bind to Ca(2+) channels, improve our knowledge of the corresponding structure-function relationship, and may be relevant for conditions where decreased atrial activity is desired. PMID:27089820

  20. Alpha-helical hydrophobic polypeptides form proton-selective channels in lipid bilayers.

    PubMed Central

    Oliver, A E; Deamer, D W

    1994-01-01

    Proton translocation is important in membrane-mediated processes such as ATP-dependent proton pumps, ATP synthesis, bacteriorhodopsin, and cytochrome oxidase function. The fundamental mechanism, however, is poorly understood. To test the theoretical possibility that bundles of hydrophobic alpha-helices could provide a low energy pathway for ion translocation through the lipid bilayer, polyamino acids were incorporated into extruded liposomes and planar lipid membranes, and proton translocation was measured. Liposomes with incorporated long-chain poly-L-alanine or poly-L-leucine were found to have proton permeability coefficients 5 to 7 times greater than control liposomes, whereas short-chain polyamino acids had relatively little effect. Potassium permeability was not increased markedly by any of the polyamino acids tested. Analytical thin layer chromatography measurements of lipid content and a fluorescamine assay for amino acids showed that there were approximately 135 polyleucine or 65 polyalanine molecules associated with each liposome. Fourier transform infrared spectroscopy indicated that a major fraction of the long-chain hydrophobic peptides existed in an alpha-helical conformation. Single-channel recording in both 0.1 N HCl and 0.1 M KCl was also used to determine whether proton-conducting channels formed in planar lipid membranes (phosphatidylcholine/phosphatidylethanolamine, 1:1). Poly-L-leucine and poly-L-alanine in HCl caused a 10- to 30-fold increase in frequency of conductive events compared to that seen in KCl or by the other polyamino acids in either solution. This finding correlates well with the liposome observations in which these two polyamino acids caused the largest increase in membrane proton permeability but had little effect on potassium permeability. Poly-L-leucine was considerably more conductive than poly-L-alanine due primarily to larger event amplitudes and, to a lesser extent, a higher event frequency. Poly-L-leucine caused two

  1. Alpha-helical hydrophobic polypeptides form proton-selective channels in lipid bilayers

    NASA Technical Reports Server (NTRS)

    Oliver, A. E.; Deamer, D. W.

    1994-01-01

    Proton translocation is important in membrane-mediated processes such as ATP-dependent proton pumps, ATP synthesis, bacteriorhodopsin, and cytochrome oxidase function. The fundamental mechanism, however, is poorly understood. To test the theoretical possibility that bundles of hydrophobic alpha-helices could provide a low energy pathway for ion translocation through the lipid bilayer, polyamino acids were incorporated into extruded liposomes and planar lipid membranes, and proton translocation was measured. Liposomes with incorporated long-chain poly-L-alanine or poly-L-leucine were found to have proton permeability coefficients 5 to 7 times greater than control liposomes, whereas short-chain polyamino acids had relatively little effect. Potassium permeability was not increased markedly by any of the polyamino acids tested. Analytical thin layer chromatography measurements of lipid content and a fluorescamine assay for amino acids showed that there were approximately 135 polyleucine or 65 polyalanine molecules associated with each liposome. Fourier transform infrared spectroscopy indicated that a major fraction of the long-chain hydrophobic peptides existed in an alpha-helical conformation. Single-channel recording in both 0.1 N HCl and 0.1 M KCl was also used to determine whether proton-conducting channels formed in planar lipid membranes (phosphatidylcholine/phosphatidylethanolamine, 1:1). Poly-L-leucine and poly-L-alanine in HCl caused a 10- to 30-fold increase in frequency of conductive events compared to that seen in KCl or by the other polyamino acids in either solution. This finding correlates well with the liposome observations in which these two polyamino acids caused the largest increase in membrane proton permeability but had little effect on potassium permeability. Poly-L-leucine was considerably more conductive than poly-L-alanine due primarily to larger event amplitudes and, to a lesser extent, a higher event frequency. Poly-L-leucine caused two

  2. Extracellular ATP directly gates a cation-selective channel in rabbit airway ciliated epithelial cells

    PubMed Central

    Korngreen, Alon; Ma, Weiyuan; Priel, Zvi; Silberberg, Shai D

    1998-01-01

    A membrane conductance activated by extracellular ATP was identified and characterized in freshly dissociated rabbit airway ciliated cells using the whole-cell and outside-out patch configurations of the patch-clamp technique. In solutions designed to maximize currents through voltage-gated calcium channels, there were no indications of voltage-gated Ba2+ currents. Extracellular ATP (but not UTP or ADP) activated a membrane conductance which remained activated for several minutes in the presence of ATP. The conductance was permeable to monovalent and divalent cations with approximate relative permeabilities (P) for PBa:PCs:PTEA of 4:1:0.1. Permeability to Cl− was negligible. Including GDP-β-S in the intracellular solution did not inhibit the effects of ATP, nor did GTP-γ-S irreversibly activate the conductance. In outside-out membrane patches, with GDP-β-S in the pipette solution, ATP activated ion channels which had a chord conductance of approximately 6 pS in symmetrical 150 mM CsCl solutions at −120 mV. Suramin (100 μM) inhibited the whole-cell currents activated by ATP (200 μM) by 93 ± 3 %. Similar effects of suramin were observed on ATP-activated channels in outside-out membrane patches. Extracellular ATP had a priming action on the response to subsequent exposure to ATP. At −40 mV, the time to half-maximal current activation (t½) was 46 ± 9 s during the first exposure to 200 μM ATP and decreased to 5 ± 3 s during a second exposure to the same concentration of ATP. The priming action of ATP was not inhibited by including GDP-β-S in the intracellular solution. The initial rate of activation increased with the concentration of ATP, and was voltage sensitive. During the first exposure to 200 μM ATP, t½ at +40 mV was 4-fold longer than t½ at −40 mV. Half-maximal activation of the conductance shifted from 210 ± 30 to 14 ± 4 μM added ATP when CaCl2 in the extracellular solution was reduced from 1.58 to 0.01 mM. The Hill coefficient for ATP

  3. Ultrastructure, pharmacologic inhibition, and transport selectivity of aquaporin channel-forming integral protein in proteoliposomes.

    PubMed

    Zeidel, M L; Nielsen, S; Smith, B L; Ambudkar, S V; Maunsbach, A B; Agre, P

    1994-02-15

    Reconstitution of highly purified aquaporin CHIP (channel-forming integral protein) into proteoliposomes was previously shown to confer high osmotic water permeability (Pf) to the membranes [Zeidel et al. (1992) Biochemistry 31, 7436-7440]. Here we report detailed ultrastructural, pharmacologic, and transport studies of human red cell CHIP in proteoliposomes. Freeze-fracture and transmission electron microscopy revealed a uniform distribution of CHIP which was incorporated into the membranes in both native and inverse orientations. Morphometric analysis of membranes reconstituted at three different concentrations of CHIP revealed that the intramembrane particles correspond to tetramers or possible higher order oligomers, and the Pf increased in direct proportion to the CHIP density. Proteolytic removal of the 4-kDa C-terminal cytoplasmic domain of CHIP did not alter the Pf or oligomerization in red cell membranes. CHIP exhibited a similar conductance for water when reconstituted into membranes of varied lipid compositions. The sensitivities of CHIP-mediated Pf to specific sulfhydryl reagents were identical to known sensitivities of red cell Pf, including a delayed response to p-(chloromercuri)benzenesulfonate. CHIP did not increase the permeability of the proteoliposome membranes to H+/OH- or NH3. These studies demonstrate that CHIP proteoliposomes exhibit all known characteristics of water channels in native red cells and therefore provide a defined system for biophysical analysis of transmembrane water movements.

  4. Average capacity of FSO links with transmit laser selection using non-uniform OOK signaling over exponential atmospheric turbulence channels.

    PubMed

    García-Zambrana, Antonio; Castillo-Vázquez, Beatriz; Castillo-Vázquez, Carmen

    2010-09-13

    A new upper bound on the capacity of power- and bandwidth-constrained optical wireless links using selection transmit diversity over exponential atmospheric turbulence channels with intensity modulation and direct detection is derived when non-uniform on-off keying (OOK) formats are used. In this strong turbulence free-space optical (FSO) scenario, average capacity is investigated subject to an average optical power constraint and not only to an average electrical power constraint when the transmit diversity technique assumed is based on the selection of the optical path with a greater value of irradiance. Simulation results for the mutual information are further demonstrated to confirm the analytical results for different diversity orders.

  5. Cerebrovascular Dilation via Selective Targeting of the Cholane Steroid-Recognition Site in the BK Channel β1-Subunit by a Novel Nonsteroidal Agent

    PubMed Central

    Bukiya, Anna N.; McMillan, Jacob E.; Fedinec, Alexander L.; Patil, Shivaputra A.; Miller, Duane D.; Leffler, Charles W.; Parrill, Abby L.

    2013-01-01

    The Ca2+/voltage-gated K+ large conductance (BK) channel β1 subunit is particularly abundant in vascular smooth muscle. By determining their phenotype, BK β1 allows the BK channels to reduce myogenic tone, facilitating vasodilation. The endogenous steroid lithocholic acid (LCA) dilates cerebral arteries via BK channel activation, which requires recognition by a BK β1 site that includes Thr169. Whether exogenous nonsteroidal agents can access this site to selectively activate β1-containing BK channels and evoke vasodilation remain unknown. We performed a chemical structure database similarity search using LCA as a template, along with a two-step reaction to generate sodium 3-hydroxyolean-12-en-30-oate (HENA). HENA activated the BK (cbv1 + β1) channels cloned from rat cerebral artery myocytes with a potency (EC50 = 53 μM) similar to and an efficacy (×2.5 potentiation) significantly greater than that of LCA. This HENA action was replicated on native channels in rat cerebral artery myocytes. HENA failed to activate the channels made of cbv1 + β2, β3, β4, or β1T169A, indicating that this drug selectively targets β1-containing BK channels via the BK β1 steroid-sensing site. HENA (3–45 μM) dilated the rat and C57BL/6 mouse pressurized cerebral arteries. Consistent with the electrophysiologic results, this effect was larger than that of LCA. HENA failed to dilate the arteries from the KCNMB1 knockout mouse, underscoring BK β1’s role in HENA action. Finally, carotid artery-infusion of HENA (45 μM) dilated the pial cerebral arterioles via selective BK-channel targeting. In conclusion, we have identified for the first time a nonsteroidal agent that selectively activates β1-containing BK channels by targeting the steroid-sensing site in BK β1, rendering vasodilation. PMID:23455312

  6. Space-time trellis coding with transmit laser selection for FSO links over strong atmospheric turbulence channels.

    PubMed

    García-Zambrana, Antonio; Castillo-Vázquez, Carmen; Castillo-Vázquez, Beatriz

    2010-03-15

    Atmospheric turbulence produces fluctuations in the irradiance of the transmitted optical beam, which is known as atmospheric scintillation, severely degrading the link performance. In this paper, a scheme combining transmit laser selection (TLS) and space-time trellis code (STTC) for multiple-input-single-output (MISO) free-space optical (FSO) communication systems with intensity modulation and direct detection (IM/DD) over strong atmospheric turbulence channels is analyzed. Assuming channel state information at the transmitter and receiver, we propose the transmit diversity technique based on the selection of two out of the available L lasers corresponding to the optical paths with greater values of scintillation to transmit the baseline STTCs designed for two transmit antennas. Based on a pairwise error probability (PEP) analysis, results in terms of bit error rate are presented when the scintillation follows negative exponential and K distributions, which cover a wide range of strong atmospheric turbulence conditions. Obtained results show a diversity order of 2L-1 when L transmit lasers are available and a simple two-state STTC with rate 1 bit/(s .Hz) is used. Simulation results are further demonstrated to confirm the analytical results.

  7. Doubly stochastic Poisson processes in artificial neural learning.

    PubMed

    Card, H C

    1998-01-01

    This paper investigates neuron activation statistics in artificial neural networks employing stochastic arithmetic. It is shown that a doubly stochastic Poisson process is an appropriate model for the signals in these circuits.

  8. Doubly slanted layer structures in holographic gelatin emulsions: solar concentrators

    NASA Astrophysics Data System (ADS)

    Hung, Jenny; Chan, Po Shan; Sun, Caiming; Wing Ho, Choi; Tam, Wing Yim

    2010-04-01

    We have fabricated doubly slanted layer structures in holographic gelatin emulsions using a double-exposure two-beam interference from two light sources with different wavelengths. The doubly slanted layers, with different spacings and overlapping with each other, are fabricated such that they are slanted in opposite directions making a 30° angle with the holographic plate. The doubly slanted layer structures exhibit photonic stop bands corresponding to the two layered structures. More importantly, diffracted light beams from the slanted layers travel in different directions and emerge, through internal reflections, at the opposite edges of the gelatin plate. The doubly slanted layer structures could be used as solar concentrators such that sunlight is separated into different components and steered directly to photovoltaics with the corresponding wavelength sensitivities to enhance energy conversion efficiency.

  9. Signatures of doubly-charged Higgsinos at colliders

    SciTech Connect

    Demir, D. A.; Frank, M.; Turan, I.; Huitu, K.; Rai, S. K.

    2008-11-23

    Several supersymmetric models with extended gauge structures predict light doubly-charged Higgsinos. Their distinctive signature at the large hadron collider is highlighted by studying its production and decay characteristics.

  10. A sodium channel mutation identified in Aedes aegypti selectively reduces cockroach sodium channel sensitivity to type I, but not type II pyrethroids.

    PubMed

    Hu, Zhaonong; Du, Yuzhe; Nomura, Yoshiko; Dong, Ke

    2011-01-01

    Voltage-gated sodium channels are the primary target of pyrethroid insecticides. Numerous point mutations in sodium channel genes have been identified in pyrethroid-resistant insect species, and many have been confirmed to reduce or abolish sensitivity of channels expressed in Xenopus oocytes to pyrethroids. Recently, several novel mutations were reported in sodium channel genes of pyrethroid-resistant Aedes mosquito populations. One of the mutations is a phenylalanine (F) to cysteine (C) change in segment 6 of domain III (IIIS6) of the Aedes mosquito sodium channel. Curiously, a previous study showed that alanine substitution of this F did not alter the action of deltamethrin, a type II pyrethroid, on a cockroach sodium channel. In this study, we changed this F to C in a pyrethroid-sensitive cockroach sodium channel and examined mutant channel sensitivity to permethrin as well as five other type I or type II pyrethroids in Xenopus oocytes. Interestingly, the F to C mutation drastically reduced channel sensitivity to three type I pyrethroids, permethrin, NRDC 157 (a deltamethrin analogue lacking the α-cyano group) and bioresemthrin, but not to three type II pyrethroids, cypermethrin, deltamethrin and cyhalothrin. These results confirm the involvement of the F to C mutation in permethrin resistance, and raise the possibility that rotation of type I and type II pyrethroids might be considered in the control of insect pest populations where this particular mutation is present.

  11. A simple formula for the energies of doubly excited states

    SciTech Connect

    Lin, C.D.; Watanabe, S.

    1986-11-01

    A simple formula for the energy levels of doubly excited states of atoms and multiply charged ions is derived and expressed in terms of a set of new correlation quantum numbers. The accuracy of the formula is checked by comparing with the results from other elaborate calculations. Modification of the formula for doubly excited states of multielectron atoms are also presented. 12 refs., 2 tabs.

  12. Relating neutrino masses to dilepton modes of doubly charged scalars

    SciTech Connect

    Chen, Chian-Shu; Geng, C. Q.

    2010-11-15

    We study a model with Majorana neutrino masses generated through doubly charged scalars at two-loop level. We give explicit relationships between the neutrino masses and the same sign dilepton decays of the doubly charged scalars. In particular, we demonstrate that in the tribimaximal limit of the neutrino mixings, the absolute neutrino masses and Majorana phases can be extracted through the measurements of the dilepton modes at colliders.

  13. Behavior Reveals Selective Summation and Max Pooling among Olfactory Processing Channels.

    PubMed

    Bell, Joseph S; Wilson, Rachel I

    2016-07-20

    The olfactory system is divided into processing channels (glomeruli), each receiving input from a different type of olfactory receptor neuron (ORN). Here we investigated how glomeruli combine to control behavior in freely walking Drosophila. We found that optogenetically activating single ORN types typically produced attraction, although some ORN types produced repulsion. Attraction consisted largely of a behavioral program with the following rules: at fictive odor onset, flies walked upwind, and at fictive odor offset, they reversed. When certain pairs of attractive ORN types were co-activated, the level of the behavioral response resembled the sum of the component responses. However, other pairs of attractive ORN types produced a response resembling the larger component (max pooling). Although activation of different ORN combinations produced different levels of behavior, the rules of the behavioral program were consistent. Our results illustrate a general method for inferring how groups of neurons work together to modulate behavioral programs. PMID:27373835

  14. Outage Performance Analysis of Relay Selection Schemes in Wireless Energy Harvesting Cooperative Networks over Non-Identical Rayleigh Fading Channels.

    PubMed

    Do, Nhu Tri; Bao, Vo Nguyen Quoc; An, Beongku

    2016-02-26

    In this paper, we study relay selection in decode-and-forward wireless energy harvesting cooperative networks. In contrast to conventional cooperative networks, the relays harvest energy from the source's radio-frequency radiation and then use that energy to forward the source information. Considering power splitting receiver architecture used at relays to harvest energy, we are concerned with the performance of two popular relay selection schemes, namely, partial relay selection (PRS) scheme and optimal relay selection (ORS) scheme. In particular, we analyze the system performance in terms of outage probability (OP) over independent and non-identical (i.n.i.d.) Rayleigh fading channels. We derive the closed-form approximations for the system outage probabilities of both schemes and validate the analysis by the Monte-Carlo simulation. The numerical results provide comprehensive performance comparison between the PRS and ORS schemes and reveal the effect of wireless energy harvesting on the outage performances of both schemes. Additionally, we also show the advantages and drawbacks of the wireless energy harvesting cooperative networks and compare to the conventional cooperative networks.

  15. The Scorpion Toxin Analogue BmKTX-D33H as a Potential Kv1.3 Channel-Selective Immunomodulator for Autoimmune Diseases.

    PubMed

    Ye, Fang; Hu, Youtian; Yu, Weiwei; Xie, Zili; Hu, Jun; Cao, Zhijian; Li, Wenxin; Wu, Yingliang

    2016-04-01

    The Kv1.3 channel-acting scorpion toxins usually adopt the conserved anti-parallel β-sheet domain as the binding interface, but it remains challenging to discover some highly selective Kv1.3 channel-acting toxins. In this work, we investigated the pharmacological profile of the Kv1.3 channel-acting BmKTX-D33H, a structural analogue of the BmKTX scorpion toxin. Interestingly, BmKTX-D33H, with its conserved anti-parallel β-sheet domain as a Kv1.3 channel-interacting interface, exhibited more than 1000-fold selectivity towards the Kv1.3 channel as compared to other K⁺ channels (including Kv1.1, Kv1.2, Kv1.7, Kv11.1, KCa2.2, KCa2.3, and KCa3.1). As expected, BmKTX-D33H was found to inhibit the cytokine production and proliferation of both Jurkat cells and human T cells in vitro. It also significantly improved the delayed-type hypersensitivity (DTH) responses, an autoreactive T cell-mediated inflammation in rats. Amino acid sequence alignment and structural analysis strongly suggest that the "evolutionary" Gly11 residue of BmKTX-D33H interacts with the turret domain of Kv1 channels; it appears to be a pivotal amino acid residue with regard to the selectivity of BmKTX-D33H towards the Kv1.3 channel (in comparison with the highly homologous scorpion toxins). Together, our data indicate that BmKTX-D33H is a Kv1.3 channel-specific blocker. Finally, the remarkable selectivity of BmKTX-D33H highlights the great potential of evolutionary-guided peptide drug design in future studies. PMID:27104568

  16. Gas-Phase Reactions of Doubly Charged Lanthanide Cations with Alkanes and Alkenes. Trends in Metal(2+) Reactivity

    SciTech Connect

    Gibson, John K.; Marcalo, Joaquim; Santos, Marta; Pires de Matos, Antonio; Haire, Richard G.

    2008-12-08

    The gas-phase reactivity of doubly-charged lanthanide cations, Ln2+ (Ln = La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu), with alkanes (methane, ethane, propane, n-butane) and alkenes (ethene, propene, 1-butene) was studied by Fourier transform ion cyclotron resonance mass spectrometry. The reaction products consisted of different combinations of doubly-charged organometallic ions?adducts or species formed via metal-ion-induced hydrogen, dihydrogen, alkyl, or alkane eliminations from the hydrocarbons?and singly-charged ions that resulted from electron, hydride, or methide transfers from the hydrocarbons to the metal ions. The only lanthanide cations capable of activating the hydrocarbons to form doubly-charged organometallic ions were La2+, Ce2+, Gd2+, and Tb2+, which have ground-state or low-lying d1 electronic configurations. Lu2+, with an accessible d1 electronic configuration but a rather high electron affinity, reacted only through transfer channels. The remaining Ln2+ reacted via transfer channels or adduct formation. The different accessibilities of d1 electronic configurations and the range of electron affinities of the Ln2+ cations allowed for a detailed analysis of the trends for metal(2+) reactivity and the conditions for occurrence of bond activation, adduct formation, and electron, hydride, and methide transfers.

  17. Selective inhibition of a slow-inactivating voltage-dependent K+ channel in rat PC12 cells by hypoxia.

    PubMed

    Conforti, L; Millhorn, D E

    1997-07-15

    1. Electrophysiological (single-channel patch clamp) and molecular biological experiments (reverse transcriptase-polymerase chain reaction) were performed to attempt to identify the O2-sensitive K+ channel in rat phaeochromocytoma (PC12) cells. 2. Four types of K+ channels were recorded in PC12 cells: a small-conductance K+ channel (14 pS), a calcium-activated K+ channel (KCa; 102 pS) and two K+ channels with similar conductance (20 pS). These last two channels differed in their time-dependent inactivation: one was a slow-inactivating channel, while the other belonged to the family of fast transient K+ channels. 3. The slow-inactivating 20 pS K+ channel was inhibited by hypoxia. Exposure to hypoxia produced a 50% reduction in channel activity (number of active channels in the patch x open probability). Hypoxia had no effect on the 20 pS transient K+ channels, whereas reduced O2 stimulated the KCa channels. 4. The genes encoding the alpha-subunits of slow-inactivating K+ channels for two members of the Shaker subfamily of K+ channels (Kv1.2 and Kv1.3) together with the Kv2.1, Kv3.1 and Kv3.2 channel genes were identified in PC12 cells. 5. The expression of the Shaker Kv1.2, but none of the other K+ channel genes, increased in cells exposed to prolonged hypoxia (18 h). The same cells were more responsive to a subsequent exposure to hypoxia (35% inhibition of K+ current measured in whole-cell voltage clamp) compared with the cells maintained in normoxia (19% inhibition). 6. These results indicate that the O2-sensitive K+ channel in PC12 cells is a 20 pS slow-inactivating K+ channel that is upregulated by hypoxia. This channel appears to belong to the Shaker subfamily of voltage-gated K+ channels. PMID:9263911

  18. Doubly stochastic coherence in complex neuronal networks

    NASA Astrophysics Data System (ADS)

    Gao, Yang; Wang, Jianjun

    2012-11-01

    A system composed of coupled FitzHugh-Nagumo neurons with various topological structures is investigated under the co-presence of two independently additive and multiplicative Gaussian white noises, in which particular attention is paid to the neuronal networks spiking regularity. As the additive noise intensity and the multiplicative noise intensity are simultaneously adjusted to optimal values, the temporal periodicity of the output of the system reaches the maximum, indicating the occurrence of doubly stochastic coherence. The network topology randomness exerts different influences on the temporal coherence of the spiking oscillation for dissimilar coupling strength regimes. At a small coupling strength, the spiking regularity shows nearly no difference in the regular, small-world, and completely random networks. At an intermediate coupling strength, the temporal periodicity in a small-world neuronal network can be improved slightly by adding a small fraction of long-range connections. At a large coupling strength, the dynamical behavior of the neurons completely loses the resonance property with regard to the additive noise intensity or the multiplicative noise intensity, and the spiking regularity decreases considerably with the increase of the network topology randomness. The network topology randomness plays more of a depressed role than a favorable role in improving the temporal coherence of the spiking oscillation in the neuronal network research study.

  19. Nerve compression activates selective nociceptive pathways and upregulates peripheral sodium channel expression in Schwann cells.

    PubMed

    Frieboes, Laura Rummler; Palispis, Winnie Anne; Gupta, Ranjan

    2010-06-01

    Chronic nerve compression (CNC) injuries, such as carpal tunnel syndrome, are common musculoskeletal conditions that affect patients with debilitating loss of sensory function and pain. Although early detection and treatment are important, our understanding of pain-related molecular mechanisms remains largely unclear. Here we investigate these mechanisms using an animal model for CNC injury. To confirm that CNC injury induces pain, we assessed expression of c-fos, a gene that is rapidly expressed in spinal sensory afferents in response to painful peripheral stimuli, and TNF-alpha and IL-6, two proinflammatory cytokines that are crucial to development of inflammatory-mediated pain. Results show c-fos upregulation 1-2 weeks postinjury in the absence of TNF-alpha or IL-6 expression, indicating increased neural sensitivity without an inflammatory response. This is consistent with previous studies that showed no morphologic evidence of inflammation in the CNC model. Surprisingly, we also found de novo expression of Na(V)1.8, a sodium channel linked to the development of neuropathic pain, in endoneurial Schwann cells following injury. Until now, Na(V)1.8 expression was thought to be restricted to sensory neurons. CNC injury appears to be a unique model of noninflammatory neuropathic pain. Further investigation of the underlying molecular basis could yield promising targets for early diagnosis and treatment.

  20. State-to-state mode selectivity in the HD + OH reaction: Perspectives from two product channels.

    PubMed

    Zhao, Bin; Sun, Zhigang; Guo, Hua

    2016-06-01

    The state-to-state quantum dynamics (Jtot = 0) of the HD + OH(υ2 = 0, 1) reaction is studied using a reactant coordinate based method, which allows the analysis of both the H + DOH and D + HOH channels with a single propagation. The stretching vibration of the newly formed bond, namely, the OD bond in DOH and one OH bond in HOH, is excited, thanks to its strong coupling with the reaction coordinate at the transition state. On the other hand, the vibrational energy deposited into the OH reactant (υ2 = 1) is sequestered during the reaction in the spectator OH mode. The combined effect leads to the excitation of both the OD and OH stretching modes in the DOH product, and the dominance of the (002) normal-mode state population in the HOH product, which in the local-mode picture corresponds to the excitation of both OH bonds with one quantum each. The energy flow in this prototypical tetratomic reaction can be understood in terms of the sudden vector projection model.

  1. Identification and selective inhibition of the channel mode of the neuronal GABA transporter 1.

    PubMed

    Krause, Stephan; Schwarz, Wolfgang

    2005-12-01

    The function of GAT1, the transporter for the inhibitory neurotransmitter GABA, is characterized by expression in Xenopus laevis oocytes and measurements of GABA-induced uptake of [3H]GABA, 22Na+, and 36Cl-, and GABA-evoked currents under voltage-clamp conditions. N-[4,4-Diphenyl-3-butenyl]-nipecotic acid (SKF-89976-A), a specific inhibitor of GAT1, is used in our system as a pharmacological tool. The GABA-evoked current can be decomposed into a transport current, which is coupled to the GABA uptake, and a transmitter-gated current, which is uncoupled from the GABA uptake. The transport current results from a fixed stoichiometry of 1 GABA/2 Na+/1 Cl- transported during each cycle, as determined by radioactive tracer flux measurements. The transmitter-gated current is mediated by an Na+-conductance pathway. As a competitive inhibitor for GABA uptake, SKF-89976-A can separate the two current components. The GABA uptake is blocked with a K(I) value of approximately 7 microM, whereas the uncoupled transmitter-gated current is inhibited with a K(I) value of approximately 0.03 microM. Thus, the results of this study not only identify the transport mode and the channel mode of GAT1 but also raise the possibility of separating these components in a physiological environment.

  2. State-to-state mode selectivity in the HD + OH reaction: Perspectives from two product channels

    NASA Astrophysics Data System (ADS)

    Zhao, Bin; Sun, Zhigang; Guo, Hua

    2016-06-01

    The state-to-state quantum dynamics (Jtot = 0) of the HD + OH(υ2 = 0, 1) reaction is studied using a reactant coordinate based method, which allows the analysis of both the H + DOH and D + HOH channels with a single propagation. The stretching vibration of the newly formed bond, namely, the OD bond in DOH and one OH bond in HOH, is excited, thanks to its strong coupling with the reaction coordinate at the transition state. On the other hand, the vibrational energy deposited into the OH reactant (υ2 = 1) is sequestered during the reaction in the spectator OH mode. The combined effect leads to the excitation of both the OD and OH stretching modes in the DOH product, and the dominance of the (002) normal-mode state population in the HOH product, which in the local-mode picture corresponds to the excitation of both OH bonds with one quantum each. The energy flow in this prototypical tetratomic reaction can be understood in terms of the sudden vector projection model.

  3. Photonic Crystal Fiber-Based Surface Plasmon Resonance Sensor with Selective Analyte Channels and Graphene-Silver Deposited Core

    PubMed Central

    Rifat, Ahmmed A.; Mahdiraji, G. Amouzad; Chow, Desmond M.; Shee, Yu Gang; Ahmed, Rajib; Adikan, Faisal Rafiq Mahamd

    2015-01-01

    We propose a surface plasmon resonance (SPR) sensor based on photonic crystal fiber (PCF) with selectively filled analyte channels. Silver is used as the plasmonic material to accurately detect the analytes and is coated with a thin graphene layer to prevent oxidation. The liquid-filled cores are placed near to the metallic channel for easy excitation of free electrons to produce surface plasmon waves (SPWs). Surface plasmons along the metal surface are excited with a leaky Gaussian-like core guided mode. Numerical investigations of the fiber’s properties and sensing performance are performed using the finite element method (FEM). The proposed sensor shows maximum amplitude sensitivity of 418 Refractive Index Units (RIU−1) with resolution as high as 2.4 × 10−5 RIU. Using the wavelength interrogation method, a maximum refractive index (RI) sensitivity of 3000 nm/RIU in the sensing range of 1.46–1.49 is achieved. The proposed sensor is suitable for detecting various high RI chemicals, biochemical and organic chemical analytes. Additionally, the effects of fiber structural parameters on the properties of plasmonic excitation are investigated and optimized for sensing performance as well as reducing the sensor’s footprint. PMID:25996510

  4. Performance of the IEEE 802.11a Wireless Lan Standard Over Frequency-Selective, Slow, Ricean Fading Channels

    NASA Astrophysics Data System (ADS)

    Kao, Chi-han

    2002-09-01

    With the rapidly growing demand for more reliable and higher data rate wireless communications, the Institute of the Electrical and Electronics Engineers (IEEE) 802.11 working group approved a standard for 5-GHz band, Wireless Local Area Networks (WLAN) in 1999. This standard, IEEE 802.lla, supports data rates from 6 up to 54 Mbps and uses Orthogonal Frequency Division Multiplexing (OFDM) for transmission in indoor wireless environments. This thesis examines the performance of the IEEE 802.lla standard for different combinations of sub-carrier modulation type and code rate and determines the signal-to-noise ratio required to obtain a probability of bit error P(b) of 10-5. The channel is modeled as frequency-selective, slow, Ricean fading channel with Additive White Gaussian Noise (AWGN). Contrary to expectations, for the combinations of sub-carrier modulation type and code rate utilized by the IEEE 802.11a standard, some of the higher data rate combinations outperform some of the lower data rate combinations. On the other hand, the results also show significant coding gain when applying convolutional coding with Viterbi decoding, and hence highlight the importance of Forward Error Correction (FEC) coding to the performance of wireless communications systems.

  5. Photonic crystal fiber-based surface plasmon resonance sensor with selective analyte channels and graphene-silver deposited core.

    PubMed

    Rifat, Ahmmed A; Mahdiraji, G Amouzad; Chow, Desmond M; Shee, Yu Gang; Ahmed, Rajib; Adikan, Faisal Rafiq Mahamd

    2015-01-01

    We propose a surface plasmon resonance (SPR) sensor based on photonic crystal fiber (PCF) with selectively filled analyte channels. Silver is used as the plasmonic material to accurately detect the analytes and is coated with a thin graphene layer to prevent oxidation. The liquid-filled cores are placed near to the metallic channel for easy excitation of free electrons to produce surface plasmon waves (SPWs). Surface plasmons along the metal surface are excited with a leaky Gaussian-like core guided mode. Numerical investigations of the fiber's properties and sensing performance are performed using the finite element method (FEM). The proposed sensor shows maximum amplitude sensitivity of 418 Refractive Index Units (RIU-1) with resolution as high as 2.4 × 10(-5) RIU. Using the wavelength interrogation method, a maximum refractive index (RI) sensitivity of 3000 nm/RIU in the sensing range of 1.46-1.49 is achieved. The proposed sensor is suitable for detecting various high RI chemicals, biochemical and organic chemical analytes. Additionally, the effects of fiber structural parameters on the properties of plasmonic excitation are investigated and optimized for sensing performance as well as reducing the sensor's footprint. PMID:25996510

  6. ZD7288, a selective hyperpolarization-activated cyclic nucleotide-gated channel blocker, inhibits hippocampal synaptic plasticity.

    PubMed

    Zhang, Xiao-Xue; Min, Xiao-Chun; Xu, Xu-Lin; Zheng, Min; Guo, Lian-Jun

    2016-05-01

    The selective hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride (ZD7288) blocks the induction of long-term potentiation in the perforant path-CA3 region in rat hippocampus in vivo. To explore the mechanisms underlying the action of ZD7288, we recorded excitatory postsynaptic potentials in perforant path-CA3 synapses in male Sprague-Dawley rats. We measured glutamate content in the hippocampus and in cultured hippocampal neurons using high performance liquid chromatography, and determined intracellular Ca(2+) concentration [Ca(2+)]i) using Fura-2. ZD7288 inhibited the induction and maintenance of long-term potentiation, and these effects were mirrored by the nonspecific HCN channel blocker cesium. ZD7288 also decreased glutamate release in hippocampal tissue and in cultured hippocampal neurons. Furthermore, ZD7288 attenuated glutamate-induced rises in [Ca(2+)]i in a concentration-dependent manner and reversed 8-Br-cAMP-mediated facilitation of these glutamate-induced [Ca(2+)]i rises. Our results suggest that ZD7288 inhibits hippocampal synaptic plasticity both glutamate release and resultant [Ca(2+)]i increases in rat hippocampal neurons. PMID:27335562

  7. Parallel Multistage Decision Feedback Equalizer for Single-Carrier Layered Space-Time Systems in Frequency-Selective Channels

    NASA Astrophysics Data System (ADS)

    Xu, Jing; Wang, Haifeng; Cheng, Shixin; Chen, Ming

    2004-12-01

    Space-time transmission techniques can greatly increase the spectral efficiency. In this paper, a parallel multistage decision feedback equalizer (PMDFE) is proposed for single-carrier layered space-time systems with a fixed cyclic prefix over frequency-selective channels. It is composed of a parallel interference canceller, a multiple-input single-output decision feedback equalizer (MISO-DFE), and a linear combiner. The soft output of the MISO-DFE is linearly combined with the previous tentative soft decision. In addition, an algorithm is proposed to obtain tentative soft and hard decisions for initializing the equalizer. The initializing complexity of the PMDFE is lower than that of MIMO-OFDM. Simulation results show that the PMDFE outperforms MIMO-OFDM and previously existing equalizers for single-carrier layered space-time systems.

  8. An easy prepared dual-channel chemosensor for selective and instant detection of fluoride based on double Schiff-base

    NASA Astrophysics Data System (ADS)

    Leng, Yan-Li; Zhang, Jian-Hui; Li, Qiao; Zhang, You-Ming; Lin, Qi; Yao, Hong; Wei, Tai-Bao

    2016-10-01

    A colorimetric and fluorescent dual-channel fluoride chemosensor N,N‧-bis (4-diethylaminosalicylidene) hydrazine (sensor S) bearing two imine groups has been designed and synthesized. This structurally simple probe displays rapid response and high selectivity for fluoride over other common anions (Cl-, Br-, I-, AcO-, H2PO4-, HSO4-, ClO4-, CN- and SCN-) in a highly polar aqueous DMSO solution. Mechanism studies suggested that the sensor firstly combined with F- through hydrogen bonds and then experienced the deprotonation process at higher concentrations of F- anion to the two Ar-OH groups. The detection limit was 5.78 × 10- 7 M of F-, which points to the high detection sensitivity. Test strips based on sensor S were fabricated, which could act as a convenient and efficient F- test kit to detect F- for "in-the-field" measurement.

  9. An easy prepared dual-channel chemosensor for selective and instant detection of fluoride based on double Schiff-base.

    PubMed

    Leng, Yan-Li; Zhang, Jian-Hui; Li, Qiao; Zhang, You-Ming; Lin, Qi; Yao, Hong; Wei, Tai-Bao

    2016-10-01

    A colorimetric and fluorescent dual-channel fluoride chemosensor N,N'-bis (4-diethylaminosalicylidene) hydrazine (sensor S) bearing two imine groups has been designed and synthesized. This structurally simple probe displays rapid response and high selectivity for fluoride over other common anions (Cl(-), Br(-), I(-), AcO(-), H2PO4(-), HSO4(-), ClO4(-), CN(-) and SCN(-)) in a highly polar aqueous DMSO solution. Mechanism studies suggested that the sensor firstly combined with F(-) through hydrogen bonds and then experienced the deprotonation process at higher concentrations of F(-) anion to the two Ar-OH groups. The detection limit was 5.78×10(-7)M of F(-), which points to the high detection sensitivity. Test strips based on sensor S were fabricated, which could act as a convenient and efficient F(-) test kit to detect F(-) for "in-the-field" measurement. PMID:27262660

  10. The Scorpion Toxin Analogue BmKTX-D33H as a Potential Kv1.3 Channel-Selective Immunomodulator for Autoimmune Diseases

    PubMed Central

    Ye, Fang; Hu, Youtian; Yu, Weiwei; Xie, Zili; Hu, Jun; Cao, Zhijian; Li, Wenxin; Wu, Yingliang

    2016-01-01

    The Kv1.3 channel-acting scorpion toxins usually adopt the conserved anti-parallel β-sheet domain as the binding interface, but it remains challenging to discover some highly selective Kv1.3 channel-acting toxins. In this work, we investigated the pharmacological profile of the Kv1.3 channel-acting BmKTX-D33H, a structural analogue of the BmKTX scorpion toxin. Interestingly, BmKTX-D33H, with its conserved anti-parallel β-sheet domain as a Kv1.3 channel-interacting interface, exhibited more than 1000-fold selectivity towards the Kv1.3 channel as compared to other K+ channels (including Kv1.1, Kv1.2, Kv1.7, Kv11.1, KCa2.2, KCa2.3, and KCa3.1). As expected, BmKTX-D33H was found to inhibit the cytokine production and proliferation of both Jurkat cells and human T cells in vitro. It also significantly improved the delayed-type hypersensitivity (DTH) responses, an autoreactive T cell-mediated inflammation in rats. Amino acid sequence alignment and structural analysis strongly suggest that the “evolutionary” Gly11 residue of BmKTX-D33H interacts with the turret domain of Kv1 channels; it appears to be a pivotal amino acid residue with regard to the selectivity of BmKTX-D33H towards the Kv1.3 channel (in comparison with the highly homologous scorpion toxins). Together, our data indicate that BmKTX-D33H is a Kv1.3 channel–specific blocker. Finally, the remarkable selectivity of BmKTX-D33H highlights the great potential of evolutionary-guided peptide drug design in future studies. PMID:27104568

  11. Structural analysis of ion selectivity in the NaK channel

    SciTech Connect

    Alam, Amer; Jiang, Youxing

    2009-09-15

    Here, we present a detailed characterization of ion binding in the NaK pore using the high resolution structures of NaK in complex with various cations. These structures reveal four ion binding sites with similar chemical environments but vastly different ion preference. The most non selective of all is site 3, which is formed exclusively by backbone carbonyl oxygen atoms and resides deep within the selectivity filter. Additionally, four water molecules in combination with four backbone carbonyl oxygen atoms are seen to participate in K{sup +} and Rb{sup +} ion chelation both at the external entrance and vestibule of the NaK filter, confirming the preference for an octahedral ligand configuration for K{sup +} and Rb{sup +} binding. In contrast, Na{sup +} binding in the NaK filter, particularly at site 4, utilizes a pyramidal ligand configuration requiring the participation of a water molecule in the cavity. Therefore, the ability of the NaK filter to bind both Na{sup +} and K{sup +} ions seemingly arises from the ions' ability to utilize the existing environment in unique ways rather than any structural rearrangements of the filter itself.

  12. Increase in cytosolic Ca2+ produced by hypoxia and other depolarizing stimuli activates a non-selective cation channel in chemoreceptor cells of rat carotid body.

    PubMed

    Kang, Dawon; Wang, Jiaju; Hogan, James O; Vennekens, Rudi; Freichel, Marc; White, Carl; Kim, Donghee

    2014-05-01

    The current model of O2 sensing by carotid body chemoreceptor (glomus) cells is that hypoxia inhibits the outward K(+) current and causes cell depolarization, Ca(2+) influx via voltage-dependent Ca(2+) channels and a rise in intracellular [Ca(2+)] ([Ca(2+)]i). Here we show that hypoxia (<5% O2), in addition to inhibiting the two-pore domain K(+) channels TASK-1/3 (TASK), indirectly activates an ∼20 pS channel in isolated glomus cells. The 20 pS channel was permeable to K(+), Na(+) and Cs(+) but not to Cl(-) or Ca(2+). The 20 pS channel was not sensitive to voltage. Inhibition of TASK by external acid, depolarization of glomus cells with high external KCl (20 mm) or opening of the Ca(2+) channel with FPL64176 activated the 20 pS channel when 1 mm Ca(2+) was present in the external solution. Ca(2+) (10 μm) applied to the cytosolic side of inside-out patches activated the 20 pS channel. The threshold [Ca(2+)]i for activation of the 20 pS channel in cell-attached patches was ∼200 nm. The reversal potential of the 20 pS channel was estimated to be -28 mV. Our results reveal a sequential mechanism in which hypoxia (<5% O2) first inhibits the K(+) conductance and then activates a Na(+)-permeable, non-selective cation channel via depolarization-induced rise in [Ca(2+)]i. Our results suggest that inhibition of K(+) efflux and stimulation of Na(+) influx both contribute to the depolarization of glomus cells during moderate to severe hypoxia.

  13. RESEARCH NOTE FROM COLLABORATION: Study of pair-produced doubly charged Higgs bosons with a four-muon final state with the CMS detector

    NASA Astrophysics Data System (ADS)

    Rommerskirchen, T.; Hebbeker, T.

    2007-03-01

    The discovery potential of doubly charged Higgs bosons pair-produced in Drell-Yan events at the CMS detector is presented in this note. The decay branching ratio into muon pairs is assumed to be 100%. The pure muonic decay channel yields a clear signal which is almost background free. Doubly charged Higgs bosons with masses in the range 100-800 GeV are studied, for a low luminosity scenario of \\mathcal{L} = 2\\times 10^{33} cm-2 s-1. The full detector simulation is used. Doubly charged Higgs bosons in this production and decay channel with masses m_{H^{\\pm\\pm}} \\le 650 GeV are expected to be observable at CMS with a significance exceeding 5σ at 10 fb-1 of integrated luminosity. If no signal will be detected for this integrated luminosity, the existence of a doubly charged Higgs boson with m_{H^{\\pm\\pm}} \\le 760 GeV can be excluded at 95% confidence level. This exceeds the current exclusion limit m_{H^{\\pm\\pm}} \\le 136 GeV, set by CDF at Tevatron Run II, by 624 GeV.

  14. Residues beyond the selectivity filter of the K+ channel kir2.1 regulate permeation and block by external Rb+ and Cs+.

    PubMed

    Thompson, G A; Leyland, M L; Ashmole, I; Sutcliffe, M J; Stanfield, P R

    2000-07-15

    1. Kir2.1 channels are blocked by Rb+ and Cs+ in a voltage-dependent manner, characteristic of many inward rectifier K+ channels. Mutation of Ser165 in the transmembrane domain M2 to Leu (S165L) abolished Rb+ blockage and lowered Cs+ blocking affinity. At negative voltages Rb+ carried large inward currents. 2. A model of the Kir2.1 channel, built by homology with the structure of the Streptomyces lividans K+ channel KcsA, suggested the existence of an intersubunit hydrogen bond between Ser165 and Thr141 in the channel pore-forming P-region that helps stabilise the structure of this region. However, mutations of Thr141 and Ser165 did not produce effects consistent with a hydrogen bond between these residues being essential for blockage. 3. An alternative alignment between the M2 regions of Kir2.1 and KcsA suggested that Ser165 is itself a pore-lining residue, more directly affecting blockage. We were able to replace Ser165 with a variety of polar and non-polar residues, consistent with this residue being pore lining. Some of these changes affected channel blockage. 4. We tested the hypothesis that Asp172 - a residue implicated in channel gating by polyamines - formed an additional selectivity filter by using the triple mutant T141A/S165L/D172N. Large Rb+ and Cs+ currents were measured in this mutant. 5. We propose that both Thr141 and Ser165 are likely to provide binding sites for monovalent blocking cations in wild-type channels. These residues lie beyond the carbonyl oxygen tunnel thought to form the channel selectivity filter, which the blocking cations must therefore traverse.

  15. Modulation by purines of calcium-activated non-selective cation channels in the outer hair cells of the guinea-pig cochlea.

    PubMed Central

    Van den Abbeele, T; Tran Ba Huy, P; Teulon, J

    1996-01-01

    1. The cell-attached and cell-free configurations of the patch-clamp technique were used to investigate whether external ATP and its derivatives modulate channel activity in outer hair cells freshly isolated from the guinea-pig cochlea. 2. Submicromolar concentrations of ATP stimulated a non-selective cation channel with a conductance of about 25 pS. The ATP-elicited stimulation was partly blocked by the membrane-permeant blocker 3',5-dichlorodiphenylamine-2-carboxylic acid (DCDPC), and mimicked by the calcium ionophore, ionomycin, suggesting that the channel activated by ATP is identical to a previously reported calcium-activated non-selective (CAN) cation channel. 3. The P2x agonist beta, gamma-methylene-ATP (beta, gamma-MeATP, 10 microM) and the P2Y agonist 2-methyl-thio-ATP (2-MeSATP, 1 microM) both activated CAN channels. The effect of ATP was inhibited by the P2 antagonist suramin but not by the P2Y antagonist Reactive Blue 2. These results suggest that both purinergic receptors are involved in the ATP-evoked response and that internal calcium acts as a second messenger for opening CAN channels. 4. In contrast, adenosine inhibited CAN channels. This effect was reproduced by the A2 agonist 5'-N-ethylcarboxyamidoadenosine (NECA) and the permeant cAMP analogue 8-bromo-adenosine 3',5'-cyclic monophosphate (8-Br-cAMP), but not by the A1 agonist N6-cyclo-hexyladenosine (CHA). CAN channels were also inhibited when the catalytic subunit of protein kinase A was applied internally on inside-out patches, suggesting that adenosine A2 receptor downregulates CAN channels via a cAMP-dependent phosphorylation. Images Figure 10 PMID:8814608

  16. Isolation, synthesis and characterization of ω-TRTX-Cc1a, a novel tarantula venom peptide that selectively targets L-type Cav channels.

    PubMed

    Klint, Julie K; Berecki, Géza; Durek, Thomas; Mobli, Mehdi; Knapp, Oliver; King, Glenn F; Adams, David J; Alewood, Paul F; Rash, Lachlan D

    2014-05-15

    Spider venoms are replete with peptidic ion channel modulators, often with novel subtype selectivity, making them a rich source of pharmacological tools and drug leads. In a search for subtype-selective blockers of voltage-gated calcium (CaV) channels, we isolated and characterized a novel 39-residue peptide, ω-TRTX-Cc1a (Cc1a), from the venom of the tarantula Citharischius crawshayi (now Pelinobius muticus). Cc1a is 67% identical to the spider toxin ω-TRTX-Hg1a, an inhibitor of CaV2.3 channels. We assembled Cc1a using a combination of Boc solid-phase peptide synthesis and native chemical ligation. Oxidative folding yielded two stable, slowly interconverting isomers. Cc1a preferentially inhibited Ba(2+) currents (IBa) mediated by L-type (CaV1.2 and CaV1.3) CaV channels heterologously expressed in Xenopus oocytes, with half-maximal inhibitory concentration (IC50) values of 825nM and 2.24μM, respectively. In rat dorsal root ganglion neurons, Cc1a inhibited IBa mediated by high voltage-activated CaV channels but did not affect low voltage-activated T-type CaV channels. Cc1a exhibited weak activity at NaV1.5 and NaV1.7 voltage-gated sodium (NaV) channels stably expressed in mammalian HEK or CHO cells, respectively. Experiments with modified Cc1a peptides, truncated at the N-terminus (ΔG1-E5) or C-terminus (ΔW35-V39), demonstrated that the N- and C-termini are important for voltage-gated ion channel modulation. We conclude that Cc1a represents a novel pharmacological tool for probing the structure and function of L-type CaV channels.

  17. Isolation, synthesis and characterization of ω-TRTX-Cc1a, a novel tarantula venom peptide that selectively targets L-type Cav channels.

    PubMed

    Klint, Julie K; Berecki, Géza; Durek, Thomas; Mobli, Mehdi; Knapp, Oliver; King, Glenn F; Adams, David J; Alewood, Paul F; Rash, Lachlan D

    2014-05-15

    Spider venoms are replete with peptidic ion channel modulators, often with novel subtype selectivity, making them a rich source of pharmacological tools and drug leads. In a search for subtype-selective blockers of voltage-gated calcium (CaV) channels, we isolated and characterized a novel 39-residue peptide, ω-TRTX-Cc1a (Cc1a), from the venom of the tarantula Citharischius crawshayi (now Pelinobius muticus). Cc1a is 67% identical to the spider toxin ω-TRTX-Hg1a, an inhibitor of CaV2.3 channels. We assembled Cc1a using a combination of Boc solid-phase peptide synthesis and native chemical ligation. Oxidative folding yielded two stable, slowly interconverting isomers. Cc1a preferentially inhibited Ba(2+) currents (IBa) mediated by L-type (CaV1.2 and CaV1.3) CaV channels heterologously expressed in Xenopus oocytes, with half-maximal inhibitory concentration (IC50) values of 825nM and 2.24μM, respectively. In rat dorsal root ganglion neurons, Cc1a inhibited IBa mediated by high voltage-activated CaV channels but did not affect low voltage-activated T-type CaV channels. Cc1a exhibited weak activity at NaV1.5 and NaV1.7 voltage-gated sodium (NaV) channels stably expressed in mammalian HEK or CHO cells, respectively. Experiments with modified Cc1a peptides, truncated at the N-terminus (ΔG1-E5) or C-terminus (ΔW35-V39), demonstrated that the N- and C-termini are important for voltage-gated ion channel modulation. We conclude that Cc1a represents a novel pharmacological tool for probing the structure and function of L-type CaV channels. PMID:24561180

  18. Ultrafast nuclear dynamics in halomethanes studied with time-resolved Coulomb explosion imaging and channel-selective Fourier spectroscopy

    NASA Astrophysics Data System (ADS)

    Malakar, Y.; Kaderiya, B.; Pearson, W. L.; Ziaee, F.; Kanaka Raju, P.; Zohrabi, M.; Jensen, K.; Rajput, J.; Ben-Itzhak, I.; Rolles, D.; Rudenko, A.

    2016-05-01

    Halomethanes have recently attracted considerable attention since they often serve as prototype systems for laser-controlled chemistry (e.g., selective bond breaking or concerted elimination reactions), and are important molecules in atmospheric chemistry. Here we combine a femtosecond laser pump-probe setup with coincident 3D ion momentum imaging apparatus to study strong-field induced nuclear dynamics in methane and several of its halogenated derivatives (CH3 I, CH2 I2, CH2 ICl). We apply a time-resolved Coulomb explosion imaging technique to map the nuclear motion on both, bound and continuum potential surfaces, disentangle different fragmentation pathways and, for halogenated molecules, observe clear signatures of vibrational wave packets in neutral or ionized states. Channel-selective and kinetic-energy resolved Fourier analysis of these data allows for unique identification of different electronic states and vibrational modes responsible for a particular structure. Supported by the Chemical Sciences, Geosciences, and Biosciences Division, Office of Basic Energy Sciences, Office of Science, U. S. DOE. K. R. P. and W. L. P. supported by NSF Award No. IIA-143049. K.J. supported by the NSF-REU Grant No. PHYS-1461251.

  19. Selective inhibition of a slow-inactivating voltage-dependent K+ channel in rat PC12 cells by hypoxia.

    PubMed Central

    Conforti, L; Millhorn, D E

    1997-01-01

    1. Electrophysiological (single-channel patch clamp) and molecular biological experiments (reverse transcriptase-polymerase chain reaction) were performed to attempt to identify the O2-sensitive K+ channel in rat phaeochromocytoma (PC12) cells. 2. Four types of K+ channels were recorded in PC12 cells: a small-conductance K+ channel (14 pS), a calcium-activated K+ channel (KCa; 102 pS) and two K+ channels with similar conductance (20 pS). These last two channels differed in their time-dependent inactivation: one was a slow-inactivating channel, while the other belonged to the family of fast transient K+ channels. 3. The slow-inactivating 20 pS K+ channel was inhibited by hypoxia. Exposure to hypoxia produced a 50% reduction in channel activity (number of active channels in the patch x open probability). Hypoxia had no effect on the 20 pS transient K+ channels, whereas reduced O2 stimulated the KCa channels. 4. The genes encoding the alpha-subunits of slow-inactivating K+ channels for two members of the Shaker subfamily of K+ channels (Kv1.2 and Kv1.3) together with the Kv2.1, Kv3.1 and Kv3.2 channel genes were identified in PC12 cells. 5. The expression of the Shaker Kv1.2, but none of the other K+ channel genes, increased in cells exposed to prolonged hypoxia (18 h). The same cells were more responsive to a subsequent exposure to hypoxia (35% inhibition of K+ current measured in whole-cell voltage clamp) compared with the cells maintained in normoxia (19% inhibition). 6. These results indicate that the O2-sensitive K+ channel in PC12 cells is a 20 pS slow-inactivating K+ channel that is upregulated by hypoxia. This channel appears to belong to the Shaker subfamily of voltage-gated K+ channels. Images Figure 4 Figure 7 PMID:9263911

  20. Subtype-selective activation of K(v)7 channels by AaTXKβ₂₋₆₄, a novel toxin variant from the Androctonus australis scorpion venom.

    PubMed

    Landoulsi, Zied; Miceli, Francesco; Palmese, Angelo; Amoresano, Angela; Marino, Gennaro; El Ayeb, Mohamed; Taglialatela, Maurizio; Benkhalifa, Rym

    2013-11-01

    K(v)7.4 channel subunits are expressed in central auditory pathways and in inner ear sensory hair cells and skeletal and smooth muscle cells. Openers of K(v)7.4 channels have been suggested to improve hearing loss, systemic or pulmonary arterial hypertension, urinary incontinence, gastrointestinal and neuropsychiatric diseases, and skeletal muscle disorders. Scorpion venoms are a large source of peptides active on K⁺ channels. Therefore, we have optimized a combined purification/screening procedure to identify specific modulator(s) of K(v)7.4 channels from the venom of the North African scorpion Androctonus australis (Aa). We report the isolation and functional characterization of AaTXKβ₂₋₆₄, a novel variant of AaTXKβ₁₋₆₄, in a high-performance liquid chromatography fraction from Aa venom (named P8), which acts as the first peptide activator of K(v)7.4 channels. In particular, in both Xenopus oocytes and mammalian Chinese hamster ovary cells, AaTXKβ₂₋₆₄, but not AaTXKβ₁₋₆₄, hyperpolarized the threshold voltage of current activation and increased the maximal currents of heterologously expressed K(v)7.4 channels. AaTXKβ₂₋₆₄ also activated K(v)7.3, K(v)7.2/3, and K(v)7.5/3 channels, whereas homomeric K(v)1.1, K(v)7.1, and K(v)7.2 channels were unaffected. We anticipate that these results may prove useful in unraveling the novel biologic roles of AaTXKβ₂₋₆₄-sensitive K(v)7 channels and developing novel pharmacologic tools that allow subtype-selective targeting of K(v)7 channels. PMID:24019223

  1. Relationship between expression of muscle-specific uncoupling protein 2 messenger RNA and genetic selection toward growth in channel catfish.

    PubMed

    Kobayashi, Y; Peterson, B C; Waldbieser, G C

    2015-04-01

    This study tested the hypothesis that increased growth in channel catfish is associated with expression of the genes that code for uncoupling proteins (UCP) 2 and 3, members of the mitochondrial channel proteins involved in nutrient sensing and metabolism. The specific objective was to contrast the levels of UCP2 messenger RNA (mRNA) in fast vs slow growing catfish as well as in fed vs fasted catfish. Two distinct UCP2 transcripts were identified and named UCP2a and UCP2b, respectively. Nucleotide and amino acid sequence of catfish UCP2s were highly similar to UCP2 and other UCPs from other fish and mammals (>75%). Expression of UCP2a mRNA was detectable at very low levels in various metabolically active tissues, whereas the expression of UCP2b mRNA was readily detectable in the muscle and heart. In a 21-wk feeding study, fish that grew faster had a greater percent body fat at the end of the study (P < 0.01). Expression of UCP2b mRNA tended to be lower (P < 0.10) in fast growing fish in the middle of the study although levels were similar at the beginning and the end of the study. In the fed vs fasted study, expression of UCP2b mRNA in muscle was increased (P < 0.05) in fish assigned to 30 d of fasting. Our results suggest that, based on the nucleotide and amino acid sequence similarities and tissue mRNA distribution, catfish UCP2b may be the analog to UCP3. Moreover, our results suggest selection toward growth and associated fat accumulation appears to be independent of muscle UCP2b mRNA expression and UCP2b-mediated mechanisms.

  2. Field evaporation of doubly charged ions from a polar liquid

    NASA Astrophysics Data System (ADS)

    Balakin, A. A.; Novikova, L. I.

    2012-11-01

    The effect of charge on field evaporation of ions from polar liquids is considered. Using the electromembrane ion source, we performed mass-spectral analysis of field evaporation of ions from the solution of sodium sulfate in a water-glycerol mixture. The composition of doubly charged cluster ions in the field evaporation from glycerol is determined. The rates of the field evaporation of doubly charged ions and singly charged ions are compared. It is shown that the ion charge as well as its localization considerably influences the efficiency of field evaporation of ions from polar liquids.

  3. Measurement of Doubly Charged Ions in Ion Thruster Plumes

    NASA Technical Reports Server (NTRS)

    Williams, George J., Jr.; Domonkos, Matthew T.; Chavez, Joy M.

    2002-01-01

    The ratio of doubly to singly charged ions was measured in the plumes of a 30 cm and of a 40 cm ion thruster. The measured ratio was correlated with observed erosion rates and thruster operating conditions. The measured and calculated erosion rates paralleled variation in the j(sup ++)/j(sup +) ratio and indicated that the erosion was dominated by Xe III. Simple models of cathode potential surfaces which were developed in support of this work were in agreement with this conclusion and provided a predictive capability of the erosion given the ratio of doubly to singly charged ion currents.

  4. Search for doubly charged Higgs bosons at LEP2

    NASA Astrophysics Data System (ADS)

    Abdallah, J.; Abreu, P.; Adam, W.; Adzic, P.; Albrecht, T.; Alderweireld, T.; Alemany-Fernandez, R.; Allmendinger, T.; Allport, P. P.; Amaldi, U.; Amapane, N.; Amato, S.; Anashkin, E.; Andreazza, A.; Andringa, S.; Anjos, N.; Antilogus, P.; Apel, W.-D.; Arnoud, Y.; Ask, S.; Asman, B.; Augustin, J. E.; Augustinus, A.; Baillon, P.; Ballestrero, A.; Bambade, P.; Barbier, R.; Bardin, D.; Barker, G.; Baroncelli, A.; Battaglia, M.; Baubillier, M.; Becks, K.-H.; Begalli, M.; Behrmann, A.; Ben-Haim, E.; Benekos, N.; Benvenuti, A.; Berat, C.; Berggren, M.; Berntzon, L.; Bertrand, D.; Besancon, M.; Besson, N.; Bloch, D.; Blom, M.; Bluj, M.; Bonesini, M.; Boonekamp, M.; Booth, P. S. L.; Borisov, G.; Botner, O.; Bouquet, B.; Bowcock, T. J. V.; Boyko, I.; Bracko, M.; Brenner, R.; Brodet, E.; Bruckman, P.; Brunet, J. M.; Bugge, L.; Buschmann, P.; Calvi, M.; Camporesi, T.; Canale, V.; Carena, F.; Castro, N.; Cavallo, F.; Chapkin, M.; Charpentier, Ph.; Checchia, P.; Chierici, R.; Chliapnikov, P.; Chudoba, J.; Chung, S. U.; Cieslik, K.; Collins, P.; Contri, R.; Cosme, G.; Cossutti, F.; Costa, M. J.; Crawley, B.; Crennell, D.; Cuevas, J.; D'Hondt, J.; Dalmau, J.; da Silva, T.; da Silva, W.; Della Ricca, G.; de Angelis, A.; de Boer, W.; de Clercq, C.; de Lotto, B.; de Maria, N.; de Min, A.; de Paula, L.; di Ciaccio, L.; di Simone, A.; Doroba, K.; Drees, J.; Dris, M.; Eigen, G.; Ekelof, T.; Ellert, M.; Elsing, M.; Espirito Santo, M. C.; Fanourakis, G.; Fassouliotis, D.; Feindt, M.; Fernandez, J.; Ferrer, A.; Ferro, F.; Flagmeyer, U.; Foeth, H.; Fokitis, E.; Fulda-Quenzer, F.; Fuster, J.; Gandelman, M.; Garcia, C.; Gavillet, Ph.; Gazis, E.; Geralis, T.; Gokieli, R.; Golob, B.; Gomez-Ceballos, G.; Goncalves, P.; Graziani, E.; Grosdidier, G.; Grzelak, K.; Guy, J.; Haag, C.; Hallgren, A.; Hamacher, K.; Hamilton, K.; Hansen, J.; Haug, S.; Hauler, F.; Hedberg, V.; Hennecke, M.; Herr, H.; Hoffman, J.; Holmgren, S.-O.; Holt, P. J.; Houlden, M. A.; Hultqvist, K.; Jackson, J. N.; Jarlskog, G.; Jarry, P.; Jeans, D.; Johansson, E. K.; Johansson, P. D.; Jonsson, P.; Joram, C.; Jungermann, L.; Kapusta, F.; Katsanevas, S.; Katsoufis, E.; Kernel, G.; Kersevan, B. P.; Kiiskinen, A.; King, B. T.; Kjaer, N. J.; Kluit, P.; Kokkinias, P.; Kourkoumelis, C.; Kouznetsov, O.; Krumstein, Z.; Kucharczyk, M.; Lamsa, J.; Leder, G.; Ledroit, F.; Leinonen, L.; Leitner, R.; Lemonne, J.; Lepeltier, V.; Lesiak, T.; Liebig, W.; Liko, D.; Lipniacka, A.; Lopes, J. H.; Lopez, J. M.; Loukas, D.; Lutz, P.; Lyons, L.; MacNaughton, J.; Malek, A.; Maltezos, S.; Mandl, F.; Marco, J.; Marco, R.; Marechal, B.; Margoni, M.; Marin, J.-C.; Mariotti, C.; Markou, A.; Martinez-Rivero, C.; Masik, J.; Mastroyiannopoulos, N.; Matorras, F.; Matteuzzi, C.; Mazzucato, F.; Mazzucato, M.; Mc Nulty, R.; Meroni, C.; Meyer, W. T.; Migliore, E.; Mitaroff, W.; Mjoernmark, U.; Moa, T.; Moch, M.; Moenig, K.; Monge, R.; Montenegro, J.; Moraes, D.; Moreno, S.; Morettini, P.; Mueller, U.; Muenich, K.; Mulders, M.; Mundim, L.; Murray, W.; Muryn, B.; Myatt, G.; Myklebust, T.; Nassiakou, M.; Navarria, F.; Nawrocki, K.; Nicolaidou, R.; Nikolenko, M.; Oblakowska-Mucha, A.; Obraztsov, V.; Olshevski, A.; Onofre, A.; Orava, R.; Osterberg, K.; Ouraou, A.; Oyanguren, A.; Paganoni, M.; Paiano, S.; Palacios, J. P.; Palka, H.; Papadopoulou, Th. D.; Pape, L.; Parkes, C.; Parodi, F.; Parzefall, U.; Passeri, A.; Passon, O.; Peralta, L.; Perepelitsa, V.; Perrotta, A.; Petrolini, A.; Piedra, J.; Pieri, L.; Pierre, F.; Pimenta, M.; Piotto, E.; Podobnik, T.; Poireau, V.; Pol, M. E.; Polok, G.; Poropat, P.; Pozdniakov, V.; Pukhaeva, N.; Pullia, A.; Rames, J.; Ramler, L.; Read, A.; Rebecchi, P.; Rehn, J.; Reid, D.; Reinhardt, R.; Renton, P.; Richard, F.; Ridky, J.; Rivero, M.; Rodriguez, D.; Romero, A.; Ronchese, P.; Rosenberg, E.; Roudeau, P.; Rovelli, T.; Ruhlmann-Kleider, V.; Ryabtchikov, D.; Sadovsky, A.; Salmi, L.; Salt, J.; Savoy-Navarro, A.; Schwickerath, U.; Segar, A.; Sekulin, R.; Siebel, M.; Sisakian, A.; Smadja, G.; Smirnova, O.; Sokolov, A.; Sopczak, A.; Sosnowski, R.; Spassov, T.; Stanitzki, M.; Stocchi, A.; Strauss, J.; Stugu, B.; Szczekowski, M.; Szeptycka, M.; Szumlak, T.; Tabarelli, T.; Taffard, A. C.; Tegenfeldt, F.; Timmermans, J.; Tkatchev, L.; Tobin, M.; Todorovova, S.; Tomaradze, A.; Tome, B.; Tonazzo, A.; Tortosa, P.; Travnicek, P.; Treille, D.; Tristram, G.; Trochimczuk, M.; Troncon, C.; Turluer, M.-L.; Tyapkin, I. A.; Tyapkin, P.; Tzamarias, S.; Uvarov, V.; Valenti, G.; van Dam, P.; van Eldik, J.; van Lysebetten, A.; van Remortel, N.; van Vulpen, I.; Vegni, G.; Veloso, F.; Venus, W.; Verbeure, F.; Verdier, P.; Verzi, V.; Vilanova, D.; Vitale, L.; Vrba, V.; Wahlen, H.; Washbrook, A. J.; Weiser, C.; Wicke, D.; Wickens, J.; Wilkinson, G.; Winter, M.; Witek, M.; Yushchenko, O.; Zalewska, A.; Zalewski, P.; Zavrtanik, D.; Zimin, N. I.; Zintchenko, A.; Zupan, M.; Delphi Collaboration

    2003-01-01

    A search for pair-produced doubly charged Higgs bosons has been performed using the data collected by the DELPHI detector at LEP at centre-of-mass energies between 189 and 209 GeV. No excess is observed in the data with respect to the Standard Model background. A lower limit for the mass of 97.3 GeV/c2 at the 95% confidence level has been set for doubly charged Higgs bosons in left-right symmetric models for any value of the Yukawa coupling between the Higgs bosons and the τ leptons.

  5. Search for doubly charged Higgs bosons at LEP2

    NASA Astrophysics Data System (ADS)

    DELPHI Collaboration; Abdallah, J.; Abreu, P.; Adam, W.; Adzic, P.; Albrecht, T.; Alderweireld, T.; Alemany-Fernandez, R.; Allmendinger, T.; Allport, P. P.; Amaldi, U.; Amapane, N.; Amato, S.; Anashkin, E.; Andreazza, A.; Andringa, S.; Anjos, N.; Antilogus, P.; Apel, W.-D.; Arnoud, Y.; Ask, S.; Asman, B.; Augustin, J. E.; Augustinus, A.; Baillon, P.; Ballestrero, A.; Bambade, P.; Barbier, R.; Bardin, D.; Barker, G.; Baroncelli, A.; Battaglia, M.; Baubillier, M.; Becks, K.-H.; Begalli, M.; Behrmann, A.; Ben-Haim, E.; Benekos, N.; Benvenuti, A.; Berat, C.; Berggren, M.; Berntzon, L.; Bertrand, D.; Besancon, M.; Besson, N.; Bloch, D.; Blom, M.; Bluj, M.; Bonesini, M.; Boonekamp, M.; Booth, P. S. L.; Borisov, G.; Botner, O.; Bouquet, B.; Bowcock, T. J. V.; Boyko, I.; Bracko, M.; Brenner, R.; Brodet, E.; Bruckman, P.; Brunet, J. M.; Bugge, L.; Buschmann, P.; Calvi, M.; Camporesi, T.; Canale, V.; Carena, F.; Castro, N.; Cavallo, F.; Chapkin, M.; Charpentier, Ph.; Checchia, P.; Chierici, R.; Chliapnikov, P.; Chudoba, J.; Chung, S. U.; Cieslik, K.; Collins, P.; Contri, R.; Cosme, G.; Cossutti, F.; Costa, M. J.; Crawley, B.; Crennell, D.; Cuevas, J.; D'Hondt, J.; Dalmau, J.; da Silva, T.; da Silva, W.; della Ricca, G.; de Angelis, A.; de Boer, W.; de Clercq, C.; de Lotto, B.; de Maria, N.; de Min, A.; de Paula, L.; di Ciaccio, L.; di Simone, A.; Doroba, K.; Drees, J.; Dris, M.; Eigen, G.; Ekelof, T.; Ellert, M.; Elsing, M.; Espirito Santo, M. C.; Fanourakis, G.; Fassouliotis, D.; Feindt, M.; Fernandez, J.; Ferrer, A.; Ferro, F.; Flagmeyer, U.; Foeth, H.; Fokitis, E.; Fulda-Quenzer, F.; Fuster, J.; Gandelman, M.; Garcia, C.; Gavillet, Ph.; Gazis, E.; Geralis, T.; Gokieli, R.; Golob, B.; Gomez-Ceballos, G.; Goncalves, P.; Graziani, E.; Grosdidier, G.; Grzelak, K.; Guy, J.; Haag, C.; Hallgren, A.; Hamacher, K.; Hamilton, K.; Hansen, J.; Haug, S.; Hauler, F.; Hedberg, V.; Hennecke, M.; Herr, H.; Hoffman, J.; Holmgren, S.-O.; Holt, P. J.; Houlden, M. A.; Hultqvist, K.; Jackson, J. N.; Jarlskog, G.; Jarry, P.; Jeans, D.; Johansson, E. K.; Johansson, P. D.; Jonsson, P.; Joram, C.; Jungermann, L.; Kapusta, F.; Katsanevas, S.; Katsoufis, E.; Kernel, G.; Kersevan, B. P.; Kiiskinen, A.; King, B. T.; Kjaer, N. J.; Kluit, P.; Kokkinias, P.; Kourkoumelis, C.; Kouznetsov, O.; Krumstein, Z.; Kucharczyk, M.; Lamsa, J.; Leder, G.; Ledroit, F.; Leinonen, L.; Leitner, R.; Lemonne, J.; Lepeltier, V.; Lesiak, T.; Liebig, W.; Liko, D.; Lipniacka, A.; Lopes, J. H.; Lopez, J. M.; Loukas, D.; Lutz, P.; Lyons, L.; MacNaughton, J.; Malek, A.; Maltezos, S.; Mandl, F.; Marco, J.; Marco, R.; Marechal, B.; Margoni, M.; Marin, J.-C.; Mariotti, C.; Markou, A.; Martinez-Rivero, C.; Masik, J.; Mastroyiannopoulos, N.; Matorras, F.; Matteuzzi, C.; Mazzucato, F.; Mazzucato, M.; Mc Nulty, R.; Meroni, C.; Meyer, W. T.; Migliore, E.; Mitaroff, W.; Mjoernmark, U.; Moa, T.; Moch, M.; Moenig, K.; Monge, R.; Montenegro, J.; Moraes, D.; Moreno, S.; Morettini, P.; Mueller, U.; Muenich, K.; Mulders, M.; Mundim, L.; Murray, W.; Muryn, B.; Myatt, G.; Myklebust, T.; Nassiakou, M.; Navarria, F.; Nawrocki, K.; Nicolaidou, R.; Nikolenko, M.; Oblakowska-Mucha, A.; Obraztsov, V.; Olshevski, A.; Onofre, A.; Orava, R.; Osterberg, K.; Ouraou, A.; Oyanguren, A.; Paganoni, M.; Paiano, S.; Palacios, J. P.; Palka, H.; Papadopoulou, Th. D.; Pape, L.; Parkes, C.; Parodi, F.; Parzefall, U.; Passeri, A.; Passon, O.; Peralta, L.; Perepelitsa, V.; Perrotta, A.; Petrolini, A.; Piedra, J.; Pieri, L.; Pierre, F.; Pimenta, M.; Piotto, E.; Podobnik, T.; Poireau, V.; Pol, M. E.; Polok, G.; Poropat, P.; Pozdniakov, V.; Pukhaeva, N.; Pullia, A.; Rames, J.; Ramler, L.; Read, A.; Rebecchi, P.; Rehn, J.; Reid, D.; Reinhardt, R.; Renton, P.; Richard, F.; Ridky, J.; Rivero, M.; Rodriguez, D.; Romero, A.; Ronchese, P.; Rosenberg, E.; Roudeau, P.; Rovelli, T.; Ruhlmann-Kleider, V.; Ryabtchikov, D.; Sadovsky, A.; Salmi, L.; Salt, J.; Savoy-Navarro, A.; Schwickerath, U.; Segar, A.; Sekulin, R.; Siebel, M.; Sisakian, A.; Smadja, G.; Smirnova, O.; Sokolov, A.; Sopczak, A.; Sosnowski, R.; Spassov, T.; Stanitzki, M.; Stocchi, A.; Strauss, J.; Stugu, B.; Szczekowski, M.; Szeptycka, M.; Szumlak, T.; Tabarelli, T.; Taffard, A. C.; Tegenfeldt, F.; Timmermans, J.; Tkatchev, L.; Tobin, M.; Todorovova, S.; Tomaradze, A.; Tome, B.; Tonazzo, A.; Tortosa, P.; Travnicek, P.; Treille, D.; Tristram, G.; Trochimczuk, M.; Troncon, C.; Turluer, M.-L.; Tyapkin, I. A.; Tyapkin, P.; Tzamarias, S.; Uvarov, V.; Valenti, G.; van Dam, P.; van Eldik, J.; van Lysebetten, A.; van Remortel, N.; van Vulpen, I.; Vegni, G.; Veloso, F.; Venus, W.; Verbeure, F.; Verdier, P.; Verzi, V.; Vilanova, D.; Vitale, L.; Vrba, V.; Wahlen, H.; Washbrook, A. J.; Weiser, C.; Wicke, D.; Wickens, J.; Wilkinson, G.; Winter, M.; Witek, M.; Yushchenko, O.; Zalewska, A.; Zalewski, P.; Zavrtanik, D.; Zimin, N. I.; Zintchenko, A.; Zupan, M.

    2003-01-01

    A search for pair-produced doubly charged Higgs bosons has been performed using the data collected by the DELPHI detector at LEP at centre-of-mass energies between 189 and 209 GeV. No excess is observed in the data with respect to the Standard Model background. A lower limit for the mass of 97.3 GeV/c2 at the 95% confidence level has been set for doubly charged Higgs bosons in left-right symmetric models for any value of the Yukawa coupling between the Higgs bosons and the /τ leptons.

  6. A mathematical model for the doubly fed wound rotor generator

    NASA Technical Reports Server (NTRS)

    Brady, F. J.

    1983-01-01

    A mathematical analysis of a doubly-fed wound rotor machine used as a constant frequency generator is presented. The purpose of this analysis is to derive a consistent set of circuit equations which produce constant stator frequency and constant stator voltage. Starting with instantaneous circuit equations, the necessary rotor voltages and currents are derived. The model, thus obtained, is assumed to be valid, since the resulting relationships between mechanical power and active volt-amperes agrees with the results of others. In addition, the model allows for a new interpretation of the power flow in the doubly-fed generator.

  7. Structural Heterogeneity of Doubly-Charged Peptide b-Ions

    NASA Astrophysics Data System (ADS)

    Li, Xiaojuan; Huang, Yiqun; O'Connor, Peter B.; Lin, Cheng

    2011-02-01

    Performing collisionally activated dissociation (CAD) and electron capture dissociation (ECD) in tandem has shown great promise in providing comprehensive sequence information that was otherwise unobtainable by using either fragmentation method alone or in duet. However, the general applicability of this MS3 approach in peptide sequencing may be undermined by the formation of non-direct sequence ions, as sometimes observed under CAD, particularly when multiple stages of CAD are involved. In this study, varied-sized doubly-charged b-ions from three tachykinin peptides were investigated by ECD. Sequence scrambling was observed in ECD of all b-ions from neurokinin A (HKTDSFVGLM-NH2), suggesting the presence of N- and C-termini linked macro-cyclic conformers. On the contrary, none of the b-ions from eledoisin (pEPSKDAFIGLM-NH2) produced non-direct sequence ions under ECD, as it does not contain a free N-terminal amino group. ECD of several b-ions from Substance P (RPKPQQFFGLM-NH2) showed series of cm-Lys fragment ions which suggested that the macro-cyclic structure may also be formed by connecting the C-terminal carbonyl group and the ɛ-amino group of the lysine side chain. Theoretical investigation of selected Substance P b-ions revealed several low energy conformers, including both linear oxazolones and macro-ring structures, in corroboration with the experimental observation. This study showed that a b-ion may exist as a mixture of several forms, with their propensities influenced by its N-terminus, length, and certain side-chain groups. Further, the presence of several macro-cyclic structures may result in erroneous sequence assignment when the combined CAD and ECD methods are used in peptide sequencing.

  8. Alzheimer's disease amyloid beta-protein forms Zn(2+)-sensitive, cation-selective channels across excised membrane patches from hypothalamic neurons.

    PubMed Central

    Kawahara, M; Arispe, N; Kuroda, Y; Rojas, E

    1997-01-01

    We have previously shown that the 40-residue peptide termed amyloid beta-protein (A beta P[1-40]) in solution forms cation-selective channels across artificial phospholipid bilayer membranes. To determine whether A beta P[1-40] also forms channels across natural membranes, we used electrically silent excised membrane patches from a cell line derived from hypothalamic gonadotrophin-releasing hormone GnRH neurons. We found that exposing either the internal or the external side of excised membrane patches to A beta P[1-40] leads to the spontaneous formation of cation-selective channels. With Cs+ as the main cation in both the external as well as the internal saline, the amplitude of the A beta P[1-40] channel currents was found to follow the Cs+ gradient and to exhibit spontaneous conductance changes over a wide range (50-500 pS). We also found that free zinc (Zn2+), reported to bind to amyloid beta-protein in solution, can block the flow of Cs+ through the A beta P[1-40] channel. Because the Zn2+ chelator o-phenanthroline can reverse this blockade, we conclude that the underlying mechanism involves a direct interaction between the transition element Zn2+ and sites in the A beta P[1-40] channel pore. These properties of the A beta P[1-40] channel are rather similar to those observed in the artificial bilayer system. We also show here, by immunocytochemical confocal microscopy, that amyloid beta-protein molecules form deposits closely associated with the plasma membrane of a substantial fraction of the GnRH neurons. Taken together, these results suggest that the interactions between amyloid beta-protein and neuronal membranes also occur in vivo, lending further support to the idea that A beta P[1-40] channel formation might be a mechanism of amyloid beta-protein neurotoxicity. Images FIGURE 5 PMID:9199772

  9. Synthesis, solution structure, and phylum selectivity of a spider delta-toxin that slows inactivation of specific voltage-gated sodium channel subtypes.

    PubMed

    Yamaji, Nahoko; Little, Michelle J; Nishio, Hideki; Billen, Bert; Villegas, Elba; Nishiuchi, Yuji; Tytgat, Jan; Nicholson, Graham M; Corzo, Gerardo

    2009-09-01

    Magi 4, now renamed delta-hexatoxin-Mg1a, is a 43-residue neurotoxic peptide from the venom of the hexathelid Japanese funnel-web spider (Macrothele gigas) with homology to delta-hexatoxins from Australian funnel-web spiders. It binds with high affinity to receptor site 3 on insect voltage-gated sodium (Na(V)) channels but, unlike delta-hexatoxins, does not compete for the related site 3 in rat brain despite being previously shown to be lethal by intracranial injection. To elucidate differences in Na(V) channel selectivity, we have undertaken the first characterization of a peptide toxin on a broad range of mammalian and insect Na(V) channel subtypes showing that delta-hexatoxin-Mg1a selectively slows channel inactivation of mammalian Na(V)1.1, Na(V)1.3, and Na(V)1.6 but more importantly shows higher affinity for insect Na(V)1 (para) channels. Consequently, delta-hexatoxin-Mg1a induces tonic repetitive firing of nerve impulses in insect neurons accompanied by plateau potentials. In addition, we have chemically synthesized and folded delta-hexatoxin-Mg1a, ascertained the bonding pattern of the four disulfides, and determined its three-dimensional solution structure using NMR spectroscopy. Despite modest sequence homology, we show that key residues important for the activity of scorpion alpha-toxins and delta-hexatoxins are distributed in a topologically similar manner in delta-hexatoxin-Mg1a. However, subtle differences in the toxin surfaces are important for the novel selectivity of delta-hexatoxin-Mg1a for certain mammalian and insect Na(V) channel subtypes. As such, delta-hexatoxin-Mg1a provides us with a specific tool with which to study channel structure and function and determinants for phylum- and tissue-specific activity.

  10. Synthesis, Solution Structure, and Phylum Selectivity of a Spider δ-Toxin That Slows Inactivation of Specific Voltage-gated Sodium Channel Subtypes*

    PubMed Central

    Yamaji, Nahoko; Little, Michelle J.; Nishio, Hideki; Billen, Bert; Villegas, Elba; Nishiuchi, Yuji; Tytgat, Jan; Nicholson, Graham M.; Corzo, Gerardo

    2009-01-01

    Magi 4, now renamed δ-hexatoxin-Mg1a, is a 43-residue neurotoxic peptide from the venom of the hexathelid Japanese funnel-web spider (Macrothele gigas) with homology to δ-hexatoxins from Australian funnel-web spiders. It binds with high affinity to receptor site 3 on insect voltage-gated sodium (NaV) channels but, unlike δ-hexatoxins, does not compete for the related site 3 in rat brain despite being previously shown to be lethal by intracranial injection. To elucidate differences in NaV channel selectivity, we have undertaken the first characterization of a peptide toxin on a broad range of mammalian and insect NaV channel subtypes showing that δ-hexatoxin-Mg1a selectively slows channel inactivation of mammalian NaV1.1, NaV1.3, and NaV1.6 but more importantly shows higher affinity for insect NaV1 (para) channels. Consequently, δ-hexatoxin-Mg1a induces tonic repetitive firing of nerve impulses in insect neurons accompanied by plateau potentials. In addition, we have chemically synthesized and folded δ-hexatoxin-Mg1a, ascertained the bonding pattern of the four disulfides, and determined its three-dimensional solution structure using NMR spectroscopy. Despite modest sequence homology, we show that key residues important for the activity of scorpion α-toxins and δ-hexatoxins are distributed in a topologically similar manner in δ-hexatoxin-Mg1a. However, subtle differences in the toxin surfaces are important for the novel selectivity of δ-hexatoxin-Mg1a for certain mammalian and insect NaV channel subtypes. As such, δ-hexatoxin-Mg1a provides us with a specific tool with which to study channel structure and function and determinants for phylum- and tissue-specific activity. PMID:19592486

  11. Doubly charged Higgs bosons and three-lepton signatures in the Higgs triplet model

    SciTech Connect

    Akeroyd, A. G.; Chiang, C.-W.

    2009-12-01

    Doubly charged Higgs bosons, H{sup {+-}}{sup {+-}}, are being searched for in the Tevatron experiments. The most recent search by the D0 Collaboration seeks three muons ({mu}{sup {+-}}{mu}{sup {+-}}{mu}{sup {+-}}), which are assumed to originate from the pair-production process, qq{yields}H{sup ++}H{sup --}, followed by the decay H{sup {+-}}{sup {+-}}{yields}{mu}{sup {+-}}{mu}{sup {+-}}. In this three-lepton (3l) channel there are six distinct signatures for l=e or {mu}. In the context of the Higgs Triplet Model, we quantify the dependence of the event numbers for the 3l channels on the parameters of the neutrino mass matrix. It is also shown that the inclusion of the production mechanism qq{sup '}{yields}H{sup {+-}}{sup {+-}}H{sup {+-}}, followed by the decay H{sup {+-}}{yields}l{sup {+-}}{nu}, would significantly increase the discovery potential in these channels. We then provide perspectives on the production of these channels at the Tevatron and LHC.

  12. Phyla- and Subtype-Selectivity of CgNa, a Na+ Channel Toxin from the Venom of the Giant Caribbean Sea Anemone Condylactis Gigantea

    PubMed Central

    Billen, Bert; Debaveye, Sarah; Béress, Lászlo; Tytgat, Jan

    2010-01-01

    Because of their prominent role in electro-excitability, voltage-gated sodium (NaV) channels have become the foremost important target of animal toxins. These toxins have developed the ability to discriminate between closely related NaV subtypes, making them powerful tools to study NaV channel function and structure. CgNa is a 47-amino acid residue type I toxin isolated from the venom of the Giant Caribbean Sea Anemone Condylactis gigantea. Previous studies showed that this toxin slows the fast inactivation of tetrodotoxin-sensitive NaV currents in rat dorsal root ganglion neurons. To illuminate the underlying NaV subtype-selectivity pattern, we have assayed the effects of CgNa on a broad range of mammalian isoforms (NaV1.2–NaV1.8) expressed in Xenopus oocytes. This study demonstrates that CgNa selectively slows the fast inactivation of rNaV1.3/β1, mNaV1.6/β1 and, to a lesser extent, hNaV1.5/β1, while the other mammalian isoforms remain unaffected. Importantly, CgNa was also examined on the insect sodium channel DmNaV1/tipE, revealing a clear phyla-selectivity in the efficacious actions of the toxin. CgNa strongly inhibits the inactivation of the insect NaV channel, resulting in a dramatic increase in peak current amplitude and complete removal of fast and steady-state inactivation. Together with the previously determined solution structure, the subtype-selective effects revealed in this study make of CgNa an interesting pharmacological probe to investigate the functional role of specific NaV channel subtypes. Moreover, further structural studies could provide important information on the molecular mechanism of NaV channel inactivation. PMID:21833172

  13. X-ray crystallographic and mass spectrometric structure determination and functional characterization of succinylated porin from Rhodobacter capsulatus: implications for ion selectivity and single-channel conductance.

    PubMed Central

    Przybylski, M.; Glocker, M. O.; Nestel, U.; Schnaible, V.; Blüggel, M.; Diederichs, K.; Weckesser, J.; Schad, M.; Schmid, A.; Welte, W.; Benz, R.

    1996-01-01

    The role of charges near the pore mouth has been discussed in theoretical work about ion channels. To introduce new negative charges in a channel protein, amino groups of porin from Rhodobacter capsulatus 37b4 were succinylated with succinic anhydride, and the precise extent and sites of succinylations and structures of the succinylporins determined by mass spectrometry and X-ray crystallography. Molecular weight and peptide mapping analyses using matrix-assisted laser desorption-ionization mass spectrometry identified selective succinylation of three lysine-epsilon-amino groups (Lys-46, Lys-298, Lys-300) and the N-terminal alpha-amino group. The structure of a tetra-succinylated porin (TS-porin) was determined to 2.4 A and was generally found unchanged in comparison to native porin to form a trimeric complex. All succinylated amino groups found in a mono/di-succinylated porin (MS-porin) and a TS-porin are localized at the inner channel surface and are solvent-accessible: Lys-46 is located at the channel constriction site, whereas Lys-298, Lys-300, and the N-terminus are all near the periplasmic entrance of the channel. The Lys-46 residue at the central constriction loop was modeled as succinyl-lysine from the electron density data and shown to bend toward the periplasmic pore mouth. The electrical properties of the MS-and TS-porins were determined by reconstitution into black lipid membranes, and showed a negative charge effect on ion transport and an increased cation selectivity through the porin channel. The properties of a typical general diffusion porin changed to those of a channel that contains point charges near the pore mouth. The single-channel conductance was no longer a linear function of the bulk aqueous salt concentration. The substantially higher cation selectivity of the succinylated porins compared with the native protein is consistent with the increase of negatively charged groups introduced. These results show tertiary structure-selective

  14. Adaptive selective relaying in cooperative free-space optical systems over atmospheric turbulence and misalignment fading channels.

    PubMed

    Boluda-Ruiz, Rubén; García-Zambrana, Antonio; Castillo-Vázquez, Carmen; Castillo-Vázquez, Beatriz

    2014-06-30

    In this paper, a novel adaptive cooperative protocol with multiple relays using detect-and-forward (DF) over atmospheric turbulence channels with pointing errors is proposed. The adaptive DF cooperative protocol here analyzed is based on the selection of the optical path, source-destination or different source-relay links, with a greater value of fading gain or irradiance, maintaining a high diversity order. Closed-form asymptotic bit error-rate (BER) expressions are obtained for a cooperative free-space optical (FSO) communication system with Nr relays, when the irradiance of the transmitted optical beam is susceptible to either a wide range of turbulence conditions, following a gamma-gamma distribution of parameters α and β, or pointing errors, following a misalignment fading model where the effect of beam width, detector size and jitter variance is considered. A greater robustness for different link distances and pointing errors is corroborated by the obtained results if compared with similar cooperative schemes or equivalent multiple-input multiple-output (MIMO) systems. Simulation results are further demonstrated to confirm the accuracy and usefulness of the derived results. PMID:24977911

  15. Adaptive selective relaying in cooperative free-space optical systems over atmospheric turbulence and misalignment fading channels.

    PubMed

    Boluda-Ruiz, Rubén; García-Zambrana, Antonio; Castillo-Vázquez, Carmen; Castillo-Vázquez, Beatriz

    2014-06-30

    In this paper, a novel adaptive cooperative protocol with multiple relays using detect-and-forward (DF) over atmospheric turbulence channels with pointing errors is proposed. The adaptive DF cooperative protocol here analyzed is based on the selection of the optical path, source-destination or different source-relay links, with a greater value of fading gain or irradiance, maintaining a high diversity order. Closed-form asymptotic bit error-rate (BER) expressions are obtained for a cooperative free-space optical (FSO) communication system with Nr relays, when the irradiance of the transmitted optical beam is susceptible to either a wide range of turbulence conditions, following a gamma-gamma distribution of parameters α and β, or pointing errors, following a misalignment fading model where the effect of beam width, detector size and jitter variance is considered. A greater robustness for different link distances and pointing errors is corroborated by the obtained results if compared with similar cooperative schemes or equivalent multiple-input multiple-output (MIMO) systems. Simulation results are further demonstrated to confirm the accuracy and usefulness of the derived results.

  16. Selective inhibition of caspases in skeletal muscle reverses the apoptotic synaptic degeneration in slow-channel myasthenic syndrome.

    PubMed

    Zhu, Haipeng; Pytel, Peter; Gomez, Christopher M

    2014-01-01

    Slow-channel syndrome (SCS) is a congenital myasthenic disorder caused by point mutations in subunits of skeletal muscle acetylcholine receptor leading to Ca(2+) overload and degeneration of the postsynaptic membrane, nuclei and mitochondria of the neuromuscular junction (NMJ). In both SCS muscle biopsies and transgenic mouse models for SCS (mSCS), the endplate regions are shrunken, and there is evidence of DNA damage in the subsynaptic region. Activated caspase-9, -3 and -7 are intensely co-localized at the NMJ, and the Ca(2+)-activated protease, calpain, and the atypical cyclin-dependent kinase (Cdk5) are overactivated in mSCS. Thus, the true mediator(s) of the disease process is not clear. Here, we demonstrate that selective inhibition of effector caspases, caspase-3 and -7, or initiator caspase, caspase-9, in limb muscle in vivo by localized expression of recombinant inhibitor proteins dramatically decreases subsynaptic DNA damage, increases endplate area and improves ultrastructural abnormalities in SCS transgenic mice. Calpain and Cdk5 are not affected by this treatment. On the other hand, inhibition of Cdk5 by expression of a dominant-negative form of Cdk5 has no effect on the degeneration. Together with previous studies, these results indicate that focal activation of caspase activity at the NMJ is the principal pathological process responsible for the synaptic apoptosis in SCS. Thus, treatments that reduce muscle caspase activity are likely to be of benefit for SCS patients.

  17. The sensitivity and selectivity of an implantable two-channel peroneal nerve stimulator system for restoration of dropped foot.

    PubMed

    Kottink, Anke I R; Buschman, Hendrik P J; Kenney, Laurence P J; Veltink, Peter H; Slycke, Per; Bultstra, Gerrit; Hermens, Hermie J

    2004-10-01

    The objective of this study was to evaluate the stimulation responses on each channel of an implantable two-channel stimulator that stimulates the peroneal nerve branches innervating the muscles for dorsiflexion and eversion movements. Currently five Dutch patients and five English patients have been implanted with this system. Isometric ankle torque measurements were carried out in the patient with the longest follow-up period (1 y). A force sensor measured the three components of moment generated at the ankle joint. Stimulation intensity can be adjusted with great accuracy. Dorsiflexion moments are almost entirely determined by the setting of channel 1. Eversion moments are determined mainly by channel 2 and to a lesser extent by channel 1. Both channels determined abduction/adduction moments. We conclude that stimulation responses in both dorsiflexion and eversion direction can be set individually and with great accuracy and are reproducible over a prolonged period. PMID:22151337

  18. Band structure of doubly-odd nuclei around mass 130

    SciTech Connect

    Higashiyama, Koji; Yoshinaga, Naotaka

    2011-05-06

    Nuclear structure of the doublet bands in the doubly-odd nuclei with mass A{approx}130 is studied in terms of a pair-truncated shell model. The model reproduces quite well the energy levels of the doublet bands and the electromagnetic transitions. The analysis of the electromagnetic transitions reveals new band structure of the doublet bands.

  19. Doubly Lopsided Models From SUSY SU(N)

    SciTech Connect

    Barr, S. M.

    2008-11-23

    It is shown that the doubly lopsided mass matrices, which are known to give realistic patterns of quark and lepton masses and mixings, arise naturally in the context of supersymmetric grand unified models based on SU(N) with N>5. An SU(7) model is presented as an illustration.

  20. TRP Channels

    NASA Astrophysics Data System (ADS)

    Voets, Thomas; Owsianik, Grzegorz; Nilius, Bernd

    The TRP superfamily represents a highly diverse group of cation-permeable ion channels related to the product of the Drosophila trp (transient receptor potential) gene. The cloning and characterization of members of this cation channel family has experienced a remarkable growth during the last decade, uncovering a wealth of information concerning the role of TRP channels in a variety of cell types, tissues, and species. Initially, TRP channels were mainly considered as phospholipase C (PLC)-dependent and/or store-operated Ca2+-permeable cation channels. More recent research has highlighted the sensitivity of TRP channels to a broad array of chemical and physical stimuli, allowing them to function as dedicated biological sensors involved in processes ranging from vision to taste, tactile sensation, and hearing. Moreover, the tailored selectivity of certain TRP channels enables them to play key roles in the cellular uptake and/or transepithelial transport of Ca2+, Mg2+, and trace metal ions. In this chapter we give a brief overview of the TRP channel superfamily followed by a survey of current knowledge concerning their structure and activation mechanisms.

  1. Small interfering RNA-mediated selective knockdown of Na(V)1.8 tetrodotoxin-resistant sodium channel reverses mechanical allodynia in neuropathic rats.

    PubMed

    Dong, X-W; Goregoaker, S; Engler, H; Zhou, X; Mark, L; Crona, J; Terry, R; Hunter, J; Priestley, T

    2007-05-11

    The biophysical properties of a tetrodotoxin resistant (TTXr) sodium channel, Na(V)1.8, and its restricted expression to the peripheral sensory neurons suggest that blocking this channel might have therapeutic potential in various pain states and may offer improved tolerability compared with existing sodium channel blockers. However, the role of Na(V)1.8 in nociception cannot be tested using a traditional pharmacological approach with small molecules because currently available sodium channel blockers do not distinguish between sodium channel subtypes. We sought to determine whether small interfering RNAs (siRNAs) might be capable of achieving the desired selectivity. Using Northern blot analysis and membrane potential measurement, several siRNAs were identified that were capable of a highly-selective attenuation of Na(V)1.8 message as well as functional expression in clonal ND7/23 cells which were stably transfected with the rat Na(V)1.8 gene. Functional knockdown of the channel was confirmed using whole-cell voltage-clamp electrophysiology. One of the siRNA probes showing a robust knockdown of Na(V)1.8 current was evaluated for in vivo efficacy in reversing an established tactile allodynia in the rat chronic constriction nerve-injury (CCI) model. The siRNA, which was delivered to lumbar dorsal root ganglia (DRG) via an indwelling epidural cannula, caused a significant reduction of Na(V)1.8 mRNA expression in lumbar 4 and 5 (L4-L5) DRG neurons and consequently reversed mechanical allodynia in CCI rats. We conclude that silencing of Na(V)1.8 channel using a siRNA approach is capable of producing pain relief in the CCI model and further support a role for Na(V)1.8 in pathological sensory dysfunction. PMID:17367951

  2. Helicobacter pylori vacuolating toxin forms anion-selective channels in planar lipid bilayers: possible implications for the mechanism of cellular vacuolation.

    PubMed Central

    Tombola, F; Carlesso, C; Szabò, I; de Bernard, M; Reyrat, J M; Telford, J L; Rappuoli, R; Montecucco, C; Papini, E; Zoratti, M

    1999-01-01

    The Helicobacter pylori VacA toxin plays a major role in the gastric pathologies associated with this bacterium. When added to cultured cells, VacA induces vacuolation, an effect potentiated by preexposure of the toxin to low pH. Its mechanism of action is unknown. We report here that VacA forms anion-selective, voltage-dependent pores in artificial membranes. Channel formation was greatly potentiated by acidic conditions or by pretreatment of VacA at low pH. No requirement for particular lipid(s) was identified. Selectivity studies showed that anion selectivity was maintained over the pH range 4.8-12, with the following permeability sequence: Cl- approximately HCO3- > pyruvate > gluconate > K+ approximately Li+ approximately Ba2+ > NH4+. Membrane permeabilization was due to the incorporation of channels with a voltage-dependent conductance in the 10-30 pS range (2 M KCl), displaying a voltage-independent high open probability. Deletion of the NH2 terminus domain (p37) or chemical modification of VacA by diethylpyrocarbonate inhibited both channel activity and vacuolation of HeLa cells without affecting toxin internalization by the cells. Collectively, these observations strongly suggest that VacA channel formation is needed to induce cellular vacuolation, possibly by inducing an osmotic imbalance of intracellular acidic compartments. PMID:10049322

  3. Cisapride, a selective serotonin 5-HT4-receptor agonist, inhibits voltage-dependent K(+) channels in rabbit coronary arterial smooth muscle cells.

    PubMed

    Kim, Hye Won; Li, Hongliang; Kim, Han Sol; Shin, Sung Eun; Jung, Won-Kyo; Ha, Kwon-Soo; Han, Eun-Taek; Hong, Seok-Ho; Choi, Il-Whan; Park, Won Sun

    2016-09-23

    We investigated the effect of cisapride, a selective serotonin 5-HT4-receptor agonist, on voltage-dependent K(+) (Kv) channels using freshly isolated smooth muscle cells from the coronary arteries of rabbits. The amplitude of Kv currents was reduced by cisapride in a concentration-dependent manner, with an IC50 value of 6.77 ± 6.01 μM and a Hill coefficient of 0.51 ± 0.18. The application of cisapride shifted the steady-state inactivation curve toward a more negative potential, but had no significant effect on the steady-state activation curve. This suggested that cisapride inhibited the Kv channel in a closed state by changing the voltage sensitivity of Kv channels. The application of another selective serotonin 5-HT4-receptor agonist, prucalopride, did not affect the basal Kv current and did not alter the inhibitory effect of cisapride on Kv channels. From these results, we concluded that cisapride inhibited vascular Kv current in a concentration-dependent manner by shifting the steady-state inactivation curve, independent of its own function as a selective serotonin 5-HT4-receptor agonist. PMID:27569285

  4. Relationship between expression of muscle-specific uncoupling protein 2 messenger RNA and genetic selection toward growth in channel catfish

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Uncoupling protein 2 is a member of the mitochondrial channel proteins that regulate the flow of hydrogen ions and ATP generation. The relationship between UCP2 and nutrient metabolism has been well-defined in humans but unclear in fish. We hypothesized that increased muscle growth in channel catf...

  5. Historical Channel Adjustment and Estimates of Selected Hydraulic Values in the Lower Sabine River and Lower Brazos River Basins, Texas and Louisiana

    USGS Publications Warehouse

    Heitmuller, Franklin T.; Greene, Lauren E.

    2009-01-01

    The U.S. Geological Survey, in cooperation with the Texas Water Development Board, evaluated historical channel adjustment and estimated selected hydraulic values at U.S. Geological Survey streamflow-gaging stations in the lower Sabine River Basin in Texas and Louisiana and lower Brazos River Basin in Texas to support geomorphic assessments of the Texas Instream Flow Program. Channel attributes including cross-section geometry, slope, and planform change were evaluated to learn how each river's morphology changed over the years in response to natural and anthropogenic disturbances. Historical and contemporary cross-sectional channel geometries at several gaging stations on each river were compared, planform changes were assessed, and hydraulic values were estimated including mean flow velocity, bed shear stress, Froude numbers, and hydraulic depth. The primary sources of historical channel morphology information were U.S. Geological Survey hard-copy discharge-measurement field notes. Additional analyses were done using computations of selected flow hydraulics, comparisons of historical and contemporary aerial photographs, comparisons of historical and contemporary ground photographs, evaluations of how frequently stage-discharge rating curves were updated, reviews of stage-discharge relations for field measurements, and considerations of bridge and reservoir construction activities. Based on historical cross sections at three gaging stations downstream from Toledo Bend Reservoir, the lower Sabine River is relatively stable, but is subject to substantial temporary scour-and-fill processes during floods. Exceptions to this characterization of relative stability include an episode of channel aggradation at the Sabine River near Bon Wier, Texas, during the 1930s, and about 2 to 3 feet of channel incision at the Sabine River near Burkeville, Texas, since the late 1950s. The Brazos River, at gaging stations downstream from Waco, Texas, has adjusted to a combination of

  6. A measurement of the top pair production cross-section in the dilepton channel using lepton plus track selection

    SciTech Connect

    Mills, Corrinne Elaine

    2007-06-01

    Using 1.1 fb-1 of data collected by the Collider Detector at Fermilab (CDF) from Run II of the Fermilab Tevatron, they measure the t$\\bar{t}$ production cross section in events with two leptons, significant missing transverse energy, and ≥ 2 jets. As the Run II dataset grows, more stringent tests of Standard Model predictions for the top quark sector are becoming possible. The dilepton channel, where both top quarks decay t → Wb → ℓvb, is of particular interest due to its high purity even in the absence of a b jet 'tagging' requirement. Use of an isolated track as the second lepton significant increases the dilepton acceptance, at the price of some increase in background, particular from W + jets events where one of the jets is identified as a lepton. With the amount of data available, it has been possible to improve the estimate of the contribution from that background, reflected in a reduced systematic uncertainty. Assuming a branching ratio of BR(W → ℓv) = 10.8% and a top mass of mt = 175 GeV/c2, the measured cross-section is σ(p$\\bar{p}$ → t$\\bar{t}$) = 8.3 ± 1.3(stat.) ± 0.7(syst.) ± 0.5(lumi.) pb. The result is consistent with the Standard Model prediction of 6.7$+0.7\\atop{-0.9}$ pb and represents a significant improvement in precision over previous results using this selection.

  7. Communication: Determining the structure of the N{sub 2}Ar van der Waals complex with laser-based channel-selected Coulomb explosion

    SciTech Connect

    Wu, Chengyin Liu, Yunquan; Gong, Qihuang; Wu, Cong; Xie, Xiguo; Li, Min; Deng, Yongkai; Song, Di; Su, Hongmei

    2014-04-14

    We experimentally reconstructed the structure of the N{sub 2}Ar van der Waals complex with the technique of laser-based channel-selected Coulomb explosion imaging. The internuclear distance between the N{sub 2} center of mass and the Ar atom, i.e., the length of the van der Waals bond, was determined to be 3.88 Å from the two-body explosion channels. The angle between the van der Waals bond and the N{sub 2} principal axis was determined to be 90° from the three-body explosion channels. The reconstructed structure was contrasted with our high level ab initio calculations. The agreement demonstrated the potential application of laser-based Coulomb explosion in imaging transient molecular structure, particularly for floppy van der Waals complexes, whose structures remain difficult to be determined by conventional spectroscopic methods.

  8. Histidines, heart of the hydrogen ion channel from influenza A virus: Toward an understanding of conductance and proton selectivity

    NASA Astrophysics Data System (ADS)

    Hu, Jun; Fu, Riqiang; Nishimura, Katsuyuki; Zhang, Li; Zhou, Huan-Xiang; Busath, David D.; Vijayvergiya, Viksita; Cross, Timothy A.

    2006-05-01

    The heart of the H+ conductance mechanism in the homotetrameric M2 H+ channel from influenza A is a set of four histidine side chains. Here, we show that protonation of the third of these imidazoles coincides with acid activation of this transmembrane channel and that, at physiological pH, the channel is closed by two imidazole-imidazolium dimers, each sharing a low-barrier hydrogen bond. This unique construct succeeds in distributing a pair of charges over four rings and many atoms in a low dielectric environment to minimize charge repulsion. These dimers form with identical pKas of 8.2 ± 0.2, suggesting cooperative H+ binding and clearly illustrating high H+ affinity for this channel. The protonation behavior of the histidine side chains has been characterized by using solid-state NMR spectroscopy on the M2 transmembrane domain in fully hydrated lipid bilayers where the tetrameric backbone structure is known. Furthermore, electrophysiological measurements of multichannel and single-channel experiments confirm that these protein constructs are functional. M2 channel | proton channel | solid-state NMR | low-barrier hydrogen bond | histidine ionization constants

  9. Vpr Protein of Human Immunodeficiency Virus Type 1 Forms Cation-Selective Channels in Planar Lipid Bilayers

    NASA Astrophysics Data System (ADS)

    Piller, S. C.; Ewart, G. D.; Premkumar, A.; Cox, G. B.; Gage, P. W.

    1996-01-01

    A small (96-aa) protein, virus protein R (Vpr), of human immunodeficiency virus type 1 contains one hydrophobic segment that could form a membrane-spanning helix. Recombinant Vpr, expressed in Escherichia coli and purified by affinity chromatography, formed ion channels in planar lipid bilayers when it was added to the cis chamber and when the trans chamber was held at a negative potential. The channels were more permeable to Na+ than to Cl- ions and were inhibited when the trans potential was made positive. Similar channel activity was caused by Vpr that had a truncated C terminus, but the potential dependence of channel activity was no longer seen. Antibody raised to a peptide mimicking part of the C terminus of Vpr (AbC) inhibited channel activity when added to the trans chamber but had no effect when added to the cis chamber. Antibody to the N terminus of Vpr (AbN) increased channel activity when added to the cis chamber but had no effect when added to the trans chamber. The effects of potential and antibodies on channel activity are consistent with a model in which the positive C-terminal end of dipolar Vpr is induced to traverse the bilayer membrane when the opposite (trans) side of the membrane is at a negative potential. The C terminus of Vpr would then be available for interaction with AbC in the trans chamber, and the N terminus would be available for interaction with AbN in the cis chamber. The ability of Vpr to form ion channels in vitro suggests that channel formation by Vpr in vivo is possible and may be important in the life cycle of human immunodeficiency virus type 1 and/or may cause changes in cells that contribute to AIDS-related pathologies.

  10. Persistent human cardiac Na+ currents in stably transfected mammalian cells: Robust expression and distinct open-channel selectivity among Class 1 antiarrhythmics.

    PubMed

    Wang, Ging Kuo; Russell, Gabriella; Wang, Sho-Ya

    2013-01-01

    Miniature persistent late Na(+) currents in cardiomyocytes have been linked to arrhythmias and sudden death. The goals of this study are to establish a stable cell line expressing robust persistent cardiac Na(+) currents and to test Class 1 antiarrhythmic drugs for selective action against resting and open states. After transient transfection of an inactivation-deficient human cardiac Na(+) channel clone (hNav1.5-CW with L409C/A410W double mutations), transfected mammalian HEK293 cells were treated with 1 mg/ml G-418. Individual G-418-resistant colonies were isolated using glass cylinders. One colony with high expression of persistent Na(+) currents was subjected to a second colony selection. Cells from this colony remained stable in expressing robust peak Na(+) currents of 996 ± 173 pA/pF at +50 mV (n = 20). Persistent late Na(+) currents in these cells were clearly visible during a 4-second depolarizing pulse albeit decayed slowly. This slow decay is likely due to slow inactivation of Na(+) channels and could be largely eliminated by 5 μM batrachotoxin. Peak cardiac hNav1.5-CW Na(+) currents were blocked by tetrodotoxin with an IC(50) value of 2.27 ± 0.08 μM (n = 6). At clinic relevant concentrations, Class 1 antiarrhythmics are much more selective in blocking persistent late Na(+) currents than their peak counterparts, with a selectivity ratio ranging from 80.6 (flecainide) to 3 (disopyramide). We conclude that (1) Class 1 antiarrhythmics differ widely in their resting- vs. open-channel selectivity, and (2) stably transfected HEK293 cells expressing large persistent hNav1.5-CW Na(+) currents are suitable for studying as well as screening potent open-channel blockers. PMID:23695971

  11. Selective Loss of Presynaptic Potassium Channel Clusters at the Cerebellar Basket Cell Terminal Pinceau in Adam11 Mutants Reveals Their Role in Ephaptic Control of Purkinje Cell Firing

    PubMed Central

    Kole, Matthew J.; Qian, Jing; Waase, Marc P.; Klassen, Tara L.; Chen, Tim T.; Augustine, George J.

    2015-01-01

    A specialized axonal ending, the basket cell “pinceau,” encapsulates the Purkinje cell axon initial segment (AIS), exerting final inhibitory control over the integrated outflow of the cerebellar cortex. This nonconventional axo-axonic contact extends beyond the perisomatic chemical GABAergic synaptic boutons to the distal AIS, lacks both sodium channels and local exocytotic machinery, and yet contains a dense cluster of voltage-gated potassium channels whose functional contribution is unknown. Here, we show that ADAM11, a transmembrane noncatalytic disintegrin, is the first reported Kv1-interacting protein essential for localizing Kv1.1 and Kv1.2 subunit complexes to the distal terminal. Selective absence of these channels at the pinceau due to mutation of ADAM11 spares spontaneous GABA release from basket cells at the perisomatic synapse yet eliminates ultrarapid ephaptic inhibitory synchronization of Purkinje cell firing. Our findings identify a critical role for presynaptic K+ channels at the pinceau in ephaptic control over the speed and stability of spike rate coding at the Purkinje cell AIS in mice. SIGNIFICANCE STATEMENT This study identifies ADAM11 as the first essential molecule for the proper localization of potassium ion channels at presynaptic nerve terminals, where they modulate excitability and the release of neural transmitters. Genetic truncation of the transmembrane disintegrin and metalloproteinase protein ADAM11 resulted in the absence of Kv1 channels that are normally densely clustered at the terminals of basket cell axons in the cerebellar cortex. These specialized terminals are responsible for the release of the neurotransmitter GABA onto Purkinje cells and also display electrical signaling. In the ADAM11 mutant, GABAergic release was not altered, but the ultrarapid electrical signal was absent, demonstrating that the dense presynaptic cluster of Kv1 ion channels at these terminals mediate electrical transmission. Therefore, ADAM11 plays a

  12. Ginsenoside Rb1 selectively inhibits the activity of L-type voltage-gated calcium channels in cultured rat hippocampal neurons

    PubMed Central

    Lin, Zhi-ying; Chen, Li-min; Zhang, Jing; Pan, Xiao-dong; Zhu, Yuan-gui; Ye, Qin-yong; Huang, Hua-pin; Chen, Xiao-chun

    2012-01-01

    Aim: To investigate the effect of ginsenoside Rb1 on voltage-gated calcium currents in cultured rat hippocampal neurons and the modulatory mechanism. Methods: Cultured hippocampal neurons were prepared from Sprague Dawley rat embryos. Whole-cell configuration of the patch-clamp technique was used to record the voltage-gated calcium currents (VGCCs) from the hippocampal neurons,and the effect of Rb1 was examined. Results: Rb1 (2–100 μmol/L) inhibited VGCCs in a concentration-dependent manner, and the current was mostly recovered upon wash-out. The specific L-type Ca2+ channel inhibitor nifedipine (10 μmol/L) occluded Rb1-induced inhibition on VGCCs. Neither the selective N-type Ca2+ channel blocker ω-conotoxin-GVIA (1 μmol/L), nor the selective P/Q-type Ca2+ channel blocker ω-agatoxin IVA (30 nmol/L) diminished Rb1-sensitive VGCCs. Rb1 induced a leftward shift of the steady-state inactivation curve of ICa to a negative potential without affecting its activation kinetics or reversal potential in the I–V curve. The inhibitory effect of Rb1 was neither abolished by the adenylyl cyclase activator forskolin (10 μmol/L), nor by the PKA inhibitor H-89 (10 μmol/L). Conclusion: Ginsenoside Rb1 selectively inhibits the activity of L-type voltage-gated calcium channels, without affecting the N-type or P/Q-type Ca2+ channels in hippocampal neurons. cAMP-PKA signaling pathway is not involved in this effect. PMID:22407229

  13. Selective inhibition of the Kir2 family of inward rectifier potassium channels by a small molecule probe: the discovery, SAR and pharmacological characterization of ML133

    PubMed Central

    Wang, Hao-Ran; Wu, Meng; Yu, Haibo; Long, Shunyou; Stevens, Amy; Engers, Darren W.; Sackin, Henry; Daniels, J. Scott; Dawson, Eric S.; Hopkins, Corey R.; Lindsley, Craig W.; Li, Min; McManus, Owen B

    2011-01-01

    The Kir inward rectifying potassium channels have a broad tissue distribution and are implicated in a variety of functional roles. At least seven classes (Kir1 – Kir7) of structurally related inward rectifier potassium channels are known, and there are no selective small molecule tools to study their function. In an effort to develop selective Kir2.1 inhibitors, we performed a high-throughput screen (HTS) of more than 300,000 small molecules within the MLPCN for modulators of Kir2.1 function. Here we report one potent Kir2.1 inhibitor, ML133, which inhibits Kir2.1 with IC50 of 1.8 μM at pH 7.4 and 290 nM at pH 8.5, but exhibits little selectivity against other members of Kir2.x family channels. However, ML133 has no effect on Kir1.1 (IC50 > 300 μM), and displays weak activity for Kir4.1 (76 μM) and Kir7.1 (33 μM), making ML133 the most selective small molecule inhibitor of the Kir family reported to date. Due to the high homology within the Kir family, the channels share a common design of a pore region flanked by two transmembrane domains, identification of site(s) critical for isoform specificity would be an important basis for future development of more specific and potent Kir inhibitors. Using chimeric channels between Kir2.1 and Kir1.1 and site-directed mutagenesis, we have identified D172 and I176 within M2 segment of Kir2.1 as molecular determinants critical for the potency of ML133 mediated inhibition. Double mutation of the corresponding residues of Kir1.1 to those of Kir2.1 (N171D and C175I) transplants ML133 inhibition to Kir1.1. Together, the combination of a potent, Kir2 family selective inhibitor and identification of molecular determinants for the specificity provides both a tool and a model system to enable further mechanistic studies of modulation of Kir2 inward rectifier potassium channels. PMID:21615117

  14. Connexin37 forms high conductance gap junction channels with subconductance state activity and selective dye and ionic permeabilities.

    PubMed Central

    Veenstra, R D; Wang, H Z; Beyer, E C; Ramanan, S V; Brink, P R

    1994-01-01

    Gap junctions are thought to mediate the direct intercellular coupling of adjacent cells by the open-closed gating of an aqueous pore permeable to ions and molecules of up to 1 kDa or 10-14 A in diameter. We symmetrically altered the ionic composition or asymmetrically added 6-carboxyfluorescein (6-CF, M(r) = 376), a fluorescent tracer, to pairs of connexin37-transfected mouse neuro2A cells to examine the ionic and dye permeability of human connexin37 channels. We demonstrate that the 300-pS channel formed by connexin37 has an effective relative anion/cation permeability ratio of 0.43, directly converts to at least one intermediate (63 pS) subconductance state, and that 6-CF dye transfer is accompanied by a 24% decrease in unitary channel conductance. These observations favor a new interpretation of the gap junction pore consistent with direct ion-channel interactions or electrostatic charge effects common to more conventional multistate ion channels. These results have distinct implications about the different forms of intercellular signaling (cationic, ionic, and/or biochemical) that can occur depending on the expression and conformation of the connexin channel proteins. Images FIGURE 4 FIGURE 5 FIGURE 6 PMID:7521227

  15. Mutating the Conserved Q-loop Glutamine 1291 Selectively Disrupts Adenylate Kinase-dependent Channel Gating of the ATP-binding Cassette (ABC) Adenylate Kinase Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and Reduces Channel Function in Primary Human Airway Epithelia.

    PubMed

    Dong, Qian; Ernst, Sarah E; Ostedgaard, Lynda S; Shah, Viral S; Ver Heul, Amanda R; Welsh, Michael J; Randak, Christoph O

    2015-05-29

    The ATP-binding cassette (ABC) transporter cystic fibrosis transmembrane conductance regulator (CFTR) and two other non-membrane-bound ABC proteins, Rad50 and a structural maintenance of chromosome (SMC) protein, exhibit adenylate kinase activity in the presence of physiologic concentrations of ATP and AMP or ADP (ATP + AMP ⇆ 2 ADP). The crystal structure of the nucleotide-binding domain of an SMC protein in complex with the adenylate kinase bisubstrate inhibitor P(1),P(5)-di(adenosine-5') pentaphosphate (Ap5A) suggests that AMP binds to the conserved Q-loop glutamine during the adenylate kinase reaction. Therefore, we hypothesized that mutating the corresponding residue in CFTR, Gln-1291, selectively disrupts adenylate kinase-dependent channel gating at physiologic nucleotide concentrations. We found that substituting Gln-1291 with bulky side-chain amino acids abolished the effects of Ap5A, AMP, and adenosine 5'-monophosphoramidate on CFTR channel function. 8-Azidoadenosine 5'-monophosphate photolabeling of the AMP-binding site and adenylate kinase activity were disrupted in Q1291F CFTR. The Gln-1291 mutations did not alter the potency of ATP at stimulating current or ATP-dependent gating when ATP was the only nucleotide present. However, when physiologic concentrations of ADP and AMP were added, adenylate kinase-deficient Q1291F channels opened significantly less than wild type. Consistent with this result, we found that Q1291F CFTR displayed significantly reduced Cl(-) channel function in well differentiated primary human airway epithelia. These results indicate that a highly conserved residue of an ABC transporter plays an important role in adenylate kinase-dependent CFTR gating. Furthermore, the results suggest that adenylate kinase activity is important for normal CFTR channel function in airway epithelia.

  16. Mutating the Conserved Q-loop Glutamine 1291 Selectively Disrupts Adenylate Kinase-dependent Channel Gating of the ATP-binding Cassette (ABC) Adenylate Kinase Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and Reduces Channel Function in Primary Human Airway Epithelia*

    PubMed Central

    Dong, Qian; Ernst, Sarah E.; Ostedgaard, Lynda S.; Shah, Viral S.; Ver Heul, Amanda R.; Welsh, Michael J.; Randak, Christoph O.

    2015-01-01

    The ATP-binding cassette (ABC) transporter cystic fibrosis transmembrane conductance regulator (CFTR) and two other non-membrane-bound ABC proteins, Rad50 and a structural maintenance of chromosome (SMC) protein, exhibit adenylate kinase activity in the presence of physiologic concentrations of ATP and AMP or ADP (ATP + AMP ⇆ 2 ADP). The crystal structure of the nucleotide-binding domain of an SMC protein in complex with the adenylate kinase bisubstrate inhibitor P1,P5-di(adenosine-5′) pentaphosphate (Ap5A) suggests that AMP binds to the conserved Q-loop glutamine during the adenylate kinase reaction. Therefore, we hypothesized that mutating the corresponding residue in CFTR, Gln-1291, selectively disrupts adenylate kinase-dependent channel gating at physiologic nucleotide concentrations. We found that substituting Gln-1291 with bulky side-chain amino acids abolished the effects of Ap5A, AMP, and adenosine 5′-monophosphoramidate on CFTR channel function. 8-Azidoadenosine 5′-monophosphate photolabeling of the AMP-binding site and adenylate kinase activity were disrupted in Q1291F CFTR. The Gln-1291 mutations did not alter the potency of ATP at stimulating current or ATP-dependent gating when ATP was the only nucleotide present. However, when physiologic concentrations of ADP and AMP were added, adenylate kinase-deficient Q1291F channels opened significantly less than wild type. Consistent with this result, we found that Q1291F CFTR displayed significantly reduced Cl− channel function in well differentiated primary human airway epithelia. These results indicate that a highly conserved residue of an ABC transporter plays an important role in adenylate kinase-dependent CFTR gating. Furthermore, the results suggest that adenylate kinase activity is important for normal CFTR channel function in airway epithelia. PMID:25887396

  17. Doubly-charged ions in the planetary ionospheres: a review.

    PubMed

    Thissen, Roland; Witasse, Olivier; Dutuit, Odile; Wedlund, Cyril Simon; Gronoff, Guillaume; Lilensten, Jean

    2011-11-01

    This paper presents a review of the current knowledge on the doubly-charged atomic and molecular positive ions in the planetary atmospheres of the Solar System. It is focused on the terrestrial planets which have a dense atmosphere of N(2) or CO(2), i.e. Venus, the Earth and Mars, but also includes Titan, the largest satellite of Saturn, which has a dense atmosphere composed mainly of N(2) and a few percent of methane. Given the composition of these neutral atmospheres, the following species are considered: C(++), N(++), O(++), CH(4)(++), CO(++), N(2)(++), NO(++), O(2)(++), Ar(++) and CO(2)(++). We first discuss the status of their detection in the atmospheres of planets. Then, we provide a comprehensive review of their complex and original photochemistry, production and loss processes. Synthesis tables are provided for those ions, while a discussion on individual species is also provided. Methods for detecting doubly-charged ions in planetary atmospheres are presented, namely with mass-spectrometry, remote sensing and fine plasma density measurements. A section covers some original applications, like the possible effect of the presence of doubly-charged ions on the escape of an atmosphere, which is a key topic of ongoing planetary exploration, related to the evolution of a planet. The results of models, displayed in a comparative way for Venus, Earth, Mars and Titan, are discussed, as they can predict the presence of doubly-charged ions and will certainly trigger new investigations. Finally we give our view concerning next steps, challenges and needs for future studies, hoping that new scientific results will be achieved in the coming years and feed the necessary interdisciplinary exchanges amongst different scientific communities. PMID:21931881

  18. Influence of curvature on the losses of doubly clad fibers.

    PubMed

    Marcuse, D

    1982-12-01

    The loss increase of the HE(11) mode of a doubly clad (depressed-index) fiber due to constant curvature is considered. The calculations presented in this paper are based on a simplified theory. We find that for typical fibers the leakage loss of the HE(11) mode begins to increase significantly when the radius of curvature of the fiber axis reaches the 1-10-cm range.

  19. Alternating parity structure in doubly odd /sup 218/Ac

    SciTech Connect

    Debray, M.E.; Davidson, M.; Kreiner, A.J.; Davidson, J.; Falcone, G.; Hojman, D.; Santos, D.

    1989-03-01

    States in doubly odd /sup 218/Ac have been studied using in-beam ..cap alpha..-, ..gamma..-, and e/sup -/-spectroscopy techniques mainly through the /sup 209/Bi(/sup 12/C,3n)= fusion-evaporation reaction. /sup 218/Ac shows a band structure, with interleaved states of alternating parities connected by enhanced B(E1) transitions, which is strikingly similar to the one in its isotone /sup 217/Ra.

  20. Doubly Excited Resonances in the Positronium Negative Ion

    NASA Technical Reports Server (NTRS)

    Ho, Y.K.

    2007-01-01

    The recent theoretical studies on the doubly excited states of the Ps' ion are described. The results obtained by using the method of complex coordinate rotation show that the three-lepton system behaves very much like an XYX tri-atomic molecule. Furthermore, the recent investigation on the positronium negative ion embedded in Debye plasma environments is discussed. The problem is modeled by the use of a screened Coulomb potential to represent the interaction between the charge particles.

  1. Doubly Excited Resonance States of Helium Atom: Complex Entropies

    NASA Astrophysics Data System (ADS)

    Kuroś, Arkadiusz; Kościk, Przemysław; Saha, Jayanta K.

    2016-09-01

    We provide a diagonal form of a reduced density matrix of S-symmetry resonance states of two electron systems determined under the framework of the complex scaling method. We have employed the variational Hylleraas type wavefunction to estimate the complex entropies in doubly excited resonance states of helium atom. Our results are in good agreement with the corresponding ones determined under the framework of the stabilization method (Lin and Ho in Few-Body Syst 56:157, 2015).

  2. Doubly curved nanofiber-reinforced optically transparent composites

    PubMed Central

    Shams, Md. Iftekhar; Yano, Hiroyuki

    2015-01-01

    Doubly curved nanofiber-reinforced optically transparent composites with low thermal expansion of 15 ppm/k are prepared by hot pressing vacuum-filtered Pickering emulsions of hydrophobic acrylic resin monomer, hydrophilic chitin nanofibers and water. The coalescence of acrylic monomer droplets in the emulsion is prevented by the chitin nanofibers network. This transparent composite has 3D shape moldability, making it attractive for optical precision parts. PMID:26552990

  3. Doubly curved nanofiber-reinforced optically transparent composites

    NASA Astrophysics Data System (ADS)

    Shams, Md. Iftekhar; Yano, Hiroyuki

    2015-11-01

    Doubly curved nanofiber-reinforced optically transparent composites with low thermal expansion of 15 ppm/k are prepared by hot pressing vacuum-filtered Pickering emulsions of hydrophobic acrylic resin monomer, hydrophilic chitin nanofibers and water. The coalescence of acrylic monomer droplets in the emulsion is prevented by the chitin nanofibers network. This transparent composite has 3D shape moldability, making it attractive for optical precision parts.

  4. Doubly heavy baryon spectra guided by lattice QCD

    NASA Astrophysics Data System (ADS)

    Garcilazo, H.; Valcarce, A.; Vijande, J.

    2016-10-01

    This paper provides results for the ground state and excited spectra of three-flavored doubly heavy baryons, b c n and b c s . We take advantage of the spin-independent interaction recently obtained to reconcile the lattice SU(3) QCD static potential and the results of nonperturbative lattice QCD for the triply heavy baryon spectra. We show that the spin-dependent potential might be constrained on the basis of nonperturbative lattice QCD results for the spin splittings of three-flavored doubly heavy baryons. Our results may also represent a challenge for future lattice QCD work, because a smaller lattice error could help in distinguishing between different prescriptions for the spin-dependent part of the interaction. Thus, by comparing with the reported baryon spectra obtained with parameters estimated from lattice QCD, one can challenge the precision of lattice calculations. The present work supports a coherent description of singly, doubly and triply heavy baryons with the same Cornell-like interacting potential. The possible experimental measurement of these states at LHCb is an incentive for this study.

  5. Doubly sensitivity-enhanced 3D TOCSY-HSQC.

    PubMed

    Wijmenga, S S; van Mierlo, C P; Steensma, E

    1996-10-01

    Recently, strategies for double sensitivity enhancement in heteronuclear three-dimensional NMR experiments were introduced (Krishnamurthy, V.V. (1995) J. Magn. Reson., B106, 170-177; Sattler et al. (1995) J. Biomol. NMR, 6, 11-22; Sattler et al. (1995) J. Magn. Reson., B108, 235-242). Since a sensitivity enhancement of a factor 2(1/2) can be achieved for each indirect dimension, nD spectra can theoretically be enhanced up to a factor of 2(((n-1)/2)). We propose and analyze a doubly enhanced three-dimensional TOCSY-HSQC sequence. The application of the doubly enhanced three-dimensional {(15)N, (1)H} TOCSY-HSQC sequence is shown for uniformly (13)C-/(15)N- and (15)N-labeled samples of the relatively large Azotobacter vinelandii flavodoxin II (179 amino acids). The main factors that contribute to the final signal-to-noise enhancement have been systematically investigated. The sensitivity enhancement obtained for the doubly enhanced TOCSY-HSQC pulse sequence as compared to the standard (unenhanced) version is close to the theoretically expected factor of two.

  6. Cd(2+) sensitivity and permeability of a low voltage-activated Ca(2+) channel with CatSper-like selectivity filter.

    PubMed

    Garza-López, Edgar; Chávez, Julio César; Santana-Calvo, Carmen; López-González, Ignacio; Nishigaki, Takuya

    2016-07-01

    CatSper is a sperm-specific Ca(2+) channel that plays an essential role in the male fertility. However, its biophysical properties have been poorly characterized mainly due to its deficient heterologous expression. As other voltage-gated Ca(2+) channels (CaVs), CatSper possesses a conserved Ca(2+)-selective filter motif ([T/S]x[D/E]xW) in the pore region. Interestingly, CatSper conserves four aspartic acids (DDDD) as the negatively charged residues in this motif while high voltage-activated CaVs have four glutamic acids (EEEE) and low voltage-activated CaVs possess two glutamic acids and two aspartic acids (EEDD). Previous studies based on site-directed mutagenesis of L- and T-type channels showed that the number of D seems to have a negative correlation with their cadmium (Cd(2+)) sensitivity. These results suggest that CatSper (DDDD) would have low sensitivity to Cd(2+). To explore Cd(2+)-sensitivity and -permeability of CatSper, we performed two types of experiments: 1) Electrophysiological analysis of heterologously expressed human CaV3.1 channel and three pore mutants (DEDD, EDDD and DDDD), 2) Cd(2+) imaging of human spermatozoa with FluoZin-1. Electrophysiological studies showed a significant increase in Cd(2+) and manganese (Mn(2+)) currents through the CaV3.1 mutants as well as a reduction in the inhibitory effect of Cd(2+) on the Ca(2+) current. In fluorescence imaging with human sperm, we observed an increase in Cd(2+) influx potentiated by progesterone, a potent activator of CatSper. These results support our hypothesis, namely that Cd(2+)-sensitivity and -permeability are related to the absolute number of D in the Ca(2+)-selective filter independently to the type of the Cav channels.

  7. CASEIN KINASE-MEDIATED PHOSPHORYLATION OF SERINE 839 IS NECESSARY FOR BASOLATERAL LOCALIZATION OF THE Ca2+-ACTIVATED NON-SELECTIVE CATION CHANNEL TRPM4

    PubMed Central

    Cerda, Oscar; Cáceres, Mónica; Park, Kang-Sik; Leiva-Salcedo, Elías; Romero, Aníbal; Varela, Diego

    2014-01-01

    TRPM4 is a Ca2+-activated non-selective cation channel expressed in a wide range of human tissues. TRPM4 participates in a variety of physiological processes such as T cell activation, myogenic vasoconstriction and allergic reactions. TRPM4 Ca2+ sensitivity is enhanced by calmodulin (CaM) and phosphathydilinositol 4, 5-biphosphate (PI(4,5)P2) binding, as well as, under certain conditions, PKC activation. However, information as to the mechanisms of modulation of this channel remain unknown, including direct identification of phosphorylation sites on TRPM4 and their role in channel features. Here, we use mass-spectrometric-based proteomic approaches (immunoprecipitation and tandem mass spectrometry), to unambiguously identify S839 as a phosphorylation site present on human TRPM4 expressed in a human cell line. Site-directed mutagenesis employing a serine to alanine mutation to eliminate phosphorylation, and a phospho-mimetic aspartate mutation, as well as biochemical and immunocytochemical experiments, revealed a role for S839 phosphorylation in the basolateral expression of TRPM4 channels in epithelial cells. Moreover, we demonstrated that casein kinase 1 (CK1) phosphorylates S839 and is responsible for the basolateral localization of TRPM4. PMID:25231975

  8. Distinct interactions of Na{sup +} and Ca{sup 2+} ions with the selectivity filter of the bacterial sodium channel Na{sub V}Ab

    SciTech Connect

    Ke, Song; Zangerl, Eva-Maria; Stary-Weinzinger, Anna

    2013-01-25

    Highlights: ► Ca{sup 2+} translocates slowly in the filter, due to lack of “loose” knock-on mechanism. ► Identification of a high affinity binding site in Na{sub V}Ab selectivity filter. ► Changes of EEEE locus triggered by electrostatic interactions with Ca{sup 2+} ions. -- Abstract: Rapid and selective ion transport is essential for the generation and regulation of electrical signaling pathways in living organisms. In this study, we use molecular dynamics simulations and free energy calculations to investigate how the bacterial sodium channel Na{sub V}Ab (Arcobacter butzleri) differentiates between Na{sup +} and Ca{sup 2+} ions. Multiple nanosecond molecular dynamics simulations revealed distinct binding patterns for these two cations in the selectivity filter and suggested a high affinity calcium binding site formed by backbone atoms of residues Leu-176 and Thr-175 (S{sub CEN}) in the sodium channel selectivity filter.

  9. 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.

    PubMed

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

    2013-09-01

    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.

  10. Combining cluster analysis, feature selection and multiple support vector machine models for the identification of human ether-a-go-go related gene channel blocking compounds.

    PubMed

    Nisius, Britta; Göller, Andreas H; Bajorath, Jürgen

    2009-01-01

    Blockade of the human ether-a-go-go related gene potassium channel is regarded as a major cause of drug toxicity and associated with severe cardiac side-effects. A variety of in silico models have been reported to aid in the identification of compounds blocking the human ether-a-go-go related gene channel. Herein, we present a classification approach for the detection of diverse human ether-a-go-go related gene blockers that combines cluster analysis of training data, feature selection and support vector machine learning. Compound learning sets are first divided into clusters of similar molecules. For each cluster, independent support vector machine models are generated utilizing preselected MACCS structural keys as descriptors. These models are combined to predict human ether-a-go-go related gene inhibition of our large compound data set with consistent experimental measurements (i.e. only patch clamp measurements on mammalian cell lines). Our combined support vector machine model achieves a prediction accuracy of 85% on this data set and performs better than alternative methods used for comparison. We also find that structural keys selected on the basis of statistical criteria are associated with molecular substructures implicated in human ether-a-go-go related gene channel binding.

  11. Nonparametric Inference of Doubly Stochastic Poisson Process Data via the Kernel Method.

    PubMed

    Zhang, Tingting; Kou, S C

    2010-01-01

    Doubly stochastic Poisson processes, also known as the Cox processes, frequently occur in various scientific fields. In this article, motivated primarily by analyzing Cox process data in biophysics, we propose a nonparametric kernel-based inference method. We conduct a detailed study, including an asymptotic analysis, of the proposed method, and provide guidelines for its practical use, introducing a fast and stable regression method for bandwidth selection. We apply our method to real photon arrival data from recent single-molecule biophysical experiments, investigating proteins' conformational dynamics. Our result shows that conformational fluctuation is widely present in protein systems, and that the fluctuation covers a broad range of time scales, highlighting the dynamic and complex nature of proteins' structure.

  12. No evidence for induction or selection of mutant sodium channel expression in the copepod Acartia husdsonica challenged with the toxic dinoflagellate Alexandrium fundyense

    PubMed Central

    Finiguerra, Michael; Avery, David E; Dam, Hans G

    2014-01-01

    Some species in the dinoflagellate genus Alexandrium spp. produce a suite of neurotoxins that block sodium channels, known as paralytic shellfish toxins (PST), which have deleterious effects on grazers. Populations of the ubiquitous copepod grazer Acartia hudsonica that have co-occurred with toxic Alexandrium spp. are better adapted than naïve populations. The mechanism of adaptation is currently unknown. We hypothesized that a mutation in the sodium channel could account for the grazer adaptation. We tested two hypotheses: (1) Expression of the mutant sodium channel could be induced by exposure to toxic Alexandrium fundyense; (2) in the absence of induction, selection exerted by toxic A. fundyense would favor copepods that predominantly express the mutant isoform. In the copepod A. hudsonica, both isoforms are expressed in all individuals in varying proportions. Thus, in addition to comparing expression ratios of wild-type to mutant isoforms for individual copepods, we also partitioned copepods into three groups: those that predominantly express the mutant (PMI) isoform, the wild-type (PWI) isoform, or both isoforms approximately equally (EI). There were no differences in isoform expression between individuals that were fed toxic and nontoxic food after three and 6 days; induction of mutant isoform expression did not occur. Furthermore, the hypothesis that mutant isoform expression responds to toxic food was also rejected. That is, no consistent evidence showed that the wild-type to mutant isoform ratios decreased, or that the relative proportion of PMI individuals increased, due to the consumption of toxic food over four generations. However, in the selected line that was continuously exposed to toxic food sources, egg production rate increased, which suggested that adaptation occurred but was unrelated to sodium channel isoform expression. PMID:25535562

  13. Identification and analysis of genome-wide SNPs provide insight into signatures of selection and domestication in channel catfish (Ictalurus punctatus).

    PubMed

    Sun, Luyang; Liu, Shikai; Wang, Ruijia; Jiang, Yanliang; Zhang, Yu; Zhang, Jiaren; Bao, Lisui; Kaltenboeck, Ludmilla; Dunham, Rex; Waldbieser, Geoff; Liu, Zhanjiang

    2014-01-01

    Domestication and selection for important performance traits can impact the genome, which is most often reflected by reduced heterozygosity in and surrounding genes related to traits affected by selection. In this study, analysis of the genomic impact caused by domestication and artificial selection was conducted by investigating the signatures of selection using single nucleotide polymorphisms (SNPs) in channel catfish (Ictalurus punctatus). A total of 8.4 million candidate SNPs were identified by using next generation sequencing. On average, the channel catfish genome harbors one SNP per 116 bp. Approximately 6.6 million, 5.3 million, 4.9 million, 7.1 million and 6.7 million SNPs were detected in the Marion, Thompson, USDA103, Hatchery strain, and wild population, respectively. The allele frequencies of 407,861 SNPs differed significantly between the domestic and wild populations. With these SNPs, 23 genomic regions with putative selective sweeps were identified that included 11 genes. Although the function for the majority of the genes remain unknown in catfish, several genes with known function related to aquaculture performance traits were included in the regions with selective sweeps. These included hypoxia-inducible factor 1β. HIFιβ.. and the transporter gene ATP-binding cassette sub-family B member 5 (ABCB5). HIF1β. is important for response to hypoxia and tolerance to low oxygen levels is a critical aquaculture trait. The large numbers of SNPs identified from this study are valuable for the development of high-density SNP arrays for genetic and genomic studies of performance traits in catfish. PMID:25313648

  14. Sodium leak channel, non-selective contributes to the leak current in human myometrial smooth muscle cells from pregnant women.

    PubMed

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

    2015-10-01

    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.

  15. Sodium leak channel, non-selective contributes to the leak current in human myometrial smooth muscle cells from pregnant women

    PubMed Central

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

    2015-01-01

    Uterine contractions are tightly regulated by the electrical activity of myometrial smooth muscle cells (MSMCs). These cells require a depolarizing current to initiate Ca2+ 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 Gd3+-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 Ca2+ 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 Gd3+ 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 Gd3+-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. PMID:26134120

  16. Molecular basis of the remarkable species selectivity of an insecticidal sodium channel toxin from the African spider Augacephalus ezendami

    PubMed Central

    Herzig, Volker; Ikonomopoulou, Maria; Smith, Jennifer J.; Dziemborowicz, Sławomir; Gilchrist, John; Kuhn-Nentwig, Lucia; Rezende, Fernanda Oliveira; Moreira, Luciano Andrade; Nicholson, Graham M.; Bosmans, Frank; King, Glenn F.

    2016-01-01

    The inexorable decline in the armament of registered chemical insecticides has stimulated research into environmentally-friendly alternatives. Insecticidal spider-venom peptides are promising candidates for bioinsecticide development but it is challenging to find peptides that are specific for targeted pests. In the present study, we isolated an insecticidal peptide (Ae1a) from venom of the African spider Augacephalus ezendami (family Theraphosidae). Injection of Ae1a into sheep blowflies (Lucilia cuprina) induced rapid but reversible paralysis. In striking contrast, Ae1a was lethal to closely related fruit flies (Drosophila melanogaster) but induced no adverse effects in the recalcitrant lepidopteran pest Helicoverpa armigera. Electrophysiological experiments revealed that Ae1a potently inhibits the voltage-gated sodium channel BgNaV1 from the German cockroach Blattella germanica by shifting the threshold for channel activation to more depolarized potentials. In contrast, Ae1a failed to significantly affect sodium currents in dorsal unpaired median neurons from the American cockroach Periplaneta americana. We show that Ae1a interacts with the domain II voltage sensor and that sensitivity to the toxin is conferred by natural sequence variations in the S1–S2 loop of domain II. The phyletic specificity of Ae1a provides crucial information for development of sodium channel insecticides that target key insect pests without harming beneficial species. PMID:27383378

  17. Amyotrophic lateral sclerosis-immunoglobulins selectively interact with neuromuscular junctions expressing P/Q-type calcium channels.

    PubMed

    Gonzalez, Laura E; Kotler, Mónica L; Vattino, Lucas G; Conti, Eugenia; Reisin, Ricardo C; Mulatz, Kirk J; Snutch, Terrance P; Uchitel, Osvaldo D

    2011-11-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a gradual loss of motoneurons. The majority of ALS cases are associated with a sporadic form whose etiology is unknown. Several pieces of evidence favor autoimmunity as a potential contributor to sporadic ALS pathology. To gain understanding concerning possible antigens interacting with IgGs from sporadic ALS patients (ALS-IgGs), we studied immunoreactivity against neuromuscular junction (NMJ), spinal cord and cerebellum of mice with and without the Ca(V) 2.1 pore-forming subunit of the P/Q-type voltage-gated calcium (Ca(2+)) channel. ALS-IgGs showed a strong reactivity against NMJs of wild-type diaphragms. ALS-IgGs also increased muscle miniature end-plate potential frequency, suggesting a functional role for ALS-IgGs on synaptic signaling. In support, in mice lacking the Ca(V) 2.1 subunit ALS-IgGs showed significantly reduced NMJ immunoreactivity and did not alter spontaneous acetylcholine release. This difference in reactivity was absent when comparing N-type Ca(2+) channel wild-type or null mice. These results are particularly relevant because motoneurons are known to be early pathogenic targets in ALS. Our findings add further evidence supporting autoimmunity as one of the possible mechanisms contributing to ALS pathology. They also suggest that serum autoantibodies in a subset of ALS patients would interact with NMJ proteins down-regulated when P/Q-type channels are absent.

  18. Molecular basis of the remarkable species selectivity of an insecticidal sodium channel toxin from the African spider Augacephalus ezendami.

    PubMed

    Herzig, Volker; Ikonomopoulou, Maria; Smith, Jennifer J; Dziemborowicz, Sławomir; Gilchrist, John; Kuhn-Nentwig, Lucia; Rezende, Fernanda Oliveira; Moreira, Luciano Andrade; Nicholson, Graham M; Bosmans, Frank; King, Glenn F

    2016-01-01

    The inexorable decline in the armament of registered chemical insecticides has stimulated research into environmentally-friendly alternatives. Insecticidal spider-venom peptides are promising candidates for bioinsecticide development but it is challenging to find peptides that are specific for targeted pests. In the present study, we isolated an insecticidal peptide (Ae1a) from venom of the African spider Augacephalus ezendami (family Theraphosidae). Injection of Ae1a into sheep blowflies (Lucilia cuprina) induced rapid but reversible paralysis. In striking contrast, Ae1a was lethal to closely related fruit flies (Drosophila melanogaster) but induced no adverse effects in the recalcitrant lepidopteran pest Helicoverpa armigera. Electrophysiological experiments revealed that Ae1a potently inhibits the voltage-gated sodium channel BgNaV1 from the German cockroach Blattella germanica by shifting the threshold for channel activation to more depolarized potentials. In contrast, Ae1a failed to significantly affect sodium currents in dorsal unpaired median neurons from the American cockroach Periplaneta americana. We show that Ae1a interacts with the domain II voltage sensor and that sensitivity to the toxin is conferred by natural sequence variations in the S1-S2 loop of domain II. The phyletic specificity of Ae1a provides crucial information for development of sodium channel insecticides that target key insect pests without harming beneficial species. PMID:27383378

  19. Gramicidin Channels: Versatile Tools

    NASA Astrophysics Data System (ADS)

    Andersen, Olaf S.; Koeppe, Roger E., II; Roux, Benoît

    Gramicidin channels are miniproteins in which two tryptophan-rich subunits associate by means of transbilayer dimerization to form the conducting channels. That is, in contrast to other ion channels, gramicidin channels do not open and close; they appear and disappear. Each subunit in the bilayer-spanning channel is tied to the bilayer/solution interface through hydrogen bonds that involve the indole NH groups as donors andwater or the phospholipid backbone as acceptors. The channel's permeability characteristics are well-defined: gramicidin channels are selective for monovalent cations, with no measurable permeability to anions or polyvalent cations; ions and water move through a pore whose wall is formed by the peptide backbone; and the single-channel conductance and cation selectivity vary when the amino acid sequence is varied, even though the permeating ions make no contact with the amino acid side chains. Given the plethora of available experimental information—for not only the wild-type channels but also for channels formed by amino acid-substituted gramicidin analogues—gramicidin channels continue to provide important insights into the microphysics of ion permeation through bilayer-spanning channels. For similar reasons, gramicidin channels constitute a system of choice for evaluating computational strategies for obtaining mechanistic insights into ion permeation through the more complex channels formed by integral membrane proteins.

  20. A novel discovery of IK1 channel agonist: zacopride selectively enhances IK1 current and suppresses triggered arrhythmias in the rat.

    PubMed

    Liu, Qing-Hua; Li, Xiao-Li; Xu, Yan-Wu; Lin, Yuan-Yuan; Cao, Ji-Min; Wu, Bo-Wei

    2012-01-01

    Modulation of the inward rectifier K current (IK1) has profound effect on cardiac excitability and underlies new antiarrhythmic strategies. However, IK1-specific pharmacological tools, especially the selective IK1 agonists, are still lacking in the market. Zacopride, a gastrointestinal prokinetic drug, was found to be a selective IK1 channel agonist. By using the whole-cell patch clamp technique, it was found that zacopride (0.1-10 μmole/L) dose dependently enhanced the IK1 current in isolated rat cardiomyocytes, had no effects on other ion channels, transporters, or pumps. At the same dosage range, zacopride hyperpolarized the resting potential and shortened the action potential duration. When applied at the optimal dose of 1.0 μmole/L, zacopride could prevent or eliminate aconitine induced after depolarization and triggered activity in isolated cardiomyocytes. In a rat model of aconitine-induced arrhythmias both ex vivo and in vivo, zacopride (1.0 μmole/L or 25 μg/kg, respectively) treatment apparently protected the heart from ventricular tachyarrhythmias, which compares favorably with 7.5 mg/kg of lidocaine, a classical aconitine antidote. In conclusion, zacopride was found to be a selective IK1 agonist, and agonizing IK1 could prevent or eliminate aconitine-induced arrhythmias in the rat.

  1. Development of a Selective Small-Molecule Inhibitor of Kir1.1, the Renal Outer Medullary Potassium ChannelS⃞

    PubMed Central

    Bhave, Gautam; Chauder, Brian A.; Liu, Wen; Dawson, Eric S.; Kadakia, Rishin; Nguyen, Thuy T.; Lewis, L. Michelle; Meiler, Jens; Weaver, C. David; Satlin, Lisa M.; Lindsley, Craig W.

    2011-01-01

    The renal outer medullary potassium (K+) channel, ROMK (Kir1.1), is a putative drug target for a novel class of loop diuretic that would lower blood volume and pressure without causing hypokalemia. However, the lack of selective ROMK inhibitors has hindered efforts to assess its therapeutic potential. In a high-throughput screen for small-molecule modulators of ROMK, we previously identified a potent and moderately selective ROMK antagonist, 7,13-bis(4-nitrobenzyl)-1,4,10-trioxa-7,13-diazacyclopentadecane (VU590), that also inhibits Kir7.1. Because ROMK and Kir7.1 are coexpressed in the nephron, VU590 is not a good probe of ROMK function in the kidney. Here we describe the development of the structurally related inhibitor 2,2′-oxybis(methylene)bis(5-nitro-1H-benzo[d]imidazole) (VU591), which is as potent as VU590 but is selective for ROMK over Kir7.1 and more than 65 other potential off-targets. VU591 seems to block the intracellular pore of the channel. The development of VU591 may enable studies to explore the viability of ROMK as a diuretic target. PMID:20926757

  2. Habitat selection of the channel darter, Percina (Cottogaster) copelandi, a surrogate for the imperiled pearl darter, Percina aurora

    USGS Publications Warehouse

    Schofield, P.J.; Ross, Stephen T.

    2003-01-01

    Percina (Cottogaster) aurora is an imperiled species under consideration for listing by the U.S. Fish and Wildlife Service. To better understand habitat Use of P. aurora, we studied a related and more abundant Cottogaster species, Percina copelandi, from the Ouachita River, Arkansas. We used a laboratory stream system to examine mesohabitat selection (pools versus riffles) and microhabitat selection (substratum particle size) of P. copelandi over three temperature regimes (summer, spring, and winter). Percina copelandi selected pool habitats over riffles and selected pools with coarse substrata (e.g., cobble) over free substrata (e.g., gravel). In riffles, P. copelandi selected large substrata during winter and spring but did not show particle size selection during summer. These data, and various published and unpublished field data for P. aurora, suggest that habitat use of P. aurora is also centered around deep runs and pools, with large substrata likely being more important at low water temperatures.

  3. Center mode of a doubly resonant optical periodic structure

    NASA Astrophysics Data System (ADS)

    Alagappan, G.; Png, C. E.

    2016-07-01

    An optical periodic structure with a single spatial resonance exhibits a stopband. When a second spatial resonance very close to the first one is added, the resulting doubly resonant structure exhibits a Gaussian enveloped, high quality factor transmission state right at the center of the original stopband. Using a slowly varying envelope approximation, we describe the optical characteristics of this transmission state analytically. The transmission state exists despite an optical structure of low refractive index contrast, and has potential applications in nano-optics, and photonics.

  4. Numerical conformal mapping methods for exterior and doubly connected regions

    SciTech Connect

    DeLillo, T.K.; Pfaltzgraff, J.A.

    1996-12-31

    Methods are presented and analyzed for approximating the conformal map from the exterior of the disk to the exterior a smooth, simple closed curve and from an annulus to a bounded, doubly connected region with smooth boundaries. The methods are Newton-like methods for computing the boundary correspondences and conformal moduli similar to Fornberg`s method for the interior of the disk. We show that the linear systems are discretizations of the identity plus a compact operator and, hence, that the conjugate gradient method converges superlinearly.

  5. Synthesis, structural characterization and selectively catalytic properties of metal-organic frameworks with nano-sized channels: A modular design strategy

    SciTech Connect

    Qiu Lingguang Gu Lina; Hu Gang; Zhang Lide

    2009-03-15

    Modular design method for designing and synthesizing microporous metal-organic frameworks (MOFs) with selective catalytical activity was described. MOFs with both nano-sized channels and potential catalytic activities could be obtained through self-assembly of a framework unit and a catalyst unit. By selecting hexaaquo metal complexes and the ligand BTC (BTC=1,3,5-benzenetricarboxylate) as framework-building blocks and using the metal complex [M(phen){sub 2}(H{sub 2}O){sub 2}]{sup 2+} (phen=1,10-phenanthroline) as a catalyst unit, a series of supramolecular MOFs 1-7 with three-dimensional nano-sized channels, i.e. [M{sup 1}(H{sub 2}O){sub 6}].[M{sup 2}(phen){sub 2}(H{sub 2}O){sub 2}]{sub 2}.2(BTC).xH{sub 2}O (M{sup 1}, M{sup 2}=Co(II), Ni(II), Cu(II), Zn(II), or Mn(II), phen=1,10-phenanthroline, BTC=1,3,5-benzenetricarboxylate, x=22-24), were synthesized through self-assembly, and their structures were characterized by IR, elemental analysis, and single-crystal X-ray diffraction. These supramolecular microporous MOFs showed significant size and shape selectivity in the catalyzed oxidation of phenols, which is due to catalytic reactions taking place in the channels of the framework. Design strategy, synthesis, and self-assembly mechanism for the construction of these porous MOFs were discussed. - Grapical abstract: A modular design strategy has been developed to synthesize microporous metal-organic frameworks with potential catalytic activity by self-assembly of the framework-building blocks and the catalyst unit.

  6. Formation of anion-selective channels in the cell plasma membrane by the toxin VacA of Helicobacter pylori is required for its biological activity.

    PubMed Central

    Szabò, I; Brutsche, S; Tombola, F; Moschioni, M; Satin, B; Telford, J L; Rappuoli, R; Montecucco, C; Papini, E; Zoratti, M

    1999-01-01

    The vacuolating toxin VacA, a major determinant of Helicobacter pylori-associated gastric diseases, forms anion-selective channels in artificial planar lipid bilayers. Here we show that VacA increases the anion permeability of the HeLa cell plasma membrane and determines membrane depolarization. Electrophysiological and pharmacological approaches indicated that this effect is due to the formation of low-conductance VacA pores in the cell plasma membrane and not to the opening of Ca(2+)- or volume-activated chloride channels. VacA-dependent increase of current conduction both in artificial planar lipid bilayers and in the cellular system was effectively inhibited by the chloride channel blocker 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), while2-[(2-cyclopentenyl-6,7dichloro-2, 3-dihydro-2-methyl-1-oxo-1H-inden-5-yl)oxy]acetic acid (IAA-94) was less effective. NPPB inhibited and partially reversed the vacuolation of HeLa cells and the increase of ion conductivity of polarized Madine Darby canine kidney cell monolayers induced by VacA, while IAA-94 had a weaker effect. We conclude that pore formation by VacA accounts for plasma membrane permeabilization and is required for both cell vacuolation and increase of trans-epithelial conductivity. PMID:10523296

  7. Drugability of extracellular targets: discovery of small molecule drugs targeting allosteric, functional, and subunit-selective sites on GPCRs and ion channels.

    PubMed

    Grigoriadis, Dimitri E; Hoare, Samuel R J; Lechner, Sandra M; Slee, Deborah H; Williams, John A

    2009-01-01

    Beginning with the discovery of the structure of deoxyribose nucleic acid in 1953, by James Watson and Francis Crick, the sequencing of the entire human genome some 50 years later, has begun to quantify the classes and types of proteins that may have relevance to human disease with the promise of rapidly identifying compounds that can modulate these proteins so as to have a beneficial and therapeutic outcome. This so called 'drugable space' involves a variety of membrane-bound proteins including the superfamily of G-protein-coupled receptors (GPCRs), ion channels, and transporters among others. The recent number of novel therapeutics targeting membrane-bound extracellular proteins that have reached the market in the past 20 years however pales in magnitude when compared, during the same timeframe, to the advancements made in the technologies available to aid in the discovery of these novel therapeutics. This review will consider select examples of extracellular drugable targets and focus on the GPCRs and ion channels highlighting the corticotropin releasing factor (CRF) type 1 and gamma-aminobutyric acid receptors, and the Ca(V)2.2 voltage-gated ion channel. These examples will elaborate current technological advancements in drug discovery and provide a prospective framework for future drug development.

  8. Hydraulic and channel characteristics of selected streams in the Kantishna Hills area, Denali National Park and Preserve, Alaska, 1982-84

    USGS Publications Warehouse

    Van Maanen, J.L.; Solin, G.L.

    1988-01-01

    The Kantishna Hills area of the Denali National Park and Preserve contains extensive placer gold deposits. In order to develop plans for the management of this natural resource, and to assess the effects of placer mining on aquatic systems, documentation of the physical characteristics of the streams in the area is needed. Channel morphology, streamflow and streambed composition data were collected at 14 stream reaches in the Kantishna Hills area in September 1982 and in June, July, August , and September of 1983 and 1984. The reaches selected include locations of historical and current mining activity and locations which are undisturbed. The data indicate only minor differences in the physical properties of the streams in mined and unmined drainage basins. The composition of streambeds below mined areas tended to consist of finer sized particles and exhibited less variation in mean particle size than streambed in unmined basins. This may be due in part to the natural sorting of material in stream channels because mined areas, and thus study reaches below them, tended to be located relatively farther downstream (nearer the stream mouth) than were study reaches in basins where no mining has occurred. Changes in the physical properties of the streams which could be directly attributed to mining activity were noted at only one location, Rainy Creek near Kantishna, where the stream had been diverted from its natural channel by the construction of settling ponds. (Author 's abstract)

  9. A semi-microscopic Monte Carlo study of permeation energetics in a gramicidin-like channel: the origin of cation selectivity.

    PubMed Central

    Dorman, V; Partenskii, M B; Jordan, P C

    1996-01-01

    The influence of a gramicidin-like channel former on ion free energy barriers is studied using Monte Carlo simulation. The model explicitly describes the ion, the water dipoles, and the peptide carbonyls; the remaining degrees of freedom, bulk electrolyte, non-polar lipid and peptide regions, and electronic (high frequency) permittivity, are treated in continuum terms. Contributions of the channel waters and peptide COs are studied both separately and collectively. We found that if constrained to their original orientations, the COs substantially increase the cationic permeation free energy; with or without water present, CO reorientation is crucial for ion-CO interaction to lower cation free energy barriers; the translocation free energy profiles for potassium-, rubidium-, and cesium-like cations exhibit no broad barriers; the lipid-bound peptide interacts more effectively with anions than cations; anionic translocation free energy profiles exhibit well defined maxima. Using experimental data to estimate transfer free energies of ions and water from bulk electrolyte to a non-polar dielectric (continuum lipid), we found reasonable ion permeation profiles; cations bind and permeate, whereas anions cannot enter the channel. Cation selectivity arises because, for ions of the same size and charge, anions bind hydration water more strongly. PMID:8770192

  10. Control of the Aquaporin-4 Channel Water Permeability by Structural Dynamics of Aromatic/Arginine Selectivity Filter Residues.

    PubMed

    Kitchen, Philip; Conner, Alex C

    2015-11-17

    The aquaporins (AQPs) make up a family of integral membrane proteins that control cellular water flow. Gating of the water channel by conformational changes induced by phosphorylation or protein-protein interactions is an established regulatory mechanism for AQPs. Recent in silico and crystallographic analyses of the structural biology of AQPs suggest that the rate of water flow can also be controlled by small movements of single-amino acid side chains lining the water pore. Here we use measurements of the membrane water permeability of mammalian cells expressing AQP4 mutants to provide the first in vitro evidence in support of this hypothesis. PMID:26512424

  11. Spectroscopy of doubly charmed baryons from lattice QCD

    SciTech Connect

    Padmanath, M.; Edwards, Robert G.; Mathur, Nilmani; Peardon, Michael

    2015-05-06

    This study presents the ground and excited state spectra of doubly charmed baryons from lattice QCD with dynamical quark fields. Calculations are performed on anisotropic lattices of size 16³ × 128, with inverse spacing in temporal direction at⁻¹=5.67(4) GeV and with a pion mass of about 390 MeV. A large set of baryonic operators that respect the symmetries of the lattice yet which retain a memory of their continuum analogues are used. These operators transform as irreducible representations of SU(3)F symmetry for flavor, SU(4) symmetry for Dirac spins of quarks and O(3) for spatial symmetry. The distillation method is utilized to generate baryon correlation functions which are analyzed using the variational fitting method to extract excited states. The lattice spectra obtained have baryonic states with well-defined total spins up to 7/2 and the pattern of low-lying states does not support the diquark picture for doubly charmed baryons. On the contrary the calculated spectra are remarkably similar to the expectations from models with an SU(6)×O(3) symmetry. Various spin-dependent energy splittings between the extracted states are also evaluated.

  12. Lensless coded aperture imaging with separable doubly Toeplitz masks

    NASA Astrophysics Data System (ADS)

    DeWeert, Michael J.; Farm, Brian P.

    2014-05-01

    In certain imaging applications, conventional lens technology is constrained by the lack of materials which can effectively focus the radiation within reasonable weight and volume. One solution is to use coded apertures -opaque plates perforated with multiple pinhole-like openings. If the openings are arranged in an appropriate pattern, the images can be decoded, and a clear image computed. Recently, computational imaging and the search for means of producing programmable software-defined optics have revived interest in coded apertures. The former state-of-the-art masks, MURAs (Modified Uniformly Redundant Arrays) are effective for compact objects against uniform backgrounds, but have substantial drawbacks for extended scenes: 1) MURAs present an inherently ill-posed inversion problem that is unmanageable for large images, and 2) they are susceptible to diffraction: a diffracted MURA is no longer a MURA. This paper presents a new class of coded apertures, Separable Doubly-Toeplitz masks, which are efficiently decodable, even for very large images -orders of magnitude faster than MURAs, and which remain decodable when diffracted. We implemented the masks using programmable spatial-lightmodulators. Imaging experiments confirmed the effectiveness of Separable Doubly-Toeplitz masks - images collected in natural light of extended outdoor scenes are rendered clearly.

  13. Validation of doubly labeled water method using a ruminant

    SciTech Connect

    Fancy, S.G.; Blanchard, J.M.; Holleman, D.F.; Kokjer, K.J.; White, R.G.

    1986-07-01

    CO/sub 2/ production (CDP, ml CO/sub 2/ . g-1 . h-1) by captive caribou and reindeer (Rangifer tarandus) was measured using the doubly labeled water method (/sup 3/H/sub 2/O and H2(18)O) and compared with CO/sub 2/ expiration rates (VCO/sub 2/), adjusted for CO/sub 2/ losses in CH4 and urine, as determined by open-circuit respirometry. CDP calculated from samples of blood or urine from a reindeer in winter was 1-3% higher than the adjusted VCO/sub 2/. Differences between values derived by the two methods of 5-20% were found in summer trials with caribou. None of these differences were statistically significant (P greater than 0.05). Differences in summer could in part be explained by the net deposition of /sup 3/H, 18O, and unlabeled CO/sub 2/ in antlers and other growing tissues. Total body water volumes calculated from /sup 3/H/sub 2/O dilution were up to 15% higher than those calculated from H/sub 2/(18)O dilution. The doubly labeled water method appears to be a reasonably accurate method for measuring CDP by caribou and reindeer in winter when growth rates are low, but the method may overestimate CDP by rapidly growing and/or fattening animals.

  14. Nonlinear vibrations of functionally graded doubly curved shallow shells

    NASA Astrophysics Data System (ADS)

    Alijani, F.; Amabili, M.; Karagiozis, K.; Bakhtiari-Nejad, F.

    2011-03-01

    Nonlinear forced vibrations of FGM doubly curved shallow shells with a rectangular base are investigated. Donnell's nonlinear shallow-shell theory is used and the shell is assumed to be simply supported with movable edges. The equations of motion are reduced using the Galerkin method to a system of infinite nonlinear ordinary differential equations with quadratic and cubic nonlinearities. Using the multiple scales method, primary and subharmonic resonance responses of FGM shells are fully discussed and the effect of volume fraction exponent on the internal resonance conditions, softening/hardening behavior and bifurcations of the shallow shell when the excitation frequency is (i) near the fundamental frequency and (ii) near two times the fundamental frequency is shown. Moreover, using a code based on arclength continuation method, a bifurcation analysis is carried out for a special case with two-to-one internal resonance between the first and second doubly symmetric modes with respect to the panel's center ( ω13≈2 ω11). Bifurcation diagrams and Poincaré maps are obtained through direct time integration of the equations of motion and chaotic regions are shown by calculating Lyapunov exponents and Lyapunov dimension.

  15. Four basic residues critical for the ion selectivity and pore blocker sensitivity of TMEM16A calcium-activated chloride channels.

    PubMed

    Peters, Christian J; Yu, Haibo; Tien, Jason; Jan, Yuh Nung; Li, Min; Jan, Lily Yeh

    2015-03-17

    TMEM16A (transmembrane protein 16) (Anoctamin-1) forms a calcium-activated chloride channel (CaCC) that regulates a broad array of physiological properties in response to changes in intracellular calcium concentration. Although known to conduct anions according to the Eisenman type I selectivity sequence, the structural determinants of TMEM16A anion selectivity are not well-understood. Reasoning that the positive charges on basic residues are likely contributors to anion selectivity, we performed whole-cell recordings of mutants with alanine substitution for basic residues within the putative pore region and identified four residues on four different putative transmembrane segments that significantly increased the permeability of the larger halides and thiocyanate relative to that of chloride. Because TMEM16A permeation properties are known to shift with changes in intracellular calcium concentration, we further examined the calcium dependence of anion selectivity. We found that WT TMEM16A but not mutants with alanine substitution at those four basic residues exhibited a clear decline in the preference for larger anions as intracellular calcium was increased. Having implicated these residues as contributing to the TMEM16A pore, we scrutinized candidate small molecules from a high-throughput CaCC inhibitor screen to identify two compounds that act as pore blockers. Mutations of those four putative pore-lining basic residues significantly altered the IC50 of these compounds at positive voltages. These findings contribute to our understanding regarding anion permeation of TMEM16A CaCC and provide valuable pharmacological tools to probe the channel pore.

  16. Selective expression of KCNS3 potassium channel α-subunit in parvalbumin-containing GABA neurons in the human prefrontal cortex.

    PubMed

    Georgiev, Danko; González-Burgos, Guillermo; Kikuchi, Mitsuru; Minabe, Yoshio; Lewis, David A; Hashimoto, Takanori

    2012-01-01

    The cognitive deficits of schizophrenia appear to be associated with altered cortical GABA neurotransmission in the subsets of inhibitory neurons that express either parvalbumin (PV) or somatostatin (SST). Identification of molecular mechanisms that operate selectively in these neurons is essential for developing targeted therapeutic strategies that do not influence other cell types. Consequently, we sought to identify, in the human cortex, gene products that are expressed selectively by PV and/or SST neurons, and that might contribute to their distinctive functional properties. Based on previously reported expression patterns in the cortex of mice and humans, we selected four genes: KCNS3, LHX6, KCNAB1, and PPP1R2, encoding K(+) channel Kv9.3 modulatory α-subunit, LIM homeobox protein 6, K(+) channel Kvβ1 subunit, and protein phosphatase 1 regulatory subunit 2, respectively, and examined their colocalization with PV or SST mRNAs in the human prefrontal cortex using dual-label in situ hybridization with (35)S- and digoxigenin-labeled antisense riboprobes. KCNS3 mRNA was detected in almost all PV neurons, but not in SST neurons, and PV mRNA was detected in >90% of KCNS3 mRNA-expressing neurons. LHX6 mRNA was detected in almost all PV and >90% of SST neurons, while among all LHX6 mRNA-expressing neurons 50% expressed PV mRNA and >44% expressed SST mRNA. KCNAB1 and PPP1R2 mRNAs were detected in much larger populations of cortical neurons than PV or SST neurons. These findings indicate that KCNS3 is a selective marker of PV neurons, whereas LHX6 is expressed by both PV and SST neurons. KCNS3 and LHX6 might be useful for characterizing cell-type specific molecular alterations of cortical GABA neurotransmission and for the development of novel treatments targeting PV and/or SST neurons in schizophrenia.

  17. Coordination numbers of K(+) and Na(+) Ions inside the selectivity filter of the KcsA potassium channel: insights from first principles molecular dynamics.

    PubMed

    Bucher, Denis; Guidoni, Leonardo; Carloni, Paolo; Rothlisberger, Ursula

    2010-05-19

    Quantum mechanics/molecular mechanics (QM/MM) Car-Parrinello simulations were performed to estimate the coordination numbers of K(+) and Na(+) ions in the selectivity filter of the KcsA channel, and in water. At the DFT/BLYP level, K(+) ions were found to display an average coordination number of 6.6 in the filter, and 6.2 in water. Na(+) ions displayed an average coordination number of 5.2 in the filter, and 5.0 in water. A comparison was made with the average coordination numbers obtained from using classical molecular dynamics (6.7 for K(+) in the filter, 6.6 for K(+) in water, 6.0 for Na(+) in the filter, and 5.2 for Na(+) in water). The observation that different coordination numbers were displayed by the ions in QM/MM simulations and in classical molecular dynamics is relevant to the discussion of selectivity in K-channels.

  18. Pyroptosis is driven by non-selective gasdermin-D pore and its morphology is different from MLKL channel-mediated necroptosis.

    PubMed

    Chen, Xin; He, Wan-Ting; Hu, Lichen; Li, Jingxian; Fang, Yuan; Wang, Xin; Xu, Xiaozheng; Wang, Zhuo; Huang, Kai; Han, Jiahuai

    2016-09-01

    Necroptosis and pyroptosis are two forms of programmed cell death with a common feature of plasma membrane rupture. Here we studied the morphology and mechanism of pyroptosis in comparison with necroptosis. Different from necroptosis, pyroptosis undergoes membrane blebbing and produces apoptotic body-like cell protrusions (termed pyroptotic bodies) prior to plasma membrane rupture. The rupture in necroptosis is explosion-like, whereas in pyroptosis it leads to flattening of cells. It is known that the execution of necroptosis is mediated by mixed lineage kinase domain-like (MLKL) oligomers in the plasma membrane, whereas gasdermin-D (GSDMD) mediates pyroptosis after its cleavage by caspase-1 or caspase-11. We show that N-terminal fragment of GSDMD (GSDMD-N) generated by caspase cleavage also forms oligomer and migrates to the plasma membrane to kill cells. Both MLKL and GSDMD-N are lipophilic and the N-terminal sequences of both proteins are important for their oligomerization and plasma membrane translocation. Unlike MLKL which forms channels on the plasma membrane that induces influx of selected ions which osmotically swell the cells to burst, GSDMD-N forms non-selective pores and does not rely on increased osmolarity to disrupt cells. Our study reveals the pore-forming activity of GSDMD and channel-forming activity of MLKL determine different ways of plasma membrane rupture in pyroptosis and necroptosis. PMID:27573174

  19. Pyroptosis is driven by non-selective gasdermin-D pore and its morphology is different from MLKL channel-mediated necroptosis

    PubMed Central

    Chen, Xin; He, Wan-ting; Hu, Lichen; Li, Jingxian; Fang, Yuan; Wang, Xin; Xu, Xiaozheng; Wang, Zhuo; Huang, Kai; Han, Jiahuai

    2016-01-01

    Necroptosis and pyroptosis are two forms of programmed cell death with a common feature of plasma membrane rupture. Here we studied the morphology and mechanism of pyroptosis in comparison with necroptosis. Different from necroptosis, pyroptosis undergoes membrane blebbing and produces apoptotic body-like cell protrusions (termed pyroptotic bodies) prior to plasma membrane rupture. The rupture in necroptosis is explosion-like, whereas in pyroptosis it leads to flattening of cells. It is known that the execution of necroptosis is mediated by mixed lineage kinase domain-like (MLKL) oligomers in the plasma membrane, whereas gasdermin-D (GSDMD) mediates pyroptosis after its cleavage by caspase-1 or caspase-11. We show that N-terminal fragment of GSDMD (GSDMD-N) generated by caspase cleavage also forms oligomer and migrates to the plasma membrane to kill cells. Both MLKL and GSDMD-N are lipophilic and the N-terminal sequences of both proteins are important for their oligomerization and plasma membrane translocation. Unlike MLKL which forms channels on the plasma membrane that induces influx of selected ions which osmotically swell the cells to burst, GSDMD-N forms non-selective pores and does not rely on increased osmolarity to disrupt cells. Our study reveals the pore-forming activity of GSDMD and channel-forming activity of MLKL determine different ways of plasma membrane rupture in pyroptosis and necroptosis. PMID:27573174

  20. Water-surface elevations and channel characteristics for a selected reach of the Applegate River, Jackson County, Oregon

    USGS Publications Warehouse

    Harris, David Dell; Alexander, Clyde W.

    1970-01-01

    In land-use planning for the Applegate River and its flood plain, consideration should be given to (1) preservation of the recreational attributes of the area, (2) allowance for optimum development of the flood plain's natural resources, and (3) protection of the rights of private landowners. Major factors that influence evaluation of the above considerations are the elevations and characteristics of floods. Heretofore, such flood data for the Applegate River have been inadequate to evaluate the flood potential or to use as a basis for delineating reasonable land-use zones. Therefore, at the request of Jackson County, this study was made to provide flood elevations, water-surface profiles, and channel characteristics (geometry and slope) for a reach of the Applegate River from the Jackson-Josephine County line upstream to the Applegate damsite (fig. 1). A similar study was previously made for reaches of adjacent Rogue River and Elk Creek (Harris, 1970).

  1. New Exotic Meson and Baryon Resonances from Doubly Heavy Hadronic Molecules.

    PubMed

    Karliner, Marek; Rosner, Jonathan L

    2015-09-18

    We predict several new exotic doubly heavy hadronic resonances, inferring from the observed exotic bottomoniumlike and charmoniumlike narrow states X(3872), Z_{b}(10610), Z_{b}(10650), Z_{c}(3900), and Z_{c}(4020/4025). We interpret the binding mechanism as mostly molecularlike isospin-exchange attraction between two heavy-light mesons in a relative S-wave state. We then generalize it to other systems containing two heavy hadrons which can couple through isospin exchange. The new predicted states include resonances in meson-meson, meson-baryon, baryon-baryon, and baryon-antibaryon channels. These include those giving rise to final states involving a heavy quark Q=c,b and antiquark Q[over ¯]^{'}=c[over ¯],b[over ¯], namely, DD[over ¯]^{*}, D^{*}D[over ¯]^{*}, D^{*}B^{*}, B[over ¯]B^{*}, B[over ¯]^{*}B^{*}, Σ_{c}D[over ¯]^{*}, Σ_{c}B^{*}, Σ_{b}D[over ¯]^{*}, Σ_{b}B^{*}, Σ_{c}Σ[over ¯]_{c}, Σ_{c}Λ[over ¯]_{c}, Σ_{c}Λ[over ¯]_{b}, Σ_{b}Σ[over ¯]_{b}, Σ_{b}Λ[over ¯]_{b}, and Σ_{b}Λ[over ¯]_{c}, as well as corresponding S-wave states giving rise to QQ^{'} or Q[over ¯]Q[over ¯]^{'}. PMID:26430989

  2. Engineering potent and selective analogues of GpTx-1, a tarantula venom peptide antagonist of the Na(V)1.7 sodium channel.

    PubMed

    Murray, Justin K; Ligutti, Joseph; Liu, Dong; Zou, Anruo; Poppe, Leszek; Li, Hongyan; Andrews, Kristin L; Moyer, Bryan D; McDonough, Stefan I; Favreau, Philippe; Stöcklin, Reto; Miranda, Les P

    2015-03-12

    NaV1.7 is a voltage-gated sodium ion channel implicated by human genetic evidence as a therapeutic target for the treatment of pain. Screening fractionated venom from the tarantula Grammostola porteri led to the identification of a 34-residue peptide, termed GpTx-1, with potent activity on NaV1.7 (IC50 = 10 nM) and promising selectivity against key NaV subtypes (20× and 1000× over NaV1.4 and NaV1.5, respectively). NMR structural analysis of the chemically synthesized three disulfide peptide was consistent with an inhibitory cystine knot motif. Alanine scanning of GpTx-1 revealed that residues Trp(29), Lys(31), and Phe(34) near the C-terminus are critical for potent NaV1.7 antagonist activity. Substitution of Ala for Phe at position 5 conferred 300-fold selectivity against NaV1.4. A structure-guided campaign afforded additive improvements in potency and NaV subtype selectivity, culminating in the design of [Ala5,Phe6,Leu26,Arg28]GpTx-1 with a NaV1.7 IC50 value of 1.6 nM and >1000× selectivity against NaV1.4 and NaV1.5.

  3. Engineering potent and selective analogues of GpTx-1, a tarantula venom peptide antagonist of the Na(V)1.7 sodium channel.

    PubMed

    Murray, Justin K; Ligutti, Joseph; Liu, Dong; Zou, Anruo; Poppe, Leszek; Li, Hongyan; Andrews, Kristin L; Moyer, Bryan D; McDonough, Stefan I; Favreau, Philippe; Stöcklin, Reto; Miranda, Les P

    2015-03-12

    NaV1.7 is a voltage-gated sodium ion channel implicated by human genetic evidence as a therapeutic target for the treatment of pain. Screening fractionated venom from the tarantula Grammostola porteri led to the identification of a 34-residue peptide, termed GpTx-1, with potent activity on NaV1.7 (IC50 = 10 nM) and promising selectivity against key NaV subtypes (20× and 1000× over NaV1.4 and NaV1.5, respectively). NMR structural analysis of the chemically synthesized three disulfide peptide was consistent with an inhibitory cystine knot motif. Alanine scanning of GpTx-1 revealed that residues Trp(29), Lys(31), and Phe(34) near the C-terminus are critical for potent NaV1.7 antagonist activity. Substitution of Ala for Phe at position 5 conferred 300-fold selectivity against NaV1.4. A structure-guided campaign afforded additive improvements in potency and NaV subtype selectivity, culminating in the design of [Ala5,Phe6,Leu26,Arg28]GpTx-1 with a NaV1.7 IC50 value of 1.6 nM and >1000× selectivity against NaV1.4 and NaV1.5. PMID:25658507

  4. Outage Performance Analysis of Relay Selection Schemes in Wireless Energy Harvesting Cooperative Networks over Non-Identical Rayleigh Fading Channels

    PubMed Central

    Do, Nhu Tri; Bao, Vo Nguyen Quoc; An, Beongku

    2016-01-01

    In this paper, we study relay selection in decode-and-forward wireless energy harvesting cooperative networks. In contrast to conventional cooperative networks, the relays harvest energy from the source’s radio-frequency radiation and then use that energy to forward the source information. Considering power splitting receiver architecture used at relays to harvest energy, we are concerned with the performance of two popular relay selection schemes, namely, partial relay selection (PRS) scheme and optimal relay selection (ORS) scheme. In particular, we analyze the system performance in terms of outage probability (OP) over independent and non-identical (i.n.i.d.) Rayleigh fading channels. We derive the closed-form approximations for the system outage probabilities of both schemes and validate the analysis by the Monte-Carlo simulation. The numerical results provide comprehensive performance comparison between the PRS and ORS schemes and reveal the effect of wireless energy harvesting on the outage performances of both schemes. Additionally, we also show the advantages and drawbacks of the wireless energy harvesting cooperative networks and compare to the conventional cooperative networks. PMID:26927119

  5. Regional Relations in Bankfull Channel Characteristics determined from flow measurements at selected stream-gaging stations in West Virginia, 1911-2002

    USGS Publications Warehouse

    Messinger, Terence; Wiley, Jeffrey B.

    2004-01-01

    Three bankfull channel characteristics?cross-sectional area, width, and depth?were significantly correlated with drainage area in regression equations developed for two regions in West Virginia. Channel characteristics were determined from analysis of flow measurements made at 74 U.S. Geological Survey stream-gaging stations at flows between 0.5 and 5.0 times bankfull flow between 1911 and 2002. Graphical and regression analysis were used to delineate an 'Eastern Region' and a 'Western Region,' which were separated by the boundary between the Appalachian Plateaus and Valley and Ridge Physiographic Provinces. Streams that drained parts of both provinces had channel characteristics typical of the Eastern Region, and were grouped with it. Standard error for the six regression equations, three for each region, ranged between 8.7 and 16 percent. Cross-sectional area and depth were greater relative to drainage area for the Western Region than they were for the Eastern Region. Regression equations were defined for streams draining between 46.5 and 1,619 square miles for the Eastern Region, and between 2.78 and 1,354 square miles for the Western Region. Stream-gaging stations with two or more cross sections where flow had been measured at flows between 0.5 and 5.0 times the 1.5-year flow showed poor replication of channel characteristics compared to the 95-percent confidence intervals of the regression, suggesting that within-reach variability for the stream-gaging stations may be substantial. A disproportionate number of the selected stream-gaging stations were on large (drainage area greater than 100 square miles) streams in the central highlands of West Virginia, and only one stream-gaging station that met data-quality criteria was available to represent the region within about 50 miles of the Ohio River north of Parkersburg, West Virginia. Many of the cross sections were at bridges, which can change channel shape. Although the data discussed in this report may not be

  6. Search for doubly charged Higgs bosons decaying to dileptons in pp collisions at square root of s=1.96 TeV.

    PubMed

    Acosta, D; Affolder, T; Akimoto, T; Albrow, M G; Ambrose, D; Amerio, S; Amidei, D; Anastassov, A; Anikeev, K; Annovi, A; Antos, J; Aoki, M; Apollinari, G; Arisawa, T; Arguin, J-F; Artikov, A; Ashmanskas, W; Attal, A; Azfar, F; Azzi-Bacchetta, P; Bacchetta, N; Bachacou, H; Badgett, W; Barbaro-Galtieri, A; Barker, G J; Barnes, V E; Barnett, B A; Baroiant, S; Barone, M; Bauer, G; Bedeschi, F; Behari, S; Belforte, S; Bellettini, G; Bellinger, J; Benjamin, D; Beretvas, A; Bhatti, A; Binkley, M; Bisello, D; Bishai, M; Blair, R E; Blocker, C; Bloom, K; Blumenfeld, B; Bocci, A; Bodek, A; Bolla, G; Bolshov, A; Booth, P S L; Bortoletto, D; Boudreau, J; Bourov, S; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Burkett, K; Busetto, G; Bussey, P; Byrum, K L; Cabrera, S; Calafiura, P; Campanelli, M; Campbell, M; Canepa, A; Casarsa, M; Carlsmith, D; Carron, S; Carosi, R; Cavalli-Sforza, M; Castro, A; Catastini, P; Cauz, D; Cerri, A; Cerri, C; Cerrito, L; Chapman, J; Chen, C; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, I; Cho, K; Chokheli, D; Chu, M L; Chuang, S; Chung, J Y; Chung, W-H; Chung, Y S; Ciobanu, C I; Ciocci, M A; Clark, A G; Clark, D; Coca, M; Connolly, A; Convery, M; Conway, J; Cooper, B; Cordelli, M; Cortiana, G; Cranshaw, J; Cuevas, J; Culbertson, R; Currat, C; Cyr, D; Dagenhart, D; Da Ronco, S; D'Auria, S; de Barbaro, P; De Cecco, S; De Lentdecker, G; Dell'agnello, S; Dell'orso, M; Demers, S; Demortier, L; Deninno, M; De Pedis, D; Derwent, P F; Dionisi, C; Dittmann, J R; Doksus, P; Dominguez, A; Donati, S; Donega, M; Donini, J; D'Onofrio, M; Dorigo, T; Drollinger, V; Ebina, K; Eddy, N; Ely, R; Erbacher, R; Erdmann, M; Errede, D; Errede, S; Eusebi, R; Fang, H-C; Farrington, S; Fedorko, I; Feild, R G; Feindt, M; Fernandez, J P; Ferretti, C; Field, R D; Fiori, I; Flanagan, G; Flaugher, B; Flores-Castillo, L R; Foland, A; Forrester, S; Foster, G W; Franklin, M; Freeman, J; Frisch, H; Fujii, Y; Furic, I; Gajjar, A; Gallas, A; Galyardt, J; Gallinaro, M; Garcia-Sciveres, M; Garfinkel, A F; Gay, C; Gerberich, H; Gerdes, D W; Gerchtein, E; Giagu, S; Giannetti, P; Gibson, A; Gibson, K; Ginsburg, C; Giolo, K; Giordani, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Goldstein, D; Goldstein, J; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Gotra, Y; Goulianos, K; Gresele, A; Grosso-Pilcher, C; Guenther, M; Guimaraes da Costa, J; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Handler, R; Happacher, F; Hara, K; Hare, M; Harr, R F; Harris, R M; Hartmann, F; Hatakeyama, K; Hauser, J; Hays, C; Hayward, H; Heider, E; Heinemann, B; Heinrich, J; Hennecke, M; Herndon, M; Hill, C; Hirschbuehl, D; Hocker, A; Hoffman, K D; Holloway, A; Hou, S; Houlden, M A; Huffman, B T; Huang, Y; Hughes, R E; Huston, J; Ikado, K; Incandela, J; Introzzi, G; Iori, M; Ishizawa, Y; Issever, C; Ivanov, A; Iwata, Y; Iyutin, B; James, E; Jang, D; Jarrell, J; Jeans, D; Jensen, H; Jeon, E J; Jones, M; Joo, K K; Jun, S; Junk, T; Kamon, T; Kang, J; Karagoz Unel, M; Karchin, P E; Kartal, S; Kato, Y; Kemp, Y; Kephart, R; Kerzel, U; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, M S; Kim, S B; Kim, S H; Kim, T H; Kim, Y K; King, B T; Kirby, M; Kirsch, L; Klimenko, S; Knuteson, B; Ko, B R; Kobayashi, H; Koehn, P; Kong, D J; Kondo, K; Konigsberg, J; Kordas, K; Korn, A; Korytov, A; Kotelnikov, K; Kotwal, A V; Kovalev, A; Kraus, J; Kravchenko, I; Kreymer, A; Kroll, J; Kruse, M; Krutelyov, V; Kuhlmann, S E; Kuznetsova, N; Laasanen, A T; Lai, S; Lami, S; Lammel, S; Lancaster, J; Lancaster, M; Lander, R; Lannon, K; Lath, A; Latino, G; Lauhakangas, R; Lazzizzera, I; Le, Y; Lecci, C; Lecompte, T; Lee, J; Lee, J; Lee, S W; Leonardo, N; Leone, S; Lewis, J D; Li, K; Lin, C; Lin, C S; Lindgren, M; Liss, T M; Litvintsev, D O; Liu, T; Liu, Y; Lockyer, N S; Loginov, A; Loreti, M; Loverre, P; Lu, R-S; Lucchesi, D; Lujan, P; Lukens, P; Lyons, L; Lys, J; Lysak, R; Macqueen, D; Madrak, R; Maeshima, K; Maksimovic, P; Malferrari, L; Manca, G; Marginean, R; Martin, M; Martin, A; Martin, V; Martínez, M; Maruyama, T; Matsunaga, H; Mattson, M; Mazzanti, P; McFarland, K S; McGivern, D; McIntyre, P M; McNamara, P; McNulty, R; Menzemer, S; Menzione, A; Merkel, P; Mesropian, C; Messina, A; Miao, T; Miladinovic, N; Miller, L; Miller, R; Miller, J S; Miquel, R; Miscetti, S; Mitselmakher, G; Miyamoto, A; Miyazaki, Y; Moggi, N; Mohr, B; Moore, R; Morello, M; Moulik, T; Movilla Fernandez, P A; Mukherjee, A; Mulhearn, M; Muller, T; Mumford, R; Munar, A; Murat, P; Nachtman, J; Nahn, S; Nakamura, I; Nakano, I; Napier, A; Napora, R; Naumov, D; Necula, V; Niell, F; Nielsen, J; Nelson, C; Nelson, T; Neu, C; Neubauer, M S; Newman-Holmes, C; Nicollerat, A-S; Nigmanov, T; Nodulman, L; Norniella, O; Oesterberg, K; Ogawa, T; Oh, S H; Oh, Y D; Ohsugi, T; Okusawa, T; Oldeman, R; Orava, R; Orejudos, W; Pagliarone, C; Palmonari, F; Paoletti, R; Papadimitriou, V; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Pauly, T; Paus, C; Pellett, D; Penzo, A; Phillips, T J; Piacentino, G; Piedra, J; Pitts, K T; Plager, C; Pompos, A; Pondrom, L; Pope, G; Poukhov, O; Prakoshyn, F; Pratt, T; Pronko, A; Proudfoot, J; Ptohos, F; Punzi, G; Rademacker, J; Rakitine, A; Rappoccio, S; Ratnikov, F; Ray, H; Reichold, A; Reisert, B; Rekovic, V; Renton, P; Rescigno, M; Rimondi, F; Rinnert, K; Ristori, L; Robertson, W J; Robson, A; Rodrigo, T; Rolli, S; Rosenson, L; Roser, R; Rossin, R; Rott, C; Russ, J; Ruiz, A; Ryan, D; Saarikko, H; Safonov, A; St Denis, R; Sakumoto, W K; Salamanna, G; Saltzberg, D; Sanchez, C; Sansoni, A; Santi, L; Sarkar, S; Sato, K; Savard, P; Savoy-Navarro, A; Schemitz, P; Schlabach, P; Schmidt, E E; Schmidt, M P; Schmitt, M; Scodellaro, L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semeria, F; Sexton-Kennedy, L; Sfiligoi, I; Shapiro, M D; Shears, T; Shepard, P F; Shimojima, M; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Siegrist, J; Siket, M; Sill, A; Sinervo, P; Sisakyan, A; Skiba, A; Slaughter, A J; Sliwa, K; Smirnov, D; Smith, J R; Snider, F D; Snihur, R; Somalwar, S V; Spalding, J; Spezziga, M; Spiegel, L; Spinella, F; Spiropulu, M; Squillacioti, P; Stadie, H; Stefanini, A; Stelzer, B; Stelzer-Chilton, O; Strologas, J; Stuart, D; Sukhanov, A; Sumorok, K; Sun, H; Suzuki, T; Taffard, A; Tafirout, R; Takach, S F; Takano, H; Takashima, R; Takeuchi, Y; Takikawa, K; Tanaka, M; Tanaka, R; Tanimoto, N; Tapprogge, S; Tecchio, M; Teng, P K; Terashi, K; Tesarek, R J; Tether, S; Thom, J; Thompson, A S; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tollefson, K; Tomura, T; Tonelli, D; Tönnesmann, M; Torre, S; Torretta, D; Trischuk, W; Tseng, J; Tsuchiya, R; Tsuno, S; Tsybychev, D; Turini, N; Turner, M; Ukegawa, F; Unverhau, T; Uozumi, S; Usynin, D; Vacavant, L; Vaiciulis, A; Varganov, A; Vataga, E; Vejcik, S; Velev, G; Veramendi, G; Vickey, T; Vidal, R; Vila, I; Vilar, R; Volobouev, I; von der Mey, M; Wagner, R G; Wagner, R L; Wagner, W; Wallny, R; Walter, T; Yamashita, T; Yamamoto, K; Wan, Z; Wang, M J; Wang, S M; Warburton, A; Ward, B; Waschke, S; Waters, D; Watts, T; Weber, M; Wester, W C; Whitehouse, B; Wicklund, A B; Wicklund, E; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolter, M; Worcester, M; Worm, S; Wright, T; Wu, X; Würthwein, F; Wyatt, A; Yagil, A; Yang, U K; Yao, W; Yeh, G P; Yi, K; Yoh, J; Yoon, P; Yorita, K; Yoshida, T; Yu, I; Yu, S; Yu, Z; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zetti, F; Zhou, J; Zsenei, A; Zucchelli, S

    2004-11-26

    We present the results of a search for doubly charged Higgs bosons (H+/-+/-) decaying to dileptons (ll(')) using approximately 240 pb(-1) of pp collision data collected by the CDF II experiment at the Fermilab Tevatron. In our search region, given by same-sign ll(') mass m(ll('))>80 GeV/c(2) (100 GeV/c(2) for ee channel), we observe no evidence for H+/-+/- production. We set limits on sigma(pp -->H++H---->l(+)l('+)l(-)l('-)) as a function of the mass of the H+/-+/- and the chirality of its couplings. Assuming exclusive same-sign dilepton decays, we derive lower mass limits on H(+/-+/-)(L) of 133, 136, and 115 GeV/c(2) in the ee, mumu, and emu channels, respectively, and a lower mass limit of 113 GeV/c(2) on H(+/-+/-)(R) in the mumu channel, all at the 95% confidence level.

  7. Near yrast states in doubly odd [sup 214]Fr

    SciTech Connect

    Debray, M.E.; Kreiner, A.J.; Kesque, J.M.; Ozafran, M.; Romo, A.; Somacal, H.; Vazquez, M.E. ); Davidson, J.; Davidson, M. ); Ahn, K.; Fossan, D.B.; Liang, Y.; Ma, R.; Paul, E.S.; Piel, W.F. Jr.; Xu, N. )

    1993-11-01

    High spin states of doubly odd [sup 214]Fr[sub 127] have been investigated using in-beam [gamma]-ray and conversion electron spectroscopy techniques through the [sup 206]Pb([sup 11]B, 3[ital n]) and [sup 208]Pb([sup 11]B, 5[ital n]) fusion-evaporation reactions. Completely new spectrocopic information has been obtained. The yrast level structure is established up to spin (19[sup +]) and some information on [gamma] transitions from higher-lying levels is also obtained. Two new isomers [ital T][sub 1/2]=174(20) ns and [ital T][sub 1/2]=11(2) ns were found. Configuration assignments for the low-lying levels are discussed. Information on residual proton-neutron interactions is extracted.

  8. Triple differential cross sections of magnesium in doubly symmetric geometry

    NASA Astrophysics Data System (ADS)

    S, Y. Sun; X, Y. Miao; Xiang-Fu, Jia

    2016-01-01

    A dynamically screened three-Coulomb-wave (DS3C) method is applied to study the single ionization of magnesium by electron impact. Triple differential cross sections (TDCS) are calculated in doubly symmetric geometry at incident energies of 13.65, 17.65, 22.65, 27.65, 37.65, 47.65, 57.65, and 67.65 eV. Comparisons are made with experimental data and theoretical predictions from a three-Coulomb-wave function (3C) approach and distorted-wave Born approximation (DWBA). The overall agreement between the predictions of the DS3C model and the DWBA approach with the experimental data is satisfactory. Project supported by the National Natural Science Foundation of China (Grant No. 11274215).

  9. Respiratory compensation in cardiac PET using doubly-gated acquisitions

    SciTech Connect

    Huesman, R.H.; Klein, G.J.; Reutter, B.W.

    1997-05-01

    We present results of respiratory compensation in cardiac PET data via doubly-gated acquisitions on a human subject. The extent of cardiac motion due to respiration has now been documented by numerous researchers. To correct for the blurring effects of this motion, we have modified the CTI/Siemens ECAT EXACT HR scanner to support acquisitions gated for different stages of both the cardiac and respiratory cycles. A human subject was injected with 11.0 mCi 18-FDG. After allowing time for the isotope to clear the blood pool, emission data were acquired for 30 minutes. The respiratory cycle was divided into five gates, the cardiac cycle into three gates for a total of fifteen 47-plane emission datasets. An ungated transmission dataset was acquired to correct for the effects of attenuation. Each gate was separately reconstructed using standard filtered backprojection techniques. Data resulting from the five respiratory gates obtained during diastole will be discussed in this paper.

  10. Doubly infinite separation of quantum information and communication

    NASA Astrophysics Data System (ADS)

    Liu, Zi-Wen; Perry, Christopher; Zhu, Yechao; Koh, Dax Enshan; Aaronson, Scott

    2016-01-01

    We prove the existence of (one-way) communication tasks with a subconstant versus superconstant asymptotic gap, which we call "doubly infinite," between their quantum information and communication complexities. We do so by studying the exclusion game [C. Perry et al., Phys. Rev. Lett. 115, 030504 (2015), 10.1103/PhysRevLett.115.030504] for which there exist instances where the quantum information complexity tends to zero as the size of the input n increases. By showing that the quantum communication complexity of these games scales at least logarithmically in n , we obtain our result. We further show that the established lower bounds and gaps still hold even if we allow a small probability of error. However in this case, the n -qubit quantum message of the zero-error strategy can be compressed polynomially.

  11. Optomechanical Enhancement of Doubly Resonant 2D Optical Nonlinearity.

    PubMed

    Yi, Fei; Ren, Mingliang; Reed, Jason C; Zhu, Hai; Hou, Jiechang; Naylor, Carl H; Johnson, A T Charlie; Agarwal, Ritesh; Cubukcu, Ertugrul

    2016-03-01

    Emerging two-dimensional semiconductor materials possess a giant second order nonlinear response due to excitonic effects while the monolayer thickness of such active materials limits their use in practical nonlinear devices. Here, we report 3300 times optomechanical enhancement of second harmonic generation from a MoS2 monolayer in a doubly resonant on-chip optical cavity. We achieve this by engineering the nonlinear light-matter interaction in a microelectro-mechanical system enabled optical frequency doubling device based on an electrostatically tunable Fabry-Perot microresonator. Our versatile optomechanical approach will pave the way for next generation efficient on-chip tunable light sources, sensors, and systems based on molecularly thin materials. PMID:26854706

  12. Doubly Cavitand-Capped Porphyrin Capsule by Hydrogen Bonds.

    PubMed

    Kishimoto, Kazuki; Nakamura, Munechika; Kobayashi, Kenji

    2016-02-18

    The components of a 1:2 mixture of meso-tetrakis(4-dodecyl-3,5-dihydroxyphenyl)porphyrin (1) and a bowl-shaped tetrakis(4-pyridylethynyl)cavitand (2) in CDCl3 or C6 D6 self-assemble quantitatively into the doubly cavitand-capped porphyrin capsule 2⋅1⋅2 through eight ArOH⋅⋅⋅Npy hydrogen bonds. Capsule 2⋅1⋅2 possesses two cavities divided by the porphyrin ring and encapsulates two molecules of 1-acetoxy-3,5-dimethoxybenzene (G) as a guest to form G/G@(2⋅1⋅2). Remarkable solvent effect was observed, in which the apparent association constant of 2⋅1⋅2 with G in C6 D6 was much greater than that in CDCl3. PMID:26728330

  13. Optomechanical Enhancement of Doubly Resonant 2D Optical Nonlinearity.

    PubMed

    Yi, Fei; Ren, Mingliang; Reed, Jason C; Zhu, Hai; Hou, Jiechang; Naylor, Carl H; Johnson, A T Charlie; Agarwal, Ritesh; Cubukcu, Ertugrul

    2016-03-01

    Emerging two-dimensional semiconductor materials possess a giant second order nonlinear response due to excitonic effects while the monolayer thickness of such active materials limits their use in practical nonlinear devices. Here, we report 3300 times optomechanical enhancement of second harmonic generation from a MoS2 monolayer in a doubly resonant on-chip optical cavity. We achieve this by engineering the nonlinear light-matter interaction in a microelectro-mechanical system enabled optical frequency doubling device based on an electrostatically tunable Fabry-Perot microresonator. Our versatile optomechanical approach will pave the way for next generation efficient on-chip tunable light sources, sensors, and systems based on molecularly thin materials.

  14. Nonsnaking doubly diffusive convectons and the twist instability

    SciTech Connect

    Beaume, Cédric Knobloch, Edgar; Bergeon, Alain

    2013-11-15

    Doubly diffusive convection in a three-dimensional horizontally extended domain with a square cross section in the vertical is considered. The fluid motion is driven by horizontal temperature and concentration differences in the transverse direction. When the buoyancy ratio N = −1 and the Rayleigh number is increased the conduction state loses stability to a subcritical, almost two-dimensional roll structure localized in the longitudinal direction. This structure exhibits abrupt growth in length near a particular value of the Rayleigh number but does not snake. Prior to this filling transition the structure becomes unstable to a secondary twist instability generating a pair of stationary, spatially localized zigzag states. In contrast to the primary branch these states snake as they grow in extent and eventually fill the whole domain. The origin of the twist instability and the properties of the resulting localized structures are investigated for both periodic and no-slip boundary conditions in the extended direction.

  15. Doubly ordered superconducting state in a doped antiferromagnet

    SciTech Connect

    Belyavskii, V. I. Kopaev, Yu. V.; Tuan, Nguyen Ngoc

    2007-10-15

    In a weakly doped quasi-two-dimensional antiferromagnet with a Fermi contour in the form of small pockets, the Coulomb repulsion gives rise to a doubly ordered superconducting state of coexisting condensates with a large pair momentum and a zero one. The pairing with the large momentum determines the superconducting transition temperature, below which the order with zero momentum coexists as an induced order until the temperature corresponding to the initiation of the phonon pairing mechanism is reached. The superconductivity-induced orbital current density wave eliminates the pairing-repulsion-caused zero points from the two-gap quasiparticle spectrum and leads to a deviation of the relative phase of the superconducting order parameter components from {pi}.

  16. Properties of Doubly Heavy Baryons in the Relativistic Quark Model

    SciTech Connect

    Ebert, D.; Faustov, R.N.; Galkin, V.O.; Martynenko, A.P.

    2005-05-01

    Mass spectra and semileptonic decay rates of baryons consisting of two heavy (b or c) and one light quark are calculated in the framework of the relativistic quark model. The doubly heavy baryons are treated in the quark-diquark approximation. The ground and excited states of both the diquark and quark-diquark bound systems are considered. The quark-diquark potential is constructed. The light quark is treated completely relativistically, while the expansion in the inverse heavy-quark mass is used. The weak transition amplitudes of heavy diquarks bb and bc going, respectively, to bc and cc are explicitly expressed through the overlap integrals of the diquark wave functions in the whole accessible kinematic range. The relativistic baryon wave functions of the quark-diquark bound system are used for the calculation of the decay matrix elements, the Isgur-Wise function, and decay rates in the heavy-quark limit.

  17. Time-resolved doubly bent crystal x-ray spectrometer

    SciTech Connect

    Hockaday, M.P.; Wilke, M.D.; Blake, R.L.; Vaninetti, J.; Gray, N.T.; Nedrow, P.T.

    1988-08-01

    X-ray spectroscopy is an essential tool in high-temperature plasma research. We describe a time-resolved x-ray spectrometer suitable for measuring spectra in harsh environments common to many very high-energy density laboratory plasma sources. The spectrometer consisted of a doubly curved Si(111) crystal diffraction element, a WL-1201 (ZnO:Ga) phosphor, a coherent fiber-optic array, and two visible streak cameras. The spectrometer design described here has a minimum time resolution of 1.3 ns with 2.8-eV spectral resolution over a 200-eV-wide bandpass in the 6--7-keV region of the spectrum. Complete system spectral throughput calibrations were done at the Cornell High Energy Synchrotron (CHESS). Details of the design and calibration results are presented.

  18. Time-resolved doubly bent crystal x-ray spectrometer

    SciTech Connect

    Hockaday, M.P.; Wilke, M.D.; Blake, R.L.; Vaninetti, J.; Gray, N.T.; Nedrow, P.T.

    1988-01-01

    X-ray spectroscopy is an essential tool in high temperature plasma research. We describe a time-resolved x-ray spectrometer suitable for measuring spectra in harsh environments common to many very high energy density laboratory plasma sources. The spectrometer consisted of a doubly curved Si(111) crystal diffraction element, a WL-1201 (ZnO:Ga) phosphor, a coherent fiber optic array, and two visible streak cameras. The spectrometer design described here has a minimum time resolution of 1.3 ns with 2.8 eV spectral resolution over a 200 eV wide bandpass in the 6-7 keV region of the spectrum. Complete system spectral throughput calibrations were done at the Cornell High Energy Synchrotron (CHESS). Details of the design and calibration results are presented. 5 refs., 5 figs.

  19. Coherence and correlation in doubly excited heliumlike atoms

    NASA Astrophysics Data System (ADS)

    Burgdörfer, Joachim; Morgenstern, Reinhard

    1988-12-01

    We analyze properties of the density matrix of doubly excited two-electron systems formed in inelastic collisions. Formulas for the two-particle joint angular probability density, the angular correlation function, and the reduced single-particle density are derived. Of particular interest is the interplay between the intrinsic correlations of the stationary two-electron state and collisionally induced coherences. We focus on its effects on the correlated and single-particle motion of the electrons. If one chooses approximate stationary wave functions reflecting the approximate O(4)×O(4)⊃O(4) dynamical symmetry, a simple quasiclassical interpretation of coherence and correlation in terms of shapes and modes of the relative motion of Kepler orbits can be given. The present description is applied to recent experimental results by Van der Straten and Morgenstern [Comments At. Mol. Phys. 19, 243 (1986)].

  20. Doubly magic nucleus (108)(270)Hs162.

    PubMed

    Dvorak, J; Brüchle, W; Chelnokov, M; Dressler, R; Düllmann, Ch E; Eberhardt, K; Gorshkov, V; Jäger, E; Krücken, R; Kuznetsov, A; Nagame, Y; Nebel, F; Novackova, Z; Qin, Z; Schädel, M; Schausten, B; Schimpf, E; Semchenkov, A; Thörle, P; Türler, A; Wegrzecki, M; Wierczinski, B; Yakushev, A; Yeremin, A

    2006-12-15

    Theoretical calculations predict 270Hs (Z=108, N=162) to be a doubly magic deformed nucleus, decaying mainly by alpha-particle emission. In this work, based on a rapid chemical isolation of Hs isotopes produced in the 26Mg+248Cm reaction, we observed 15 genetically linked nuclear decay chains. Four chains were attributed to the new nuclide 270Hs, which decays by alpha-particle emission with Qalpha=9.02+/-0.03 MeV to 266Sg which undergoes spontaneous fission with a half-life of 444(-148)(+444) ms. A production cross section of about 3 pb was measured for 270Hs. Thus, 270Hs is the first nucleus for which experimental nuclear decay properties have become available for comparison with theoretical predictions of the N=162 shell stability. PMID:17280272

  1. Quasi-collinear tunable acousto-optic paratellurite crystal filters for wavelength division multiplexing and optical channel selection

    SciTech Connect

    Molchanov, V Ya; Makarov, O Yu; Voloshinov, V B

    2009-04-30

    Quasi-collinear acousto-optic interaction is studied in acoustically and optically anisotropic paratellurite crystals. The possible applications of this interaction in acousto-optic tunable filters with a high spectral resolution are discussed. Different modifications of devices are compared and variants of devices intended for processing light beams and selection of light signals in fibreoptic communication systems with wavelength division multiplexing (WDM) at {lambda} {approx_equal} 1550 nm are considered. (light modulation)

  2. Absolute doubly differential bremsstrahlung cross sections from rare gas atoms

    NASA Astrophysics Data System (ADS)

    Portillo, Salvador

    The absolute doubly differential bremsstrahlung cross section has been measured for 28 and 50 keV electrons incident on the rare gases Xe, Kr, Ar and Ne. The cross sections are differential with respect to energy and photon emission. A SiLi solid state detector measured data at 90° with respect to the beam line. A thorough analysis of the experimental systematic error yielded a high degree of confidence in the experimental data. The absolute bremsstrahlung doubly differential cross sections provided for a rigorous test of the normal bremsstrahlung theory, tabulated by Kissel, Quarles and Pratt1 (KQP) and of the SA theory2 that includes the contribution from polarization bremsstrahlung. To test the theories a comparison of the overall magnitude of the cross section as well as comparison of the photon energy dependence was carried out. The KQP theoretical values underestimated the magnitude of the cross section for all targets and for both energies. The SA values were in excellent agreement with the 28 keV data. For the 50keV data the fit was also very good. However, there were energy regions where there was a small discrepancy between the theory and the data. This suggests that the Polarization Bremsstrahlung (PB) mechanism does contribute to the overall spectrum and is detectable in this parameter space. 1Kissel, L., Quarles, C. A., Pratt, R. H., Atom. Data Nucl. Data Tables 28, 381 (1983). 2Avdonina N. B., Pratt, R. H., J. Phys. B: At. Mol. Opt. Phys. 32 4261 (1999).

  3. Selection of Mother Wavelet Functions for Multi-Channel EEG Signal Analysis during a Working Memory Task

    PubMed Central

    Al-Qazzaz, Noor Kamal; Hamid Bin Mohd Ali, Sawal; Ahmad, Siti Anom; Islam, Mohd Shabiul; Escudero, Javier

    2015-01-01

    We performed a comparative study to select the efficient mother wavelet (MWT) basis functions that optimally represent the signal characteristics of the electrical activity of the human brain during a working memory (WM) task recorded through electro-encephalography (EEG). Nineteen EEG electrodes were placed on the scalp following the 10–20 system. These electrodes were then grouped into five recording regions corresponding to the scalp area of the cerebral cortex. Sixty-second WM task data were recorded from ten control subjects. Forty-five MWT basis functions from orthogonal families were investigated. These functions included Daubechies (db1–db20), Symlets (sym1–sym20), and Coiflets (coif1–coif5). Using ANOVA, we determined the MWT basis functions with the most significant differences in the ability of the five scalp regions to maximize their cross-correlation with the EEG signals. The best results were obtained using “sym9” across the five scalp regions. Therefore, the most compatible MWT with the EEG signals should be selected to achieve wavelet denoising, decomposition, reconstruction, and sub-band feature extraction. This study provides a reference of the selection of efficient MWT basis functions. PMID:26593918

  4. Development of regional curves relating bankfull-channel geometry and discharge to drainage area for streams in Pennsylvania and selected areas of Maryland

    USGS Publications Warehouse

    Chaplin, Jeffrey J.

    2005-01-01

    Natural-stream designs are commonly based on the dimensions of the bankfull channel, which is capable of conveying discharges that transport sediment without excessive erosion or deposition. Regional curves relate bankfull-channel geometry and discharge to drainage area in watersheds with similar runoff characteristics and commonly are utilized by practitioners of natural-stream design to confirm or refute selection of the field-identified bankfull channel. Data collected from 66 streamflow-gaging stations and associated stream reaches between December 1999 and December 2003 were used in one-variable ordinary least-squares regression analyses to develop regional curves relating drainage area to cross-sectional area, discharge, width, and mean depth of the bankfull channel. Watersheds draining to these stations are predominantly within the Piedmont, Ridge and Valley, and Appalachian Plateaus Physiographic Provinces of Pennsylvania and northern Maryland. Statistical analyses of physiography, percentage of watershed area underlain by carbonate bedrock, and percentage of watershed area that is glaciated indicate that carbonate bedrock, not physiography or glaciation, has a controlling influence on the slope of regional curves. Regional curves developed from stations in watersheds underlain by 30 percent or less carbonate bedrock generally had steeper slopes than the corresponding relations developed from watersheds underlain by greater than 30 percent carbonate bedrock. In contrast, there is little evidence to suggest that regional curves developed from stations in the Piedmont or Ridge and Valley Physiographic Province are different from the corresponding relations developed from stations in the Appalachian Plateaus Physiographic Province. On the basis of these findings, regional curves are presented to represent two settings that are independent of physiography: (1) noncarbonate settings characterized by watersheds with carbonate bedrock underlying 30 percent or less

  5. Selective Activation of Nociceptor TRPV1 Channel and Reversal of Inflammatory Pain in Mice by a Novel Coumarin Derivative Muralatin L from Murraya alata.

    PubMed

    Wei, Ning-Ning; Lv, Hai-Ning; Wu, Yang; Yang, Shi-Long; Sun, Xiao-Ying; Lai, Ren; Jiang, Yong; Wang, KeWei

    2016-01-01

    Coumarin and its derivatives are fragrant natural compounds isolated from the genus Murraya that are flowering plants widely distributed in East Asia, Australia, and the Pacific Islands. Murraya plants have been widely used as medicinal herbs for relief of pain, such as headache, rheumatic pain, toothache, and snake bites. However, little is known about their analgesic components and the molecular mechanism underlying pain relief. Here, we report the bioassay-guided fractionation and identification of a novel coumarin derivative, named muralatin L, that can specifically activate the nociceptor transient receptor potential vanilloid 1 (TRPV1) channel and reverse the inflammatory pain in mice through channel desensitization. Muralatin L was identified from the active extract of Murraya alata against TRPV1 transiently expressed in HEK-293T cells in fluorescent calcium FlexStation assay. Activation of TRPV1 current by muralatin L and its selectivity were further confirmed by whole-cell patch clamp recordings of TRPV1-expressing HEK-293T cells and dorsal root ganglion neurons isolated from mice. Furthermore, muralatin L could reverse inflammatory pain induced by formalin and acetic acid in mice but not in TRPV1 knock-out mice. Taken together, our findings show that muralatin L specifically activates TRPV1 and reverses inflammatory pain, thus highlighting the potential of coumarin derivatives from Murraya plants for pharmaceutical and medicinal applications such as pain therapy. PMID:26515068

  6. Selective Activation of Nociceptor TRPV1 Channel and Reversal of Inflammatory Pain in Mice by a Novel Coumarin Derivative Muralatin L from Murraya alata.

    PubMed

    Wei, Ning-Ning; Lv, Hai-Ning; Wu, Yang; Yang, Shi-Long; Sun, Xiao-Ying; Lai, Ren; Jiang, Yong; Wang, KeWei

    2016-01-01

    Coumarin and its derivatives are fragrant natural compounds isolated from the genus Murraya that are flowering plants widely distributed in East Asia, Australia, and the Pacific Islands. Murraya plants have been widely used as medicinal herbs for relief of pain, such as headache, rheumatic pain, toothache, and snake bites. However, little is known about their analgesic components and the molecular mechanism underlying pain relief. Here, we report the bioassay-guided fractionation and identification of a novel coumarin derivative, named muralatin L, that can specifically activate the nociceptor transient receptor potential vanilloid 1 (TRPV1) channel and reverse the inflammatory pain in mice through channel desensitization. Muralatin L was identified from the active extract of Murraya alata against TRPV1 transiently expressed in HEK-293T cells in fluorescent calcium FlexStation assay. Activation of TRPV1 current by muralatin L and its selectivity were further confirmed by whole-cell patch clamp recordings of TRPV1-expressing HEK-293T cells and dorsal root ganglion neurons isolated from mice. Furthermore, muralatin L could reverse inflammatory pain induced by formalin and acetic acid in mice but not in TRPV1 knock-out mice. Taken together, our findings show that muralatin L specifically activates TRPV1 and reverses inflammatory pain, thus highlighting the potential of coumarin derivatives from Murraya plants for pharmaceutical and medicinal applications such as pain therapy.

  7. Allosteric coupling between proximal C-terminus and selectivity filter is facilitated by the movement of transmembrane segment 4 in TREK-2 channel

    PubMed Central

    Zhuo, Ren-Gong; Peng, Peng; Liu, Xiao-Yan; Yan, Hai-Tao; Xu, Jiang-Ping; Zheng, Jian-Quan; Wei, Xiao-Li; Ma, Xiao-Yun

    2016-01-01

    TREK-2, a member of two-pore-domain potassium channel family, regulates cellular excitability in response to diverse stimuli. However, how such stimuli control channel function remains unclear. Here, by characterizing the responses of cytosolic proximal C-terminus deletant (ΔpCt) and transmembrane segment 4 (M4)-glycine hinge mutant (G312A) to 2-Aminoethoxydiphenyl borate (2-APB), an activator of TREK-2, we show that the transduction initiated from pCt domain is allosterically coupled with the conformation of selectivity filter (SF) via the movements of M4, without depending on the original status of SF. Moreover, ΔpCt and G312A also exhibited blunted responses to extracellular alkalization, a model to induce SF conformational transition. These results suggest that the coupling between pCt domain and SF is bidirectional, and M4 movements are involved in both processes. Further mechanistic exploration reveals that the function of Phe316, a residue close to the C-terminus of M4, is associated with such communications. However, unlike TREK-2, M4-hinge of TREK-1 only controls the transmission from pCt to SF, rather than SF conformational changes triggered by pHo changes. Together, our findings uncover the unique gating properties of TREK-2, and elucidate the mechanisms for how the extracellular and intracellular stimuli harness the pore gating allosterically. PMID:26879043

  8. Selected cysteine point mutations confer mercurial sensitivity to the mercurial-insensitive water channel MIWC/AQP-4.

    PubMed

    Shi, L B; Verkman, A S

    1996-01-16

    The mercurial-insensitive water channel (MIWC or AQP-4) is a 30-32 kDA integral membrane protein expressed widely in fluid-transporting epithelia [Hasegawa et al. (1994) J. Biol. Chem. 269, 5497-5500]. To investigate the mercurial insensitivity and key residues involved in MIWC-mediated water transport, amino acids just proximal to the conserved NPA motifs (residues 69-74 and 187-190) were mutated individually to cysteine. Complementary RNAs were expressed in Xenopus oocytes for assay of osmotic water permeability (Pf) and HgCl2 inhibition dose-response. Oocytes expressing the cysteine mutants were highly water permeable, with Pf values (24-33 x 10(-3) cm/s) not different from that of wild-type (WT) MIWC. Pf was reversibly inhibited by HgCl2 in mutants S70C, G71C, G72C, H73C, and S189C but insensitive to HgCl2 in the other mutants. K1/2 values for 50% inhibition of Pf by HgCl2 were as follows (in millimolar): 0.40 (S70C), 0.36 (G71C), 0.14 (G72C), 0.45 (H73C), 0.24 (S189C), and > 1 for WT MIWC and the other mutants. To test the hypothesis that these residues are near the MIWC aqueous pore, residues 72 and 188 were mutated individually to the larger amino acid tryptophan. Pf in oocytes expressing mutants G72W or A188W (1.3-1.4 x 10(-3) cm/s) was not greater than that in water-injected oocytes even though these proteins were expressed at the oocyte plasma membrane as shown by quantitative immunofluorescence. Coinjection of cRNAs encoding WT MIWC and G72W or A188W indicated a dominant negative effect; Pf (x 10(-3) cm/s) was 22 (0.25 ng of WT), 10 (0.25 ng of WT + 0.25 ng of G72W), and 12 (0.25 ng of WT + 0.25 ng of A188W). Taken together, these results suggest the MIWC is mercurial-insensitive because of absence of a cysteine residue near the NPA motifs and that residues 70-73 and 189 are located at or near the MIWC aqueous pore. In contrast to previous data for the channel-forming integral protein of 28kDa (CHIP28), the finding of a dominant negative phenotype for

  9. Flood-plain and channel aggradation of selected bridge sites in the Iowa and Skunk River basins, Iowa

    USGS Publications Warehouse

    Eash, D.A.

    1996-01-01

    Flood-plain and channel-aggradation rates were estimated at 10 bridge sites on the Iowa River upstream of Coralville Lake and at two bridge sites in the central part of the Skunk River Basin. Four measurement methods were used to quantify aggradation rates: (1) a dendrogeomorphic method that used tree-age data and sediment-deposition depths, (2) a bridge-opening cross-section method that compared historic and recent cross sections of bridge openings, (3) a stage-discharge rating-curve method that compared historic and recent stages for the 5-year flood discharge and the average discharge, and (4) nine sediment pads that were installed on the Iowa River flood plain at three bridge sites in the vicinity of Marshalltown. The sediment pads were installed prior to overbank flooding in 1993. Sediments deposited on the pads as a result of the 1993 flood ranged in depth from 0.004 to 2.95 feet. Measurement periods used to estimate average aggradation rates ranged from 1 to 98 years and varied among methods and sites. The highest aggradation rates calculated for the Iowa River Basin using the dendrogeomorphic and rating- curve measurement methods were for the State Highway 14 crossing at Marshalltown, where these highest rates were 0.045 and 0.124 feet per year, respectively. The highest aggradation rates calculated for the Skunk River Basin were for the U.S. Highway 63 crossing of the South Skunk River near Oskaloosa, where these highest rates were 0.051 and 0.298 feet per year, respectively.

  10. Improving efficiency and robustness of the doubly robust estimator for a population mean with incomplete data.

    PubMed

    Cao, Weihua; Tsiatis, Anastasios A; Davidian, Marie

    2009-09-01

    Considerable recent interest has focused on doubly robust estimators for a population mean response in the presence of incomplete data, which involve models for both the propensity score and the regression of outcome on covariates. The usual doubly robust estimator may yield severely biased inferences if neither of these models is correctly specified and can exhibit nonnegligible bias if the estimated propensity score is close to zero for some observations. We propose alternative doubly robust estimators that achieve comparable or improved performance relative to existing methods, even with some estimated propensity scores close to zero. PMID:20161511

  11. Doubly charged CO2 clusters formed by ionization of doped helium nanodroplets☆

    PubMed Central

    Daxner, Matthias; Denifl, Stephan; Scheier, Paul; Echt, Olof

    2014-01-01

    Helium nanodroplets are doped with carbon dioxide and ionized by electrons. Doubly charged cluster ions are, for the first time, identified based on their characteristic patterns of isotopologues. Thanks to the high mass resolution, large dynamic range, and a novel method to eliminate contributions from singly charged ions from the mass spectra, we are able to observe doubly charged cluster ions that are smaller than the ones reported in the past. The likely mechanism by which doubly charged ions are formed in doped helium droplets is discussed. PMID:25844051

  12. High-efficient photo-electron transport channel in SiC constructed by depositing cocatalysts selectively on specific surface sites for visible-light H2 production

    NASA Astrophysics Data System (ADS)

    Wang, Da; Peng, Yuan; Wang, Qi; Pan, Nanyan; Guo, Zhongnan; Yuan, Wenxia

    2016-04-01

    Control cocatalyst location on a metal-free semiconductor to promote surface charge transfer for decreasing the electron-hole recombination is crucial for enhancing solar energy conversion. Based on the findings that some metals have an affinity for bonding with the specific atoms of polar semiconductors at a heterostructure interface, we herein control Pt deposition selectively on the Si sites of a micro-SiC photocatalyst surface via in-situ photo-depositing. The Pt-Si bond forming on the interface constructs an excellent channel, which is responsible for accelerating photo-electron transfer from SiC to Pt and then reducing water under visible-light. The hydrogen production is enhanced by two orders of magnitude higher than that of bare SiC, and 2.5 times higher than that of random-depositing nano-Pt with the same loading amount.

  13. Oscillations of critical superconducting current in thin doubly-connected Sn films in an external perpendicular magnetic field

    NASA Astrophysics Data System (ADS)

    Sivakov, A. G.; Pokhila, A. S.; Glukhov, A. M.; Kuplevakhsky, S. V.; Omelyanchouk, A. N.

    2014-05-01

    We report the results of experimental and theoretical studies of critical current oscillations in thin doubly-connected Sn films in an external perpendicular magnetic field. The experiments were performed on samples that consisted of two wide electrodes joined together by two narrow channels. The length of the channels l satisfied the condition l ≫ ξ (ξ is the Ginzburg-Landau coherence length). At temperatures close to the critical temperature Tc, the dependence of the critical current Ic on average external magnetic flux Φ¯e has the form of a piecewise linear function, periodic with respect to the flux quantum Φ0. The amplitude of the Ic oscillation at a given temperature is proportional to the factor ξ/l. Moreover, the dependence Ic=Ic(Φ ¯e) is found to be multivalued, hence indicating the presence of metastable states. Based on the Ginzburg-Landau approximation, a theory was constructed that explains the above features of the oscillation phenomenon taking a perfectly symmetric system as an example. Further, the experiments displayed the effects related to the critical currents imbalance between the superconducting channels, i.e., shift of the maxima of the dependence Ic=Ic(Φ ¯e) accompanied by an asymmetry with respect to the transport current direction.

  14. Ab initio Approach to Effective Single-Particle Energies in Doubly Closed Shell Nuclei

    SciTech Connect

    Duguet, T.

    2012-01-01

    The present work discusses, from an ab initio standpoint, the definition, the meaning, and the usefulness of effective single-particle energies (ESPEs) in doubly closed shell nuclei. We perform coupled-cluster calculations to quantify to what extent selected closed-shell nuclei in the oxygen and calcium isotopic chains can effectively be mapped onto an effective independent-particle picture. To do so, we revisit in detail the notion of ESPEs in the context of strongly correlated many-nucleon systems and illustrate the necessity of extracting ESPEs through the diagonalization of the centroid matrix, as originally argued by Baranger. For the purpose of illustration, we analyze the impact of correlations on observable one-nucleon separation energies and nonobservable ESPEs in selected closed-shell oxygen and calcium isotopes. We then state and illustrate the nonobservability of ESPEs. Similarly to spectroscopic factors, ESPEs can indeed be modified by a redefinition of inaccessible quantities while leaving actual observables unchanged. This leads to the absolute necessity of employing consistent structure and reaction models based on the same nuclear Hamiltonian to extract the shell structure in a meaningful fashion from experimental data.

  15. Measurement of the top quark pair production cross section in the dilepton channel using lepton+track selection

    SciTech Connect

    Wagner, Robert Emil

    2008-11-01

    The production cross section for t$\\bar{t}$ pairs decaying into two lepton final states was measured using data from the D0 detector at Fermilab. The measurement was made using a lepton+track selection, where one lepton is fully identified and the second lepton is observed as an isolated track. This analysis is designed to complement similar studies using two fully identified leptons [1]. The cross section for the lepton+track selection was found to be σ = 5.2-1.4+1.6(stat)-0.8+0.9(syst) ± 0.3(lumi) pb. The combined cross section using both the lepton+track data and the data from the electron+electron, electron+muon, and muon+muon samples is: σ = 6.4-0.9+0.9(stat)-0.7+0.8(syst) ± 0.4(lumi) pb.

  16. Recent development of doubly curved crystal focusing optics and their applications for micro XRF

    NASA Astrophysics Data System (ADS)

    Chen, Zewu

    1999-11-01

    Three-dimensional focusing of x-rays can be achieved by doubly-curved crystals through diffraction from a small laboratory x-ray source. Recently it has been demonstrated that an intense monochromatic x-ray microprobe can be obtained with the use of a doubly-curved mica crystal. Due to monochromatic excitation using doubly-curved crystal optics, exceptionally low background has been demonstrated in the application to micro x-ray fluorescence (MXRF). Low background and high intensity gain significantly improve the detection limit for MXRF. In this paper, the focusing and diffraction properties of a doubly-curved Johann point-focusing crystal optic for Cu K(alpha) x-rays from a microfocus x-ray source is presented. Experimental data on spot size, beam intensity, effect of source position for the optics, and MXRF spectra are discussed.

  17. The membrane interface dictates different anchor roles for "inner pair" and "outer pair" tryptophan indole rings in gramicidin A channels.

    PubMed

    Gu, Hong; Lum, Kevin; Kim, Jung H; Greathouse, Denise V; Andersen, Olaf S; Koeppe, Roger E

    2011-06-01

    We investigated the effects of substituting two of the four tryptophans (the "inner pair" Trp(9) and Trp(11) or the "outer pair" Trp(13) and Trp(15)) in gramicidin A (gA) channels. The conformational preferences of the doubly substituted gA analogues were assessed using circular dichroism spectroscopy and size-exclusion chromatography, which show that the inner tryptophans 9 and 11 are critical for the gA's conformational preference in lipid bilayer membranes. [Phe(13,15)]gA largely retains the single-stranded helical channel structure, whereas [Phe(9,11)]gA exists primarily as double-stranded conformers. Within this context, the (2)H NMR spectra from labeled tryptophans were used to examine the changes in average indole ring orientations, induced by the Phe substitutions and by the shift in conformational preference. Using a method for deuterium labeling of already synthesized gAs, we introduced deuterium selectively onto positions C2 and C5 of the remaining tryptophan indole rings in the substituted gA analogues for solid-state (2)H NMR spectroscopy. The (least possible) changes in orientation and overall motion of each indole ring were estimated from the experimental spectra. Regardless of the mixture of backbone folds, the indole ring orientations observed in the analogues are similar to those found previously for gA channels. Both Phe-substituted analogues form single-stranded channels, as judged from the formation of heterodimeric channels with the native gA. [Phe(13,15)]gA channels have Na(+) currents that are ~50% and lifetimes that are ~80% of those of native gA channels. The double-stranded conformer(s) of [Phe(9,11)]gA do not form detectable channels. The minor single-stranded population of [Phe(9,11)]gA forms channels with Na(+) currents that are ~25% and single-channel lifetimes that are ~300% of those of native gA channels. Our results suggest that Trp(9) and Trp(11), when "reaching" for the interface, tend to drive both monomer folding (to "open" a

  18. High Performance Variable Speed Drive System and Generating System with Doubly Fed Machines

    NASA Astrophysics Data System (ADS)

    Tang, Yifan

    Doubly fed machines are another alternative for variable speed drive systems. The doubly fed machines, including doubly fed induction machine, self-cascaded induction machine and doubly excited brushless reluctance machine, have several attractive advantages for variable speed drive applications, the most important one being the significant cost reduction with a reduced power converter rating. With a better understanding, improved machine design, flexible power converters and innovated controllers, the doubly fed machines could favorably compete for many applications, which may also include variable speed power generations. The goal of this research is to enhance the attractiveness of the doubly fed machines for both variable speed drive and variable speed generator applications. Recognizing that wind power is one of the favorable clean, renewable energy sources that can contribute to the solution to the energy and environment dilemma, a novel variable-speed constant-frequency wind power generating system is proposed. By variable speed operation, energy capturing capability of the wind turbine is improved. The improvement can be further enhanced by effectively utilizing the doubly excited brushless reluctance machine in slip power recovery configuration. For the doubly fed machines, a stator flux two -axis dynamic model is established, based on which a flexible active and reactive power control strategy can be developed. High performance operation of the drive and generating systems is obtained through advanced control methods, including stator field orientation control, fuzzy logic control and adaptive fuzzy control. System studies are pursued through unified modeling, computer simulation, stability analysis and power flow analysis of the complete drive system or generating system with the machine, the converter and the control. Laboratory implementations and tested results with a digital signal processor system are also presented.

  19. Search for doubly charged Higgs bosons in like-sign dilepton final states at √s¯= 7 TeV with the ATLAS detector

    SciTech Connect

    Aad, G.

    2012-12-04

    A search for doubly-charged Higgs bosons decaying to pairs of electrons and/or muons is presented. The search is performed using a data sample corresponding to an integrated luminosity of 4.7 fb-1 of pp collisions at √s¯ = 7 TeV collected by the ATLAS detector at the LHC. Pairs of prompt, isolated, high-pT leptons with the same electric charge (e±e±, e±μ±, μ±μ±) are selected, and their invariant mass distribution is searched for a narrow resonance. No significant excess over Standard Model background expectations is observed, and limits are placed on the cross section times branching ratio for pair production of doubly-charged Higgs bosons. The masses of doubly-charged Higgs bosons are constrained depending on the branching ratio into these leptonic final states. Assuming pair production, coupling to left-handed fermions, and a branching ratio of 100% for each final state, masses below 409 GeV, 375 GeV, and 398 GeV are excluded for e±e±, e±μ±, and μ±μ±, respectively.

  20. Search for doubly charged Higgs bosons in like-sign dilepton final states at √s¯= 7 TeV with the ATLAS detector

    DOE PAGES

    Aad, G.

    2012-12-04

    A search for doubly-charged Higgs bosons decaying to pairs of electrons and/or muons is presented. The search is performed using a data sample corresponding to an integrated luminosity of 4.7 fb-1 of pp collisions at √s¯ = 7 TeV collected by the ATLAS detector at the LHC. Pairs of prompt, isolated, high-pT leptons with the same electric charge (e±e±, e±μ±, μ±μ±) are selected, and their invariant mass distribution is searched for a narrow resonance. No significant excess over Standard Model background expectations is observed, and limits are placed on the cross section times branching ratio for pair production of doubly-chargedmore » Higgs bosons. The masses of doubly-charged Higgs bosons are constrained depending on the branching ratio into these leptonic final states. Assuming pair production, coupling to left-handed fermions, and a branching ratio of 100% for each final state, masses below 409 GeV, 375 GeV, and 398 GeV are excluded for e±e±, e±μ±, and μ±μ±, respectively.« less

  1. Asymptotic error-rate analysis of FSO links using transmit laser selection over gamma-gamma atmospheric turbulence channels with pointing errors.

    PubMed

    García-Zambrana, Antonio; Castillo-Vázquez, Beatriz; Castillo-Vázquez, Carmen

    2012-01-30

    Since free-space optical (FSO) systems are usually installed on high buildings and building sway may cause vibrations in the transmitted beam, an unsuitable alignment between transmitter and receiver together with fluctuations in the irradiance of the transmitted optical beam due to the atmospheric turbulence can severely degrade the performance of optical wireless communication systems. In this paper, asymptotic bit error-rate (BER) performance for FSO communication systems using transmit laser selection over atmospheric turbulence channels with pointing errors is analyzed. Novel closed-form asymptotic expressions are derived when the irradiance of the transmitted optical beam is susceptible to either a wide range of turbulence conditions (weak to strong), following a gamma-gamma distribution of parameters α and β, or pointing errors, following a misalignment fading model where the effect of beam width, detector size and jitter variance is considered. Obtained results provide significant insight into the impact of various system and channel parameters, showing that the diversity order is independent of the pointing error when the equivalent beam radius at the receiver is at least 2(min{α,β})(1/2) times the value of the pointing error displacement standard deviation at the receiver. Moreover, since proper FSO transmission requires transmitters with accurate control of their beamwidth, asymptotic expressions are used to find the optimum beamwidth that minimizes the BER at different turbulence conditions. Simulation results are further demonstrated to confirm the accuracy and usefulness of the derived results, showing that asymptotic expressions here obtained lead to simple bounds on the bit error probability that get tighter over a wider range of signal-to-noise ratio (SNR) as the turbulence strength increases.

  2. Z944, a Novel Selective T-Type Calcium Channel Antagonist Delays the Progression of Seizures in the Amygdala Kindling Model.

    PubMed

    Casillas-Espinosa, Pablo Miguel; Hicks, Ashleigh; Jeffreys, Amy; Snutch, Terrance P; O'Brien, Terence J; Powell, Kim L

    2015-01-01

    Temporal lobe epilepsy (TLE) is the most common form of drug resistant epilepsy. Current treatment is symptomatic, suppressing seizures, but has no disease modifying effect on epileptogenesis. We examined the effects of Z944, a potent T-type calcium channel antagonist, as an anti-seizure agent and against the progression of kindling in the amygdala kindling model of TLE. The anti-seizure efficacy of Z944 (5mg/kg, 10mg/kg, 30mg/kg and 100mg/kg) was assessed in fully kindled rats (5 class V seizures) as compared to vehicle, ethosuximide (ETX, 100mg/kg) and carbamazepine (30mg/kg). Each animal received the seven treatments in a randomised manner. Seizure class and duration elicited by six post-drug stimulations was determined. To investigate for effects in delaying the progression of kindling, naive animals received Z944 (30mg/kg), ETX (100mg/kg) or vehicle 30-minutes prior to each kindling stimulation up to a maximum of 30 stimulations, with seizure class and duration recorded after each stimulation. At the completion of drug treatment, CaV3.1, CaV3.2 and CaV3.3 mRNA expression levels were assessed in the hippocampus and amygdala using qPCR. Z944 was not effective at suppressing seizures in fully kindled rats compared to vehicle. Animals receiving Z944 required significantly more stimulations to evoke a class III (p<0.05), IV (p<0.01) or V (p<0.0001) seizure, and to reach a fully kindled state (p<0.01), than animals receiving vehicle. There was no significant difference in the mRNA expression of the T-type Ca2+ channels in the hippocampus or amygdala. Our results show that selectively targeting T-type Ca2+ channels with Z944 inhibits the progression of amygdala kindling. This could be a potential for a new therapeutic intervention to mitigate the development and progression of epilepsy.

  3. Z944, a Novel Selective T-Type Calcium Channel Antagonist Delays the Progression of Seizures in the Amygdala Kindling Model

    PubMed Central

    Casillas-Espinosa, Pablo Miguel; Hicks, Ashleigh; Jeffreys, Amy; Snutch, Terrance P.; O’Brien, Terence J.; Powell, Kim L.

    2015-01-01

    Temporal lobe epilepsy (TLE) is the most common form of drug resistant epilepsy. Current treatment is symptomatic, suppressing seizures, but has no disease modifying effect on epileptogenesis. We examined the effects of Z944, a potent T-type calcium channel antagonist, as an anti-seizure agent and against the progression of kindling in the amygdala kindling model of TLE. The anti-seizure efficacy of Z944 (5mg/kg, 10mg/kg, 30mg/kg and 100mg/kg) was assessed in fully kindled rats (5 class V seizures) as compared to vehicle, ethosuximide (ETX, 100mg/kg) and carbamazepine (30mg/kg). Each animal received the seven treatments in a randomised manner. Seizure class and duration elicited by six post-drug stimulations was determined. To investigate for effects in delaying the progression of kindling, naive animals received Z944 (30mg/kg), ETX (100mg/kg) or vehicle 30-minutes prior to each kindling stimulation up to a maximum of 30 stimulations, with seizure class and duration recorded after each stimulation. At the completion of drug treatment, CaV3.1, CaV3.2 and CaV3.3 mRNA expression levels were assessed in the hippocampus and amygdala using qPCR. Z944 was not effective at suppressing seizures in fully kindled rats compared to vehicle. Animals receiving Z944 required significantly more stimulations to evoke a class III (p<0.05), IV (p<0.01) or V (p<0.0001) seizure, and to reach a fully kindled state (p<0.01), than animals receiving vehicle. There was no significant difference in the mRNA expression of the T-type Ca2+ channels in the hippocampus or amygdala. Our results show that selectively targeting T-type Ca2+ channels with Z944 inhibits the progression of amygdala kindling. This could be a potential for a new therapeutic intervention to mitigate the development and progression of epilepsy. PMID:26274319

  4. High-resolution single-channel seismic reflection surveys of Orange Lake and other selected sites of north central Florida

    USGS Publications Warehouse

    Kindinger, Jack G.; Davis, Jeffrey B.; Flocks, James G.

    1994-01-01

    and faulting. The largest and most important features in the lake are the collapse sinkholes found along the southwestern shore that provide conduits for exchange between the lake and subsurface aquifer. There are two basic differences between the southwest and other areas of the lake: (1) the features found towards the central part of the lake are smaller in scale (1to 10 m across) and tend to be singular structures compare to the southwest area where features combined to form larger sinkholes (>400 m), and; (2) the southwest area is the only site where collapse dolines were identified. These dolines are located along the southwestern shoreline adjacent to Heagy-Burry Park. The comparison of seismic profiles from the several other selected lake and river sites to the Orange Lake profiles showed that other study areas were constructed of one or two large subsidences or a combination of sinkholes to form one large sinkhole. Aside from the difference in scale the basic characteristics of the subsidence sinkholes were similar.

  5. Discovery of four doubly imaged quasar lenses from the Sloan digital sky survey

    SciTech Connect

    Inada, Naohisa; Oguri, Masamune; Rusu, Cristian E.; Kayo, Issha; Morokuma, Tomoki

    2014-06-01

    We report the discovery of four doubly imaged quasar lenses. All the four systems are selected as lensed quasar candidates from the Sloan Digital Sky Survey data. We confirm their lensing hypothesis with additional imaging and spectroscopic follow-up observations. The discovered lenses are SDSS J0743+2457 with the source redshift z{sub s} = 2.165, the lens redshift z{sub l} = 0.381, and the image separation θ = 1.''034, SDSS J1128+2402 with z{sub s} = 1.608 and θ = 0.''844, SDSS J1405+0959 with z{sub s} = 1.810, z{sub l} ≈ 0.66, and θ = 1.''978, and SDSS J1515+1511 with z{sub s} = 2.054, z{sub l} = 0.742, and θ = 1.''989. It is difficult to estimate the lens redshift of SDSS J1128+2402 from the current data. Two of the four systems (SDSS J1405+0959 and SDSS J1515+1511) are included in our final statistical lens sample to derive constraints on dark energy and the evolution of massive galaxies.

  6. Fragmentation network of doubly charged methionine: Interpretation using graph theory

    NASA Astrophysics Data System (ADS)

    Ha, D. T.; Yamazaki, K.; Wang, Y.; Alcamí, M.; Maeda, S.; Kono, H.; Martín, F.; Kukk, E.

    2016-09-01

    The fragmentation of doubly charged gas-phase methionine (HO2CCH(NH2)CH2CH2SCH3) is systematically studied using the self-consistent charge density functional tight-binding molecular dynamics (MD) simulation method. We applied graph theory to analyze the large number of the calculated MD trajectories, which appears to be a highly effective and convenient means of extracting versatile information from the large data. The present theoretical results strongly concur with the earlier studied experimental ones. Essentially, the dication dissociates into acidic group CO2H and basic group C4NSH10. The former may carry a single or no charge and stays intact in most cases, whereas the latter may hold either a single or a double charge and tends to dissociate into smaller fragments. The decay of the basic group is observed to follow the Arrhenius law. The dissociation pathways to CO2H and C4NSH10 and subsequent fragmentations are also supported by ab initio calculations.

  7. Brushless Doubly-Fed Machine system development program, phase 3

    NASA Astrophysics Data System (ADS)

    Alexander, G. C.; Spee, R.; Wallace, A. K.

    Since the inception of the Brushless Doubly-Fed Machine (BDFM) System Development Program in 1989, the value of BDFM technology has become apparent. The BDFM provides for adjustable speed, synchronous operation while keeping costs associated with the required power conversion equipment lower than in competing technologies. This provides for an advantage in initial as well as maintenance expenses over conventional drive system. Thus, the BDFM enables energy efficient, adjustable speed process control for applications where established drive technology has not been able to deliver satisfactory returns on investment. At the same time, the BDFM challenges conventional drive technologies in established markets by providing for improved performance at lower cost. BDFM converter rating is kept at a minimum, which significantly improves power quality at the utility interface over competing power conversion equipment. In summary, BDFM technology can be expected to provide significant benefits to utilities as well as their customers. This report discusses technical research and development activities related to Phase 3 of the BDFM System Development Program, including work made possible by supplemental funds for laboratory improvement and prototype construction.

  8. Doubly robust estimation in missing data and causal inference models.

    PubMed

    Bang, Heejung; Robins, James M

    2005-12-01

    The goal of this article is to construct doubly robust (DR) estimators in ignorable missing data and causal inference models. In a missing data model, an estimator is DR if it remains consistent when either (but not necessarily both) a model for the missingness mechanism or a model for the distribution of the complete data is correctly specified. Because with observational data one can never be sure that either a missingness model or a complete data model is correct, perhaps the best that can be hoped for is to find a DR estimator. DR estimators, in contrast to standard likelihood-based or (nonaugmented) inverse probability-weighted estimators, give the analyst two chances, instead of only one, to make a valid inference. In a causal inference model, an estimator is DR if it remains consistent when either a model for the treatment assignment mechanism or a model for the distribution of the counterfactual data is correctly specified. Because with observational data one can never be sure that a model for the treatment assignment mechanism or a model for the counterfactual data is correct, inference based on DR estimators should improve upon previous approaches. Indeed, we present the results of simulation studies which demonstrate that the finite sample performance of DR estimators is as impressive as theory would predict. The proposed method is applied to a cardiovascular clinical trial.

  9. Study of doubly strange systems using stored antiprotons

    NASA Astrophysics Data System (ADS)

    Singh, B.; Erni, W.; Krusche, B.; Steinacher, M.; Walford, N.; Liu, B.; Liu, H.; Liu, Z.; Shen, X.; Wang, C.; Zhao, J.; Albrecht, M.; Erlen, T.; Fink, M.; Heinsius, F.; Held, T.; Holtmann, T.; Jasper, S.; Keshk, I.; Koch, H.; Kopf, B.; Kuhlmann, M.; Kümmel, M.; Leiber, S.; Mikirtychyants, M.; Musiol, P.; Mustafa, A.; Pelizäus, M.; Pychy, J.; Richter, M.; Schnier, C.; Schröder, T.; Sowa, C.; Steinke, M.; Triffterer, T.; Wiedner, U.; Ball, M.; Beck, R.; Hammann, C.; Ketzer, B.; Kube, M.; Mahlberg, P.; Rossbach, M.; Schmidt, C.; Schmitz, R.; Thoma, U.; Urban, M.; Walther, D.; Wendel, C.; Wilson, A.; Bianconi, A.; Bragadireanu, M.; Caprini, M.; Pantea, D.; Patel, B.; Czyzycki, W.; Domagala, M.; Filo, G.; Jaworowski, J.; Krawczyk, M.; Lisowski, E.; Lisowski, F.; Michałek, M.; Poznański, P.; Płażek, J.; Korcyl, K.; Kozela, A.; Kulessa, P.; Lebiedowicz, P.; Pysz, K.; Schäfer, W.; Szczurek, A.; Fiutowski, T.; Idzik, M.; Mindur, B.; Przyborowski, D.; Swientek, K.; Biernat, J.; Kamys, B.; Kistryn, S.; Korcyl, G.; Krzemien, W.; Magiera, A.; Moskal, P.; Psyzniak, A.; Rudy, Z.; Salabura, P.; Smyrski, J.; Strzempek, P.; Wronska, A.; Augustin, I.; Böhm, R.; Lehmann, I.; Nicmorus Marinescu, D.; Schmitt, L.; Varentsov, V.; Al-Turany, M.; Belias, A.; Deppe, H.; Dzhygadlo, R.; Ehret, A.; Flemming, H.; Gerhardt, A.; Götzen, K.; Gromliuk, A.; Gruber, L.; Karabowicz, R.; Kliemt, R.; Krebs, M.; Kurilla, U.; Lehmann, D.; Löchner, S.; Lühning, J.; Lynen, U.; Orth, H.; Patsyuk, M.; Peters, K.; Saito, T.; Schepers, G.; Schmidt, C. J.; Schwarz, C.; Schwiening, J.; Täschner, A.; Traxler, M.; Ugur, C.; Voss, B.; Wieczorek, P.; Wilms, A.; Zühlsdorf, M.; Abazov, V. M.; Alexeev, G.; Arefiev, A.; Astakhov, V. I.; Barabanov, M. Yu.; Batyunya, B. V.; Davydov, Yu. I.; Dodokhov, V. Kh.; Efremov, A. A.; Fechtchenko, A.; Fedunov, A. G.; Galoyan, A.; Grigoryan, S.; Koshurnikov, E. K.; Lobanov, V. I.; Lobanov, Y. Yu.; Makarov, A. F.; Malinina, L. V.; Malyshev, V. L.; Olshevskiy, A.; Perevalova, E.; Piskun, A. A.; Pocheptsov, T.; Pontecorvo, G.; Rodionov, V.; Rogov, Y.; Salmin, R.; Samartsev, A.; Sapozhnikov, M. G.; Shabratova, G.; Skachkov, N. B.; Skachkova, A. N.; Strokovsky, E. A.; Suleimanov, M.; Teshev, R.; Tokmenin, V.; Uzhinsky, V.; Vodopyanov, A.; Zaporozhets, S. A.; Zhuravlev, N. I.; Zorin, A. G.; Branford, D.; Glazier, D.; Watts, D.; Böhm, M.; Britting, A.; Eyrich, W.; Lehmann, A.; Pfaffinger, M.; Uhlig, F.; Dobbs, S.; Seth, K.; Tomaradze, A.; Xiao, T.; Bettoni, D.; Carassiti, V.; Cotta Ramusino, A.; Dalpiaz, P.; Drago, A.; Fioravanti, E.; Garzia, I.; Savriè, M.; Akishina, V.; Kisel, I.; Kozlov, G.; Pugach, M.; Zyzak, M.; Gianotti, P.; Guaraldo, C.; Lucherini, V.; Bersani, A.; Bracco, G.; Macri, M.; Parodi, R. F.; Biguenko, K.; Brinkmann, K.; Di Pietro, V.; Diehl, S.; Dormenev, V.; Drexler, P.; Düren, M.; Etzelmüller, E.; Galuska, M.; Gutz, E.; Hahn, C.; Hayrapetyan, A.; Kesselkaul, M.; Kühn, W.; Kuske, T.; Lange, J. S.; Liang, Y.; Metag, V.; Nanova, M.; Nazarenko, S.; Novotny, R.; Quagli, T.; Reiter, S.; Rieke, J.; Rosenbaum, C.; Schmidt, M.; Schnell, R.; Stenzel, H.; Thöring, U.; Ullrich, M.; Wagner, M. N.; Wasem, T.; Wohlfarth, B.; Zaunick, H.; Ireland, D.; Rosner, G.; Seitz, B.; Deepak, P. N.; Kulkarni, A.; Apostolou, A.; Babai, M.; Kavatsyuk, M.; Lemmens, P.; Lindemulder, M.; Loehner, H.; Messchendorp, J.; Schakel, P.; Smit, H.; Tiemens, M.; van der Weele, J. C.; Veenstra, R.; Vejdani, S.; Dutta, K.; Kalita, K.; Kumar, A.; Roy, A.; Sohlbach, H.; Bai, M.; Bianchi, L.; Büscher, M.; Cao, L.; Cebulla, A.; Dosdall, R.; Gillitzer, A.; Goldenbaum, F.; Grunwald, D.; Herten, A.; Hu, Q.; Kemmerling, G.; Kleines, H.; Lehrach, A.; Nellen, R.; Ohm, H.; Orfanitski, S.; Prasuhn, D.; Prencipe, E.; Pütz, J.; Ritman, J.; Schadmand, S.; Sefzick, T.; Serdyuk, V.; Sterzenbach, G.; Stockmanns, T.; Wintz, P.; Wüstner, P.; Xu, H.; Zambanini, A.; Li, S.; Li, Z.; Sun, Z.; Xu, H.; Rigato, V.; Isaksson, L.; Achenbach, P.; Corell, O.; Denig, A.; Distler, M.; Hoek, M.; Karavdina, A.; Lauth, W.; Liu, Z.; Merkel, H.; Müller, U.; Pochodzalla, J.; Schlimme, S.; Sfienti, C.; Thiel, M.; Ahmadi, H.; Ahmed, S.; Bleser, S.; Capozza, L.; Cardinali, M.; Dbeyssi, A.; Deiseroth, M.; Feldbauer, F.; Fritsch, M.; Fröhlich, B.; Jasinski, P.; Kang, D.; Khaneft, D.; Klasen, R.; Leithoff, H. H.; Lin, D.; Maas, F.; Maldaner, S.; Martìnez Rojo, M.; Marta, M.; Michel, M.; Mora Espì, M. C.; Morales Morales, C.; Motzko, C.; Nerling, F.; Noll, O.; Pflüger, S.; Pitka, A.; Rodríguez Piñeiro, D.; Sanchez Lorente, A.; Steinen, M.; Valente, R.; Weber, T.; Zambrana, M.; Zimmermann, I.; Fedorov, A.; Korjik, M.; Missevitch, O.; Boukharov, A.; Malyshev, O.; Marishev, I.; Balanutsa, P.; Balanutsa, V.; Chernetsky, V.; Demekhin, A.; Dolgolenko, A.; Fedorets, P.; Gerasimov, A.; Goryachev, V.; Chandratre, V.; Datar, V.; Dutta, D.; Jha, V.; Kumawat, H.; Mohanty, A. K.; Parmar, A.; Roy, B.; Sonika, G.; Fritzsch, C.; Grieser, S.; Hergemöller, A. K.; Hetz, B.; Hüsken, N.; Khoukaz, A.; Wessels, J. P.; Khosonthongkee, K.; Kobdaj, C.; Limphirat, A.; Srisawad, P.; Yan, Y.; Barnyakov, M.; Barnyakov, A. Yu.; Beloborodov, K.; Blinov, A. E.; Blinov, V. E.; Bobrovnikov, V. S.; Kononov, S.; Kravchenko, E. A.; Kuyanov, I. A.; Martin, K.; Onuchin, A. P.; Serednyakov, S.; Sokolov, A.; Tikhonov, Y.; Atomssa, E.; Kunne, R.; Marchand, D.; Ramstein, B.; Van de Wiele, J.; Wang, Y.; Boca, G.; Costanza, S.; Genova, P.; Montagna, P.; Rotondi, A.; Abramov, V.; Belikov, N.; Bukreeva, S.; Davidenko, A.; Derevschikov, A.; Goncharenko, Y.; Grishin, V.; Kachanov, V.; Kormilitsin, V.; Levin, A.; Melnik, Y.; Minaev, N.; Mochalov, V.; Morozov, D.; Nogach, L.; Poslavskiy, S.; Ryazantsev, A.; Ryzhikov, S.; Semenov, P.; Shein, I.; Uzunian, A.; Vasiliev, A.; Yakutin, A.; Tomasi-Gustafsson, E.; Roy, U.; Yabsley, B.; Belostotski, S.; Gavrilov, G.; Izotov, A.; Manaenkov, S.; Miklukho, O.; Veretennikov, D.; Zhdanov, A.; Makonyi, K.; Preston, M.; Tegner, P.; Wölbing, D.; Bäck, T.; Cederwall, B.; Rai, A. K.; Godre, S.; Calvo, D.; Coli, S.; De Remigis, P.; Filippi, A.; Giraudo, G.; Lusso, S.; Mazza, G.; Mignone, M.; Rivetti, A.; Wheadon, R.; Balestra, F.; Iazzi, F.; Introzzi, R.; Lavagno, A.; Olave, J.; Amoroso, A.; Bussa, M. P.; Busso, L.; De Mori, F.; Destefanis, M.; Fava, L.; Ferrero, L.; Greco, M.; Hu, J.; Lavezzi, L.; Maggiora, M.; Maniscalco, G.; Marcello, S.; Sosio, S.; Spataro, S.; Birsa, R.; Bradamante, F.; Bressan, A.; Martin, A.; Calen, H.; Ikegami Andersson, W.; Johansson, T.; Kupsc, A.; Marciniewski, P.; Papenbrock, M.; Pettersson, J.; Schönning, K.; Wolke, M.; Galnander, B.; Diaz, J.; Pothodi Chackara, V.; Chlopik, A.; Kesik, G.; Melnychuk, D.; Slowinski, B.; Trzcinski, A.; Wojciechowski, M.; Wronka, S.; Zwieglinski, B.; Bühler, P.; Marton, J.; Steinschaden, D.; Suzuki, K.; Widmann, E.; Zmeskal, J.; Gerl, Jürgen; Kojouharov, Ivan; Kojouharova, Jasmina

    2016-10-01

    Bound nuclear systems with two units of strangeness are still poorly known despite their importance for many strong interaction phenomena. Stored antiprotons beams in the GeV range represent an unparalleled factory for various hyperon-antihyperon pairs. Their outstanding large production probability in antiproton collisions will open the floodgates for a series of new studies of systems which contain two or even more units of strangeness at the P ‾ ANDA experiment at FAIR. For the first time, high resolution γ-spectroscopy of doubly strange ΛΛ-hypernuclei will be performed, thus complementing measurements of ground state decays of ΛΛ-hypernuclei at J-PARC or possible decays of particle unstable hypernuclei in heavy ion reactions. High resolution spectroscopy of multistrange Ξ--atoms will be feasible and even the production of Ω--atoms will be within reach. The latter might open the door to the | S | = 3 world in strangeness nuclear physics, by the study of the hadronic Ω--nucleus interaction. For the first time it will be possible to study the behavior of Ξ‾+ in nuclear systems under well controlled conditions.

  10. Fragmentation network of doubly charged methionine: Interpretation using graph theory.

    PubMed

    Ha, D T; Yamazaki, K; Wang, Y; Alcamí, M; Maeda, S; Kono, H; Martín, F; Kukk, E

    2016-09-01

    The fragmentation of doubly charged gas-phase methionine (HO2CCH(NH2)CH2CH2SCH3) is systematically studied using the self-consistent charge density functional tight-binding molecular dynamics (MD) simulation method. We applied graph theory to analyze the large number of the calculated MD trajectories, which appears to be a highly effective and convenient means of extracting versatile information from the large data. The present theoretical results strongly concur with the earlier studied experimental ones. Essentially, the dication dissociates into acidic group CO2H and basic group C4NSH10. The former may carry a single or no charge and stays intact in most cases, whereas the latter may hold either a single or a double charge and tends to dissociate into smaller fragments. The decay of the basic group is observed to follow the Arrhenius law. The dissociation pathways to CO2H and C4NSH10 and subsequent fragmentations are also supported by ab initio calculations. PMID:27608997

  11. Discovery and biological evaluation of potent, selective, orally bioavailable, pyrazine-based blockers of the Na(v)1.8 sodium channel with efficacy in a model of neuropathic pain.

    PubMed

    Scanio, Marc J C; Shi, Lei; Drizin, Irene; Gregg, Robert J; Atkinson, Robert N; Thomas, James B; Johnson, Matthew S; Chapman, Mark L; Liu, Dong; Krambis, Michael J; Liu, Yi; Shieh, Char-Chang; Zhang, Xufeng; Simler, Gricelda H; Joshi, Shailen; Honore, Prisca; Marsh, Kennan C; Knox, Alison; Werness, Stephen; Antonio, Brett; Krafte, Douglas S; Jarvis, Michael F; Faltynek, Connie R; Marron, Brian E; Kort, Michael E

    2010-11-15

    Na(v)1.8 (also known as PN3) is a tetrodotoxin-resistant (TTx-r) voltage-gated sodium channel (VGSC) that is highly expressed on small diameter sensory neurons. It has been implicated in the pathophysiology of inflammatory and neuropathic pain, and we envisioned that selective blockade of Na(v)1.8 would be analgesic, while reducing adverse events typically associated with non-selective VGSC blocking therapeutic agents. Herein, we describe the preparation and characterization of a series of 6-aryl-2-pyrazinecarboxamides, which are potent blockers of the human Na(v)1.8 channel and also block TTx-r sodium currents in rat dorsal root ganglia (DRG) neurons. Selected derivatives display selectivity versus human Na(v)1.2. We further demonstrate that an example from this series is orally bioavailable and produces antinociceptive activity in vivo in a rodent model of neuropathic pain following oral administration. PMID:20965738

  12. Inhibition of cell proliferation by a selective inhibitor of the Ca{sup 2+}-activated Cl{sup -} channel, Ano1

    SciTech Connect

    Mazzone, Amelia; Eisenman, Seth T.; Strege, Peter R.; Yao, Zhen; Ordog, Tamas; Gibbons, Simon J.; Farrugia, Gianrico

    2012-10-19

    Highlights: Black-Right-Pointing-Pointer T16A{sub inh}-A01 blocked Ano1 currents in HEK cells expressing Ano1. Black-Right-Pointing-Pointer T16A{sub inh}-A01 reduced proliferation in ICC primary cultures and CFPAC-1 cell line. Black-Right-Pointing-Pointer T16A{sub inh}-A01 reduced proliferation of ICC in intact smooth muscle strips. -- Abstract: Background: Ion channels play important roles in regulation of cellular proliferation. Ano1 (TMEM16A) is a Ca{sup 2+}-activated Cl{sup -} channel expressed in several tumors and cell types. In the muscle layers of the gastrointestinal tract Ano1 is selectively expressed in interstitial cells of Cajal (ICC) and appears to be required for normal gastrointestinal slow wave electrical activity. However, Ano1 is expressed in all classes of ICC, including those that do not generate slow waves suggesting that Ano1 may have other functions. Indeed, a role for Ano1 in regulating proliferation of tumors and ICC has been recently suggested. Recently, a high-throughput screen identified a small molecule, T16A{sub inh}-A01 as a specific inhibitor of Ano1. Aim: To investigate the effect of the T16A{sub inh}-A01 inhibitor on proliferation in ICC and in the Ano1-expressing human pancreatic cancer cell line CFPAC-1. Methods: Inhibition of Ano1 was demonstrated by whole cell voltage clamp recordings of currents in cells transfected with full-length human Ano1. The effect of T16A{sub inh}-A01 on ICC proliferation was examined in situ in organotypic cultures of intact mouse small intestinal smooth muscle strips and in primary cell cultures prepared from these tissues. ICC were identified by Kit immunoreactivity. Proliferating ICC and CFPAC-1 cells were identified by immunoreactivity for the nuclear antigen Ki67 or EdU incorporation, respectively. Results: T16A{sub inh}-A01 inhibited Ca{sup 2+}-activated Cl{sup -} currents by 60% at 10 {mu}M in a voltage-independent fashion. Proliferation of ICC was significantly reduced in primary cultures

  13. Holographic recording in a doubly doped lithium niobate crystal with two wavelengths: a blue laser diode and a green laser

    NASA Astrophysics Data System (ADS)

    Komori, Yuichi; Ishii, Yukihiro

    2010-08-01

    A doubly-doped LiNbO3 (LN) crystal has been well used as a nonvolatile two-wavelength recording material. By using two levels of the crystal, two-kind holograms can be recorded on one crystal; a hologram is recorded with a 405-nm blue laser diode (LD) for a deep Mn level, and another hologram is with a 532-nm green laser for a shallow Fe level. The recording capacity doubles. A 780-nm LD is non-volatile reconstructing source since the LD line is insensitive to both levels. Multiplexed reconstructed images are demonstrated by using a sharp angular selectivity of a volume LN crystal keeping Bragg condition with spherical reconstructions.

  14. Encoderless Model Predictive Control of Doubly-Fed Induction Generators in Variable-Speed Wind Turbine Systems

    NASA Astrophysics Data System (ADS)

    Abdelrahem, Mohamed; Hackl, Christoph; Kennel, Ralph

    2016-09-01

    In this paper, an encoderless finite-control-set model predictive control (FCS-MPC) strategy for doubly-fed induction generators (DFIGs) based on variable-speed wind turbine systems (WTSs) is proposed. According to the FCS-MPC concept, the discrete states of the power converter are taken into account and the future converter performance is predicted for each sampling period. Subsequently, the voltage vector that minimizes a predefined cost function is selected to be applied in the next sampling instant. Furthermore, a model reference adaptive system (MRAS) observer is used to estimate the rotor speed and position of the DFIG. Estimation and control performance of the proposed encoderless control method are validated by simulation results for all operation conditions. Moreover, the performance of the MRAS observer is tested under variations of the DFIG parameters.

  15. The vertical distribution of selected trace metals and organic compounds in bottom materials of the proposed lower Columbia River export channel, Oregon, 1984

    USGS Publications Warehouse

    Fuhrer, Gregory J.; Horowitz, Arthur J.

    1989-01-01

    A proposal to deepen the lower Columbia River navigation channel in Oregon prompted a study of the vertical distribution of selected trace metals and organic compounds in bottom sediments. These data are needed to evaluate the effects of dredging and disposal operations. Elutriation testing of bottom material indicated chemical concentrations as large as 900 ug/L for barium, 6,500 ug/L for manganese, and 14 ug/L for nickel. The amount of oxygen present during elutriation testing of reduced bottom material was shown to have a negligble effect on manganese elutriate-test concentrations, but it did affect barium and iron concentrations. Sediment-associated organochlorine compounds detected in bottom-sediment core samples were as large as 0.1 ug/kg (micrograms/kilogram) for aldrin, 2.0 ug/kg for chlordane, 27 ug/kg for DDD, 5.0 ug/kg for DDE, 0.2 ug/kg for DDT, 0.2 ug/kg for dieldrin, 37 ug/kg for PCB 's 1.0 ug/kg for PCN 's and 1.0 ug/kg for heptachlor epoxide. Concentrations of cadmium, lead, and zinc in selected cores were found to exceed those of local basalts. Concentrations of cadmium, lead, and zinc were as large as 3.6 ug/g, 26 ug/g, and 210 ug/g respectively. Bottom-sediment concentrations of cadmium , chromium, copper, iron, and zinc associated with the less-than-100-micrometer size fraction are larger than those associated with the greater-than-100-micrometer fraction. (USGS)

  16. Cotton plasma membrane intrinsic protein 2s (PIP2s) selectively interact to regulate their water channel activities and are required for fibre development.

    PubMed

    Li, Deng-Di; Ruan, Xiang-Mei; Zhang, Jie; Wu, Ya-Jie; Wang, Xiu-Lan; Li, Xue-Bao

    2013-08-01

    Aquaporins are thought to be associated with water transport and play important roles in cotton (Gossypium hirsutum) fibre elongation. Among aquaporins, plasma membrane intrinsic proteins (PIPs) constitute a plasma-membrane-specific subfamily and are further subdivided into PIP1 and PIP2 groups. In this study, four fibre-preferential GhPIP2 genes were functionally characterized. The selective interactions among GhPIP2s and their interaction proteins were studied in detail to elucidate the molecular mechanism of cotton fibre development. GhPIP2;3 interacted with GhPIP2;4 and GhPIP2;6, but GhPIP2;6 did not interact with GhPIP2;4. Coexpression of GhPIP2;3/2;4 or GhPIP2;3/2;6 resulted in a positive cooperative effect which increased the permeability coefficient of oocytes, while GhPIP2;4/2;6 did not. GhBCP2 (a blue copper-binding protein) inhibited GhPIP2;6 water channel activity through their interaction. Overexpression of GhPIP2 genes in yeast induced longitudinal growth of the host cells. By contrast, knockdown of expression of GhPIP2 genes in cotton by RNA interference markedly hindered fibre elongation. In conclusion, GhPIP2 proteins are the primary aquaporin isoforms in fibres. They selectively form hetero-oligomers in order to regulate their activities to meet the requirements for rapid fibre elongation.

  17. Identification of mud crab reovirus VP12 and its interaction with the voltage-dependent anion-selective channel protein of mud crab Scylla paramamosain.

    PubMed

    Xu, Hai-Dong; Su, Hong-Jun; Zou, Wei-Bin; Liu, Shan-Shan; Yan, Wen-Rui; Wang, Qian-Qian; Yuan, Li-Li; Chan, Siuming Francis; Yu, Xiao-Qiang; He, Jian-Guo; Weng, Shao-Ping

    2015-05-01

    Mud crab reovirus (MCRV) is the causative agent of a severe disease in cultured mud crab (Scylla paramamosain), which has caused huge economic losses in China. MCRV is a double-stranded RNA virus with 12 genomic segments. In this paper, SDS-PAGE, mass spectrometry and Western blot analyses revealed that the VP12 protein encoded by S12 gene is a structural protein of MCRV. Immune electron microscopy assay indicated that MCRV VP12 is a component of MCRV outer shell capsid. Yeast two hybrid cDNA library of mud crab was constructed and mud crab voltage-dependent anion-selective channel (mcVDAC) was obtained by MCRV VP12 screening. The full length of mcVDAC was 1180 bp with an open reading frame (ORF) of 849 bp encoding a 282 amino acid protein. The mcVDAC had a constitutive expression pattern in different tissues of mud crab. The interaction between MCRV VP12 and mcVDAC was determined by co-immunoprecipitation assay. The results of this study have provided an insight on the mechanisms of MCRV infection and the interactions between the virus and mud crab.

  18. Performance of Reverse-Link Synchronous DS-CDMA System on a Frequency-Selective Multipath Fading Channel with Imperfect Power Control

    NASA Astrophysics Data System (ADS)

    Hwang, Seung-Hoon; Kim, Duk Kyung

    2002-12-01

    We analyze the performance for reverse-link synchronous DS-CDMA system in a frequency-selective Rayleigh fading channel with an imperfect power control scheme. The performance degradation due to power control error (PCE), which is approximated by a log-normally distributed random variable, is estimated as a function of the standard deviation of the PCE. In addition, we investigate the impacts of the multipath intensity profile (MIP) shape and the number of resolvable paths on the performance. Finally, the coded bit error performance is evaluated in order to estimate the system capacity. Comparing with the conventional CDMA system, we show an achievable gain of from 59% to 23% for reverse-link synchronous transmission technique (RLSTT) in the presence of imperfect power control over asynchronous transmission for[InlineEquation not available: see fulltext.]. As well, the effect of tradeoff between orthogonality and diversity can be seen according to the number of multipaths, and the tendency is kept even in the presence of PCE. We conclude that the capacity can be further improved via the RLSTT, because the DS-CDMA system is very sensitive to power control imperfections.

  19. Structure and orientation of two voltage-dependent anion-selective channel isoforms. An attenuated total reflection fourier-transform infrared spectroscopy study.

    PubMed

    Abrecht, H; Goormaghtigh, E; Ruysschaert, J M; Homble, F

    2000-12-29

    Two VDAC (voltage-dependent anion-selective channel) isoforms were purified from seed cotyledons of Phaseolus vulgaris by chromatofocusing chromatography. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy was used to study the structural properties of the two isoforms reconstituted in a mixture of asolectin and 5% stigmasterol. The IR spectra of the two VDAC isoforms were highly similar indicating 50 to 53% anti-parallel beta-sheet. The orientation of the beta-strands relative to the barrel axis was calculated from the experimentally obtained dichroic ratios of the amide I beta-sheet component and the amide II band. Comparing the IR spectra of the reconstituted VDAC isoforms with the IR spectra of the bacterial porin OmpF, for which a high resolution structure is available, provided evidence for a general structural organization of the VDAC isoforms similar to that of bacterial porins. Hydrogen-deuterium exchange measurements indicated that the exchange of the amide protons occurs to a higher extent in the two VDAC isoforms than in the OmpF porin.

  20. Pharmacophore mapping based inhibitor selection and molecular interaction studies for identification of potential drugs on calcium activated potassium channel blockers, tamulotoxin

    PubMed Central

    Kumar, R. Barani; Suresh, M. Xavier

    2013-01-01

    Background: Tamulotoxin (TmTx) from Buthus tamulus was found to be a highly venomous toxin which accelerates the neurotransmitter release that directly affects the cardiovascular tissues and the respiratory system leading to death. TmTx from red Indian scorpion is a crucial inhibitor for Ca2+ activated K+ channel in humans. Objective: The study is aimed at the identification of potential inhibitors of TmTx through pharmacophore based inhibitor screening and understanding the molecular level interactions. Materials and Method: The potential inhibitors for TmTx were identified using pharmacophore model based descriptor information present in existing drugs with the analysis of pharmacokinetic properties. The compounds with good ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) descriptors were subjected to molecular interaction studies. The stability of bound toxin-inhibitor complex was studied using molecular dynamics simulation over a period of one nanosecond. Results: From a dataset of 3406 compounds, few compounds were selected as potential inhibitors based on the generated best pharmacophore models, pharmacokinetic analysis, molecular docking and molecular dynamics studies. Conclusion: In conclusion, two compounds containing better inhibition properties against TmTx are suggested to be better lead molecules for drug development in future and this study will help us to explore more inhibitors from natural origin against tamulotoxin. PMID:23772102

  1. Simultaneous marginal survival estimators when doubly censored data is present.

    PubMed

    Julià, Olga; Gómez, Guadalupe

    2011-07-01

    A doubly censoring scheme occurs when the lifetimes T being measured,from a well-known time origin, are exactly observed within a window [L, R] of observational time and are otherwise censored either from above (right-censored observations)or below (left-censored observations). Sample data consists on the pairs (U, δ)where U = min{R, max{T, L}} and δ indicates whether T is exactly observed (δ = 0),right-censored (δ = 1) or left-censored (δ = −1). We are interested in the estimation of the marginal behaviour of the three random variables T, L and R based on the observed pairs (U, δ).We propose new nonparametric simultaneous marginal estimators Ŝ(T) , Ŝ(L) and Ŝ(R) for the survival functions of T, L and R, respectively, by means of an inverse-probability-of-censoring approach. The proposed estimators Ŝ(T) , Ŝ(L) and Ŝ(R) are not computationally intensive, generalize the empirical survival estimator and reduce to the Kaplan-Meier estimator in the absence of left-censored data. Furthermore,Ŝ(T) is equivalent to a self-consistent estimator, is uniformly strongly consistent and asymptotically normal. The method is illustrated with data from a cohort of drug users recruited in a detoxification program in Badalona (Spain). For these data we estimate the survival function for the elapsed time from starting IV-drugs to AIDS diagnosis, as well as the potential follow-up time. A simulation study is discussed to assess the performance of the three survival estimators for moderate sample sizes and different censoring levels.

  2. The Torsional Spectrum of Doubly Deuterated Methanol CHD_2OH

    NASA Astrophysics Data System (ADS)

    Ndao, M.; Coudert, L. H.; Kwabia Tchana, F.; Barros, J.; Margulès, L.; Manceron, Laurent; Roy, P.

    2014-06-01

    Although the torsional spectrum of several isotopic species of methanol with a symmetrical CH_3 or CD_3 was analyzed some time ago, it is recently, and only for the monodeuterated species CH_2DOH, that such an analysis was extended to the case of an asymmetrical methyl group. In this talk, based on a Fourier transform high-resolution spectrum recorded in the 20 to 670 wn region, the first analysis of the torsional spectrum of doubly deuterated methanol CHD_2OH will be presented. The Q branch of many torsional subbands could be observed and their assignment was initiated using a theoretical torsion-rotation spectrum computed with an approach accounting for the torsion-rotation Coriolis coupling and for the dependence of the generalized inertia tensor on the angle of internal rotation. 46 torsional subbands were thus assigned. For 28 of them, their rotational structure could be assigned and fitted using an effective Hamiltonian expressed as a J(J+1) expansion; and for 2 of them microwave transitions within the lower torsional level could also be included in the analysis. In several cases these analysis revealed that the torsional levels are strongly perturbed. In the talk, the torsional parameters retrieved in the analysis of the torsional subband centers will be discussed. The results of the analysis of the rotational structure of the torsional subbands will be presented and we will also try to understand the nature of the perturbations. At last, preliminary results about the analysis of the microwave spectrum will be presented. El Hilali, Coudert, Konov, and Klee, J. Chem. Phys. 135 (2011) 194309 Lauvergnat, Coudert, Klee, and Smirnov, J. Mol. Spectrosc. 256 (2009) 204 Quade, Liu, Mukhopadhyay, and Su, J. Mol. Spectrosc. 192 (1998) 378 Pearson, Yu, and Drouin, J. Mol. Spectrosc. 280 (2012) 119

  3. Comparison of doubly labeled water with respirometry at low- and high-activity levels

    SciTech Connect

    Westerterp, K.R.; Brouns, F.; Saris, W.H.; ten Hoor, F.

    1988-07-01

    In previous studies the doubly labeled water method for measuring energy expenditure in free-living humans has been validated against respirometry under sedentary conditions. In the present investigation, energy expenditure is measured simultaneously with doubly labeled water and respirometry at low- and high-activity levels. Over 6 days, five subjects were measured doing mainly sedentary activities like desk work; their average daily metabolic rate was 1.40 +/- 0.09 (SD) times sleeping metabolic rate. Four subjects were measured twice over 3.5 days, including 2 days with heavy bicycle ergometer work, resulting in an average daily metabolic rate of 2.61 +/- 0.25 (SD) times sleeping metabolic rate. At the low-activity level, energy expenditures from the doubly labeled water method were on the average 1.4 +/- 3.9% (SD) larger than those from respirometry. At the high-activity level, the doubly labeled water method yielded values that were 1.0 +/- 7.0% (SD) lower than those from respirometry. Results demonstrate the utility of the doubly labeled water method for the determination of energy expenditure in the range of activity levels in daily life.

  4. The Doubly Labeled Water Method for Measuring Human Energy Expenditure: Adaptations for Spaceflight

    NASA Technical Reports Server (NTRS)

    Schulz, Leslie O.

    1991-01-01

    It is essential to determine human energy requirements in space, and the doubly labeled water method has been identified as the most appropriate means of indirect calorimetry to meet this need. The method employs naturally occurring, stable isotopes of hydrogen (H-2, deuterium) and oxygen (O-18) which, after dosing, mix with body water. The deuterium is lost from the body as water while the O-18 is eliminated as both water and CO2. The difference between the two isotope elimination rates is therefore a measure of CO2 production and hence energy expenditure. Spaceflight will present a unique challenge to the application of the doubly labeled water method. Specifically, interpretation of doubly labeled water results assumes that the natural abundance or 'background' levels of the isotopes remain constant during the measurement interval. To address this issue, an equilibration model will be developed in an ongoing ground-based study. As energy requirements of women matched to counterparts in the Astronauts Corps are being determined by doubly labeled water, the baseline isotope concentration will be changed by consumption of 'simulated Shuttle water' which is artificially enriched. One group of subjects will be equilibrated on simulated Shuttle water prior to energy determinations by doubly labeled water while the others will consume simulated Shuttle water after dosing. This process will allow us to derive a prediction equation to mathematically model the effect of changing background isotope concentrations.

  5. Nanomolar potency and selectivity of a Ca2+ release-activated Ca2+ channel inhibitor against store-operated Ca2+ entry and migration of vascular smooth muscle cells

    PubMed Central

    Li, Jing; McKeown, Lynn; Ojelabi, Ogooluwa; Stacey, Martin; Foster, Richard; O'Regan, David; Porter, Karen E; Beech, David J

    2011-01-01

    BACKGROUND AND PURPOSE The aim was to advance the understanding of Orai proteins and identify a specific inhibitor of the associated calcium entry mechanism in vascular smooth muscle cells (VSMCs). EXPERIMENTAL APPROACH Proliferating VSMCs were cultured from human saphenous veins. Intracellular calcium was measured using fura-2, whole-cell current was recorded using patch-clamp and cell migration quantified in modified Boyden chambers. Subcellular protein localization was determined by microscopy. Isometric tension was recorded from mouse aortic rings. KEY RESULTS Molecular disruption and rescue experiments indicated the importance of Orai1 in calcium entry caused by store depletion evoked passively or by platelet-derived growth factor (PDGF), suggesting the presence of Ca2+ release-activated Ca2+ (CRAC) channels like those of the immune system. The CRAC channel blocker, S66, was a potent inhibitor of the VSMC signals, IC50 26 nM, which was almost two orders of magnitude greater than with leucocytes. S66 had no effect on PDGF- and ATP-evoked calcium release, overexpressed transient receptor potential canonical (TRPC)5 channels, native TRPC1/5-containing channels, stromal interaction molecule 1 clustering, non-selective cationic current evoked by store depletion and phenylephrine-evoked aortic contraction. S66 reduced PDGF-evoked VSMC migration while having only modest effects on cell proliferation and no effect on cell viability. CONCLUSIONS AND IMPLICATIONS The data suggest that Orai1 has a role in human VSMC migration, and that a CRAC channel inhibitor has high potency and selectivity for the associated calcium entry, suggesting a distinct characteristic of vascular CRAC channels and the potential for selective chemical suppression of vascular remodelling. PMID:21545575

  6. Continuum model for chiral induced spin selectivity in helical molecules

    SciTech Connect

    Medina, Ernesto; González-Arraga, Luis A.; Finkelstein-Shapiro, Daniel; Mujica, Vladimiro; Berche, Bertrand

    2015-05-21

    A minimal model is exactly solved for electron spin transport on a helix. Electron transport is assumed to be supported by well oriented p{sub z} type orbitals on base molecules forming a staircase of definite chirality. In a tight binding interpretation, the spin-orbit coupling (SOC) opens up an effective π{sub z} − π{sub z} coupling via interbase p{sub x,y} − p{sub z} hopping, introducing spin coupled transport. The resulting continuum model spectrum shows two Kramers doublet transport channels with a gap proportional to the SOC. Each doubly degenerate channel satisfies time reversal symmetry; nevertheless, a bias chooses a transport direction and thus selects for spin orientation. The model predicts (i) which spin orientation is selected depending on chirality and bias, (ii) changes in spin preference as a function of input Fermi level and (iii) back-scattering suppression protected by the SO gap. We compute the spin current with a definite helicity and find it to be proportional to the torsion of the chiral structure and the non-adiabatic Aharonov-Anandan phase. To describe room temperature transport, we assume that the total transmission is the result of a product of coherent steps.

  7. The dependence of Ag+ block of a potassium channel, murine kir2.1, on a cysteine residue in the selectivity filter.

    PubMed

    Dart, C; Leyland, M L; Barrett-Jolley, R; Shelton, P A; Spencer, P J; Conley, E C; Sutcliffe, M J; Stanfield, P R

    1998-08-15

    Externally applied Ag+ (100-200 nM) irreversibly blocked the strong inwardly rectifying K+ channel, Kir2.1. Mutation to serine of a cysteine residue at position 149 in the pore-forming H5 region of Kir2.1 abolished Ag+ blockage. To determine how many of the binding sites must be occupied by Ag+ before the channel is blocked, we measured the rate of channel block and found that our results were best fitted assuming that only one Ag+ ion need bind to eliminate channel current. We tested our hypothesis further by constructing covalently linked dimers and tetramers of Kir2.1 in which cysteine had been replaced by serine in one (dimer) or three (tetramer) of the linked subunits. When expressed, these constructs yielded functional channels with either two (dimer) or one (tetramer) cysteines per channel at position 149. Blockage in the tetramer was complete after sufficient exposure to 200 nM Ag+, a result that is also consistent with only one Ag+ being required to bind to Cys149 to block fully. The rate of development of blockage was 16 times slower than in wild-type channels; the rate was 4 times slower in channels formed from dimers.

  8. (ggr, 2ggr) studies on doubly excited states of molecular hydrogen

    NASA Astrophysics Data System (ADS)

    Odagiri, Takeshi; Murata, Makoto; Kato, Masahiro; Kouchi, Noriyuki

    2004-10-01

    The doubly differential cross sections for the emission of two Lyman-agr photons in photoexcitation of H2 have been measured as a function of incident photon energy in the range of 30-44 eV with a photon-photon coincidence technique. A cross section curve that is free from ionization and thus is attributed entirely to the doubly excited states of H2 has been obtained for the first time. A simple theoretical calculation based on the reflection approximation and semiclassical treatment of the decay dynamics in the Q21Pgru(1) state of H2 has reproduced well the experimental cross section curve. It has been shown that this method, the (ggr, 2ggr) method, is an excellent tool for investigating spectroscopy and dynamics of doubly or multiply excited molecules.

  9. Three-loop neutrino mass model with doubly charged particles from isodoublets

    NASA Astrophysics Data System (ADS)

    Okada, Hiroshi; Yagyu, Kei

    2016-01-01

    We propose a new type of a three-loop induced neutrino mass model with dark matter candidates which are required for the neutrino mass generation. The smallness of neutrino masses can be naturally explained without introducing super heavy particles, namely, much heavier than a TeV scale and quite small couplings as compared to the gauge couplings. We find that as a bonus, the anomaly of the muon anomalous magnetic moment can simultaneously be explained by loop effects of new particles. In our model, there are doubly charged scalar bosons and leptons from isospin doublet fields which give characteristic collider signatures. In particular, the doubly charged scalar bosons can decay into the same-sign dilepton with its chirality of both right-handed or left- and right-handed. This can be a smoking gun signature to identify our model and be useful to distinguish other models with doubly charged scalar bosons at collider experiments.

  10. Model of the anisotropic behavior of doubly oriented and non-oriented materials using coenergy: Application to a large generator

    SciTech Connect

    Mekhiche, M.; Pera, T.; Marechal, Y.

    1995-05-01

    The anisotropic and nonlinear behavior of doubly oriented and non-oriented sheets are modeled using the coenergy density. These models have been implemented in a finite element computation. A large generator has been modeled and the advantages of doubly oriented sheets compared to the conventional non-oriented ones are shown.

  11. Dynamic stability of a doubly quantized vortex in a three-dimensional condensate

    SciTech Connect

    Lundh, Emil; Nilsen, Halvor M.

    2006-12-15

    The Bogoliubov equations are solved for a three-dimensional Bose-Einstein condensate containing a doubly quantized vortex, trapped in a harmonic potential. Complex frequencies, signifying dynamical instability, are found for certain ranges of parameter values. The existence of alternating windows of stability and instability, respectively, is explained qualitatively and quantitatively using variational calculus and direct numerical solutions. It is seen that the windows of stability disappear in the limit of a cigar-shaped condensate, which is consistent with recent experimental results on the lifetime of a doubly quantized vortex in that regime.

  12. Permeation in potassium channels: implications for channel structure.

    PubMed

    Yellen, G

    1987-01-01

    The SR K+ channel is a single-ion channel with a tunnel that is not very selective, while the DR and CaK channels are both more selective, multi-ion channels. The permeation mechanisms of the three channels are probably most systematically distinguished by the length of their tunnels; the SR has the shortest and the DR the longest. Although different in their mechanisms of activation, the DR and CaK channels have very similar permeation characteristics, down to the details of selectivity and blockade. The longer tunnel and reduced conductance (perhaps a result of the extra tunnel length) of the DR K+ channel are the main differences. The selectivity of the rate-limiting barriers and the binding sites within the channels, however, are strikingly similar. A successful potassium channel must satisfy two criteria: It must let potassium ions through and not much else, and it must let many potassium ions through. To be selective the channel must have a narrow selectivity filter, so that an ion must shed some of its waters of hydration to pass through. Sodium ions are excluded because they are more reluctant to lose their water, and they are not adequately compensated for this loss by interaction with the selectivity filter. To carry a large current the narrow region must be short, with wide antechambers to reduce the diffusional access resistance (48). Energetically, the channel must strike a balance. There must be enough binding energy to compensate the ions for their lost hydration energy, so that the energy barrier to permeation is small. If the channel binds the ion too tightly, however, the ion will not be able to exit, and the current will be small. Some of the shared properties of different potassium channels are probably consequences of these requirements; others may be incidental to function, suggesting a common origin. Barium ions have almost exactly the same radius as potassium ions but twice the charge, so it is perhaps not surprising that barium can block

  13. A selective blocker of Kv1.2 and Kv1.3 potassium channels from the venom of the scorpion Centruroides suffusus suffusus.

    PubMed

    Corzo, Gerardo; Papp, Ferenc; Varga, Zoltan; Barraza, Omar; Espino-Solis, Pavel G; Rodríguez de la Vega, Ricardo C; Gaspar, Rezso; Panyi, Gyorgy; Possani, Lourival D

    2008-10-30

    A novel potassium channel blocker peptide was purified from the venom of the scorpion Centruroides suffusus suffusus by high-performance liquid chromatography and its amino acid sequence was completed by Edman degradation and mass spectrometry analysis. It contains 38 amino acid residues with a molecular weight of 4000.3Da, tightly folded by three disulfide bridges. This peptide, named Css20, was shown to block preferentially the currents of the voltage-dependent K+-channels Kv1.2 and Kv1.3. It did not affect several other ion channels tested at 10 nM concentration. Concentration-response curves of Css20 yielded an IC50 of 1.3 and 7.2 nM for Kv1.2- and Kv1.3-channels, respectively. Interestingly, despite the similar affinities for the two channels the association and dissociation rates of the toxin were much slower for Kv1.2, implying that different interactions may be involved in binding to the two channel types; an implication further supported by in silico docking analyses. Based on the primary structure of Css20, the systematic nomenclature proposed for this toxin is alpha-KTx 2.13.

  14. Search for doubly Cabibbo suppressed decays of the charged D meson

    SciTech Connect

    Labs, J.F.

    1992-03-01

    The doubly Cabibbo suppressed decayed D{sup +} {yields} K{sup +}{pi}{sup {minus}}{pi}{sup +}, D{sup +} {yields} K{sup +}{pi}{sup 0}and D{sup +} {yields} K*{sup +}{pi}{sup 0} are searched for in a 9.56 pb{sup {minus}1} data sample of e{sup +}e{sup {minus}} annihilation events collected near the {psi}(3770) resonance with the Mark 3 detector at the SPEAR storage ring, at the Stanford Linear Accelerator Center. These rare weak decays are naively expected at a rate of tan{sup 4}{theta}{sub c} relative to corresponding Cabibbo allowed decays. In the context of presently accepted models of hadronic weak decays, however, they are anticipated to be enhanced, making their experimental detection feasible in the Mark 3 data set. The experimentally simplest decay channel D{sup +} {yields} K{sup +}{pi}{sup {minus}}{pi}{sup +} is searched for inclusively through conventional analysis techniques. A signal of approximately 2.5 {sigma} significance is obtained. An independent analysis is performed to establish examples of this decay of D{sup +} {yields} K{sup +}{pi}{sup 0} and K*{sup +}{pi}{sup 0} by full reconstruction of D{sup +}D{sup {minus}} events. Exploiting the two body kinematics of {psi}(3770) {yields} D{bar D}, this second approach obtains significantly smaller backgrounds than the inclusive study. Consistent with the inclusive results, three D{sup +} {yields} K{sup +}{pi}{sup {minus}}{pi}{sup +} candidate events are observed. No events are observed for either D{sup +} {yields} K{sup +}{pi}{sup 0} or K*{sup +}{pi}{sup 0}. The branching fraction for D{sup +} {yields} K{sup +}{pi}{sup {minus}}{pi}{sup +} is measured, and limits are established on the branching fractions for D{sup +} {yields} K{sup +}{pi}{sup 0} and K*{sup +}{pi}{sup 0}. These results are used to confront the theoretical predictions from models of the weak hadronic decays of charmed mesons.

  15. Ion channel regulation by phosphoinositides analyzed with VSPs-PI(4,5)P2 affinity, phosphoinositide selectivity, and PI(4,5)P2 pool accessibility.

    PubMed

    Rjasanow, Alexandra; Leitner, Michael G; Thallmair, Veronika; Halaszovich, Christian R; Oliver, Dominik

    2015-01-01

    The activity of many proteins depends on the phosphoinositide (PI) content of the membrane. E.g., dynamic changes of the concentration of PI(4,5)P2 are cellular signals that regulate ion channels. The susceptibility of a channel to such dynamics depends on its affinity for PI(4,5)P2. Yet, measuring affinities for endogenous PIs has not been possible directly, but has relied largely on the response to soluble analogs, which may not quantitatively reflect binding to native lipids. Voltage-sensitive phosphatases (VSPs) turn over PI(4,5)P2 to PI(4)P when activated by depolarization. In combination with voltage-clamp electrophysiology VSPs are useful tools for rapid and reversible depletion of PI(4,5)P2. Because cellular PI(4,5)P2 is resynthesized rapidly, steady state PI(4,5)P2 changes with the degree of VSP activation and thus depends on membrane potential. Here we show that titration of endogenous PI(4,5)P2 with Ci-VSP allows for the quantification of relative PI(4,5)P2 affinities of ion channels. The sensitivity of inward rectifier and voltage-gated K(+) channels to Ci-VSP allowed for comparison of PI(4,5)P2 affinities within and across channel subfamilies and detected changes of affinity in mutant channels. The results also reveal that VSPs are useful only for PI effectors with high binding specificity among PI isoforms, because PI(4,5)P2 depletion occurs at constant overall PI level. Thus, Kir6.2, a channel activated by PI(4,5)P2 and PI(4)P was insensitive to VSP. Surprisingly, despite comparable PI(4,5)P2 affinity as determined by Ci-VSP, the Kv7 and Kir channel families strongly differed in their sensitivity to receptor-mediated depletion of PI(4,5)P2. While Kv7 members were highly sensitive to activation of PLC by Gq-coupled receptors, Kir channels were insensitive even when PI(4,5)P2 affinity was lowered by mutation. We hypothesize that different channels may be associated with distinct pools of PI(4,5)P2 that differ in their accessibility to PLC and VSPs.

  16. Ion channel regulation by phosphoinositides analyzed with VSPs—PI(4,5)P2 affinity, phosphoinositide selectivity, and PI(4,5)P2 pool accessibility

    PubMed Central

    Rjasanow, Alexandra; Leitner, Michael G.; Thallmair, Veronika; Halaszovich, Christian R.; Oliver, Dominik

    2015-01-01

    The activity of many proteins depends on the phosphoinositide (PI) content of the membrane. E.g., dynamic changes of the concentration of PI(4,5)P2 are cellular signals that regulate ion channels. The susceptibility of a channel to such dynamics depends on its affinity for PI(4,5)P2. Yet, measuring affinities for endogenous PIs has not been possible directly, but has relied largely on the response to soluble analogs, which may not quantitatively reflect binding to native lipids. Voltage-sensitive phosphatases (VSPs) turn over PI(4,5)P2 to PI(4)P when activated by depolarization. In combination with voltage-clamp electrophysiology VSPs are useful tools for rapid and reversible depletion of PI(4,5)P2. Because cellular PI(4,5)P2 is resynthesized rapidly, steady state PI(4,5)P2 changes with the degree of VSP activation and thus depends on membrane potential. Here we show that titration of endogenous PI(4,5)P2 with Ci-VSP allows for the quantification of relative PI(4,5)P2 affinities of ion channels. The sensitivity of inward rectifier and voltage-gated K+ channels to Ci-VSP allowed for comparison of PI(4,5)P2 affinities within and across channel subfamilies and detected changes of affinity in mutant channels. The results also reveal that VSPs are useful only for PI effectors with high binding specificity among PI isoforms, because PI(4,5)P2 depletion occurs at constant overall PI level. Thus, Kir6.2, a channel activated by PI(4,5)P2 and PI(4)P was insensitive to VSP. Surprisingly, despite comparable PI(4,5)P2 affinity as determined by Ci-VSP, the Kv7 and Kir channel families strongly differed in their sensitivity to receptor-mediated depletion of PI(4,5)P2. While Kv7 members were highly sensitive to activation of PLC by Gq-coupled receptors, Kir channels were insensitive even when PI(4,5)P2 affinity was lowered by mutation. We hypothesize that different channels may be associated with distinct pools of PI(4,5)P2 that differ in their accessibility to PLC and VSPs. PMID

  17. Measuring doubly 13C-substituted ethane by mass spectrometry

    NASA Astrophysics Data System (ADS)

    Clog, M.; Ling, C.; Eiler, J. M.

    2012-12-01

    Ethane (C2H6) is present in non-negligible amounts in most natural gas reservoirs and is used to produce ethylene for petrochemical industries. It is one of the by-products of lipid metabolism and is the arguably simplest molecule that can manifest multiple 13C substitutions. There are several plausible controls on the relative abundances of 13C2H6 in natural gases: thermodynamically controlled homogeneous isotope exchange reactions analogous to those behind carbonate clumped isotope thermometry; inheritance from larger biomolecules that under thermal degradation to produce natural gas; mixing of natural gases that differ markedly in bulk isotopic composition; or combinations of these and/or other, less expected fractionations. There is little basis for predicting which of these will dominate in natural samples. Here, we focus on an analytical techniques that will provide the avenue for exploring these phenomena. The method is based on high-resolution gas source isotope ratio mass spectrometry, using the Thermo 253-Ultra (a new prototype mass spectrometer). This instrument achieves the mass resolution (M/Δ M) up to 27,000, permitting separation of the isobaric interferences of potential contaminants and isotopologues of an analtye or its fragments which share a cardinal mass. We present techniques to analyze several isotopologues of molecular and fragment ions of C2H6. The critical isobaric separations for our purposes include: discrimination of 13C2H6 from 13C12CDH5 at mass 32 and separation of the 13CH3 fragment from 12CH4 at mass 16, both requiring at least a mass resolution of 20000 to make an adequate measurement. Other obvious interferences are either cleanly separated (e.g., O2, O) or accounted for by peak-stripping (CH3OH on mass 32 and NH2 on mass 16). We focus on a set of measurements which constrain: the doubly-substituted isotopologue, 13C2H6, and the 13CH3/12CH3 ratio of the methyl fragment, which constrains the bulk δ 13C. Similar methods can be

  18. New decay studies near the doubly-magic ^78Ni

    NASA Astrophysics Data System (ADS)

    Rykaczewski, Krzysztof

    2008-10-01

    The nucleus ^78Ni, with a closed proton shell at Z=28 and a closed neutron shell at N=50, is the most neutron-rich doubly-magic nucleus identified to date [1,2]. Spectroscopic studies of nuclei around ^78Ni are important for understading both the evolution of nuclear structure in neutron rich matter and the rapid neutron capture nucleosynthesis process. Additionaly, the beta-delayed neutron emission from neutron-rich fission products contributes to the total number of neutrons inducing fission in nuclear fuel and should be accounted for when running power reactors. The neutrons filling the large 1g9/2 shell between N=40 and N=50 impact the spin-orbit splitting of the respective proton orbital pairs, 2p3/2-2p1/2 and 1f7/2-1f5/2. This can trigger a change in the ground-state proton configuration of very neutron rich nuclei above Z=28 [3,4]. Further, the energy difference beetwen the 2d5/2 and 3s1/2 neutron orbitals above N=50 is decreasing when approaching the ^78Ni region possibly resulting in the appearance of a new subshell closure at N=58. Nuclei in the ^78Ni region are produced at the Holifield Radioactive Ion Beam Facility (HRIBF, Oak Ridge National Laboratory) by means of an on-line isotope separation technique using the fission of a ^238U target induced by a 50 MeV, 10 microAmp proton beam. The decay studies performed at the HRIBF profitted from the post-acceleration of mass-separated radioactive beams to about 200 MeV. A novel method, the so-called ranging- out technique, allowed us to separate the most neutron-rich component of the isobaric cocktail beam [5,6]. New results on the decay of A=76 to A=79 Cu isotopes and of A=83 to A=85 Ga isotopes will be presented. In particular, the measured beta-delayed neutron branching ratios for the Cu isotopes are two to four times larger than previously reported [7]. An energy of 247 keV was established for the 3s1/2 neutron state above the 2d5/2 ground- state in the N=51 isotone ^83Ge suggesting the existence of low

  19. Discovery and biological evaluation of 5-aryl-2-furfuramides, potent and selective blockers of the Nav1.8 sodium channel with efficacy in models of neuropathic and inflammatory pain.

    PubMed

    Kort, Michael E; Drizin, Irene; Gregg, Robert J; Scanio, Marc J C; Shi, Lei; Gross, Michael F; Atkinson, Robert N; Johnson, Matthew S; Pacofsky, Gregory J; Thomas, James B; Carroll, William A; Krambis, Michael J; Liu, Dong; Shieh, Char-Chang; Zhang, Xufeng; Hernandez, Gricelda; Mikusa, Joseph P; Zhong, Chengmin; Joshi, Shailen; Honore, Prisca; Roeloffs, Rosemarie; Marsh, Kennan C; Murray, Bernard P; Liu, Jinrong; Werness, Stephen; Faltynek, Connie R; Krafte, Douglas S; Jarvis, Michael F; Chapman, Mark L; Marron, Brian E

    2008-02-14

    Nav1.8 (also known as PN3) is a tetrodotoxin-resistant (TTx-r) voltage-gated sodium channel (VGSC) that is highly expressed on small diameter sensory neurons and has been implicated in the pathophysiology of inflammatory and neuropathic pain. Recent studies using an Nav1.8 antisense oligonucleotide in an animal model of chronic pain indicated that selective blockade of Nav1.8 was analgesic and could provide effective analgesia with a reduction in the adverse events associated with nonselective VGSC blocking therapeutic agents. Herein, we describe the preparation and characterization of a series of 5-substituted 2-furfuramides, which are potent, voltage-dependent blockers (IC50 < 10 nM) of the human Nav1.8 channel. Selected derivatives, such as 7 and 27, also blocked TTx-r sodium currents in rat dorsal root ganglia (DRG) neurons with comparable potency and displayed >100-fold selectivity versus human sodium (Nav1.2, Nav1.5, Nav1.7) and human ether-a-go-go (hERG) channels. Following systemic administration, compounds 7 and 27 dose-dependently reduced neuropathic and inflammatory pain in experimental rodent models. PMID:18176998

  20. NOAA OTEC CWP (National Oceanic and Atmospheric Administration Ocean Thermal Energy Conversion Cold Water Pipe) at-sea test. Volume 3, part 1: Tabulation of the power spectra for selected channels

    NASA Astrophysics Data System (ADS)

    1983-11-01

    Data collected during the Ocean Thermal Energy Conversion (OTEC) Cold Water Pipe At-Sea Test was analyzed. Data presented included: (1)sensor factors and off sets and the data processing algorithms used to convert the recorded sensor measurements from electrical units to engineering units; (2) plots of the power spectra estimates obtained from a fast Fourier transform (FFT) analysis of selected channels; (3) plots of selected sensor measurements as a function of time; and (4) plots of bending strain along the pipe. The mean, root-mean-square (RMS) maximum, and minimum values at each depth are shown in each plot.

  1. Production of doubly heavy-flavored hadrons at e+e- colliders

    NASA Astrophysics Data System (ADS)

    Zheng, Xu-Chang; Chang, Chao-Hsi; Pan, Zan

    2016-02-01

    Production of the doubly heavy-flavored hadrons (Bc meson, doubly heavy baryons Ξc c , Ξb c , Ξb b , their excited states, and antiparticles of them as well) at e+e- colliders is investigated under two different approaches: LO (leading-order QCD complete calculation) and LL (leading-logarithm fragmentation calculation). The results for the production obtained by the LO and LL approaches, including the angle distributions of the produced hadrons with unpolarized and polarized incoming beams, the behaviors on the energy fraction of the produced doubly heavy-flavored hadron, and comparisons of results between the two approaches, are presented in tables and figures. Thus, characteristics of the production and uncertainties of the approaches are shown precisely, and it is concluded that only if the colliders run at the energies around the Z pole (which may be called the Z factories) and the luminosity of the colliders is as high as possible is the study of the doubly heavy-flavored hadrons completely accessible.

  2. The application of value distribution theory to a doubly anharmonic oscillator

    NASA Astrophysics Data System (ADS)

    Hu, Juan; Yu, Guo-Fu

    2011-07-01

    The model of doubly anharmonic oscillators is first transformed into certain periodic second ordinary differential equations. A class of exact solutions for eigenfunctions and eigenvalues is obtained from Bank and Laine's theory on periodic ordinary differential equations, which is expressed in the form of the products of the polynomial and exponential functions when parameters satisfy some special relations.

  3. Periodic orbits in the doubly synchronous binary asteroid systems and their applications in space missions

    NASA Astrophysics Data System (ADS)

    Shang, Haibin; Wu, Xiaoyu; Cui, Pingyuan

    2015-01-01

    This paper investigates the periodic motion of a particle in the doubly synchronous binary asteroid systems. Two typical doubly synchronous systems, 809 Lundia and 3169 Ostro, are discussed in detail. Under the Roche figure assumption, the two bodies of doubly synchronous system can be modeled as two triaxial ellipsoids. The Ivory's theorem is used to derive the gravitational potential of the system. Then, a global numerical method, which combines grid searching and differential correction, is developed for systematically searching periodic orbits in the doubly synchronous systems. A total of 30 and 28 families of periodic orbits around Lundia and Ostro are found, respectively. Furthermore, on the basis of the analysis of morphology, stabilities and invariant manifolds, the potential applications of these periodic orbit families are studied. Several quasi-circular orbit families with low instability index are found to be suitable for the observation of the two typical binary systems. The invariant manifolds of some periodic orbits near the equilibrium points can provide the fuel-free trajectories to achieve the ballistic landing to the surface of the asteroids and transfer between the binary asteroids.

  4. Production of doubly charmed baryons at energy {radical}s=10.58 GeV

    SciTech Connect

    Kiselev, V.V.; Likhoded, A.K.; Shevlyagin, M.V.

    1995-06-01

    The cross section for the production of doubly charmed baryons at a B-factory is estimated on the basis of perturbative QCD calculations of the cross sections for cc-diquark production and of the quark-hadron duality. 14 refs., 2 figs.

  5. An overview of historical channel adjustment and selected hydraulic values in the Lower Sabine and Lower Brazos River Basins, Texas and Louisiana

    USGS Publications Warehouse

    Heitmuller, Franklin T.; Greene, Lauren E.; John D. Gordon, John D.

    2010-01-01

    The Sabine and Brazos are alluvial rivers; alluvial rivers are dynamic systems that adjust their geometry in response to changes in streamflow (discharge) and sediment load. In fluvial geomorphology, the term 'channel adjustment' refers to river channel changes in three geometric dimensions: (1) channel slope (profile); (2) the outline or shape, such as meandering or braided, projected on a horizontal plane (planform); and (3) cross-sectional form (shape). The primary objective of the study was to investigate how the channel morphology of these rivers has changed in response to reservoirs and other anthropogenic disturbances that have altered streamflow and sediment load. The results of this study are expected to aid ecological assessments in the lower Sabine River and lower Brazos River Basins for the Texas Instream Flow Program. Starting in the 1920s, several dams have been constructed on the Sabine and Brazos Rivers and their tributaries, and numerous bridges have been built and sometimes replaced multiple times, which have changed the natural flow regime and reduced or altered sediment loads downstream. Changes in channel geometry over time can reduce channel conveyance and thus streamflow, which can have adverse ecological effects. Channel attributes including cross-section form, channel slope, and planform change were evaluated to learn how each river's morphology changed over many years in response to natural and anthropogenic disturbances. Climate has large influence on the hydrologic regimes of the lower Sabine and lower Brazos River Basins. Equally important as climate in controlling the hydrologic regime of the two river systems are numerous reservoirs that regulate downstream flow releases. The hydrologic regimes of the two rivers and their tributaries reflect the combined influences of climate, flow regulation, and drainage area. Historical and contemporary cross-sectional channel geometries at 15 streamflow-gaging stations in the lower Sabine and

  6. In vitro evaluation of the antimicrobial agent AquaFrin(TM) as a bactericide and selective algicide for use in channel catfish (Ictalurus punctatus) aquaculture

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Producers of pond-raised channel catfish in the southeastern United States can experience huge economic losses due to the bacterial diseases enteric septicemia of catfish (ESC) and columnaris and to the presence of the certain odor-producing cyanobacteria in production ponds that result in “off-flav...

  7. Roughness characteristics of natural channels

    USGS Publications Warehouse

    Barnes, Harry Hawthorne

    1967-01-01

    Color photographs and descriptive data are presented for 50 stream channels for which roughness coefficients have been determined. All hydraulic computations involving flow in open channels require an evaluation of the roughness characteristics of the channel. In the absence of a satisfactory quantitative procedure this evaluation remains chiefly an art. The ability to evaluate roughness coefficients must be developed through experience. One means of gaining this experience is by examining and becoming acquainted with the appearance of some typical channels whose roughness coefficients are known. The photographs and data contained in this report represent a wide range of channel conditions. Familiarity with the appearance, geometry, and roughness characteristics of these channels will improve the engineer's ability to sel