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Sample records for random channel kinetics

  1. Estimation of ion channel kinetics from fluctuations of macroscopic currents.

    PubMed

    Moffatt, Luciano

    2007-07-01

    For single channel recordings, the maximum likelihood estimation (MLE) of kinetic rates and conductance is well established. A direct extrapolation of this method to macroscopic currents is computationally prohibitive: it scales as a power of the number of channels. An approximated MLE that ignored the local time correlation of the data has been shown to provide estimates of the kinetic parameters. In this article, an improved approximated MLE that takes into account the local time correlation is proposed. This method estimates the channel kinetics using both the time course and the random fluctuations of the macroscopic current generated by a homogeneous population of ion channels under white noise. It allows arbitrary kinetic models and stimulation protocols. The application of the proposed algorithm to simulated data from a simple three-state model on nonstationary conditions showed reliable estimates of all the kinetic constants, the conductance and the number of channels, and reliable values for the standard error of those estimates. Compared to the previous approximated MLE, it reduces by a factor of 10 the amount of data needed to secure a given accuracy and it can even determine the kinetic rates in macroscopic stationary conditions.

  2. Estimation of Ion Channel Kinetics from Fluctuations of Macroscopic Currents

    PubMed Central

    Moffatt, Luciano

    2007-01-01

    For single channel recordings, the maximum likelihood estimation (MLE) of kinetic rates and conductance is well established. A direct extrapolation of this method to macroscopic currents is computationally prohibitive: it scales as a power of the number of channels. An approximated MLE that ignored the local time correlation of the data has been shown to provide estimates of the kinetic parameters. In this article, an improved approximated MLE that takes into account the local time correlation is proposed. This method estimates the channel kinetics using both the time course and the random fluctuations of the macroscopic current generated by a homogeneous population of ion channels under white noise. It allows arbitrary kinetic models and stimulation protocols. The application of the proposed algorithm to simulated data from a simple three-state model on nonstationary conditions showed reliable estimates of all the kinetic constants, the conductance and the number of channels, and reliable values for the standard error of those estimates. Compared to the previous approximated MLE, it reduces by a factor of 10 the amount of data needed to secure a given accuracy and it can even determine the kinetic rates in macroscopic stationary conditions. PMID:17416622

  3. Simulating complex ion channel kinetics with IonChannelLab

    PubMed Central

    Covarrubias, Manuel; Sánchez-Rodríguez, Jorge E; Perez-Cornejo, Patricia; Arreola, Jorge

    2010-01-01

    In-silico simulation based on Markov chains is a powerful way to describe and predict the activity of many transport proteins including ion channels. However, modeling and simulation using realistic models of voltage- or ligand-gated ion channels exposed to a wide range of experimental conditions require building complex kinetic schemes and solving complicated differential equations. To circumvent these problems, we developed IonChannelLab a software tool that includes a user-friendly Graphical User Interface and a simulation library. This program supports channels with Ohmic or Goldman-Hodgkin-Katz behavior and can simulate the time-course of ionic and gating currents, single channel behavior and steady-state conditions. The program allows the simulation of experiments where voltage, ligand and ionic concentration are varied independently or simultaneously. PMID:20935453

  4. Wave kinetics of random fibre lasers

    PubMed Central

    Churkin, D V.; Kolokolov, I V.; Podivilov, E V.; Vatnik, I D.; Nikulin, M A.; Vergeles, S S.; Terekhov, I S.; Lebedev, V V.; Falkovich, G.; Babin, S A.; Turitsyn, S K.

    2015-01-01

    Traditional wave kinetics describes the slow evolution of systems with many degrees of freedom to equilibrium via numerous weak non-linear interactions and fails for very important class of dissipative (active) optical systems with cyclic gain and losses, such as lasers with non-linear intracavity dynamics. Here we introduce a conceptually new class of cyclic wave systems, characterized by non-uniform double-scale dynamics with strong periodic changes of the energy spectrum and slow evolution from cycle to cycle to a statistically steady state. Taking a practically important example—random fibre laser—we show that a model describing such a system is close to integrable non-linear Schrödinger equation and needs a new formalism of wave kinetics, developed here. We derive a non-linear kinetic theory of the laser spectrum, generalizing the seminal linear model of Schawlow and Townes. Experimental results agree with our theory. The work has implications for describing kinetics of cyclical systems beyond photonics. PMID:25645177

  5. Kinetic Models with Randomly Perturbed Binary Collisions

    NASA Astrophysics Data System (ADS)

    Bassetti, Federico; Ladelli, Lucia; Toscani, Giuseppe

    2011-02-01

    We introduce a class of Kac-like kinetic equations on the real line, with general random collisional rules which, in some special cases, identify models for granular gases with a background heat bath (Carrillo et al. in Discrete Contin. Dyn. Syst. 24(1):59-81, 2009), and models for wealth redistribution in an agent-based market (Bisi et al. in Commun. Math. Sci. 7:901-916, 2009). Conditions on these collisional rules which guarantee both the existence and uniqueness of equilibrium profiles and their main properties are found. The characterization of these stationary states is of independent interest, since we show that they are stationary solutions of different evolution problems, both in the kinetic theory of rarefied gases (Cercignani et al. in J. Stat. Phys. 105:337-352, 2001; Villani in J. Stat. Phys. 124:781-822, 2006) and in the econophysical context (Bisi et al. in Commun. Math. Sci. 7:901-916, 2009).

  6. Kinetics of gravity-driven water channels under steady rainfall.

    PubMed

    Cejas, Cesare M; Wei, Yuli; Barrois, Remi; Frétigny, Christian; Durian, Douglas J; Dreyfus, Rémi

    2014-10-01

    We investigate the formation of fingered flow in dry granular media under simulated rainfall using a quasi-two-dimensional experimental setup composed of a random close packing of monodisperse glass beads. Using controlled experiments, we analyze the finger instabilities that develop from the wetting front as a function of fundamental granular (particle size) and fluid properties (rainfall, viscosity). These finger instabilities act as precursors for water channels, which serve as outlets for water drainage. We look into the characteristics of the homogeneous wetting front and channel size as well as estimate relevant time scales involved in the instability formation and the velocity of the channel fingertip. We compare our experimental results with that of the well-known prediction developed by Parlange and Hill [D. E. Hill and J. Y. Parlange, Soil Sci. Soc. Am. Proc. 36, 697 (1972)]. This model is based on linear stability analysis of the growth of perturbations arising at the interface between two immiscible fluids. Results show that, in terms of morphology, experiments agree with the proposed model. However, in terms of kinetics we nevertheless account for another term that describes the homogenization of the wetting front. This result shows that the manner we introduce the fluid to a porous medium can also influence the formation of finger instabilities. The results also help us to calculate the ideal flow rate needed for homogeneous distribution of water in the soil and minimization of runoff, given the grain size, fluid density, and fluid viscosity. This could have applications in optimizing use of irrigation water.

  7. Kinetics of gravity-driven water channels under steady rainfall

    NASA Astrophysics Data System (ADS)

    Cejas, Cesare M.; Wei, Yuli; Barrois, Remi; Frétigny, Christian; Durian, Douglas J.; Dreyfus, Rémi

    2014-10-01

    We investigate the formation of fingered flow in dry granular media under simulated rainfall using a quasi-two-dimensional experimental setup composed of a random close packing of monodisperse glass beads. Using controlled experiments, we analyze the finger instabilities that develop from the wetting front as a function of fundamental granular (particle size) and fluid properties (rainfall, viscosity). These finger instabilities act as precursors for water channels, which serve as outlets for water drainage. We look into the characteristics of the homogeneous wetting front and channel size as well as estimate relevant time scales involved in the instability formation and the velocity of the channel fingertip. We compare our experimental results with that of the well-known prediction developed by Parlange and Hill [D. E. Hill and J. Y. Parlange, Soil Sci. Soc. Am. Proc. 36, 697 (1972), 10.2136/sssaj1972.03615995003600050010x]. This model is based on linear stability analysis of the growth of perturbations arising at the interface between two immiscible fluids. Results show that, in terms of morphology, experiments agree with the proposed model. However, in terms of kinetics we nevertheless account for another term that describes the homogenization of the wetting front. This result shows that the manner we introduce the fluid to a porous medium can also influence the formation of finger instabilities. The results also help us to calculate the ideal flow rate needed for homogeneous distribution of water in the soil and minimization of runoff, given the grain size, fluid density, and fluid viscosity. This could have applications in optimizing use of irrigation water.

  8. The Kinetics and the Permeation Properties of Piezo Channels.

    PubMed

    Gnanasambandam, R; Gottlieb, P A; Sachs, F

    2017-01-01

    Piezo channels are eukaryotic, cation-selective mechanosensitive channels (MSCs), which show rapid activation and voltage-dependent inactivation. The kinetics of these channels are largely consistent across multiple cell types and different stimulation paradigms with some minor variability. No accessory subunits that associate with Piezo channels have been reported. They are homotrimers and each ∼300kD monomer has an N-terminal propeller blade-like mechanosensing module, which can confer mechanosensing capabilities on ASIC-1 (the trimeric non-MSC, acid-sensing ion channel-1) and a C-terminal pore module, which influences conductance, selectivity, and channel inactivation. Repeated stimulation can cause domain fracture and diffusion of these channels leading to synchronous loss of inactivation. The reconstituted channels spontaneously open only in asymmetric bilayers but lack inactivation. Mutations that cause hereditary xerocytosis alter PIEZO1 kinetics. The kinetics of the wild-type PIEZO1 and alterations thereof in mutants (M2225R, R2456K, and DhPIEZO1) are summarized in the form of a quantitative model and hosted online. The pore is permeable to alkali ions although Li(+) permeates poorly. Divalent cations, notably Ca(2+), traverse the channel and inhibit the flux of monovalents. The large monovalent organic cations such as tetramethyl ammonium and tetraethyl ammonium can traverse the channel, but slowly, suggesting a pore diameter of ∼8Å, and the estimated in-plane area change upon opening is around 6-20nm(2). Ruthenium red can enter the channel only from the extracellular side and seems to bind in a pocket close to residue 2496. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Emergence of ion channel modal gating from independent subunit kinetics.

    PubMed

    Bicknell, Brendan A; Goodhill, Geoffrey J

    2016-09-06

    Many ion channels exhibit a slow stochastic switching between distinct modes of gating activity. This feature of channel behavior has pronounced implications for the dynamics of ionic currents and the signaling pathways that they regulate. A canonical example is the inositol 1,4,5-trisphosphate receptor (IP3R) channel, whose regulation of intracellular Ca(2+) concentration is essential for numerous cellular processes. However, the underlying biophysical mechanisms that give rise to modal gating in this and most other channels remain unknown. Although ion channels are composed of protein subunits, previous mathematical models of modal gating are coarse grained at the level of whole-channel states, limiting further dialogue between theory and experiment. Here we propose an origin for modal gating, by modeling the kinetics of ligand binding and conformational change in the IP3R at the subunit level. We find good agreement with experimental data over a wide range of ligand concentrations, accounting for equilibrium channel properties, transient responses to changing ligand conditions, and modal gating statistics. We show how this can be understood within a simple analytical framework and confirm our results with stochastic simulations. The model assumes that channel subunits are independent, demonstrating that cooperative binding or concerted conformational changes are not required for modal gating. Moreover, the model embodies a generally applicable principle: If a timescale separation exists in the kinetics of individual subunits, then modal gating can arise as an emergent property of channel behavior.

  10. Emergence of ion channel modal gating from independent subunit kinetics

    PubMed Central

    Bicknell, Brendan A.

    2016-01-01

    Many ion channels exhibit a slow stochastic switching between distinct modes of gating activity. This feature of channel behavior has pronounced implications for the dynamics of ionic currents and the signaling pathways that they regulate. A canonical example is the inositol 1,4,5-trisphosphate receptor (IP3R) channel, whose regulation of intracellular Ca2+ concentration is essential for numerous cellular processes. However, the underlying biophysical mechanisms that give rise to modal gating in this and most other channels remain unknown. Although ion channels are composed of protein subunits, previous mathematical models of modal gating are coarse grained at the level of whole-channel states, limiting further dialogue between theory and experiment. Here we propose an origin for modal gating, by modeling the kinetics of ligand binding and conformational change in the IP3R at the subunit level. We find good agreement with experimental data over a wide range of ligand concentrations, accounting for equilibrium channel properties, transient responses to changing ligand conditions, and modal gating statistics. We show how this can be understood within a simple analytical framework and confirm our results with stochastic simulations. The model assumes that channel subunits are independent, demonstrating that cooperative binding or concerted conformational changes are not required for modal gating. Moreover, the model embodies a generally applicable principle: If a timescale separation exists in the kinetics of individual subunits, then modal gating can arise as an emergent property of channel behavior. PMID:27551100

  11. On the estimation of cooperativity in ion channel kinetics: activation free energy and kinetic mechanism of Shaker K+ channel.

    PubMed

    Banerjee, Kinshuk; Das, Biswajit; Gangopadhyay, Gautam

    2013-04-28

    In this paper, we have explored generic criteria of cooperative behavior in ion channel kinetics treating it on the same footing with multistate receptor-ligand binding in a compact theoretical framework. We have shown that the characterization of cooperativity of ion channels in terms of the Hill coefficient violates the standard Hill criteria defined for allosteric cooperativity of ligand binding. To resolve the issue, an alternative measure of cooperativity is proposed here in terms of the cooperativity index that sets a unified criteria for both the systems. More importantly, for ion channel this index can be very useful to describe the cooperative kinetics as it can be readily determined from the experimentally measured ionic current combined with theoretical modelling. We have analyzed the correlation between the voltage value and slope of the voltage-activation curve at the half-activation point and consequently determined the standard free energy of activation of the ion channel using two well-established mechanisms of cooperativity, namely, Koshland-Nemethy-Filmer (KNF) and Monod-Wyman-Changeux (MWC) models. Comparison of the theoretical results for both the models with appropriate experimental data of mutational perturbation of Shaker K(+) channel supports the experimental fact that the KNF model is more suitable to describe the cooperative behavior of this class of ion channels, whereas the performance of the MWC model is unsatisfactory. We have also estimated the mechanistic performance through standard free energy of channel activation for both the models and proposed a possible functional disadvantage in the MWC scheme.

  12. Electrodiffusion kinetics of ionic transport in a simple membrane channel.

    PubMed

    Valent, Ivan; Petrovič, Pavol; Neogrády, Pavel; Schreiber, Igor; Marek, Miloš

    2013-11-21

    We employ numerical techniques for solving time-dependent full Poisson-Nernst-Planck (PNP) equations in 2D to analyze transient behavior of a simple ion channel subject to a sudden electric potential jump across the membrane (voltage clamp). Calculated spatiotemporal profiles of the ionic concentrations and electric potential show that two principal exponential processes can be distinguished in the electrodiffusion kinetics, in agreement with original Planck's predictions. The initial fast process corresponds to the dielectric relaxation, while the steady state is approached in a second slower exponential process attributed to the nonlinear ionic redistribution. Effects of the model parameters such as the channel length, height of the potential step, boundary concentrations, permittivity of the channel interior, and ionic mobilities on electrodiffusion kinetics are studied. Numerical solutions are used to determine spatiotemporal profiles of the electric field, ionic fluxes, and both the conductive and displacement currents. We demonstrate that the displacement current is a significant transient component of the total electric current through the channel. The presented results provide additional information about the classical voltage-clamp problem and offer further physical insights into the mechanism of electrodiffusion. The used numerical approach can be readily extended to multi-ionic models with a more structured domain geometry in 2D or 3D, and it is directly applicable to other systems, such as synthetic nanopores, nanofluidic channels, and nanopipettes.

  13. Acetylcholine receptor: channel-opening kinetics evaluated by rapid chemical kinetic and single-channel current measurements.

    PubMed Central

    Udgaonkar, J. B.; Hess, G. P.

    1987-01-01

    A combination of rapid chemical kinetic (quench-flow) and single-channel current measurements was used to evaluate kinetic parameters governing the opening of acetylcholine-receptor channels in the electric organ (electroplax) of Electrophorus electricus. Chemical kinetic measurements made on membrane vesicles, prepared from the E. electricus electroplax, using carbamoylcholine (200 microM-20 mM) at 12 degrees C, pH 7.0, and in the absence of a transmembrane voltage, yielded values for K1 (dissociation constant for receptor activation), phi (channel closing equilibrium constant), J (specific reaction rate for ion flux), and alpha max (maximum inactivation rate constant) of 1 mM, 3.4, 4 x 10(7) M-1 s-1, and 12 s-1, respectively. The single-channel current recordings were made with cells also from the E. electricus electroplax, at the same temperature and pH as the chemical kinetic measurements, using carbamoylcholine (50 microM-2 mM), acetylcholine (500 nM), or suberyldicholine (20 nM). Single-channel current measurements indicated the presence of a single, unique open-channel state of the E. electricus receptor, in concurrence with previous, less extensive measurements. The rate constant for channel closing (kc) obtained from the mean open time of the receptor channel is 1,100 s-1 for carbamoylcholine, 1,200 s-1 for acetylcholine, and 360 s-1 for suberyldicholine at zero membrane potential; and it decreases e-fold for an 80 mV decrease in transmembrane voltage in each case. The decrease in mean open times of the receptor channel that is associated with increasing the carbamoylcholine concentration is interpreted to be due to carbamoylcholine binding to the regulatory (inhibitory) site on the receptor. An analysis of data obtained with carbamoylcholine showed that the closed times within a burst of channel activity fit a two-exponential distribution, with a concentration-independent time constant considered to be the time constant for carbamoylcholine to dissociate

  14. Gating Kinetics and Ion Transfer in Channels of Nerve Membrane.

    DTIC Science & Technology

    1987-10-21

    and sea hare ( Aplysia ). In the classical squid axon preparation a detailed comparison between estimates of the relaxation time obtained via Hodgkin...Mrra nr . r -W, ,.r w -. r- _ ,,- Fishman, H.M. N00014-87-K-0055 Inward K Rectifier Channel Kinetics from Analysis of Complex Conductances in Aplysia ...Neuronal Membrane. The inward K rectifier in Aplysia neuron and Ba* blockade of the recti- fication process were studied by rapid measurement of

  15. Dual channel RESOLFT nanoscopy by using fluorescent state kinetics.

    PubMed

    Testa, Ilaria; D'Este, Elisa; Urban, Nicolai T; Balzarotti, Francisco; Hell, Stefan W

    2015-01-14

    We show that RESOLFT fluorescence nanoscopy, a low light level scanning superresolution technique employing reversibly switchable fluorescent proteins (rsFPs), is capable of dual-channel live-cell imaging that is virtually free of chromatic errors and temporal offsets. This is accomplished using rsEGFP and Dronpa, two rsFPs having similar spectra but different kinetics of switching and fluorescence emission. Our approach is demonstrated by imaging protein distributions and dynamics in living neurons and neuronal tissues.

  16. Kinetics of 9-aminoacridine block of single Na channels

    PubMed Central

    1984-01-01

    The kinetics of 9-aminoacridine (9-AA) block of single Na channels in neuroblastoma N1E-115 cells were studied using the gigohm seal, patch clamp technique, under the condition in which the Na current inactivation had been eliminated by treatment with N-bromoacetamide (NBA). Following NBA treatment, the current flowing through individual Na channels was manifested by square-wave open events lasting from several to tens of milliseconds. When 9-AA was applied to the cytoplasmic face of Na channels at concentrations ranging from 30 to 100 microM, it caused repetitive rapid transitions (flickering) between open and blocked states within single openings of Na channels, without affecting the amplitude of the single channel current. The histograms for the duration of blocked states and the histograms for the duration of open states could be fitted with a single-exponential function. The mean open time (tau o) became shorter as the drug concentration was increased, while the mean blocked time (tau b) was concentration independent. The association (blocking) rate constant, kappa, calculated from the slope of the curve relating the reciprocal mean open time to 9-AA concentration, showed little voltage dependence, the rate constant being on the order of 1 X 10(7) M-1s-1. The dissociation (unblocking) rate constant, l, calculated from the mean blocked time, was strongly voltage dependent, the mean rate constant being 214 s-1 at 0 mV and becoming larger as the membrane being hyperpolarized. The voltage dependence suggests that a first-order blocking site is located at least 63% of the way through the membrane field from the cytoplasmic surface. The equilibrium dissociation constant for 9-AA to block the Na channel, defined by the relation of l/kappa, was calculated to be 21 microM at 0 mV. Both tau -1o and tau -1b had a Q10 of 1.3, which suggests that binding reaction was diffusion controlled. The burst time in the presence of 9-AA, which is the sum of open times and blocked

  17. A kinetic model of NMDA ion channel under varying noise

    NASA Astrophysics Data System (ADS)

    Wang, Rubin; Chen, Hao; Zhang, Zhikang

    2004-05-01

    It is well known that when transmitters are applied to the postsynaptic membrane, the resulting depolarization is noisy that is due to the random opening and closing of the ion channels activated by the transmitters[1]. In other words, the energy of noise is associated with changes in ion channels. On the base of these ideas, we explore a model of relationship between NMDA (n-methyl-D-aspartate) ion channels and LTP (long-term synaptic potentiation). We have proved that NMDA ion channel and calcium-dependent protein kinases, which are the triggers for the inducement of LTP, could be regarded as "molecular machines". In this system all of these molecules require energy and the energy of the system is supplied from the random motion of water molecules generated through heat energy of ATP hydrolysis[2]. So the appropriate framework to describe them comes from bioenergetics. Models of LTP previously reported are all on the macroscopic level [3-7]. Instead, we research a model at the molecular level by applying energy parameters [8].

  18. [Kinetics of ligand binding to nucleic acids at random fillings].

    PubMed

    Arakelian, V B; Babaian, S Iu; Tairian, V I; Arakelian, A V; Parsadanian, M A; Vardevanian, P O

    2006-01-01

    Ligand binding with nucleic acids is described in frames of the theory of random processes. It is shown that the probabilistic description of binding of a ligand to nucleic acid allows one to describe not only the kinetics of changes in the number of bound ligands at arbitrary fillings but also to calculate stationary values of the number of bound ligands and its dispersion. A general analysis of absorption isotherms and the kinetics of ligand binding with nucleic acids allows one to determine the rate constants of formation and decomposition of the ligand-nucleic acid complex. A comparison of the results obtained with the case of low fillings is conducted.

  19. Macroscopic kinetics of pentameric ligand gated ion channels: comparisons between two prokaryotic channels and one eukaryotic channel.

    PubMed

    Laha, Kurt T; Ghosh, Borna; Czajkowski, Cynthia

    2013-01-01

    Electrochemical signaling in the brain depends on pentameric ligand-gated ion channels (pLGICs). Recently, crystal structures of prokaryotic pLGIC homologues from Erwinia chrysanthemi (ELIC) and Gloeobacter violaceus (GLIC) in presumed closed and open channel states have been solved, which provide insight into the structural mechanisms underlying channel activation. Although structural studies involving both ELIC and GLIC have become numerous, thorough functional characterizations of these channels are still needed to establish a reliable foundation for comparing kinetic properties. Here, we examined the kinetics of ELIC and GLIC current activation, desensitization, and deactivation and compared them to the GABAA receptor, a prototypic eukaryotic pLGIC. Outside-out patch-clamp recordings were performed with HEK-293T cells expressing ELIC, GLIC, or α1β2γ2L GABAA receptors, and ultra-fast ligand application was used. In response to saturating agonist concentrations, we found both ELIC and GLIC current activation were two to three orders of magnitude slower than GABAA receptor current activation. The prokaryotic channels also had slower current desensitization on a timescale of seconds. ELIC and GLIC current deactivation following 25 s pulses of agonist (cysteamine and pH 4.0 buffer, respectively) were relatively fast with time constants of 24.9 ± 5.1 ms and 1.2 ± 0.2 ms, respectively. Surprisingly, ELIC currents evoked by GABA activated very slowly with a time constant of 1.3 ± 0.3 s and deactivated even slower with a time constant of 4.6 ± 1.2 s. We conclude that the prokaryotic pLGICs undergo similar agonist-mediated gating transitions to open and desensitized states as eukaryotic pLGICs, supporting their use as experimental models. Their uncharacteristic slow activation, slow desensitization and rapid deactivation time courses are likely due to differences in specific structural elements, whose future identification may help uncover mechanisms underlying p

  20. Domain III regulates N-type (CaV2.2) calcium channel closing kinetics

    PubMed Central

    Yarotskyy, Viktor; Gao, Guofeng; Peterson, Blaise Z.

    2012-01-01

    CaV2.2 (N-type) and CaV1.2 (L-type) calcium channels gate differently in response to membrane depolarization, which is critical to the unique physiological functions mediated by these channels. We wondered if the source for these differences could be identified. As a first step, we examined the effect of domain exchange between N-type and L-type channels on activation-deactivation kinetics, which were significantly different between these channels. Kinetic analysis of chimeric channels revealed N-channel-like deactivation for all chimeric channels containing N-channel domain III, while activation appeared to be a more distributed function across domains. This led us to hypothesize that domain III was an important regulator of N-channel closing. This idea was further examined with R-roscovitine, which is a trisubstituted purine that slows N-channel deactivation by exclusively binding to activated N-channels. L-channels lack this response to roscovitine, which allowed us to use N-L chimeras to test the role of domain III in roscovitine modulation of N-channel deactivation. In support of our hypothesis, all chimeric channels containing the N-channel domain III responded to roscovitine with slowed deactivation, while those chimeric channels with L-channel domain III did not. Thus a combination of kinetic and pharmacological evidence supports the hypothesis that domain III is an important regulator of N-channel closing. Our results support specialization of gating functions among calcium channel domains. PMID:22205645

  1. Fractional kinetics emerging from ergodicity breaking in random media

    NASA Astrophysics Data System (ADS)

    Molina-García, Daniel; Pham, Tuan Minh; Paradisi, Paolo; Manzo, Carlo; Pagnini, Gianni

    2016-11-01

    We present a modeling approach for diffusion in a complex medium characterized by a random length scale. The resulting stochastic process shows subdiffusion with a behavior in qualitative agreement with single-particle tracking experiments in living cells, such as ergodicity breaking, p variation, and aging. In particular, this approach recapitulates characteristic features previously described in part by the fractional Brownian motion and in part by the continuous-time random walk. Moreover, for a proper distribution of the length scale, a single parameter controls the ergodic-to-nonergodic transition and, remarkably, also drives the transition of the diffusion equation of the process from nonfractional to fractional, thus demonstrating that fractional kinetics emerges from ergodicity breaking.

  2. Modified kinetics and selectivity of sodium channels in frog skeletal muscle fibers treated with aconitine

    PubMed Central

    1982-01-01

    The effect of the plant alkaloid aconitine on sodium channel kinetics, ionic selectivity, and blockage by protons and tetrodotoxin (TTX) has been studied in frog skeletal muscle. Treatment with 0.25 or 0.3 mM aconitine alters sodium channels so that the threshold of activation is shifted 40-50 mV in the hyperpolarized direction. In contrast to previous results in frog nerve, inactivation is complete for depolarizations beyond about -60 mV. After aconitine treatment, the steady state level of inactivation is shifted approximately 20 mV in the hyperpolarizing direction. Concomitant with changes in channel kinetics, the relative permeability of the sodium channel to NH4,K, and Cs is increased. This altered selectivity is not accompanied by altered block by protons or TTX. The results suggest that sites other than those involved in channel block by protons and TTX are important in determining sodium channel selectivity. PMID:6294221

  3. Helix-Coil Kinetics of Individual Polyadenylic Acid Molecules in a Protein Channel

    NASA Astrophysics Data System (ADS)

    Lin, Jianxun; Kolomeisky, Anatoly; Meller, Amit

    2010-04-01

    Helix-coil transition kinetics of polyadenylic acid [poly(A)] inside a small protein channel is investigated for the first time, at the single molecule level. The confinement of a RNA molecule inside the channel slows its kinetics by nearly 3 orders of magnitude as compared to bulk measurements of free poly(A). These findings are related to the interaction energy of the RNA structure with the interior of the pore, explained by a simple two-state model. These results shed light on the way intermolecular interactions alter nucleic acid kinetics.

  4. Helix-coil kinetics of individual polyadenylic acid molecules in a protein channel.

    PubMed

    Lin, Jianxun; Kolomeisky, Anatoly; Meller, Amit

    2010-04-16

    Helix-coil transition kinetics of polyadenylic acid [poly(A)] inside a small protein channel is investigated for the first time, at the single molecule level. The confinement of a RNA molecule inside the channel slows its kinetics by nearly 3 orders of magnitude as compared to bulk measurements of free poly(A). These findings are related to the interaction energy of the RNA structure with the interior of the pore, explained by a simple two-state model. These results shed light on the way intermolecular interactions alter nucleic acid kinetics.

  5. Kinetics of open channel block by penicillin of single GABAA receptor channels from mouse spinal cord neurones in culture.

    PubMed Central

    Twyman, R E; Green, R M; MacDonald, R L

    1992-01-01

    1. Reduction by penicillin of single gamma-aminobutyric acidA (GABAA) receptor currents from somata of mouse spinal cord neurones in culture was investigated using the excised outside-out patch-clamp recording technique. 2. GABA (2 microM) alone or with penicillin (100-5000 microM) applied by pressure ejection from micropipettes evoked inward currents when patches were voltage-clamped at -75 mV in symmetrical chloride solutions. Averaged GABA receptor currents were decreased in the presence of penicillin. 3. GABA receptor currents were recorded with at least two conductance states, a more frequent or main-conductance state of about 27 pS and a less frequent sub-conductance state of about 19-20 pS. The conductances of the two states were unchanged in the presence of penicillin. The kinetic properties of the main-conductance state were analysed and are summarized below. 4. Penicillin produced a concentration-dependent reduction of GABA receptor open properties by reduction of average GABA receptor channel open duration and an increase in channel opening frequency. 5. Penicillin shifted frequency histograms of GABA receptor channel open durations to shorter durations in a concentration-dependent manner. Three exponential functions were required to fit best the frequency histograms of open durations, suggesting that the channel had at least three open states. Penicillin produced a concentration-dependent reduction in the time constants obtained from the open duration frequency histograms. 6. Frequency histograms of GABA receptor channel closed durations could be fitted with five to seven exponential functions, suggesting that the channel had multiple closed states. In the presence of increased concentration of penicillin, there was a reduction in the relative frequency of brief gaps and the appearance of new closed time constants. 7. With increased penicillin concentration, GABA receptor channel burst frequency was unchanged, burst durations were increased, the number

  6. Tetramerization domain mutations in KCNA5 affect channel kinetics and cause abnormal trafficking patterns

    PubMed Central

    Burg, Elyssa D.; Platoshyn, Oleksandr; Tsigelny, Igor F.; Lozano-Ruiz, Beatriz; Rana, Brinda K.

    2010-01-01

    The activity of voltage-gated K+ (KV) channels plays an important role in regulating pulmonary artery smooth muscle cell (PASMC) contraction, proliferation, and apoptosis. The highly conserved NH2-terminal tetramerization domain (T1) of KV channels is important for proper channel assembly, association with regulatory KV β-subunits, and localization of the channel to the plasma membrane. We recently reported two nonsynonymous mutations (G182R and E211D) in the KCNA5 gene of patients with idiopathic pulmonary arterial hypertension, which localize to the T1 domain of KCNA5. To study the electrophysiological properties and expression patterns of the mutants compared with the wild-type (WT) channel in vitro, we transfected HEK-293 cells with WT KCNA5, G182R, E211D, or the double mutant G182R/E211D channel. The mutants form functional channels; however, whole cell current kinetic differences between WT and mutant channels exist. Steady-state inactivation curves of the G182R and G182R/E211D channels reveal accelerated inactivation; the mutant channels inactivated at more hyperpolarized potentials compared with the WT channel. Channel protein expression was also decreased by the mutations. Compared with the WT channel, which was present in its mature glycosylated form, the mutant channels are present in greater proportion in their immature form in HEK-293 cells. Furthermore, G182R protein level is greatly reduced in COS-1 cells compared with WT. Immunostaining data support the hypothesis that, while WT protein localizes to the plasma membrane, mutant protein is mainly retained in intracellular packets. Overall, these data support a role for the T1 domain in channel kinetics as well as in KCNA5 channel subcellular localization. PMID:20018952

  7. Synaptotagmin restores kinetic properties of a syntaxin-associated N-type voltage sensitive calcium channel.

    PubMed

    Wiser, O; Tobi, D; Trus, M; Atlas, D

    1997-03-10

    The voltage sensitive N-type calcium channel interacts functionally and biochemically with synaptotagmin (p65). N-type channel interaction with p65 is demonstrated in the Xenopus oocyte expression system, where p65 alters the steady state voltage inactivation of the N-channel, and fully restores the syntaxin-modified current amplitude and inactivation kinetics in a calcium dependent manner. In agreement with the functional results, GST-p65 fusion protein binds to a cytosolic region, amino acids 710-1090 of the N-type channel (N-loop(710-1090)). The results of the combined approach provide a functional and biochemical basis for proposing that p65 interaction with the N-type channel brings p65 into a close association with a syntaxin-coupled channel. In turn, calcium entry through the liberated channel initiates fusion of the primed vesicles with the cell membrane at a short distance from the site of calcium entry.

  8. Calcium channel kinetics of melanotrope cells in Xenopus laevis depend on environmental stimulation.

    PubMed

    Zhang, Hongyan; Langeslag, Michiel; Breukels, Vincent; Jenks, Bruce G; Roubos, Eric W; Scheenen, Wim J J M

    2008-03-01

    We have tested the hypothesis that the type and kinetics of voltage-activated Ca(2+) channels in a neuroendocrine cell depend on the cell's long-term external input. For this purpose, the presence and kinetics of both low (LVA) and high-voltage-activated (HVA) L-type Ca(2+) channels have been assessed in melanotrope pituitary cells of the amphibian Xenopus laevis. The secretory activity of this cell type can readily be manipulated in vivo by changing the animal's environmental light condition, from a black to a white background. We here show that, compared to white background-adapted Xenopus, melanotropes from black background-adapted frogs have (1) a much larger size, as revealed by their 2.5 times larger membrane capacitance (P<0.001), (2) a 2 times higher HVA current density (P<0.05), (3) a clearly smaller Ca(2+)-dependent inactivation (10%; P<0.05), (4) L-type channels with 5 times slower activation and inactivation kinetics (P<0.05), and (5) slower kinetics of L-type channels that become faster and more similar to those in white-background adapted cells when the intracellular Ca(2+)-buffering capacity is reduced. Furthermore, white-adapted melanotropes possess LVA-type Ca(2+) channels, which are lacking from cells from black-adapted animals. The melanotrope calmodulin mRNA level does not differ between the two adaptation states. These results indicate that HVA L-type channel kinetics differ in relation to environmentally induced changes in cellular secretory state, probably mediated via intracellular Ca(2+)-buffering, whereas the occurrence of LVA Ca(2+) channels may depend on environmentally controlled channel gene expression.

  9. Kinetics of veratridine action on Na channels of skeletal muscle

    PubMed Central

    Sutro, JB

    1986-01-01

    Veratridine bath-applied to frog muscle makes inactivation of INa incomplete during a depolarizing voltage-clamp pulse and leads to a persistent veratridine-induced Na tail current. During repetitive depolarizations, the size of successive tail currents grows to a plateau and then gradually decreases. When pulsing is stopped, the tail current declines to zero with a time constant of approximately 3 s. Higher rates of stimulation result in a faster build-up of the tail current and a larger maximum value. I propose that veratridine binds only to open channels and, when bound, prevents normal fast inactivation and rapid shutting of the channel on return to rest. Veratridine-modified channels are also subject to a "slow" inactivation during long depolarizations or extended pulse trains. At rest, veratridine unbinds with a time constant of approximately 3 s. Three tests confirm these hypotheses: (a) the time course of the development of veratridine-induced tail currents parallels a running time integral of gNa during the pulse; (b) inactivating prepulses reduce the ability to evoke tails, and the voltage dependence of this reduction parallels the voltage dependence of h infinity; (c) chloramine-T, N-bromoacetamide, and scorpion toxin, agents that decrease inactivation in Na channels, each greatly enhance the tail currents and alter the time course of the appearance of the tails as predicted by the hypothesis. Veratridine-modified channels shut during hyperpolarizations from -90 mV and reopen on repolarization to -90 mV, a process that resembles normal activation gating. Veratridine appears to bind more rapidly during larger depolarizations. PMID:2419478

  10. Plasmonic Nanoholes in a Multi-Channel Microarray Format for Parallel Kinetic Assays and Differential Sensing

    PubMed Central

    Im, Hyungsoon; Lesuffleur, Antoine; Lindquist, Nathan C.; Oh, Sang-Hyun

    2009-01-01

    We present nanohole arrays in a gold film integrated with a 6-channel microfluidic chip for parallel measurements of molecular binding kinetics. Surface plasmon resonance effects in the nanohole arrays enable real-time label-free measurements of molecular binding events in each channel, while adjacent negative reference channels can record measurement artifacts such as bulk solution index changes, temperature variations, or changing light absorption in the liquid. Using this platform, streptavidin-biotin specific binding kinetics are measured at various concentrations with negative controls. A high-density microarray of 252 biosensing pixels is also demonstrated with a packing density of 106 sensing elements/cm2, which can potentially be coupled with a massively parallel array of microfluidic channels for protein microarray applications. PMID:19284776

  11. Blocking kinetics of the anomalous potassium rectifier of tunicate egg studied by single channel recording

    PubMed Central

    Fukushima, Yasuo

    1982-01-01

    1. The kinetics of the anomalous K current produced by blocking cations Na, Cs and Sr were analysed by single channel recording in the tunicate egg cell. 2. The open—close kinetics in a single channel with the presence of blocking cation were consistent with the blocking kinetics of the total anomalous K current. The open—close kinetics in a single anomalous K rectifier channel could be regarded as the first order transition between the open and closed states. 3. The closing rate constants of the single channel for the first order transition increased almost linearly on a semilogarithmic scale as the membrane potential became more negative, while the opening rate constants decreased and then increased, showing the minimum at a certain potential level. The latter indicated that the channel was released from the blocking by excessive hyperpolarization. 4. The opening rate constant increased in spite of the fixed concentration of the blocking cation (10 μM-Cs), when the external K concentration was raised from 200 mM to 400 mM. This result suggested that there are interactions within the channel between the blocking cation and the K ion. 5. When there were two kinds of blocking cations such as Na and Cs, the kinetic properties in a single channel indicated that the two kinds of blocking cations blocked the single channel independently. 6. The single channel conductance of the anomalous K rectifier in 200 mM-Na-containing 200 mM-K solutions was about 1·5 times larger than that in Na-free 200 mM-K solutions. 7. The single channel conductances in 100, 200 and 400 mM-K solution with 10 μM-Cs were 5·0, 7·1 and 12·3 pS respectively, being roughly proportional to the square root of the K concentration. 8. The density of the anomalous K rectifier channel in the tunicate egg cell was 0·039/μm2. 9. The amplitude of the single channel current increased with the rise of temperature, the Q10 being 1·5. PMID:6296368

  12. Kinetics of random sequential adsorption on disordered substrates

    NASA Astrophysics Data System (ADS)

    Lee, Jae Woo

    1996-01-01

    The kinetics of the random sequential adsorption of line segments has been studied on a disordered substrate occupied with point impurities. The coverage of the surface and the jamming limits are calculated by a Monte Carlo method. The coverage 0305-4470/29/1/007/img1 has an asymptotically exponential behaviour at low concentration of the impurities. The jamming limits depend on the concentration of the impurities p. At 0305-4470/29/1/007/img2 the jamming limits decrease as p increases. At 0305-4470/29/1/007/img3 the jamming limits increase as p increases. The one-dimensional results are in good agreement with Ben-Naim and Krapivsky's analytic results. The coverage and the jamming limits on a two-dimensional disordered lattice are similar to the one-dimensional cases. The jamming limits decrease monotonically as the length of line segments increases. The minimum locations of the jamming limits for both one and two dimensions are on the same values for a given length of the k-mer.

  13. Graphs, random sums, and sojourn time distributions, with application to ion-channel modeling.

    PubMed

    Edeson, R O; Yeo, G F; Milne, R K; Madsen, B W

    1990-11-01

    This paper considers the distribution of a sojourn time in a class of states of a stochastic process having finite discrete state space where sojourn times in any individual state are independent and identically distributed, and transitions between states follow a Markov chain. The state space and possible transitions of the process are represented by a graph. Class sojourn time distributions are derived by modifying this graph using 'composition' of states, defining a new Markov chain on the modified graph, and expressing the sojourn time in a composition state as a random sum. Appropriate compositions are chosen according to the possible "cores" of sojourns in the particular class, where a core describes the structure of a sojourn in terms of a single state or a chain in the original graph. Graph methods provide an algorithmic basis for the derivation, which can be simplified by using symmetry results. Models of ion-channel kinetics are used throughout for illustration; class sojourn time distributions are important in such models because individual states are often indistinguishable experimentally. Markov processes are the special case where sojourn times in individual states are exponentially distributed. In this case kinetic parameter estimation based on the observed class sojourn time distribution is briefly discussed; explicit estimating equations applicable to sequential models of nicotinic receptor kinetics are given.

  14. Kinetic Limited Water Evaporation in Hydrophilic Nanofluidic Channels

    NASA Astrophysics Data System (ADS)

    Li, Yinxiao; Alibakhshi, Mohammad Amin; Xie, Quan; Duan, Chuanhua

    2015-11-01

    Capillary evaporation is one of the most efficient approaches for heat and mass transfer, but the interfacial resistance in capillary evaporation governed by the kinetic theory has remained poorly understood. Here we report experimental studies of the kinetic-limited water capillary evaporation in 2-D hydrophilic nanochannels. A novel hybrid nanochannel design is employed to guarantee sufficient water supply to the liquid/vapor evaporation interface and to enable precise evaporation rate measurements. We study the effects of confinement (16 ~ 105nm), temperature (20 ~ 40 °C), and relative humidity (0% ~ 60%) on the evaporation rate and the evaporation coefficient. A maximum evaporation flux of 21287 micron/s is obtained in 16-nm nanochannels at 40°C and RH =0%, which corresponds to a heat flux of 4804 W/cm°. The evaporation coefficient is found to be independent on geometrical confinement, but shows a clear dependence on temperature, decreasing from 0.55 at 20°C to 0.5 at 40 °C. These findings have implications for understanding heat and mass transport in nanofluidic devices and porous media, and shed light on further development of evaporation-based technologies for thermal management, membrane purification and lab-on-a-chip devices. The work is supported by the American Chemical Society Petroleum Research Fund (ACS PRF # 54118-DNI7) and the Faculty Startup Fund (Boston University, USA).

  15. Phenol derivatives accelerate inactivation kinetics in one inactivation-deficient mutant human skeletal muscle Na(+) channel.

    PubMed

    Haeseler, G; Piepenbrink, A; Bufler, J; Dengler, R; Hecker, H; Aronson, J; Piepenbrock, S; Leuwer, M

    2001-03-23

    Altered inactivation kinetics in skeletal muscle Na(+) channels due to mutations in the encoding gene are causal for the alterations in muscle excitability in nondystrophic myotonia. Na(+) channel blockers like lidocaine and mexiletine, suggested for therapy of myotonia, do not reconstitute inactivation in channels with defective inactivation in vitro. We examined the effects of four methylated and/or halogenated phenol derivatives on one heterologously expressed inactivation-deficient Paramyotonia congenita-mutant (R1448H) muscle Na(+) channel in vitro. All these compounds accelerated delayed inactivation of R1448H-whole-cell currents during a depolarization and delayed accelerated recovery from inactivation. The potency of these effects paralleled the potency of the drugs to block the peak current amplitude. We conclude that the investigated phenol derivatives affect inactivation-deficient Na(+) channels more specifically than lidocaine and mexiletine. However, for all compounds, the effect on inactivation was accompanied by a substantial block of the peak current amplitude.

  16. Steady-state kinetics of solitary batrachotoxin-treated sodium channels. Kinetics on a bounded continuum of polymer conformations.

    PubMed Central

    Rubinson, K A

    1992-01-01

    The underlying principles of the kinetics and equilibrium of a solitary sodium channel in the steady state are examined. Both the open and closed kinetics are postulated to result from round-trip excursions from a transition region that separates the openable and closed forms. Exponential behavior of the kinetics can have origins different from small-molecule systems. These differences suggest that the probability density functions (PDFs) that describe the time dependences of the open and closed forms arise from a distribution of rate constants. The distribution is likely to arise from a thermal modulation of the channel structure, and this provides a physical basis for the following three-variable equation: [formula; see text] Here, A0 is a scaling term, k is the mean rate constant, and sigma quantifies the Gaussian spread for the contributions of a range of effective rate constants. The maximum contribution is made by k, with rates faster and slower contributing less. (When sigma, the standard deviation of the spread, goes to zero, then p(f) = A0 e-kt.) The equation is applied to the single-channel steady-state probability density functions for batrachotoxin-treated sodium channels (1986. Keller et al. J. Gen. Physiol. 88: 1-23). The following characteristics are found: (a) The data for both open and closed forms of the channel are fit well with the above equation, which represents a Gaussian distribution of first-order rate processes. (b) The simple relationship [formula; see text] holds for the mean effective rat constants. Or, equivalently stated, the values of P open calculated from the k values closely agree with the P open values found directly from the PDF data. (c) In agreement with the known behavior of voltage-dependent rate constants, the voltage dependences of the mean effective rate constants for the opening and closing of the channel are equal and opposite over the voltage range studied. That is, [formula; see text] "Bursts" are related to the well

  17. Rectified motion in an asymmetrically structured channel due to induced-charge electrokinetic and thermo-kinetic phenomena

    SciTech Connect

    Sugioka, Hideyuki

    2016-02-15

    It would be advantageous to move fluid by the gradient of random thermal noises that are omnipresent in the natural world. To achieve this motion, we propose a rectifier that uses a thermal noise along with induced-charge electroosmosis and electrophoresis (ICEO and ICEP) around a metal post cylinder in an asymmetrically structured channel and numerically examine its rectification performance. By the boundary element method combined with the thin double layer approximation, we find that rectified motion occurs in the asymmetrically structured channel due to ICEO and ICEP. Further, by thermodynamical and equivalent circuit methods, we discuss a thermal voltage that drives a rectifier consisting of a fluidic channel of an electrolyte and an impedance as a noise source. Our calculations show that fluid can be moved in the asymmetrically structured channel by the fluctuation of electric fields due to a thermal noise only when there is a temperature difference. In addition, our simple noise argument provides a different perspective for the thermo-kinetic phenomena (around a metal post) which was predicted based on the electrolyte Seebeck effect in our previous paper [H. Sugioka, “Nonlinear thermokinetic phenomena due to the Seebeck effect,” Langmuir 30, 8621 (2014)].

  18. Phosphatidic acid stimulates cardiac KATP channels like phosphatidylinositols, but with novel gating kinetics.

    PubMed

    Fan, Zheng; Gao, Lizhi; Wang, Wenxia

    2003-01-01

    Membrane-bound anionic phospholipids such as phosphatidylinositols have the capacity to modulate ATP-sensitive potassium (K(ATP)) channels through a mechanism involving long-range electrostatic interaction between the lipid headgroup and channel. However, it has not yet been determined whether the multiple effects of phosphatidylinositols reported in the literature all result from this general electrostatic interaction or require a specific headgroup structure. The present study investigated whether phosphatidic acid (PA), an anionic phospholipid substantially different in structure from phosphatidylinositols, evokes effects similar to phosphatidylinositols on native K(ATP) channels of rat heart and heterogeneous Kir6.2/SUR2A channels. Channels treated with PA (0.2-1 mg/ml applied to the cytoplasmic side of the membrane) exhibited higher activity, lower sensitivity to ATP inhibition, less Mg(2+)-dependent nucleotide stimulation, and poor sulfonylurea inhibition. These effects match the spectrum of phosphatidylinositols' effects, but, in addition, PA also induced a novel pattern in gating kinetics, represented by a decreased mean open time (from 12.2 +/- 2.0 to 3.3 +/- 0.7 ms). This impact on gating kinetics clearly distinguishes PA's effects from those of phosphatidylinositols. Results indicate that multiple effects of anionic phospholipids on K(ATP) channels are related phenomena and can likely be attributed to a common mechanism, but additional specific effects due to other mechanisms may also coincide.

  19. Investigation of the alpha(1)-glycine receptor channel-opening kinetics in the submillisecond time domain.

    PubMed Central

    Grewer, C

    1999-01-01

    The activation and desensitization kinetics of the human alpha(1)-homooligomeric glycine receptor, which was transiently expressed in HEK 293 cells, were studied with a 100-microseconds time resolution to determine the rate and equilibrium constants of individual receptor reaction steps. Concentration jumps of the activating ligands glycine and beta-alanine were initiated by photolysis of caged, inactive precursors and were followed by neurotransmitter binding, receptor-channel opening, and receptor desensitization steps that were separated along the time axis. Analysis of the ligand concentration-dependence of these processes allows the determination of 1) the rate constants of glycine binding, k(+1) approximately 10(7) M(-1) s(-1), and dissociation, k(-1) = 1900 s(-1); 2) the rates of receptor-channel opening, k(op) = 2200 s(-1), and closing, k(cl) = 38 s(-1); 3) the receptor desensitization rate, alpha = 0.45 s(-1); 4) the number of occupied ligand binding sites necessary for receptor-channel activation and desensitization, n >/= 3; and 5) the maximum receptor-channel open probability, p(0) > 0.95. The kinetics of receptor-channel activation are insensitive to the transmembrane potential. A general model for glycine receptor activation explaining the experimental data consists of a sequential mechanism based on rapid ligand-binding steps preceding a rate-limiting receptor-channel opening reaction and slow receptor desensitization. PMID:10423421

  20. Kinetic effects of quaternary lidocaine block of cardiac sodium channels: a gating current study

    PubMed Central

    1994-01-01

    The interaction of antiarrhythmic drugs with ion channels is often described within the context of the modulated receptor hypothesis, which explains the action of drugs by proposing that the binding site has a variable affinity for drugs, depending upon whether the channel is closed, open, or inactivated. Lack of direct evidence for altered gating of cardiac Na channels allowed for the suggestion of an alternative model for drug interaction with cardiac channels, which postulated a fixed affinity receptor with access limited by the conformation of the channel (guarded receptor hypothesis). We report measurement of the gating currents of Na channels in canine cardiac Purkinje cells in the absence and presence of QX-222, a quaternary derivative of lidocaine, applied intracellularly, and benzocaine, a neutral local anesthetic. These data demonstrate that the cardiac Na channel behaves as a modulated rather than a guarded receptor in that drug-bound channels gate with altered kinetics. In addition, the results suggest a new interpretation of the modulated receptor hypothesis whereby drug occupancy reduces the overall voltage- dependence of gating, preventing full movement of the voltage sensor. PMID:8169596

  1. Hidden Markov modeling for single channel kinetics with filtering and correlated noise.

    PubMed Central

    Qin, F; Auerbach, A; Sachs, F

    2000-01-01

    Hidden Markov modeling (HMM) can be applied to extract single channel kinetics at signal-to-noise ratios that are too low for conventional analysis. There are two general HMM approaches: traditional Baum's reestimation and direct optimization. The optimization approach has the advantage that it optimizes the rate constants directly. This allows setting constraints on the rate constants, fitting multiple data sets across different experimental conditions, and handling nonstationary channels where the starting probability of the channel depends on the unknown kinetics. We present here an extension of this approach that addresses the additional issues of low-pass filtering and correlated noise. The filtering is modeled using a finite impulse response (FIR) filter applied to the underlying signal, and the noise correlation is accounted for using an autoregressive (AR) process. In addition to correlated background noise, the algorithm allows for excess open channel noise that can be white or correlated. To maximize the efficiency of the algorithm, we derive the analytical derivatives of the likelihood function with respect to all unknown model parameters. The search of the likelihood space is performed using a variable metric method. Extension of the algorithm to data containing multiple channels is described. Examples are presented that demonstrate the applicability and effectiveness of the algorithm. Practical issues such as the selection of appropriate noise AR orders are also discussed through examples. PMID:11023898

  2. Acetylcholine receptor kinetics. A description from single-channel currents at snake neuromuscular junctions.

    PubMed Central

    Dionne, V E; Leibowitz, M D

    1982-01-01

    Single-channel currents from acetylcholine receptor channels of garter snake neuromuscular junctions were recorded using the patch-clamp technique. Low concentrations of acetylcholine or carbamylcholine induced populations of single current events whose amplitudes and durations had unimodal distributions. The probability with which channel opening transitions occurred was time dependent, so that it was more probable for channels to open during the several hundred microseconds following a closing transition than during any later equivalent interval. The time-dependent distributions of duration and opening-transition probability were fitted by a sequential, reversible kinetic model in which the agonist binding steps occur before, and separately from, channel activation. This description allowed estimates to be obtained of both the opening (approximately 750s-1) and closing (approximately 500s-1) transition rates of these channels and of the mean lifetimes of the open- (approximately 2 ms) and the closed-channel state (approximately 200 mus) to which the open state was reversibly related. PMID:6291654

  3. Electrostatics at the membrane define MscL channel mechanosensitivity and kinetics

    PubMed Central

    Zhong, Dalian; Blount, Paul

    2014-01-01

    The bacterial mechanosensitive channel of large conductance (MscL) serves as a biological emergency release valve, preventing the occurrence of cell lysis caused by acute osmotic stress. Its tractable nature allows it to serve as a paradigm for how a protein can directly sense membrane tension. Although much is known of the importance of the hydrophobicity of specific residues in channel gating, it has remained unclear whether electrostatics at the membrane plays any role. We studied MscL chimeras derived from functionally distinct orthologues: Escherichia coli and Staphylococcus aureus. Dissection of one set led to an observation that changing the charge of a single residue, K101, of E. coli (Ec)-MscL, effects a channel phenotype: when mutated to a negative residue, the channel is less mechanosensitive and has longer open dwell times. Assuming electrostatic interactions, we determined whether they are due to protein–protein or protein–lipid interactions by performing site-directed mutagenesis elsewhere in the protein and reconstituting channels into defined lipids, with and without negative head groups. We found that although both interactions appear to play some role, the primary determinant of the channel phenotype seems to be protein–lipid electrostatics. The data suggest a model for the role of electrostatic interactions in the dynamics of MscL gating.—Zhong, D., Blount, P. Electrostatics at the membrane define MscL channel mechanosensitivity and kinetics. PMID:25223610

  4. Xerocytosis is caused by mutations that alter the kinetics of the mechanosensitive channel PIEZO1.

    PubMed

    Bae, Chilman; Gnanasambandam, Radhakrishnan; Nicolai, Chris; Sachs, Frederick; Gottlieb, Philip A

    2013-03-19

    Familial xerocytosis (HX) in humans is an autosomal disease that causes dehydration of red blood cells resulting in hemolytic anemia which has been traced to two individual mutations in the mechanosensitive ion channel, PIEZO1. Each mutation alters channel kinetics in ways that can explain the clinical presentation. Both mutations slowed inactivation and introduced a pronounced latency for activation. A conservative substitution of lysine for arginine (R2456K) eliminated inactivation and also slowed deactivation, indicating that this mutant's loss of charge is not responsible for HX. Fitting the current vs. pressure data to Boltzmann distributions showed that the half-activation pressure, P1/2, for M2225R was similar to that of WT, whereas mutations at position 2456 were left shifted. The absolute stress sensitivity was calibrated by cotransfection and comparison with MscL, a well-characterized mechanosensitive channel from bacteria that is driven by bilayer tension. The slope sensitivity of WT and mutant human PIEZO1 (hPIEZO1) was similar to that of MscL implying that the in-plane area increased markedly, by ∼6-20 nm(2) during opening. In addition to the behavior of individual channels, groups of hPIEZO1 channels could undergo simultaneous changes in kinetics including a loss of inactivation and a long (∼200 ms), silent latency for activation. These observations suggest that hPIEZO1 exists in spatial domains whose global properties can modify channel gating. The mutations that create HX affect cation fluxes in two ways: slow inactivation increases the cation flux, and the latency decreases it. These data provide a direct link between pathology and mechanosensitive channel dysfunction in nonsensory cells.

  5. Xerocytosis is caused by mutations that alter the kinetics of the mechanosensitive channel PIEZO1

    PubMed Central

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

    2013-01-01

    Familial xerocytosis (HX) in humans is an autosomal disease that causes dehydration of red blood cells resulting in hemolytic anemia which has been traced to two individual mutations in the mechanosensitive ion channel, PIEZO1. Each mutation alters channel kinetics in ways that can explain the clinical presentation. Both mutations slowed inactivation and introduced a pronounced latency for activation. A conservative substitution of lysine for arginine (R2456K) eliminated inactivation and also slowed deactivation, indicating that this mutant’s loss of charge is not responsible for HX. Fitting the current vs. pressure data to Boltzmann distributions showed that the half-activation pressure, P1/2, for M2225R was similar to that of WT, whereas mutations at position 2456 were left shifted. The absolute stress sensitivity was calibrated by cotransfection and comparison with MscL, a well-characterized mechanosensitive channel from bacteria that is driven by bilayer tension. The slope sensitivity of WT and mutant human PIEZO1 (hPIEZO1) was similar to that of MscL implying that the in-plane area increased markedly, by ∼6–20 nm2 during opening. In addition to the behavior of individual channels, groups of hPIEZO1 channels could undergo simultaneous changes in kinetics including a loss of inactivation and a long (∼200 ms), silent latency for activation. These observations suggest that hPIEZO1 exists in spatial domains whose global properties can modify channel gating. The mutations that create HX affect cation fluxes in two ways: slow inactivation increases the cation flux, and the latency decreases it. These data provide a direct link between pathology and mechanosensitive channel dysfunction in nonsensory cells. PMID:23487776

  6. Gating Kinetics of the α1i T-Type Calcium Channel

    PubMed Central

    Frazier, Charles J.; Serrano, Jose R.; George, Eric G.; Yu, Xiaofeng; Viswanathan, Ahalya; Perez-Reyes, Edward; Jones, Stephen W.

    2001-01-01

    The α1I T-type calcium channel inactivates almost 10-fold more slowly than the other family members (α1G and α1H) or most native T-channels. We have examined the underlying mechanisms using whole-cell recordings from rat α1I stably expressed in HEK293 cells. We found several kinetic differences between α1G and α1I, including some properties that at first appear qualitatively different. Notably, α1I tail currents require two or even three exponentials, whereas α1G tails were well described by a single exponential over a wide voltage range. Also, closed-state inactivation is more significant for α1I, even for relatively strong depolarizations. Despite these differences, gating of α1I can be described by the same kinetic scheme used for α1G, where voltage sensor movement is allosterically coupled to inactivation. Nearly all of the rate constants in the model are 5–12-fold slower for α1I, but the microscopic rate for channel closing is fourfold faster. This suggests that T-channels share a common gating mechanism, but with considerable quantitative variability. PMID:11696605

  7. An efficient method for modeling kinetic behavior of channel proteins in cardiomyocytes.

    PubMed

    Wang, Chong; Beyerlein, Peter; Pospisil, Heike; Krause, Antje; Nugent, Chris; Dubitzky, Werner

    2012-01-01

    Characterization of the kinetic and conformational properties of channel proteins is a crucial element in the integrative study of congenital cardiac diseases. The proteins of the ion channels of cardiomyocytes represent an important family of biological components determining the physiology of the heart. Some computational studies aiming to understand the mechanisms of the ion channels of cardiomyocytes have concentrated on Markovian stochastic approaches. Mathematically, these approaches employ Chapman-Kolmogorov equations coupled with partial differential equations. As the scale and complexity of such subcellular and cellular models increases, the balance between efficiency and accuracy of algorithms becomes critical. We have developed a novel two-stage splitting algorithm to address efficiency and accuracy issues arising in such modeling and simulation scenarios. Numerical experiments were performed based on the incorporation of our newly developed conformational kinetic model for the rapid delayed rectifier potassium channel into the dynamic models of human ventricular myocytes. Our results show that the new algorithm significantly outperforms commonly adopted adaptive Runge-Kutta methods. Furthermore, our parallel simulations with coupled algorithms for multicellular cardiac tissue demonstrate a high linearity in the speedup of large-scale cardiac simulations.

  8. Modification of sodium and potassium channel gating kinetics by ether and halothane

    SciTech Connect

    Bean, B.P.; Shrager, P.; Goldstein, D.A.

    1981-03-01

    The effects of ether and halothane on the kinetics of sodium and potassium currents were investigated in the crayfish giant axon. Both general anesthetics produced a reversible, dose-dependent speeding up of sodium current inactivation at all membrane potentials, with no change in the rising phase of the currents. Double-pulse inactivation experiments with ether also showed faster inactivation, but the rate of recovery from inactivation at negative potentials was not affected. Ether shifted the midpoint of the steady-state fast inactivation curve in the hyperpolarizing direction and made the curve steeper. The activation of potassium currents was faster with ether present, with no change in the voltage dependence of steady-state potassium currents. Ether and halothane are known to perturb the structure of lipid bilayer membranes; the alterations in sodium and potassium channel gating kinetics are consistent with the hypothesis that the rats of the gating processes of the channels can be affected by the state of the lipids surrounding the channels, but a direct effect of ether and halothane on the protein part of the channels cannot be ruled out.

  9. Kinetic properties and functional dynamics of sodium channels during repetitive spiking in a slow pacemaker neuron

    PubMed Central

    Milescu, Lorin S.; Yamanishi, Tadashi; Ptak, Krzysztof; Smith, Jeffrey C.

    2010-01-01

    We examined the kinetic properties of voltage-gated Na+ channels and their contribution to the repetitive spiking activity of medullary raphé neurons, which exhibit slow pacemaking and strong spiking adaptation. The study is based on a combination of whole-cell patch clamp, modeling and real-time computation. Na+ currents were recorded from neurons in brain slices obtained from male and female neonatal rats, using voltage-clamp protocols designed to reduce space-clamp artifacts and to emphasize functionally relevant kinetic features. A detailed kinetic model was formulated to explain the broad range of transient and stationary voltage-dependent properties exhibited by Na+ currents. The model was tested by injecting via dynamic clamp a model-based current as a substitute for the native TTX-sensitive Na+ currents, which were pharmacologically blocked. The model-based current reproduced well the native spike shape and spiking frequency. The dynamics of Na+ channels during repetitive spiking were indirectly examined through this model. By comparing the spiking activities generated with different kinetic models in dynamic clamp experiments, we determined that state-dependent slow inactivation contributes significantly to spiking adaptation. Through real-time manipulation of the model-based current, we established that suprathreshold Na+ current mainly controls spike shape, whereas subthreshold Na+ current modulates spiking frequency and contributes to the pacemaking mechanism. Since the model-based current was injected in the soma, the results also suggest that somatic Na+ channels are sufficient to establish the essential spiking properties of raphé neurons in vitro. PMID:20826674

  10. Light transmission channels in random scattering media (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Cao, Hui

    2016-03-01

    Recently it has been shown that shaping the wavefront of an incident laser beam can significantly enhance the total transmission of light through strong scattering media [1]. This is done by coupling light to high transmission channels. However, optical absorption would modify such transmission channels. In a disordered system with uniform absorption, the maximal transmission channel changes from diffusive to ballistic-like transport [2]. This ballistic-like transport may enable new modes of imaging in absorbing media. If the absorption is distributed non-uniformly in space, the high transmission channels redirect the energy flows to circumvent the absorbing regions to minimize loss. Thus the attenuation of high transmission channels by inhomogeneous absorption becomes lower than that by homogeneous absorption [3]. Since the maximum transmission channel is the most efficient in bypassing the absorbing region, the ratio of its transmittance to the average transmittance increases with absorption, eventually exceeds the ratio without absorption. The finding that inhomogeneous absorption may have a weaker impact on open channels than homogeneous absorption is promising for practical applications. [1] S. M. Popoff, A. Goetschy, S. F. Liew, A. D. Stone, and H. Cao. Phys. Rev. Lett. 112, 133903 (2014). [2] S. F. Liew, S. M. Popoff, A. P. Mosk, W. L. Vos, and H. Cao. Phys. Rev. B 89, 224202 (2014). [3] S. F. Liew and H. Cao. Opt. Express 23, 11043 (2015).

  11. In vitro characterization of HCN channel kinetics and frequency dependence in myocytes predicts biological pacemaker functionality

    PubMed Central

    Zhao, Xin; Bucchi, Annalisa; Oren, Ronit V; Kryukova, Yelena; Dun, Wen; Clancy, Colleen E; Robinson, Richard B

    2009-01-01

    The pacemaker current, mediated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, contributes to the initiation and regulation of cardiac rhythm. Previous experiments creating HCN-based biological pacemakers in vivo found that an engineered HCN2/HCN1 chimeric channel (HCN212) resulted in significantly faster rates than HCN2, interrupted by 1–5 s pauses. To elucidate the mechanisms underlying the differences in HCN212 and HCN2 in vivo functionality as biological pacemakers, we studied newborn rat ventricular myocytes over-expressing either HCN2 or HCN212 channels. The HCN2- and HCN212-over-expressing myocytes manifest similar voltage dependence, current density and sensitivity to saturating cAMP concentrations, but HCN212 has faster activation/deactivation kinetics. Compared with HCN2, myocytes expressing HCN212 exhibit a faster spontaneous rate and greater incidence of irregular rhythms (i.e. periods of rapid spontaneous rate followed by pauses). To explore these rhythm differences further, we imposed consecutive pacing and found that activation kinetics of the two channels are slower at faster pacing frequencies. As a result, time-dependent HCN current flowing during diastole decreases for both constructs during a train of stimuli at a rapid frequency, with the effect more pronounced for HCN2. In addition, the slower deactivation kinetics of HCN2 contributes to more pronounced instantaneous current at a slower frequency. As a result of the frequency dependence of both instantaneous and time-dependent current, HCN2 exhibits more robust negative feedback than HCN212, contributing to the maintenance of a stable pacing rhythm. These results illustrate the benefit of screening HCN constructs in spontaneously active myocyte cultures and may provide the basis for future optimization of HCN-based biological pacemakers. PMID:19171659

  12. Autonomic control of cardiac action potentials: role of potassium channel kinetics in response to sympathetic stimulation.

    PubMed

    Terrenoire, Cecile; Clancy, Colleen E; Cormier, Joseph W; Sampson, Kevin J; Kass, Robert S

    2005-03-18

    I(Ks), the slowly activating component of the delayed rectifier current, plays a major role in repolarization of the cardiac action potential (AP). Genetic mutations in the alpha- (KCNQ1) and beta- (KCNE1) subunits of I(Ks) underlie Long QT Syndrome type 1 and 5 (LQT-1 and LQT-5), respectively, and predispose carriers to the development of polymorphic ventricular arrhythmias and sudden cardiac death. beta-adrenergic stimulation increases I(Ks) and results in rate dependent AP shortening, a control system that can be disrupted by some mutations linked to LQT-1 and LQT-5. The mechanisms by which I(Ks) regulates action potential duration (APD) during beta-adrenergic stimulation at different heart rates are not known, nor are the consequences of mutation induced disruption of this regulation. Here we develop a complementary experimental and theoretical approach to address these questions. We reconstituted I(Ks) in CHO cells (ie, KCNQ1 coexpressed with KCNE1 and the adaptator protein Yotiao) and quantitatively examined the effects of beta-adrenergic stimulation on channel kinetics. We then developed theoretical models of I(Ks) in the absence and presence of beta-adrenergic stimulation. We simulated the effects of sympathetic stimulation on channel activation (speeding) and deactivation (slowing) kinetics on the whole cell action potential under different pacing conditions. The model suggests these kinetic effects are critically important in rate-dependent control of action potential duration. We also investigate the effects of two LQT-5 mutations that alter kinetics and impair sympathetic stimulation of I(Ks) and show the likely mechanism by which they lead to tachyarrhythmias and indicate a distinct role of I(KS) kinetics in this electrical dysfunction. The full text of this article is available online at http://circres.ahajournals.org.

  13. A Conserved Residue Cluster That Governs Kinetics of ATP-dependent Gating of Kir6.2 Potassium Channels.

    PubMed

    Zhang, Roger S; Wright, Jordan D; Pless, Stephan A; Nunez, John-Jose; Kim, Robin Y; Li, Jenny B W; Yang, Runying; Ahern, Christopher A; Kurata, Harley T

    2015-06-19

    ATP-sensitive potassium (KATP) channels are heteromultimeric complexes of an inwardly rectifying Kir channel (Kir6.x) and sulfonylurea receptors. Their regulation by intracellular ATP and ADP generates electrical signals in response to changes in cellular metabolism. We investigated channel elements that control the kinetics of ATP-dependent regulation of KATP (Kir6.2 + SUR1) channels using rapid concentration jumps. WT Kir6.2 channels re-open after rapid washout of ATP with a time constant of ∼60 ms. Extending similar kinetic measurements to numerous mutants revealed fairly modest effects on gating kinetics despite significant changes in ATP sensitivity and open probability. However, we identified a pair of highly conserved neighboring amino acids (Trp-68 and Lys-170) that control the rate of channel opening and inhibition in response to ATP. Paradoxically, mutations of Trp-68 or Lys-170 markedly slow the kinetics of channel opening (500 and 700 ms for W68L and K170N, respectively), while increasing channel open probability. Examining the functional effects of these residues using φ value analysis revealed a steep negative slope. This finding implies that these residues play a role in lowering the transition state energy barrier between open and closed channel states. Using unnatural amino acid incorporation, we demonstrate the requirement for a planar amino acid at Kir6.2 position 68 for normal channel gating, which is potentially necessary to localize the ϵ-amine of Lys-170 in the phosphatidylinositol 4,5-bisphosphate-binding site. Overall, our findings identify a discrete pair of highly conserved residues with an essential role for controlling gating kinetics of Kir channels.

  14. A Conserved Residue Cluster That Governs Kinetics of ATP-dependent Gating of Kir6.2 Potassium Channels*

    PubMed Central

    Zhang, Roger S.; Wright, Jordan D.; Pless, Stephan A.; Nunez, John-Jose; Kim, Robin Y.; Li, Jenny B. W.; Yang, Runying; Ahern, Christopher A.; Kurata, Harley T.

    2015-01-01

    ATP-sensitive potassium (KATP) channels are heteromultimeric complexes of an inwardly rectifying Kir channel (Kir6.x) and sulfonylurea receptors. Their regulation by intracellular ATP and ADP generates electrical signals in response to changes in cellular metabolism. We investigated channel elements that control the kinetics of ATP-dependent regulation of KATP (Kir6.2 + SUR1) channels using rapid concentration jumps. WT Kir6.2 channels re-open after rapid washout of ATP with a time constant of ∼60 ms. Extending similar kinetic measurements to numerous mutants revealed fairly modest effects on gating kinetics despite significant changes in ATP sensitivity and open probability. However, we identified a pair of highly conserved neighboring amino acids (Trp-68 and Lys-170) that control the rate of channel opening and inhibition in response to ATP. Paradoxically, mutations of Trp-68 or Lys-170 markedly slow the kinetics of channel opening (500 and 700 ms for W68L and K170N, respectively), while increasing channel open probability. Examining the functional effects of these residues using φ value analysis revealed a steep negative slope. This finding implies that these residues play a role in lowering the transition state energy barrier between open and closed channel states. Using unnatural amino acid incorporation, we demonstrate the requirement for a planar amino acid at Kir6.2 position 68 for normal channel gating, which is potentially necessary to localize the ϵ-amine of Lys-170 in the phosphatidylinositol 4,5-bisphosphate-binding site. Overall, our findings identify a discrete pair of highly conserved residues with an essential role for controlling gating kinetics of Kir channels. PMID:25934393

  15. Kramers' diffusion theory applied to gating kinetics of voltage-dependent ion channels.

    PubMed Central

    Sigg, D; Qian, H; Bezanilla, F

    1999-01-01

    Kramers' diffusion theory of reaction rates in the condensed phase is considered as an alternative to the traditional discrete-state Markov (DSM) model in describing ion channel gating current kinetics. Diffusion theory can be expected to be particularly relevant in describing high-frequency (>100 kHz) events in channel activation. The generalized voltage sensor of a voltage-dependent ion channel is treated as a Brownian motion particle undergoing spatial diffusion along a one-dimensional energy landscape. Two classes of energy landscapes are considered. The first class contains large barriers, which give rise to gating currents with two distinct time scales: the usual low-frequency decay, which can modeled with a DSM scheme, and a high-frequency component arising from intrastate relaxation. Large depolarizations reduce potential barriers to such a degree that activation rates are diffusion limited, causing the two time scales to merge. Landscapes of the second class are either featureless or contain barriers that are small compared to kT; these are termed "drift landscapes." These landscapes require a larger friction coefficient to generate slow gating kinetics. The high-frequency component that appears with barrier models is not present in pure drift motion. The presence of a high-frequency component can be tested experimentally with large-bandwidth recordings of gating currents. Topics such as frequency domain analysis, spatial dependence of the friction coefficient, methods for determining the adequacy of a DSM model, and the development of physical models of gating are explored. PMID:9929481

  16. Quadratic Forms on Complex Random Matrices and Multi-Antenna Channel Capacity

    DTIC Science & Technology

    2004-03-16

    channel capacity and capacity versus outage of multiple - input multiple - output ( MIMO ) Rayleigh-distributed wireless communication channels. Both... output ( MIMO ) wireless communication systems.jointLet us denote the number of inputs (or transmitters) and formation theory. These densities are...be represented channel capacity and capacity versus outage of multiple - by an n, ×nt complex random matrix H - CN(0, Er®Et), input multiple - output

  17. Multiple kinetic components of sodium channel inactivation in rabbit Schwann cells.

    PubMed Central

    Howe, J R; Ritchie, J M

    1992-01-01

    steady-state amount of slow inactivation. 5. Records of single-channel sodium currents tended to cluster into records which either did, or did not, contain openings. This apparently non-random behaviour depended on membrane potential, and on the frequency at which the test steps were repeated, in the way expected if it resulted from slow inactivation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1336556

  18. Distributed reservation control protocols for random access broadcasting channels

    NASA Astrophysics Data System (ADS)

    Greene, E. P.; Ephremides, A.

    1981-05-01

    Attention is given to a communication network consisting of an arbitrary number of nodes which can communicate with each other via a time-division multiple access (TDMA) broadcast channel. The reported investigation is concerned with the development of efficient distributed multiple access protocols for traffic consisting primarily of single packet messages in a datagram mode of operation. The motivation for the design of the protocols came from the consideration of efficient multiple access utilization of moderate to high bandwidth (4-40 Mbit/s capacity) communication satellite channels used for the transmission of short (1000-10,000 bits) fixed length packets. Under these circumstances, the ratio of roundtrip propagation time to packet transmission time is between 100 to 10,000. It is shown how a TDMA channel can be adaptively shared by datagram traffic and constant bandwidth users such as in digital voice applications. The distributed reservation control protocols described are a hybrid between contention and reservation protocols.

  19. Distributed reservation control protocols for random access broadcasting channels

    NASA Technical Reports Server (NTRS)

    Greene, E. P.; Ephremides, A.

    1981-01-01

    Attention is given to a communication network consisting of an arbitrary number of nodes which can communicate with each other via a time-division multiple access (TDMA) broadcast channel. The reported investigation is concerned with the development of efficient distributed multiple access protocols for traffic consisting primarily of single packet messages in a datagram mode of operation. The motivation for the design of the protocols came from the consideration of efficient multiple access utilization of moderate to high bandwidth (4-40 Mbit/s capacity) communication satellite channels used for the transmission of short (1000-10,000 bits) fixed length packets. Under these circumstances, the ratio of roundtrip propagation time to packet transmission time is between 100 to 10,000. It is shown how a TDMA channel can be adaptively shared by datagram traffic and constant bandwidth users such as in digital voice applications. The distributed reservation control protocols described are a hybrid between contention and reservation protocols.

  20. Understanding the kinetics of adsorption in narrow channel metal organic frameworks

    NASA Astrophysics Data System (ADS)

    Zhou, Wei; Simmons, Jason; Yildirim, Taner

    2010-03-01

    Advancements in the controlled synthesis of metal organic frameworks (MOFs) have lead to impressive increases in hydrogen storage capacities and enhanced binding energies that may offer higher temperature operation. Given that the optimum pore size for hydrogen adsorption is on the order of 7 Angstroms, diffusion of hydrogen into these materials can play an important role in their ultimate implementation. In this presentation we use a combination of experimental and computational techniques, including gas sorption and neutron scattering measurements and detailed first-principles calculations, to better understand the kinetic limitations to adsorption in narrow channel MOF. In particular we show that the adsorption is diffusion limited with a significant activation barrier of ˜70 meV, and that this barrier is phonon-mediated. This work demonstrates the importance of considering kinetic effects in addition to pore volume and heats of adsorption when optimizing MOF materials for hydrogen storage.

  1. The onset of sediment transport in vegetated channels predicted by turbulent kinetic energy

    NASA Astrophysics Data System (ADS)

    Yang, J. Q.; Chung, H.; Nepf, H. M.

    2016-11-01

    This laboratory study advances our understanding of sediment transport in vegetated regions, by describing the impact of stem density on the critical velocity, Ucrit, at which sediment motion is initiated. Sparse emergent vegetation was modeled with rigid cylinders arranged in staggered arrays of different stem densities. The sediment transport rate, Qs, was measured over a range of current speeds using digital imaging, and the critical velocity was selected as the condition at which the magnitude of Qs crossed the noise threshold. For both grain sizes considered here (0.6-0.85 mm and 1.7-2 mm), Ucrit decreased with increasing stem density. This dependence can be explained by a threshold condition based on turbulent kinetic energy, kt, suggesting that near-bed turbulence intensity may be a more important control than bed shear stress on the initiation of sediment motion. The turbulent kinetic energy model unified the bare bed and vegetated channel measurements.

  2. Kinetic and inhibition studies on substrate channelling in the bifunctional enzyme catalysing C-terminal amidation.

    PubMed Central

    Moore, A B; May, S W

    1999-01-01

    A series of experiments has been conducted to investigate the possibility that substrate channelling might occur in the bifunctional forms of enzymes carrying out C-terminal amidation, a post-translational modification essential to the biological activity of many neuropeptides. C-terminal amidation entails sequential action by peptidylglycine mono-oxygenase (PAM, EC 1.14.17.3) and peptidylamidoglycolate lyase (PGL, EC 4.3.2.5), with the mono-oxygenase catalysing conversion of a glycine-extended pro-peptide into the corresponding alpha-hydroxyglycine derivative, which is then converted by the lyase into amidated peptide plus glyoxylate. Since the mono-oxygenase and lyase reactions exhibit tandem reaction stereospecificities, channelling of the alpha-hydroxy intermediate might occur, as is the case for some other multifunctional enzymes. Selective inhibition of the mono-oxygenase domain by competitive ester inhibitors, as well as mechanism-based mono-oxygenase inactivation by the novel olefinic inhibitor 5-acetamido-4-oxo-6-phenylhex-2-enoate (N-acetylphenylalanyl acrylate), has little to no effect on the kinetic parameters of the lyase domain of the AE from Xenopus laevis. Similarly, inhibition of the lyase domain by the potent dioxo inhibitor 2,4-dioxo-5-acetamido-6-phenylhexanoate has little effect on the activity of the monooxygenase domain in the bifunctional enzyme. A series of experiments on intermediate accumulation and conversion were also carried out, along with kinetic investigations of the reactivities of the monofunctional and bifunctional forms of PAM and PGL towards substrates and inhibitors. Taken together, the results demonstrate the kinetic independence of the mono-oxygenase and lyase domains, and provide no evidence for substrate channelling between these domains in the bifunctional amidating enzyme. PMID:10377242

  3. Differences in mechano-transducer channel kinetics underlie tonotopic distribution of fast adaptation in auditory hair cells.

    PubMed

    Ricci, Anthony

    2002-04-01

    The first step in audition is a deflection of the sensory hair bundle that opens mechanically gated channels, depolarizing the sensory hair cells. Two mechanism of adaptation of mechano-electric transducer (MET) channels have been identified in turtle auditory hair cells. The rate of fast adaptation varies tonotopically and is postulated to underlie a mechanical tuning mechanism in turtle auditory hair cells. Fast adaptation is driven by a calcium-dependent feedback process associated with MET channels. The purpose of this paper is to test the hypothesis that fast adaptation contributes to MET channel kinetics and that variations in channel kinetics underlie the tonotopic distribution of fast adaptation. To test for kinetic differences, the open channel blocker dihydrostreptomycin (DHS) was used. DHS blocked MET currents from low-frequency cells (IC(50) = 14 +/- 2 microM) more effectively than high-frequency cells (IC(50) = 75 +/- 5 microM), suggesting differences in MET channel properties. DHS block showed similar calcium sensitivities at both papilla locations. No difference in calcium permeation or block of the transducer channels was observed, indicating that the DHS effect was not due to differences in the channel pore. Slowing adaptation increased DHS efficacy, and speeding adaptation decreased DHS efficacy, suggesting that adaptation was influencing DHS block. DHS block of MET channels slowed adaptation, most likely by reducing the peak intraciliary calcium concentration achieved, supporting the hypothesis that the rate of adaptation varies with the calcium load per stereocilia. Another channel blocker, amiloride showed similar efficacy for high- and low-frequency cells with an IC(50) of 24.2 +/- 0.5 microM and a Hill coefficient of 2 but appeared to block high-frequency channels faster than low-frequency channels. To further explore MET channel differences between papilla locations, stationary noise analysis was performed. Spectral analysis of the noise

  4. Universality of Poisson indicator and Fano factor of transport event statistics in ion channels and enzyme kinetics.

    PubMed

    Chaudhury, Srabanti; Cao, Jianshu; Sinitsyn, Nikolai A

    2013-01-17

    We consider a generic stochastic model of ion transport through a single channel with arbitrary internal structure and kinetic rates of transitions between internal states. This model is also applicable to describe kinetics of a class of enzymes in which turnover events correspond to conversion of substrate into product by a single enzyme molecule. We show that measurement of statistics of single molecule transition time through the channel contains only restricted information about internal structure of the channel. In particular, the most accessible flux fluctuation characteristics, such as the Poisson indicator (P) and the Fano factor (F) as function of solute concentration, depend only on three parameters in addition to the parameters of the Michaelis-Menten curve that characterizes average current through the channel. Nevertheless, measurement of Poisson indicator or Fano factor for such renewal processes can discriminate reactions with multiple intermediate steps as well as provide valuable information about the internal kinetic rates.

  5. Kinetic theory of random graphs: from paths to cycles.

    PubMed

    Ben-Naim, E; Krapivsky, P L

    2005-02-01

    The structural properties of evolving random graphs are investigated. Treating linking as a dynamic aggregation process, rate equations for the distribution of node to node distances (paths) and of cycles are formulated and solved analytically. At the gelation point, the typical length of paths and cycles, l , scales with the component size k as l approximately k(1/2) . Dynamic and finite-size scaling laws for the behavior at and near the gelation point are obtained. Finite-size scaling laws are verified using numerical simulations.

  6. Wanderlust kinetics and variable Ca(2+)-sensitivity of Drosophila, a large conductance Ca(2+)-activated K+ channel, expressed in oocytes.

    PubMed Central

    Silberberg, S D; Lagrutta, A; Adelman, J P; Magleby, K L

    1996-01-01

    Cloned large conductance Ca(2+)-activated K+ channels (BK or maxi-K+ channels) from Drosophila (dSlo) were expressed in Xenopus oocytes and studied in excised membrane patches with the patch-clamp technique. Both a natural variant and a mutant that eliminated a putative cyclic AMP-dependent protein kinase phosphorylation site exhibited large, slow fluctuations in open probability with time. These fluctuations, termed "wanderlust kinetics," occurred with a time course of tens of seconds to minutes and had kinetic properties inconsistent with simple gating models. Wanderlust kinetics was still observed in the presence of 5 mM caffeine or 50 nM thapsigargin, or when the Ca2+ buffering capacity of the solution was increased by the addition of 5 mM HEDTA, suggesting that the wanderlust kinetics did not arise from Ca2+ release from caffeine and thapsigargin sensitive internal stores in the excised patch. The slow changes in kinetics associated with wanderlust kinetics could be generated with a discrete-state Markov model with transitions among three or more kinetic modes with different levels of open probability. To average out the wanderlust kinetics, large amounts of data were analyzed and demonstrated up to a threefold difference in the [Ca2+]i required for an open probability of 0.5 among channels expressed from the same injected mRNA. These findings indicate that cloned dSlo channels in excised patches from Xenopus oocytes can exhibit large variability in gating properties, both within a single channel and among channels. PMID:8744301

  7. Two pacemaker channels from human heart with profoundly different activation kinetics.

    PubMed Central

    Ludwig, A; Zong, X; Stieber, J; Hullin, R; Hofmann, F; Biel, M

    1999-01-01

    Cardiac pacemaking is produced by the slow diastolic depolarization phase of the action potential. The hyperpolarization-activated cation current (If) forms an important part of the pacemaker depolarization and consists of two kinetic components (fast and slow). Recently, three full-length cDNAs encoding hyperpolarization-activated and cyclic nucleotide-gated cation channels (HCN1-3) have been cloned from mouse brain. To elucidate the molecular identity of cardiac pacemaker channels, we screened a human heart cDNA library using a highly conserved neuronal HCN channel segment and identified two cDNAs encoding HCN channels. The hHCN2 cDNA codes for a protein of 889 amino acids. The HCN2 gene is localized on human chromosome 19p13.3 and contains eight exons spanning approximately 27 kb. The second cDNA, designated hHCN4, codes for a protein of 1203 amino acids. Northern blot and PCR analyses showed that both hHCN2 and hHCN4 are expressed in heart ventricle and atrium. When expressed in HEK 293 cells, either cDNA gives rise to hyperpolarization-activated cation currents with the hallmark features of native If. hHCN2 and hHCN4 currents differ profoundly from each other in their activation kinetics, being fast and slow, respectively. We thus conclude that hHCN2 and hHCN4 may underlie the fast and slow component of cardiac If, respectively. PMID:10228147

  8. Classical-quantum arbitrarily varying wiretap channel: common randomness assisted code and continuity

    NASA Astrophysics Data System (ADS)

    Boche, Holger; Cai, Minglai; Deppe, Christian; Nötzel, Janis

    2017-01-01

    We determine the secrecy capacities under common randomness assisted coding of arbitrarily varying classical-quantum wiretap channels. Furthermore, we determine the secrecy capacity of a mixed channel model which is compound from the sender to the legitimate receiver and varies arbitrarily from the sender to the eavesdropper. We examine when the secrecy capacity is a continuous function of the system parameters as an application and show that resources, e.g., having access to a perfect copy of the outcome of a random experiment, can guarantee continuity of the capacity function of arbitrarily varying classical-quantum wiretap channels.

  9. Permeant ion effects on the gating kinetics of the type L potassium channel in mouse lymphocytes

    PubMed Central

    1991-01-01

    Permeant ion species was found to profoundly affect the gating kinetics of type l K+ currents in mouse T lymphocytes studied with the whole- cell or on-cell patch gigaohm-seal techniques. Replacing external K+ with Rb+ (as the sole monovalent cation, at 160 mM) shifted the peak conductance voltage (g-V) relation by approximately 20 mV to more negative potentials, while NH4+ shifted the g-V curve by 15 mV to more positive potentials. Deactivation (the tail current time constant, tau tail) was slowed by an average of 14-fold at -70 mV in external Rb+, by approximately 8-fold in Cs+, and by a factor of two to three in NH4+. Changing the external K+ concentration, [K+]o, from 4.5 to 160 mM or [Rb+]o from 10 to 160 mM had no effect on tau tail. With all the internal K+ replaced by Rb+ or Cs+ and either isotonic Rb+ or K+ in the bath, tau tail was indistinguishable from that with K+ in the cell. With the exception of NH4+, activation time constants were insensitive to permeant ion species. These results indicate that external permeant ions have stronger effects than internal permeant ions, suggesting an external modulatory site that influences K+ channel gating. However, in bi-ionic experiments with reduced external permeant ion concentrations, tau tail was sensitive to the direction of current flow, indicating that the modulatory site is either within the permeation pathway or in the outer vestibule of the channel. The latter interpretation implies that outward current through an open type l K+ channel significantly alters local ion concentrations at the modulatory site in the outer vestibule, and consequently at the mouth of the channel. Experiments with mixtures of K+ and Rb+ in the external solution reveal that deactivation kinetics are minimally affected by addition of Rb+ until the Rb+ mole fraction approaches unity. This relationship between mole fraction and tau tail, together with the concentration independence of tau tail, was hard to reconcile with simple

  10. Kinetic modeling of ion conduction in KcsA potassium channel.

    PubMed

    Mafé, Salvador; Pellicer, Julio; Cervera, Javier

    2005-05-22

    KcsA constitutes a potassium channel of known structure that shows both high conduction rates and selectivity among monovalent cations. A kinetic model for ion conduction through this channel that assumes rapid ion transport within the filter has recently been presented by Nelson. In a recent, brief communication, we used the model to provide preliminary explanations to the experimental current-voltage J-V and conductance-concentration g-S curves obtained for a series of monovalent ions (K(+),Tl(+), and Rb(+)). We did not assume rapid ion transport in the calculations, since ion transport within the selectivity filter could be rate limiting for ions other than native K(+). This previous work is now significantly extended to the following experimental problems. First, the outward rectification of the J-V curves in K(+) symmetrical solutions is analyzed using a generalized kinetic model. Second, the J-V and g-S curves for NH(4) (+) are obtained and compared with those of other ions (the NH(4) (+) J-V curve is qualitatively different from those of Rb(+) and Tl(+)). Third, the effects of Na(+) block on K(+) and Rb(+) currents through single KcsA channels are studied and the different blocking behavior is related to the values of the translocation rate constants characteristic of ion transport within the filter. Finally, the significantly decreased K(+) conductance caused by mutation of the wild-type channel is also explained in terms of this rate constant. In order to keep the number of model parameters to a minimum, we do not allow the electrical distance (an empirical parameter of kinetic models that controls the exponential voltage dependence of the dissociation rate) to vary with the ionic species. Without introducing the relatively high number of adjustable parameters of more comprehensive site-based models, we show that ion association to the filter is rate controlling at low concentrations, but ion dissociation from the filter and ion transport within the filter

  11. Kinetic modeling of ion conduction in KcsA potassium channel

    NASA Astrophysics Data System (ADS)

    Mafé, Salvador; Pellicer, Julio; Cervera, Javier

    2005-05-01

    KcsA constitutes a potassium channel of known structure that shows both high conduction rates and selectivity among monovalent cations. A kinetic model for ion conduction through this channel that assumes rapid ion transport within the filter has recently been presented by Nelson. In a recent, brief communication, we used the model to provide preliminary explanations to the experimental current-voltage J-V and conductance-concentration g-S curves obtained for a series of monovalent ions (K+,Tl+, and Rb+). We did not assume rapid ion transport in the calculations, since ion transport within the selectivity filter could be rate limiting for ions other than native K+. This previous work is now significantly extended to the following experimental problems. First, the outward rectification of the J-V curves in K+ symmetrical solutions is analyzed using a generalized kinetic model. Second, the J-V and g-S curves for NH4+ are obtained and compared with those of other ions (the NH4+ J-V curve is qualitatively different from those of Rb+ and Tl+). Third, the effects of Na+ block on K+ and Rb+ currents through single KcsA channels are studied and the different blocking behavior is related to the values of the translocation rate constants characteristic of ion transport within the filter. Finally, the significantly decreased K+ conductance caused by mutation of the wild-type channel is also explained in terms of this rate constant. In order to keep the number of model parameters to a minimum, we do not allow the electrical distance (an empirical parameter of kinetic models that controls the exponential voltage dependence of the dissociation rate) to vary with the ionic species. Without introducing the relatively high number of adjustable parameters of more comprehensive site-based models, we show that ion association to the filter is rate controlling at low concentrations, but ion dissociation from the filter and ion transport within the filter could limit conduction at high

  12. Gating Kinetics of the Cyclic-GMP-Activated Channel of Retinal Rods: Flash Photolysis and Voltage-Jump Studies

    NASA Astrophysics Data System (ADS)

    Karpen, Jeffrey W.; Zimmerman, Anita L.; Stryer, Lubert; Baylor, Denis A.

    1988-02-01

    The gating kinetics of the cGMP-activated cation channel of salamander retinal rods have been studied in excised membrane patches. Relaxations in patch current were observed after two kinds of perturbation: (i) fast jumps of cGMP concentration, generated by laser flash photolysis of a cGMP ester (``caged'' cGMP), and (ii) membrane voltage jumps, which perturb activation of the channel by cGMP. In both methods the speed of activation increased with the final cGMP concentration. The results are explained by a simple kinetic model in which activation involves three sequential cGMP binding steps with bimolecular rate constants close to the diffusion-controlled limit; fully liganded channels undergo rapid open-closed transitions. Voltage perturbs activation by changing the rate constant for channel closing, which increases with hyperpolarization. Intramolecular transitions of the fully liganded channel limit the kinetics of activation at high cGMP concentrations (>50 μ M), whereas at physiological cGMP concentrations (<5 μ M), the kinetics of activation are limited by the third cGMP binding step. The channel appears to be optimized for rapid responses to changes in cytoplasmic cGMP concentration.

  13. Neurosteroid prolongs GABAA channel deactivation by altering kinetics of desensitized states.

    PubMed

    Zhu, W J; Vicini, S

    1997-06-01

    Fast applications of GABA (1 mM) to nucleated and outside-out patches excised from granule neurons in cerebellar slices from developing rats evoked currents with a double exponential time course reminiscent of that of IPSCs. A neurosteroid 3alpha, 21dihydroxy-5alpha-pregnan-20-one (THDOC) remarkably increased the slow deactivation time constant and slowed down recovery from desensitization, as estimated by paired-pulse GABA applications. THDOC also reduced the amplitude of GABA currents, whereas it failed to affect the fast deactivation component and its relative contribution to peak amplitude. The effects of THDOC on slow deactivation were greater in rats younger than postnatal day 13 (P13) as compared with rats at P30-P35. THDOC failed to alter deactivation of short responses induced by a less-potent agonist taurine at saturating doses. These responses had deactivation kinetics described by a fast single exponential decay, little desensitization, and quick recovery. However, THDOC slowed deactivation if taurine responses were long enough to allow consistent desensitization, suggesting that desensitized states are required for the neurosteroid to modulate GABA responses. In outside-out patches, just as desensitized states prolonged GABA responses by producing reopening of channels activated by brief GABA pulses, THDOC increased the channel open probability by further increasing the number of late channel openings, resulting in a prolongation of the slow deactivation. Our data suggest that neurosteroid potentiates the inhibitory postsynaptic transmission via the prolongation of the slow deactivation and that the alteration of kinetics of entry and exit from desensitized states underlies the allosteric modification of GABAA receptors by neurosteroids.

  14. Capacity of Multi-Channel Wireless Networks with Random Channel Assignment: A Tight Bound

    DTIC Science & Technology

    2006-10-01

    common cells), then all n flows are able to transition w.h.p. Proof: Consider a flow traversing a sequence of cells D1, D2 , .... Then if the representative...that enter any cell on a given channel is O( n √ a(n) c ) w.h.p. Proof: A flow on route D1, D2 , ...,D j−1,D j.... may enter a cell D j on a channel i...switching constraints,” Technical Report, CSL , UIUC (revised Sept. 2006 (original version dated August 2006)). [2] P. Gupta and P. R. Kumar, “The

  15. Estimating the number of channels in patch-clamp recordings: application to kinetic analysis of multichannel data from voltage-operated channels.

    PubMed Central

    Baumgartner, W; Hohenthanner, K; Höfer, G F; Groschner, K; Romanin, C

    1997-01-01

    Important kinetic information of voltage-operated ion channels can be obtained by estimating the open probability, the availability, and the first latency, and by applying run analysis. In the case of multichannel patches, estimation of the number of available channels is a prerequisite for the above analysis. Here we describe a method for calculation of the a posteriori probability of the number of available channels in each sweep by using the Bayes formula. This probability serves as a measure for the number of channels and allows for first latency determination and run analysis. The methods described were applied to simulated and experimental data obtained from L-type Ca2+ channel recordings. PMID:9138562

  16. ``Random-force-dominated'' reaction kinetics: Reactants moving under random forces

    NASA Astrophysics Data System (ADS)

    Araujo, Mariela; Havlin, Shlomo; Larralde, Hernan; Stanley, H. Eugene

    1992-03-01

    We investigate the reaction kinetics for systems in which the dynamics of the particles is governed by a Langevin equation with negligible damping, and we find the expressions for the survival probability, residual concentrations, and reaction rates. We discover that the integral in time of the reaction front for d=1 is t1-β exp(-||x||/tα) for both the low- and high-damping limits, and we estimate the exponents α and β in each case.

  17. Real-Time Kinetic Modeling of Voltage-Gated Ion Channels Using Dynamic Clamp

    PubMed Central

    Milescu, Lorin S.; Yamanishi, Tadashi; Ptak, Krzysztof; Mogri, Murtaza Z.; Smith, Jeffrey C.

    2008-01-01

    We propose what to our knowledge is a new technique for modeling the kinetics of voltage-gated ion channels in a functional context, in neurons or other excitable cells. The principle is to pharmacologically block the studied channel type, and to functionally replace it with dynamic clamp, on the basis of a computational model. Then, the parameters of the model are modified in real time (manually or automatically), with the objective of matching the dynamical behavior of the cell (e.g., action potential shape and spiking frequency), but also the transient and steady-state properties of the model (e.g., those derived from voltage-clamp recordings). Through this approach, one may find a model and parameter values that explain both the observed cellular dynamics and the biophysical properties of the channel. We extensively tested the method, focusing on Nav models. Complex Markov models (10–12 states or more) could be accurately integrated in real time at >50 kHz using the transition probability matrix, but not the explicit Euler method. The practicality of the technique was tested with experiments in raphe pacemaker neurons. Through automated real-time fitting, a Hodgkin-Huxley model could be found that reproduced well the action potential shape and the spiking frequency. Adding a virtual axonal compartment with a high density of Nav channels further improved the action potential shape. The computational procedure was implemented in the free QuB software, running under Microsoft Windows and featuring a friendly graphical user interface. PMID:18375511

  18. Random activation energy model and disordered kinetics, from static to dynamic disorder.

    PubMed

    Vlad, Marcel Ovidiu; Cerofolini, Gianfranco; Oefner, Peter; Ross, John

    2005-11-17

    We suggest a unified path integral approach for random rate processes with random energy barriers, which includes systems with static and dynamic disorder as particular cases. We assume that the random component of the activation energy barrier can be described by a generalized Zubarev-McLennan nonequilibrum statistical ensemble that can be derived from the maximum information entropy approach by assuming that the time history of the fluctuations of the random components of the energy barrier are known. We show that the average survival function, which is an experimental observable in disorderd kinetics, can be computed exactly in terms of the characteristic functional of this generalized Zubarev-McLennan nonequilibrium statistical ensemble. We investigate different types of disorder described by our approach, ranging from static disorder with infinite memory to random processes with long or short memory, and finally to rapidly fluctuating independent random processes with no memory. We derive expressions of the average survival function for all these types of disorder and discuss their implications in the evaluation of kinetic parameters from experimental data. We illustrate our approach by studying a simple model of dynamic disorder of the renewal type. Finally we discuss briefly the implications of our approach in molecular biology and genetics.

  19. Degradation kinetics and pathways of three calcium channel blockers under UV irradiation.

    PubMed

    Zhu, Bing; Zonja, Bozo; Gonzalez, Oscar; Sans, Carme; Pérez, Sandra; Barceló, Damia; Esplugas, Santiago; Xu, Ke; Qiang, Zhimin

    2015-12-01

    Calcium channel blockers (CCBs) are a group of pharmaceuticals widely prescribed to lower blood pressure and treat heart diseases. They have been frequently detected in wastewater treatment plant (WWTP) effluents and downstream river waters, thus inducing a potential risk to aquatic ecosystems. However, little is known about the behavior and fate of CCBs under UV irradiation, which has been adopted as a primary disinfection method for WWTP effluents. This study investigated the degradation kinetics and pathways of three commonly-used CCBs, including amlodipine (AML), diltiazem (DIL), and verapamil (VER), under UV (254 nm) irradiation. The chemical structures of transformation byproducts (TBPs) were first identified to assess the potential ecological hazards. On that basis, a generic solid-phase extraction method, which simultaneously used four different cartridges, was adopted to extract and enrich the TBPs. Thereafter, the photo-degradation of target CCBs was performed under UV fluences typical for WWTP effluent disinfection. The degradation of all three CCBs conformed to the pseudo-first-order kinetics, with rate constants of 0.031, 0.044 and 0.011 min(-1) for AML, DIL and VER, respectively. By comparing the MS(2) fragments and the evolution (i.e., formation or decay) trends of identified TBPs, the degradation pathways were proposed. In the WWTP effluent, although the target CCBs could be degraded, several TBPs still contained the functional pharmacophores and reached peak concentrations under UV fluences of 40-100 mJ cm(-2).

  20. Reaction Kinetics of HBr with HO2: A New Channel for Isotope Scrambling Reactions.

    PubMed

    Church, Jonathan R; Skodje, Rex T

    2016-11-03

    The gas phase reaction kinetics of HBr with the HO2 radical are investigated over the temperature range of T = 200-1500 K using a theoretical approach based on transition state theory. The parameters for the potential energy surface are computed using density functional theory with the M11 exchange functional. The rate coefficient for the HBr + HO2 → Br + H2O2 abstraction channel is found to be somewhat larger than previous estimates at low temperatures due to quantum tunneling. The present study reveals the existence of a novel exchange pathway, HBr + H'O2 → H'Br + HO2, which exhibits a much lower reaction barrier than does the abstraction route. The transition state for this process is a symmetrical planar five-membered-ring-shaped structure. At low temperatures, this concerted double hydrogen transfer reaction is several orders of magnitude faster than the abstraction channel. The exchange process may be observed using isotope scrambling reactions; such reactions may contribute to observed isotope abundances in the atmosphere. The rate coefficients for the isotopically labeled reactions are computed.

  1. BK-Type K(Ca) channels in two parasympathetic cell types: differences in kinetic properties and developmental expression.

    PubMed

    Cameron, J S; Dryer, S E

    2000-12-01

    The intrinsic electrical properties of identified choroid and ciliary neurons of the chick ciliary ganglion were examined by patch-clamp recording methods. These neurons are derived from a common pool of mesencephalic neural crest precursor cells but innervate different target tissues and have markedly different action potential waveforms and intrinsic patterns of repetitive spike discharge. Therefore it is important to determine whether these cell types express different types of plasma membrane ionic channels, and to ascertain the developmental stages at which these cell types begin to diverge. This study has focused on large-conductance Ca(2+)-activated K(+) channels (K(Ca)), which are known to regulate spike waveform and repetitive firing in many cell types. Both ciliary ganglion cell types, identified on the basis of size and somatostatin immunoreactivity, express a robust macroscopic K(Ca) carried by a kinetically homogeneous population of large-conductance (BK-type) K(Ca) channels. However, the kinetic properties of these channels are different in the two cell types. Steady-state fluctuation analyses of macroscopic K(Ca) produced power spectra that could be fitted with a single Lorentzian curve in both cell types. However, the resulting corner frequency was significantly lower in choroid neurons than in ciliary neurons, suggesting that the underlying K(Ca) channels have a longer mean open-time in choroid neurons. Consistent with fluctuation analyses, significantly slower gating of K(Ca) channels in choroid neurons was also observed during macroscopic activation and deactivation at membrane potentials positive to -30 mV. Differences in the kinetic properties of K(Ca) channels could also be observed directly in single-channel recordings from identified embryonic day 13 choroid and ciliary neurons. The mean open-time of large-conductance K(Ca) channels was significantly greater in choroid neurons than in ciliary neurons in excised inside-out patches. The

  2. Method for Evaluation of Outage Probability on Random Access Channel in Mobile Communication Systems

    NASA Astrophysics Data System (ADS)

    Kollár, Martin

    2012-05-01

    In order to access the cell in all mobile communication technologies a so called random-access procedure is used. For example in GSM this is represented by sending the CHANNEL REQUEST message from Mobile Station (MS) to Base Transceiver Station (BTS) which is consequently forwarded as an CHANNEL REQUIRED message to the Base Station Controller (BSC). If the BTS decodes some noise on the Random Access Channel (RACH) as random access by mistake (so- called ‘phantom RACH') then it is a question of pure coincidence which èstablishment cause’ the BTS thinks to have recognized. A typical invalid channel access request or phantom RACH is characterized by an IMMEDIATE ASSIGNMENT procedure (assignment of an SDCCH or TCH) which is not followed by sending an ESTABLISH INDICATION from MS to BTS. In this paper a mathematical model for evaluation of the Power RACH Busy Threshold (RACHBT) in order to guaranty in advance determined outage probability on RACH is described and discussed as well. It focuses on Global System for Mobile Communications (GSM) however the obtained results can be generalized on remaining mobile technologies (ie WCDMA and LTE).

  3. An experimental study of the kinetics of lherzolite reactive dissolution with applications to melt channel formation

    NASA Astrophysics Data System (ADS)

    Morgan, Zachary; Liang, Yan

    2005-11-01

    The kinetics of lherzolite dissolution in an alkali basalt and a basaltic andesite was examined experimentally at 1,300°C and 1 GPa using the dissolution couple method. Dissolution of lherzolite in basaltic liquids produces either the melt-bearing dunite-harzburgite-lherzolite (DHL) sequence or the melt-bearing harzburgite-lherzolite sequence depending on whether the reacting melt is or close to olivine saturation (alkali basalt) or olivine + orthopyroxene saturation (basaltic andesite). The dunite in the DHL sequence is pyroxene-free and the harzburgites in both sequences are clinopyroxene-free. The melt fraction and olivine grain size in the dunite are larger than those in the harzburgite. The olivine grain size in the dunite and harzburgite in the DHL sequence also increases as a function experimental run time. Across the sharp dunite-harzburgite and harzburgite-lherzolite interfaces, systematic compositional variations are observed in the reacting melt, interstitial melt, olivine, and to a lesser extent, pyroxenes as functions of distance and time. The systematic variations in lithology, grain size, mineral chemistry, and melt compositions are broadly similar to those observed in the mantle sections of ophiolites. The processes of lherzolite dissolution in basaltic liquids involve dissolution, precipitation, reprecipitation, and diffusive transport in the interstitial melts and surrounding minerals. Preferential dissolution of olivine and clinopyroxene and precipitation of orthopyroxene in the basaltic andesite produces the melt-bearing harzburgite-lherzolite sequence. Preferential dissolution of clinopyroxene and orthopyroxene and precipitation of olivine results in the melt-bearing DHL sequence. Preferential mineral dissolution can also affect the composition of the through-going melt in a dunite channel or harzburgite matrix. Systematic variations in melt fraction and mineral grain size in the peridotite sequences are likely to play an important role in the

  4. Influence of channel subunit composition on L-type Ca2+ current kinetics and cardiac wave stability.

    PubMed

    Gudzenko, Vadim; Shiferaw, Yohannes; Savalli, Nicoletta; Vyas, Roshni; Weiss, James N; Olcese, Riccardo

    2007-09-01

    Previous studies have demonstrated that the slope of the function relating the action potential duration (APD) and the diastolic interval, known as the APD restitution curve, plays an important role in the initiation and maintenance of ventricular fibrillation. Since the APD restitution slope critically depends on the kinetics of the L-type Ca(2+) current, we hypothesized that manipulation of the subunit composition of these channels may represent a powerful strategy to control cardiac arrhythmias. We studied the kinetic properties of the human L-type Ca(2+) channel (Ca(v)1.2) coexpressed with the alpha(2)delta-subunit alone (alpha(1C) + alpha(2)delta) or in combination with beta(2a), beta(2b), or beta(3) subunits (alpha(1C) + alpha(2)delta + beta), using Ca(2+) as the charge carrier. We then incorporated the kinetic properties observed experimentally into the L-type Ca(2+) current mathematical model of the cardiac action potential to demonstrate that the APD restitution slope can be selectively controlled by altering the subunit composition of the Ca(2+) channel. Assuming that beta(2b) most closely resembles the native cardiac L-type Ca(2+) current, the absence of beta, as well as the coexpression of beta(2a), was found to flatten restitution slope and stabilize spiral waves. These results imply that subunit modification of L-type Ca(2+) channels can potentially be used as an antifibrillatory strategy.

  5. TARP-associated AMPA receptors display an increased maximum channel conductance and multiple kinetically distinct open states.

    PubMed

    Shelley, Chris; Farrant, Mark; Cull-Candy, Stuart G

    2012-11-15

    Fast excitatory synaptic transmission in the CNS is mediated mainly by AMPA-type glutamate receptors (AMPARs), whose biophysical properties are dramatically modulated by the presence of transmembrane AMPAR regulatory proteins (TARPs). To help construct a kinetic model that will realistically describe native AMPAR/TARP function, we have examined the single-channel properties of homomeric GluA1 AMPARs in combination with the TARPs, γ-2, γ-4 and γ-5. In a saturating concentration of agonist, each of these AMPAR/TARP combinations gave rise to single-channel currents with multiple conductance levels that appeared intrinsic to the receptor-channel complex, and showed long-lived subconductance states. The open time and burst length distributions of the receptor complexes displayed multiple dwell-time components. In the case of γ-2- and γ-4-associated receptors, these distributions included a long-lived component lasting tens of milliseconds that was absent from both GluA1 alone and γ-5-associated receptors. The open time distributions for each conductance level required two dwell-time components, indicating that at each conductance level the channel occupies a minimum of two kinetically distinct open states. We have explored how these data place novel constraints on possible kinetic models of TARP-associated AMPARs that may be used to define AMPAR-mediated synaptic transmission.

  6. Characterizing channel change along a multithread gravel-bed river using random forest image classification

    NASA Astrophysics Data System (ADS)

    Overstreet, B. T.; Legleiter, C. J.

    2012-12-01

    The Snake River in Grand Teton National Park is a dam-regulated but highly dynamic gravel-bed river that alternates between a single thread and a multithread planform. Identifying key drivers of channel change on this river could improve our understanding of 1) how flow regulation at Jackson Lake Dam has altered the character of the river over time; 2) how changes in the distribution of various types of vegetation impacts river dynamics; and 3) how the Snake River will respond to future human and climate driven disturbances. Despite the importance of monitoring planform changes over time, automated channel extraction and understanding the physical drivers contributing to channel change continue to be challenging yet critical steps in the remote sensing of riverine environments. In this study we use the random forest statistical technique to first classify land cover within the Snake River corridor and then extract channel features from a sequence of high-resolution multispectral images of the Snake River spanning the period from 2006 to 2012, which encompasses both exceptionally dry years and near-record runoff in 2011. We show that the random forest technique can be used to classify images with as few as four spectral bands with far greater accuracy than traditional single-tree classification approaches. Secondly, we couple random forest derived land cover maps with LiDAR derived topography, bathymetry, and canopy height to explore physical drivers contributing to observed channel changes on the Snake River. In conclusion we show that the random forest technique is a powerful tool for classifying multispectral images of rivers. Moreover, we hypothesize that with sufficient data for calculating spatially distributed metrics of channel form and more frequent channel monitoring, this tool can also be used to identify areas with high probabilities of channel change. Land cover maps of a portion of the Snake River produced from digital aerial photography from 2010 and

  7. Nonequilibrium phase transitions in lattice systems with random-field competing kinetics

    NASA Astrophysics Data System (ADS)

    López-Lacomba, A. I.; Marro, J.

    1992-10-01

    We study a class of lattice interacting-spin systems evolving stochastically under the simultaneous operation of several spin-flip mechanisms, each acting independently and responding to a different applied magnetic field. This induces an extra randomness which may occur in real systems, e.g., a magnetic system under the action of a field varying with a much shorter period than the mean time between successive transitions. Such a situation-in which one may say in some sense that frustration has a dynamical origin- may also be viewed as a nonequilibrium version of the random-field Ising model. By following a method of investigating stationary probability distributions in systems with competing kinetics [P. L. Garrido and J. Marro, Phys. Rev. Lett. 62, 1929 (1989)], we solve one-dimensional lattices supporting different field distributions and transition rates for the elementary kinetical processes, thus revealing a rich variety of phase transitions and critical phenomena. Some exact results for lattices of arbitrary dimension, and comparisons with the standard quenched and annealed random-field models, and with a nonequilibrium diluted antiferromagnetic system, are also reported.

  8. Acquisition and analysis of fast single channel kinetic data on an Apple IIe microcomputer.

    PubMed

    Kits, K S; Mos, G J; Leeuwerik, F J; Wattel, C

    1987-05-01

    We describe a method for acquisition and analysis of single channel kinetic data, that uses a ubiquitous microcomputer, the Apple IIe (and is thus cheap), and is yet sensitive and powerful (analysis of up to 6000 events per run of the program; event detection only limited by the amplifier bandwidth). For data acquisition, the original record is converted into an idealized record of open and closed times, using half amplitude threshold analysis or a two-cursor window discriminator. A Time Interval Meter (TIM) has been developed that measures the durations of the TTL-signal from the window discriminator and stores up to 256 intervals in a FIFO-buffer. Each cycle of the TIM is completed within 1 microsecond. The, largely Pascal, software reads the intervals from the FIFO-buffer and stores them in the main memory of the microcomputer (cycle time 70 microseconds). The package is completed with Pascal programs for statistical analysis, including histogram construction of open and closed times, non-linear fit of up to 3 exponentials and correlation analysis.

  9. Discharge Kinetics of N2-O2 Laser Generated Plasma Channels

    NASA Astrophysics Data System (ADS)

    Ladouceur, Harold; Baronavski, Andrew; Petrova, Tzvetelina

    2006-10-01

    We study both experimentally and theoretically the effects of recombination and attachment of different N2--O2 gas compositions upon the plasma channel dynamics at one atmosphere. The time-dependent DC electrical conductivity technique [1] has been applied to determine the electron density decay. The rate constants have been determined from the electron balance equation by curve fitting of voltage-time measurements over the decay time interval. The measured electron density decay time for air is hundreds of nanoseconds while for pure nitrogen it is much longer, about 2 μs. For air, we derive an attachment rate ηair=1.39x10^7;s-1 and an electron-ion recombination rate βair=1.02x10-8;cm^31pts-1. In order to investigate in details the kinetics of N2--O2 gas mixture we developed a time-dependent collisional-radiative model based upon the numerical solution of the electron Boltzmann equation for the electron energy distribution function. It is coupled with the time-dependent balance equations of electrons, atomic and molecular ions under consideration, and various nitrogen and oxygen species in ground and excited states. The validity of the model was verified by comparison of the swarm parameters derived from the model with experimental parameters for pure oxygen, pure nitrogen, and air. [1] H.D. Ladouceur at al., Optics Communications, 189 (2001) 107 * NRL-NRC Postdoc

  10. Acetylcholine receptor (from Electrophorus electricus): a comparison of single-channel current recordings and chemical kinetic measurements.

    PubMed

    Hess, G P; Kolb, H A; Läuger, P; Schoffeniels, E; Schwarze, W

    1984-09-01

    We report a direct comparison between two types of measurements of the dynamic properties of the acetylcholine receptor: single-channel currents recorded using the patch-clamp technique and chemical kinetic measurements. Electrophorus electricus electroplax cells, and membrane vesicles prepared from these cells, were used. Such a comparison, and single-channel currents recorded from these cells, have not previously been reported. We first give the theoretical basis for the comparison and define the conditions under which the comparisons are elegantly simple. We relate (i) measurements of currents through receptor channels in the cell membranes to measurements of the rates of ion translocation through the receptor channels in vesicles and (ii) measurements of the lifetimes of receptor states (for instance, the lifetime of the active state of the receptor--i.e., the state in which it can form open channels) to rate coefficients obtained in chemical kinetic measurements (for instance, those for the interconversions between different states of the receptor). In eel Ringer's solution we have found the single-channel conductance (gamma) of the receptor in E. electricus electroplax cells to be 53 pS. From this value, a specific reaction rate for ion translocation, J, of 5 X 10(7) M-1 X sec-1 was calculated. When membrane vesicles prepared from the electroplax cells and the same solution compositions were used, chemical kinetic measurements gave a J value of 3 X 10(7) M-1 X sec-1. The agreement between the two measurements is important because (i) they reflect different experimental conditions, which require different assumptions in interpreting the results, and (ii) it indicates that the two techniques can be used to obtain complementary information: the methods have different time resolutions and can be used in different ranges of acetylcholine concentrations.

  11. Acetylcholine receptor (from Electrophorus electricus): a comparison of single-channel current recordings and chemical kinetic measurements.

    PubMed Central

    Hess, G P; Kolb, H A; Läuger, P; Schoffeniels, E; Schwarze, W

    1984-01-01

    We report a direct comparison between two types of measurements of the dynamic properties of the acetylcholine receptor: single-channel currents recorded using the patch-clamp technique and chemical kinetic measurements. Electrophorus electricus electroplax cells, and membrane vesicles prepared from these cells, were used. Such a comparison, and single-channel currents recorded from these cells, have not previously been reported. We first give the theoretical basis for the comparison and define the conditions under which the comparisons are elegantly simple. We relate (i) measurements of currents through receptor channels in the cell membranes to measurements of the rates of ion translocation through the receptor channels in vesicles and (ii) measurements of the lifetimes of receptor states (for instance, the lifetime of the active state of the receptor--i.e., the state in which it can form open channels) to rate coefficients obtained in chemical kinetic measurements (for instance, those for the interconversions between different states of the receptor). In eel Ringer's solution we have found the single-channel conductance (gamma) of the receptor in E. electricus electroplax cells to be 53 pS. From this value, a specific reaction rate for ion translocation, J, of 5 X 10(7) M-1 X sec-1 was calculated. When membrane vesicles prepared from the electroplax cells and the same solution compositions were used, chemical kinetic measurements gave a J value of 3 X 10(7) M-1 X sec-1. The agreement between the two measurements is important because (i) they reflect different experimental conditions, which require different assumptions in interpreting the results, and (ii) it indicates that the two techniques can be used to obtain complementary information: the methods have different time resolutions and can be used in different ranges of acetylcholine concentrations. PMID:6089188

  12. Trans-Channel Interactions in Batrachotoxin-Modified Rat Skeletal Muscle Sodium Channels: Kinetic Analysis of Mutual Inhibition between μ-Conotoxin GIIIA Derivatives and Amine Blockers

    PubMed Central

    Ma, Quanli; Pavlov, Evgeny; Britvina, Tatiana; Zamponi, Gerald W.; French, Robert J.

    2008-01-01

    R13X derivatives of μ-conotoxin GIIIA bind externally to single sodium channels and block current incompletely with mean “blocked” durations of several seconds. We studied interactions between two classes of blockers (μ-conotoxins and amines) by steady state, kinetic analysis of block of BTX-modified Na channels in planar bilayers. The amines cause all-or-none block at a site internal to the selectivity filter. TPrA and DEA block single Na channels with very different kinetics. TPrA induces discrete, all-or-none, blocked events (mean blocked durations, ∼100 ms), whereas DEA produces a concentration-dependent reduction of the apparent single channel amplitude (“fast” block). These distinct modes of action allow simultaneous evaluation of block by TPrA and DEA, showing a classical, competitive interaction between them. The apparent affinity of TPrA decreases with increasing [DEA], based on a decrease in the association rate for TPrA. When an R13X μ-conotoxin derivative and one of the amines are applied simultaneously on opposite sides of the membrane, a mutually inhibitory interaction is observed. Dissociation constants, at +50 mV, for TPrA (∼4 mM) and DEA (∼30 mM) increase by ∼20%–50% when R13E (nominal net charge, +4) or R13Q (+5) is bound. Analysis of the slow blocking kinetics for the two toxin derivatives showed comparable decreases in affinity of the μ-conotoxins in the presence of an amine. Although this mutual inhibition seems to be qualitatively consistent with an electrostatic interaction across the selectivity filter, quantitative considerations raise questions about the mechanistic details of the interaction. PMID:18658223

  13. A kinetic model for voltage-gated ion channels in cell membranes based on the path integral method

    NASA Astrophysics Data System (ADS)

    Erdem, Rıza; Ekiz, Cesur

    2005-04-01

    A kinetic model of cell membrane ion channels is proposed based on the path integral method. From the Pauli-type master equations valid on a macroscopic time scale, we derive a first-order differential equation or the kinetic equation which governs temporal evolution of the channel system along the paths of extreme probability. Using known parameters for the batrachotoxin (BTX)-modified sodium channels in squid giant axon, the time dependence of the channel activation and the voltage dependence of the corresponding time constants ( τ) are examined numerically. It is found that the channel activation relaxes to the steady (or equilibrium)-state values for a given membrane potential and the corresponding time constant reaches a maximum at a certain potential and thereafter decreases in magnitude as the membrane potential increases. A qualitative comparison between these results and the results of Hodgkin-Huxley theory, path probability method and thermodynamic models as well as the cut-open axon technique is presented. Good agreement is achieved.

  14. Cosmic rays in a random magnetic field: Breakdown of the quasilinear derivation of the kinetic equation

    NASA Technical Reports Server (NTRS)

    Kaiser, T. B.; Jones, F. C.; Birmingham, T. J.

    1972-01-01

    The problem of deriving a kinetic equation for the cosmic ray distribution function in a random magnetic field is considered. A model is adopted which is mathematically simple but which contains the essential physics. The perturbation expansion upon which the quasi-linear treatment is based is investigated. The existence of resonant particles causes the breakdown of the adiabatic approximation frequently used in this theory. Resonant particles cause a general secular growth of higher order terms in the expansion which invalidates the entire perturbative approach.

  15. Comparative analysis of the kinetic characteristics of L-type calcium channels in cardiac cells of hibernators.

    PubMed Central

    Alekseev, A E; Markevich, N I; Korystova, A F; Terzic, A; Kokoz, Y M

    1996-01-01

    An undefined property of L-type Ca2+ channels is believed to underlie the unique phenotype of hibernating hearts. Therefore, L-type Ca2+ channels in single cardiomyocytes isolated from hibernating versus awake ground-squirrels (Citellus undulatus) were compared using the perforated mode of the patch-clamp technique, and interpreted by way of a kinetic model of Ca2+ channel behavior based upon the concept of independence of the activation and inactivation processes. We find that, in hibernating ground-squirrels, the cardiac L-type Ca2+ current is lower in magnitude when compared to awake animals. Both in the awake or hibernating states, kinetics of L-type Ca2+ channels could be described by a d2f1(2)f2 model with an activation and two inactivation processes. The activation (or d) process relates to the movement of the gating charge. The slow (or f1) inactivation is associated with movement of gating charge and is current-dependent. The rapid (or f2) inactivation is a complex process which cannot be represented as a single-step conformational transition induced by the gating charge movement, and is regulated by beta-adrenoceptor stimulation. When compared to awake animals, the kinetic properties of Ca2+ channels from hibernating ground-squirrels differed in the following parameters: (1) pronounced shift (15-20 mV) toward depolarization in the normalized conductance of both inactivation components, and moderate shift in the activation component; (2) 1.5-2-fold greater time constants; and (3) two-fold greater activation gating charge. Thus, L-type Ca2+ channels apparently switch their phenotype during the hibernating transition. Stimulation of beta-adrenoceptors by isoproterenol, reversed the hibernating kinetic- (but not amplitude-) phenotype toward the awake type. Therefore, an aberrance in the beta-adrenergic system can not fully explain the observed changes in the L-type Ca2+ current. This suggests that during hibernation additional mechanisms may reduce the single

  16. The random energy model in a magnetic field and joint source channel coding

    NASA Astrophysics Data System (ADS)

    Merhav, Neri

    2008-09-01

    We demonstrate that there is an intimate relationship between the magnetic properties of Derrida’s random energy model (REM) of spin glasses and the problem of joint source-channel coding in Information Theory. In particular, typical patterns of erroneously decoded messages in the coding problem have “magnetization” properties that are analogous to those of the REM in certain phases, where the non-uniformity of the distribution of the source in the coding problem plays the role of an external magnetic field applied to the REM. We also relate the ensemble performance (random coding exponents) of joint source-channel codes to the free energy of the REM in its different phases.

  17. Bupivacaine Blocks N-Type Inactivating Kv Channels in the Open State: No Allosteric Effect on Inactivation Kinetics

    PubMed Central

    Nilsson, Johanna; Madeja, Michael; Elinder, Fredrik; Århem, Peter

    2008-01-01

    Local anesthetics bind to ion channels in a state-dependent manner. For noninactivating voltage-gated K channels the binding mainly occurs in the open state, while for voltage-gated inactivating Na channels it is assumed to occur mainly in inactivated states, leading to an allosterically caused increase in the inactivation probability, reflected in a negative shift of the steady-state inactivation curve, prolonged recovery from inactivation, and a frequency-dependent block. How local anesthetics bind to N-type inactivating K channels is less explored. In this study, we have compared bupivacaine effects on inactivating (Shaker and Kv3.4) and noninactivating (Shaker-IR and Kv3.2) channels, expressed in Xenopus oocytes. Bupivacaine was found to block these channels time-dependently without shifting the steady-state inactivation curve markedly, without a prolonged recovery from inactivation, and without a frequency-dependent block. An analysis, including computational testing of kinetic models, suggests binding to the channel mainly in the open state, with affinities close to those estimated for corresponding noninactivating channels (300 and 280 μM for Shaker and Shaker-IR, and 60 and 90 μM for Kv3.4 and Kv3.2). The similar magnitudes of Kd, as well as of blocking and unblocking rate constants for inactivating and noninactivating Shaker channels, most likely exclude allosteric interactions between the inactivation mechanism and the binding site. The relevance of these results for understanding the action of local anesthetics on Na channels is discussed. PMID:18790854

  18. Random alloy diffusion kinetics for the application to multicomponent alloy systems

    NASA Astrophysics Data System (ADS)

    Paul, T. R.; Belova, I. V.; Murch, G. E.

    2016-04-01

    In this paper, extensive Monte Carlo simulation results are reported on tracer and collective diffusion correlation effects in the random ternary alloy, as an example of a multicomponent alloy system. The problem of analytically describing both collective and tracer diffusion kinetics is also addressed for the random multicomponent alloy by application of a combination of the Manning theory and Holdsworth and Elliott theory. It is found that the overall results from the combined theory agree reasonably well with Monte Carlo results. This combined approach is much more accurate than Manning's approach itself and much more manageable than the almost exact, but unfortunately difficult to use, self-consistent theory of Moleko, Allnatt and Allnatt. Some relations between the Onsager phenomenological coefficients and tracer diffusion coefficients are derived and are tested with our Monte Carlo data. Good agreement is found.

  19. Drosophila QVR/SSS modulates the activation and C-type inactivation kinetics of Shaker K(+) channels.

    PubMed

    Dean, Terry; Xu, Rong; Joiner, William; Sehgal, Amita; Hoshi, Toshinori

    2011-08-03

    The quiver/sleepless (qvr/sss) gene encodes a small, glycosylphosphatidylinositol-anchored protein that plays a critical role in the regulation of sleep in Drosophila. Loss-of-function mutations in qvr/sss severely suppress sleep and effect multiple changes in in situ Shaker K(+) currents, including decreased magnitude, slower time-to-peak, and cumulative inactivation. Recently, we demonstrated that SLEEPLESS (SSS) protein modulates Shaker channel activity, possibly through a direct interaction at the plasma membrane. We show here that SSS accelerates the activation of heterologously expressed Shaker channels with no effect on deactivation or fast N-type inactivation. Furthermore, this SSS-induced acceleration is sensitive to the pharmacological disruption of lipid rafts and sufficiently accounts for the slower time-to-peak of in situ Shaker currents seen in qvr/sss mutants. We also find that SSS decreases the rate of C-type inactivation of heterologously expressed Shaker channels, providing a potential mechanism for the cumulative inactivation phenotype induced by qvr/sss loss-of-function mutations. Kinetic modeling based on the in vitro results suggests that the SSS-dependent regulation of channel kinetics accounts for nearly 40% of the decrease in Shaker current magnitude in flies lacking SSS. Sleep duration in qvr/sss-null mutants is restored to normal by a qvr/sss transgene that fully rescues the Shaker kinetic phenotypes but only partially rescues the decrease in current magnitude. Together, these results suggest that the role of SSS in the regulation of sleep in Drosophila correlates more strongly with the effects of SSS on Shaker kinetics than current magnitude.

  20. Drosophila QVR/SSS modulates the activation and C-type inactivation kinetics of Shaker K+ channels

    PubMed Central

    Dean, Terry; Xu, Rong; Joiner, William; Sehgal, Amita; Hoshi, Toshinori

    2011-01-01

    The quiver/sleepless (qvr/sss) gene encodes a small, glycosylphosphatidylinositol-anchored protein that plays a critical role in the regulation of sleep in Drosophila. Loss-of-function mutations in qvr/sss severely suppress sleep and effect multiple changes in in situ Shaker K+ currents, including decreased magnitude, slower time-to-peak, and cumulative inactivation. Recently, we demonstrated that SLEEPLESS (SSS) protein modulates Shaker channel activity, possibly through a direct interaction at the plasma membrane. We show here that SSS accelerates the activation of heterologously expressed Shaker channels with no effect on deactivation or fast N-type inactivation. Furthermore, this SSS-induced acceleration is sensitive to the pharmacological disruption of lipid rafts and sufficiently accounts for the slower time-to-peak of in situ Shaker currents seen in qvr/sss mutants. We also find that SSS decreases the rate of C-type inactivation of heterologously expressed Shaker channels, providing a potential mechanism for the cumulative inactivation phenotype induced by qvr/sss loss of function mutations. Kinetic modeling based on the in vitro results suggests that the SSS-dependent regulation of channel kinetics accounts for nearly 40% of the decrease in Shaker current magnitude in flies lacking SSS. Sleep duration in qvr/sss null mutants is restored to normal by a qvr/sss transgene that fully rescues the Shaker kinetic phenotypes but only partially rescues the decrease in current magnitude. Together, these results suggest that the role of SSS in the regulation of sleep in Drosophila correlates more strongly with the effects of SSS on Shaker kinetics than current magnitude. PMID:21813698

  1. Effects of unsaturated fatty acids on the kinetics of voltage‐gated proton channels heterologously expressed in cultured cells

    PubMed Central

    Kawanabe, Akira

    2016-01-01

    Key points Arachidonic acid (AA) greatly enhances the activity of the voltage‐gated proton (Hv) channel, although its mechanism of action and physiological function remain unclear.In the present study, we analysed the effects of AA on proton currents through Hv channels heterologously expressed in HEK293T cells.The dramatic increase in proton current amplitude elicited by AA was accompanied by accelerated activation kinetics and a leftward shift in the voltage‐dependence of activation.Mutagenesis studies suggest the two aforementioned effects of AA reflect two distinct structural mechanisms.Application of phospholipase A2, which liberates AA from phospholipids in the membrane, also enhances Hv channel activity, supporting the idea that AA modulates Hv channel activity within physiological contexts. Abstract Unsaturated fatty acids are key components of the biological membranes of all cells, and precursors of mediators for cell signalling. Arachidonic acid (AA) is an unsaturated fatty acid known to modulate the activities of various ion channels, including the voltage‐gated proton (Hv) channel, which supports the rapid production of reactive oxygen species (ROS) in phagocytes through regulation of pH and membrane potential. However, the molecular mechanisms and physiological functions of the effects of AA on Hv channels remain unclear. In the present study, we report an electrophysiological analysis of the effects of AA on the mouse Hv channel (mHv1) heterologously expressed in HEK293T cells. Application of AA to excised inside‐out patch membranes rapidly induced a robust increase in the amplitude of the proton current through mHv1. The current increase was accompanied by accelerated activation kinetics and a small leftward shift of the current–voltage relationship. In monomeric channels lacking the coiled‐coil region of the channel protein, the shift in the current–voltage relationship was diminished but activation and deactivation remained

  2. Kinetics of spin relaxation in quantum wires and channels: Boundary spin echo and formation of a persistent spin helix

    SciTech Connect

    Slipko, Valeriy A.; Pershin, Yuriy V.

    2011-10-15

    In this paper we use a spin kinetic equation to study spin-polarization dynamics in one-dimensional (1D) wires and 2D channels. The spin kinetic equation is valid in both diffusive and ballistic spin transport regimes and therefore is more general than the usual spin drift-diffusion equations. In particular, we demonstrate that in infinite 1D wires with Rashba spin-orbit interaction the exponential spin-relaxation decay can be modulated by an oscillating function. In the case of spin relaxation in finite length 1D wires, it is shown that an initially homogeneous spin polarization spontaneously transforms into a persistent spin helix. We find that a propagating spin-polarization profile reflects from a system boundary and returns back to its initial position similarly to the reflectance of sound waves from an obstacle. The Green's function of the spin kinetic equation is derived for both finite and infinite 1D systems. Moreover, we demonstrate explicitly that the spin relaxation in specifically oriented 2D channels with Rashba and Dresselhaus spin-orbit interactions of equal strength occurs similarly to that in 1D wires of finite length. Finally, a simple transformation mapping 1D spin kinetic equation into the Klein-Gordon equation with an imaginary mass is found thus establishing an interesting connection between semiconductor spintronics and relativistic quantum mechanics.

  3. Voltage gating by molecular subunits of Na+ and K+ ion channels: higher-dimensional cubic kinetics, rate constants, and temperature

    PubMed Central

    2015-01-01

    The structural similarity between the primary molecules of voltage-gated Na and K channels (alpha subunits) and activation gating in the Hodgkin-Huxley model is brought into full agreement by increasing the model's sodium kinetics to fourth order (m3 → m4). Both structures then virtually imply activation gating by four independent subprocesses acting in parallel. The kinetics coalesce in four-dimensional (4D) cubic diagrams (16 states, 32 reversible transitions) that show the structure to be highly failure resistant against significant partial loss of gating function. Rate constants, as fitted in phase plot data of retinal ganglion cell excitation, reflect the molecular nature of the gating transitions. Additional dimensions (6D cubic diagrams) accommodate kinetically coupled sodium inactivation and gating processes associated with beta subunits. The gating transitions of coupled sodium inactivation appear to be thermodynamically irreversible; response to dielectric surface charges (capacitive displacement) provides a potential energy source for those transitions and yields highly energy-efficient excitation. A comparison of temperature responses of the squid giant axon (apparently Arrhenius) and mammalian channel gating yields kinetic Q10 = 2.2 for alpha unit gating, whose transitions are rate-limiting at mammalian temperatures; beta unit kinetic Q10 = 14 reproduces the observed non-Arrhenius deviation of mammalian gating at low temperatures; the Q10 of sodium inactivation gating matches the rate-limiting component of activation gating at all temperatures. The model kinetics reproduce the physiologically large frequency range for repetitive firing in ganglion cells and the physiologically observed strong temperature dependence of recovery from inactivation. PMID:25867741

  4. Voltage gating by molecular subunits of Na+ and K+ ion channels: higher-dimensional cubic kinetics, rate constants, and temperature.

    PubMed

    Fohlmeister, Jürgen F

    2015-06-01

    The structural similarity between the primary molecules of voltage-gated Na and K channels (alpha subunits) and activation gating in the Hodgkin-Huxley model is brought into full agreement by increasing the model's sodium kinetics to fourth order (m(3) → m(4)). Both structures then virtually imply activation gating by four independent subprocesses acting in parallel. The kinetics coalesce in four-dimensional (4D) cubic diagrams (16 states, 32 reversible transitions) that show the structure to be highly failure resistant against significant partial loss of gating function. Rate constants, as fitted in phase plot data of retinal ganglion cell excitation, reflect the molecular nature of the gating transitions. Additional dimensions (6D cubic diagrams) accommodate kinetically coupled sodium inactivation and gating processes associated with beta subunits. The gating transitions of coupled sodium inactivation appear to be thermodynamically irreversible; response to dielectric surface charges (capacitive displacement) provides a potential energy source for those transitions and yields highly energy-efficient excitation. A comparison of temperature responses of the squid giant axon (apparently Arrhenius) and mammalian channel gating yields kinetic Q10 = 2.2 for alpha unit gating, whose transitions are rate-limiting at mammalian temperatures; beta unit kinetic Q10 = 14 reproduces the observed non-Arrhenius deviation of mammalian gating at low temperatures; the Q10 of sodium inactivation gating matches the rate-limiting component of activation gating at all temperatures. The model kinetics reproduce the physiologically large frequency range for repetitive firing in ganglion cells and the physiologically observed strong temperature dependence of recovery from inactivation.

  5. Revealing the activation pathway for TMEM16A chloride channels from macroscopic currents and kinetic models.

    PubMed

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

    2016-07-01

    TMEM16A (ANO1), the pore-forming subunit of calcium-activated chloride channels, regulates several physiological and pathophysiological processes such as smooth muscle contraction, cardiac and neuronal excitability, salivary secretion, tumour growth and cancer progression. Gating of TMEM16A is complex because it involves the interplay between increases in intracellular calcium concentration ([Ca(2+)]i), membrane depolarization, extracellular Cl(-) or permeant anions and intracellular protons. Our goal here was to understand how these variables regulate TMEM16A gating and to explain four observations. (a) TMEM16A is activated by voltage in the absence of intracellular Ca(2+). (b) The Cl(-) conductance is decreased after reducing extracellular Cl(-) concentration ([Cl(-)]o). (c) ICl is regulated by physiological concentrations of [Cl(-)]o. (d) In cells dialyzed with 0.2 μM [Ca(2+)]i, Cl(-) has a bimodal effect: at [Cl(-)]o <30 mM TMEM16A current activates with a monoexponential time course, but above 30 mM, [Cl(-)]o ICl activation displays fast and slow kinetics. To explain the contribution of Vm, Ca(2+) and Cl(-) to gating, we developed a 12-state Markov chain model. This model explains TMEM16A activation as a sequential, direct, and Vm-dependent binding of two Ca(2+) ions coupled to a Vm-dependent binding of an external Cl(-) ion, with Vm-dependent transitions between states. Our model predicts that extracellular Cl(-) does not alter the apparent Ca(2+) affinity of TMEM16A, which we corroborated experimentally. Rather, extracellular Cl(-) acts by stabilizing the open configuration induced by Ca(2+) and by contributing to the Vm dependence of activation.

  6. Voltage-dependent modulation of single N-Type Ca2+ channel kinetics by receptor agonists in IMR32 cells.

    PubMed Central

    Carabelli, V; Lovallo, M; Magnelli, V; Zucker, H; Carbone, E

    1996-01-01

    The voltage-dependent inhibition of single N-type Ca(2+) channels by noradrenaline (NA) and the delta-opioid agonist D-Pen(2)-D-Pen (5)-enkephalin (DPDPE) was investigated in cell-attached patches of human neuroblastoma IMR32 cells with 100 mM Ba(2+) and 5 microM nifedipine to block L-type channels. In 70% of patches, addition of 20 microM NA + 1 microM DPDPE delayed markedly the first channel openings, causing a four- to fivefold increase of the first latency at +20 mV. The two agonists or NA alone decreased also by 35% the open probability (P(o)), prolonged partially the mean closed time, and increased the number of null sweeps. In contrast, NA + DPDPE had little action on the single-channel conductance (19 versus 19.2 pS) and minor effects on the mean open time. Similarly to macroscopic Ba(2+) currents, the ensemble currents were fast activating at control but slowly activating and depressed with the two agonists. Inhibition of single N-type channels was effectively removed (facilitated) by short and large depolarizations. Facilitatory pre-pulses increased P(o) significantly and decreased fourfold the first latency. Ensemble currents were small and slowly activating before pre-pulses and became threefold larger and fast decaying after facilitation. Our data suggest that slowdown of Ca(2+) channel activation by transmitters is mostly due to delayed transitions from a modified to a normal (facilitated) gating mode. This single-channel gating modulation could be well simulated by a Monte Carlo method using previously proposed kinetic models predicting marked prolongation of first channel openings. Images FIGURE 3 FIGURE 4 FIGURE 7 PMID:9172738

  7. In silico screening of the impact of hERG channel kinetic abnormalities on channel block and susceptibility to acquired long QT syndrome

    PubMed Central

    Romero, Lucia; Trenor, Beatriz; Yang, Pei-Chi; Saiz, Javier; Clancy, Colleen E.

    2016-01-01

    Accurate diagnosis of predisposition to long QT syndrome is crucial for reducing the risk of cardiac arrhythmias. In recent years, drug-induced provocative tests have proved useful to unmask some latent mutations linked to cardiac arrhythmias. In this study we expanded this concept by developing a prototype for a computational provocative screening test to reveal genetic predisposition to acquired long-QT syndrome (aLQTS). We developed a computational approach to reveal the pharmacological properties of IKr blocking drugs that are most likely to cause aLQTS in the setting of subtle alterations in IKr channel gating that would be expected to result from benign genetic variants. We used the model to predict the most potentially lethal combinations of kinetic anomalies and drug properties. In doing so, we also implicitly predicted ideal inverse therapeutic properties of K channel openers that would be expected to remedy a specific defect. We systematically performed “in silico mutagenesis” by altering discrete kinetic transition rates of the Fink et al. Markov model of human IKr channels, corresponding to activation, inactivation, deactivation and recovery from inactivation of IKr channels. We then screened and identified the properties of IKr blockers that caused acquired long QT and therefore unmasked mutant phenotypes for mild, moderate and severe variants. Mutant IKr channels were incorporated into the O'Hara et al. human ventricular action potential (AP) model and subjected to simulated application of a wide variety of IKr–drug interactions in order to identify the characteristics that selectively exacerbate the AP duration (APD) differences between wild-type and IKr mutated cells. Our results show that drugs with disparate affinities to conformation states of the IKr channel are key to amplify variants underlying susceptibility to acquired long QT syndrome, an effect that is especially pronounced at slow frequencies. Finally, we developed a mathematical

  8. In silico screening of the impact of hERG channel kinetic abnormalities on channel block and susceptibility to acquired long QT syndrome

    PubMed Central

    Romero, Lucia; Trenor, Beatriz; Yang, Pei-Chi; Saiz, Javier; Clancy, Colleen E.

    2014-01-01

    Accurate diagnosis of predisposition to long QT syndrome is crucial for reducing the risk of cardiac arrhythmias. In recent years, drug-induced provocative tests have proved useful to unmask some latent mutations linked to cardiac arrhythmias. In this study we expanded this concept by developing a prototype for a computational provocative screening test to reveal genetic predisposition to acquired Long-QT Syndrome (aLTQS). We developed a computational approach to reveal the pharmacological properties of IKr blocking drugs that are most likely to cause aLQTS in the setting of subtle alterations in IKr channel gating that would be expected to result from benign genetic variants. We used the model to predict the most potentially lethal combinations of kinetic anomalies and drug properties. In doing so, we also implicitly predicted ideal inverse therapeutic properties of K channel openers that would be expected to remedy a specific defect. We systematically performed “in silico mutagenesis” by altering discrete kinetic transition rates of the Fink et al. Markov model of human IKr channels, corresponding to activation, inactivation, deactivation and recovery from inactivation of IKr channels. We then screened and identified the properties of IKr blockers that caused acquired Long QT and therefore unmasked mutant phenotypes for mild, moderate and severe variants. Mutant IKr channels were incorporated into the O’Hara et al. human ventricular action potential (AP) model and subjected to simulated application of a wide variety of IKr-drug interactions in order to identify the characteristics that selectively exacerbate the AP duration (APD) differences between wild-type and IKr mutated cells. Our results show that drugs with disparate affinities to conformation states of the IKr channel are key to amplify variants underlying susceptibility to acquired Long QT Syndrome, an effect that is especially pronounced at slow frequencies. Finally, we developed a mathematical

  9. In silico screening of the impact of hERG channel kinetic abnormalities on channel block and susceptibility to acquired long QT syndrome.

    PubMed

    Romero, Lucia; Trenor, Beatriz; Yang, Pei-Chi; Saiz, Javier; Clancy, Colleen E

    2015-10-01

    Accurate diagnosis of predisposition to long QT syndrome is crucial for reducing the risk of cardiac arrhythmias. In recent years, drug-induced provocative tests have proved useful to unmask some latent mutations linked to cardiac arrhythmias. In this study we expanded this concept by developing a prototype for a computational provocative screening test to reveal genetic predisposition to acquired long-QT syndrome (aLQTS). We developed a computational approach to reveal the pharmacological properties of I(Kr) blocking drugs that are most likely to cause aLQTS in the setting of subtle alterations in I(Kr) channel gating that would be expected to result from benign genetic variants.Weused themodel to predict themost potentially lethal combinations of kinetic anomalies and drug properties. In doing so, we also implicitly predicted ideal inverse therapeutic properties of K channel openers that would be expected to remedy a specific defect. We systematically performed “in silico mutagenesis” by altering discrete kinetic transition rates of the Fink et al. Markov model of human I(Kr) channels, corresponding to activation, inactivation, deactivation and recovery from inactivation of I(Kr) channels. We then screened and identified the properties of I(Kr) blockers that caused acquired long QT and therefore unmasked mutant phenotypes formild,moderate and severe variants. Mutant I(Kr) channels were incorporated into the O'Hara et al. human ventricular action potential (AP) model and subjected to simulated application of a wide variety of I(Kr)-drug interactions in order to identify the characteristics that selectively exacerbate the AP duration (APD) differences between wild-type and I(Kr) mutated cells. Our results show that drugs with disparate affinities to conformation states of the I(Kr) channel are key to amplify variants underlying susceptibility to acquired long QT syndrome, an effect that is especially pronounced at slow frequencies. Finally, we developed a

  10. In silico screening of the impact of hERG channel kinetic abnormalities on channel block and susceptibility to acquired long QT syndrome.

    PubMed

    Romero, Lucia; Trenor, Beatriz; Yang, Pei-Chi; Saiz, Javier; Clancy, Colleen E

    2014-07-01

    Accurate diagnosis of predisposition to long QT syndrome is crucial for reducing the risk of cardiac arrhythmias. In recent years, drug-induced provocative tests have proved useful to unmask some latent mutations linked to cardiac arrhythmias. In this study we expanded this concept by developing a prototype for a computational provocative screening test to reveal genetic predisposition to acquired long-QT syndrome (aLQTS). We developed a computational approach to reveal the pharmacological properties of IKr blocking drugs that are most likely to cause aLQTS in the setting of subtle alterations in IKr channel gating that would be expected to result from benign genetic variants. We used the model to predict the most potentially lethal combinations of kinetic anomalies and drug properties. In doing so, we also implicitly predicted ideal inverse therapeutic properties of K channel openers that would be expected to remedy a specific defect. We systematically performed "in silico mutagenesis" by altering discrete kinetic transition rates of the Fink et al. Markov model of human IKr channels, corresponding to activation, inactivation, deactivation and recovery from inactivation of IKr channels. We then screened and identified the properties of IKr blockers that caused acquired long QT and therefore unmasked mutant phenotypes for mild, moderate and severe variants. Mutant IKr channels were incorporated into the O'Hara et al. human ventricular action potential (AP) model and subjected to simulated application of a wide variety of IKr-drug interactions in order to identify the characteristics that selectively exacerbate the AP duration (APD) differences between wild-type and IKr mutated cells. Our results show that drugs with disparate affinities to conformation states of the IKr channel are key to amplify variants underlying susceptibility to acquired long QT syndrome, an effect that is especially pronounced at slow frequencies. Finally, we developed a mathematical

  11. Online distribution channel increases article usage on Mendeley: a randomized controlled trial.

    PubMed

    Kudlow, Paul; Cockerill, Matthew; Toccalino, Danielle; Dziadyk, Devin Bissky; Rutledge, Alan; Shachak, Aviv; McIntyre, Roger S; Ravindran, Arun; Eysenbach, Gunther

    2017-01-01

    Prior research shows that article reader counts (i.e. saves) on the online reference manager, Mendeley, correlate to future citations. There are currently no evidenced-based distribution strategies that have been shown to increase article saves on Mendeley. We conducted a 4-week randomized controlled trial to examine how promotion of article links in a novel online cross-publisher distribution channel (TrendMD) affect article saves on Mendeley. Four hundred articles published in the Journal of Medical Internet Research were randomized to either the TrendMD arm (n = 200) or the control arm (n = 200) of the study. Our primary outcome compares the 4-week mean Mendeley saves of articles randomized to TrendMD versus control. Articles randomized to TrendMD showed a 77% increase in article saves on Mendeley relative to control. The difference in mean Mendeley saves for TrendMD articles versus control was 2.7, 95% CI (2.63, 2.77), and statistically significant (p < 0.01). There was a positive correlation between pageviews driven by TrendMD and article saves on Mendeley (Spearman's rho r = 0.60). This is the first randomized controlled trial to show how an online cross-publisher distribution channel (TrendMD) enhances article saves on Mendeley. While replication and further study are needed, these data suggest that cross-publisher article recommendations via TrendMD may enhance citations of scholarly articles.

  12. Dual-channel in-line digital holographic double random phase encryption.

    PubMed

    Das, Bhargab; Yelleswarapu, Chandra S; Rao, D V G L N

    2012-10-01

    We present a robust encryption method for the encoding of 2D/3D objects using digital holography and virtual optics. Using our recently developed dual-plane in-line digital holography technique, two in-line digital holograms are recorded at two different planes and are encrypted using two different double random phase encryption configurations, independently. The process of using two mutually exclusive encryption channels makes the system more robust against attacks since both the channels should be decrypted accurately in order to get a recognizable reconstruction. Results show that the reconstructed object is unrecognizable even when the portion of the correct phase keys used during decryption is close to 75%. The system is verified against blind decryptions by evaluating the SNR and MSE. Validation of the proposed method and sensitivities of the associated parameters are quantitatively analyzed and illustrated.

  13. Dual-channel in-line digital holographic double random phase encryption

    PubMed Central

    Das, Bhargab; Yelleswarapu, Chandra S; Rao, D V G L N

    2012-01-01

    We present a robust encryption method for the encoding of 2D/3D objects using digital holography and virtual optics. Using our recently developed dual-plane in-line digital holography technique, two in-line digital holograms are recorded at two different planes and are encrypted using two different double random phase encryption configurations, independently. The process of using two mutually exclusive encryption channels makes the system more robust against attacks since both the channels should be decrypted accurately in order to get a recognizable reconstruction. Results show that the reconstructed object is unrecognizable even when the portion of the correct phase keys used during decryption is close to 75%. The system is verified against blind decryptions by evaluating the SNR and MSE. Validation of the proposed method and sensitivities of the associated parameters are quantitatively analyzed and illustrated. PMID:23471012

  14. Numerical analysis of ultrafast physical random number generator using dual-channel optical chaos

    NASA Astrophysics Data System (ADS)

    Elsonbaty, Amr; Hegazy, Salem F.; Obayya, Salah S. A.

    2016-09-01

    Fast physical random number generators (PRNGs) are essential elements in the development of many modern applications. We numerically demonstrate an extraction scheme to establish an ultrafast PRNG using dual-channel optical-chaos source. Simultaneous suppression of time-delay signature in all observables of the output is verified using autocorrelation-function method. The proposed technique compares the level of the chaotic signal at time t with M levels of its delayed version. The comparators [1-bit analog-to-digital converters (ADCs)] are triggered using a clock subject to an incremental delay. All the delays of the chaotic signal before the ADCs and the relative delays of the clock are mutually incommensurable. The outputs of the ADCs are then combined using parity-check logic to produce physically true random numbers. The randomness quality of the generated random bits is evaluated by the statistical tests of National Institute of Standards and Technology Special Publication 800-22. The results verify that all tests are passed from M=1 to M=39 at sampling rate up to 34.5 GHz, which indicates that the maximum generation rate of random bits is 2.691 Tb/s without employing any preprocessing techniques. This rate, to the best of our knowledge, is higher than any previously reported PRNG.

  15. On random search: Collection kinetics of Paramecia into a trap embedded in a closed domain

    NASA Astrophysics Data System (ADS)

    Deforet, Maxime; Duplat, Jérôme; Vandenberghe, Nicolas; Villermaux, Emmanuel

    2010-06-01

    We study the kinetics of a large number of organisms initially spread uniformly in a circular two-dimensional medium, at the center of which a smaller circular trap has been introduced. We take advantage of the acidophily of Paramecium caudatum, which, coming from a neutral medium, penetrates a region of moderate acidity but moves back in the opposite situation when it meets a sharp negative acidity gradient to quantify its rate of irreversible aggregation into a spot of acidified medium in water. Two regimes are distinguished: A ballistic regime characteristic of "fresh" paramecia where the organisms swim in a straight path with a well defined velocity and a Brownian regime characteristic of older paramecia where the mean free path of the organisms is smaller than the system size. Both regimes are characterized by distinct aggregation laws. They both result from a pure random trapping process that appears to have no adaptive strategy.

  16. Random-phase-approximation calculations and residual interactions in the sigmatau channel

    SciTech Connect

    Cohen, J.

    1986-05-01

    We compare numerical results for renormalized spin-isospin matrix elements within the random phase approximation. Extended calculations are carried out for a pionlike excitation in a finite nucleus; the effects of contact versus momentum-dependent residual interactions, and of ..delta..-h configurations, are demonstrated. We point out the implications of our results on nuclear structure calculations, where such effects are sometimes neglected. The role of the finite geometry of the system is crucial in determining the features of the spin-isospin responses. We emphasize that a crucial test of the theory can only be achieved through a direct comparison of the longitudinal and transverse channels.

  17. A multichannel Markov random field approach for automated segmentation of breast cancer tumor in DCE-MRI data using kinetic observation model.

    PubMed

    Ashraf, Ahmed B; Gavenonis, Sara; Daye, Dania; Mies, Carolyn; Feldman, Michael; Rosen, Mark; Kontos, Despina

    2011-01-01

    We present a multichannel extension of Markov random fields (MRFs) for incorporating multiple feature streams in the MRF model. We prove that for making inference queries, any multichannel MRF can be reduced to a single channel MRF provided features in different channels are conditionally independent given the hidden variable, Using this result we incorporate kinetic feature maps derived from breast DCE MRI into the observation model of MRF for tumor segmentation. Our algorithm achieves an ROC AUC of 0.97 for tumor segmentation, We present a comparison against the commonly used approach of fuzzy C-means (FCM) and the more recent method of running FCM on enhancement variance features (FCM-VES). These previous methods give a lower AUC of 0.86 and 0.60 respectively, indicating the superiority of our algorithm. Finally, we investigate the effect of superior segmentation on predicting breast cancer recurrence using kinetic DCE MRI features from the segmented tumor regions. A linear prediction model shows significant prediction improvement when segmenting the tumor using the proposed method, yielding a correlation coefficient r = 0.78 (p < 0.05) to validated cancer recurrence probabilities, compared to 0.63 and 0.45 when using FCM and FCM-VES respectively.

  18. Symmetry, randomness, and process in the structure of branched channel networks

    NASA Astrophysics Data System (ADS)

    Shelef, Eitan; Hilley, George E.

    2014-05-01

    The branched structure of channel networks has a primary impact on the spatial distribution of elevation, water, and life across Earth's surface from the hillslope to the continental scale and is also observed on other planets. However, the link between this dendritic multiscale structure and the erosional processes that sculpt it has remained elusive for more than six decades. In fact, many topologic measures fail to distinguish natural networks from those generated by random walks. Here we show that a fundamental multiscale topologic symmetry is ingrained into the structure of these networks and reflects the equal elevation drop spanned by flows that split at the drainage divide and meet again downslope. We demonstrate that this symmetry distinguishes random-walk networks from natural ones, captures the temporal evolution of these networks, and divulges information about the processes that shape them.

  19. Entanglement in correlated random spin chains, RNA folding and kinetic roughening

    NASA Astrophysics Data System (ADS)

    Rodríguez-Laguna, Javier; Santalla, Silvia N.; Ramírez, Giovanni; Sierra, Germán

    2016-07-01

    Average block entanglement in the 1D XX-model with uncorrelated random couplings is known to grow as the logarithm of the block size, in similarity to conformal systems. In this work we study random spin chains whose couplings present long range correlations, generated as gaussian fields with a power-law spectral function. Ground states are always planar valence bond states, and their statistical ensembles are characterized in terms of their block entropy and their bond-length distribution, which follow power-laws. We conjecture the existence of a critical value for the spectral exponent, below which the system behavior is identical to the case of uncorrelated couplings. Above that critical value, the entanglement entropy violates the area law and grows as a power law of the block size, with an exponent which increases from zero to one. Interestingly, we show that XXZ models with positive anisotropy present the opposite behavior, and strong correlations in the couplings lead to lower entropies. Similar planar bond structures are also found in statistical models of RNA folding and kinetic roughening, and we trace an analogy between them and quantum valence bond states. Using an inverse renormalization procedure we determine the optimal spin-chain couplings which give rise to a given planar bond structure, and study the statistical properties of the couplings whose bond structures mimic those found in RNA folding.

  20. Channels

    NASA Image and Video Library

    2014-04-29

    Two channels are visible in this image from NASA 2001 Mars Odyssey spacecraft . The smaller one near the bottom did not carve as deeply as the larger channel at the top. The channel near the top of the image is near the origin of Mamers Valles.

  1. Investigations on Physical Random Access Channel Structure in Evolved UTRA Uplink

    NASA Astrophysics Data System (ADS)

    Kishiyama, Yoshihisa; Higuchi, Kenichi; Sawahashi, Mamoru

    This paper presents the optimum physical random access channel (PRACH) structure in terms of the number of control signaling bits accommodated and the transmission bandwidth based on the link budget in order to satisfy the coverage requirement for the single-carrier (SC)-FDMA based E-UTRA uplink. First, we present the design concept of the PRACH structure considering the purposes of the random access procedure in the E-UTRA. Simulation evaluations including a system-level simulation show that a PRACH comprising a 0.5-msec preamble sequence can convey a 6-bit control signal at the cell edge when the inter-site distance (ISD) is 500m under full channel load conditions with one-cell frequency reuse. It is also shown, however, that a PRACH longer than one-sub-frame, e.g., 1.0msec, is necessary to support the ISD of 1732m assuming the same conditions. We also show that the best transmission bandwidth for the PRACH is approximately 1.08-4.5MHz from the viewpoint of the misdetection probability, and a 1.08-MHz transmission bandwidth is suitable considering other aspects such as flexible resource assignment in the time domain and a small number of options in the transmission bandwidth.

  2. Wanderlust kinetics and variable Ca(2+)-sensitivity of dSlo [correction of Drosophila], a large conductance CA(2+)-activated K+ channel, expressed in oocytes.

    PubMed Central

    Silberberg, S D; Lagrutta, A; Adelman, J P; Magleby, K L

    1996-01-01

    Cloned large conductance Ca2+-activated K+ channels (BK or maxi-K+ channels) from Drosophila (dSlo) were expressed in Xenopus oocytes and studied in excised membrane patches with the patch-clamp technique. Both a natural variant and a mutant that eliminated a putative cyclic AMP-dependent protein kinase phosphorylation site exhibited large, slow fluctuations in open probability with time. These fluctuations, termed "wanderlust kinetics," occurred with a time course of tens of seconds to minutes and had kinetic properties inconsistent with simple gating models. Wanderlust kinetics was still observed in the presence of 5mM caffeine or 50 nM thapsigargin, or when the Ca2+ buffering capacity of the solution was increased by the addition of 5 mM HEDTA, suggesting that the wanderlust kinetics did not arise from Ca2+ release from caffeine and thapsigargin sensitive internal stores in the excised patch. The slow changes in kinetics associated with wanderlust kinetics could be generated with a discrete-state Markov model with transitions among three or more kinetic modes with different levels of open probability. To average out the wanderlust kinetics, large amounts of data were analyzed and demonstrated up to a threefold difference in the [Ca2+]i required for an open probability of 0.5 among channels expressed from the same injected mRNA. These findings indicate that cloned dSlo channels in excised patches from Xenopus oocytes can exhibit large variability in gating properties, both within a single channel and among channels. PMID:9643949

  3. The use of steerable channels for detecting asymmetrical signals with random orientations

    NASA Astrophysics Data System (ADS)

    Goossens, Bart; Platiša, Ljiljana; Vansteenkiste, Ewout; Philips, Wilfried

    2010-02-01

    In the optimization of medical imaging systems, there is a stringent need to shift from human observer studies to numerical observer studies, because of both cost and time limitations. Numerical models give an objective measure for the quality of displayed images for a given task and can be designed to predict the performance of medical specialists performing the same task. For the task of signal detection, the channelized Hotelling observer (CHO) has been successfully used, although several studies indicate an overefficiency of the CHO compared to human observers. One of the main causes of this overefficiency is attributed to the intrinsic uncertainty about the signal (such as its orientation) that a human observer is dealing with. Deeper knowledge of the discrepancies of the CHO and the human observer may provide extra insight in the processing of the human visual system and this knowledge can be utilized to better fine-tune medical imaging systems. In this paper, we investigate the optimal detection of asymmetrical signals with statistically known random orientation, based on joint detection and estimation theory. We derive the optimal channelized observer for this task and we show that the optimal detection in channel space requires the use of steerable channels, which are used in steerable pyramid transforms in image processing. Even though the use of CHOs for SKS tasks has not been studied so far, our findings indicate that CHO models can be further extended to incorporate intrinsic uncertainty about the signal to behave closer to humans. Experimental results are provided to illustrate these findings.

  4. Electrostatics at the membrane define MscL channel mechanosensitivity and kinetics.

    PubMed

    Zhong, Dalian; Blount, Paul

    2014-12-01

    The bacterial mechanosensitive channel of large conductance (MscL) serves as a biological emergency release valve, preventing the occurrence of cell lysis caused by acute osmotic stress. Its tractable nature allows it to serve as a paradigm for how a protein can directly sense membrane tension. Although much is known of the importance of the hydrophobicity of specific residues in channel gating, it has remained unclear whether electrostatics at the membrane plays any role. We studied MscL chimeras derived from functionally distinct orthologues: Escherichia coli and Staphylococcus aureus. Dissection of one set led to an observation that changing the charge of a single residue, K101, of E. coli (Ec)-MscL, effects a channel phenotype: when mutated to a negative residue, the channel is less mechanosensitive and has longer open dwell times. Assuming electrostatic interactions, we determined whether they are due to protein-protein or protein-lipid interactions by performing site-directed mutagenesis elsewhere in the protein and reconstituting channels into defined lipids, with and without negative head groups. We found that although both interactions appear to play some role, the primary determinant of the channel phenotype seems to be protein-lipid electrostatics. The data suggest a model for the role of electrostatic interactions in the dynamics of MscL gating. © FASEB.

  5. Probing kinetic drug binding mechanism in voltage-gated sodium ion channel: open state versus inactive state blockers.

    PubMed

    Pal, Krishnendu; Gangopadhyay, Gautam

    2015-01-01

    The kinetics and nonequilibrium thermodynamics of open state and inactive state drug binding mechanisms have been studied here using different voltage protocols in sodium ion channel. We have found that for constant voltage protocol, open state block is more efficient in blocking ionic current than inactive state block. Kinetic effect comes through peak current for mexiletine as an open state blocker and in the tail part for lidocaine as an inactive state blocker. Although the inactivation of sodium channel is a free energy driven process, however, the two different kinds of drug affect the inactivation process in a different way as seen from thermodynamic analysis. In presence of open state drug block, the process initially for a long time remains entropy driven and then becomes free energy driven. However in presence of inactive state block, the process remains entirely entropy driven until the equilibrium is attained. For oscillating voltage protocol, the inactive state blocking is more efficient in damping the oscillation of ionic current. From the pulse train analysis it is found that inactive state blocking is less effective in restoring normal repolarisation and blocks peak ionic current. Pulse train protocol also shows that all the inactive states behave differently as one inactive state responds instantly to the test pulse in an opposite manner from the other two states.

  6. 980-nm infrared laser modulation of sodium channel kinetics in a neuron cell linearly mediated by photothermal effect

    NASA Astrophysics Data System (ADS)

    Li, Xinyu; Liu, Jia; Liang, Shanshan; Sun, Changsen

    2014-10-01

    Photothermal effect (PE) plays a major role in the near-infrared laser interaction with biological tissue. But, quite few interactions can be quantitatively depicted. Here, a two-step model is proposed to describe a 980-nm infrared laser interaction with neuron cell in vitro. First, the laser-induced temperature rises in the cell surrounding area were measured by using an open pipette method and also calculated by solving the heat conduction equation. Second, we recorded the modifications on sodium (Na) channel current in neuron cells directly by using a patch clamp to synchronize the 980-nm laser irradiation and obtained how the electrophysiological function of neuron cells respond to the temperature rise. Then, the activation time constants, τm, were extracted by fitting the sodium currents with the Hodgkin-Huxley model. The infrared laser modulation effect on sodium currents kinetics was examined by taking a ratio between the time constants with and without the laser irradiations. The analysis revealed that the averaged ratio at a specific laser exposure could be well related to the temperature properties of the Na channel protein. These results proved that the modulation of sodium current kinetics of a neuron cell in vitro by 980-nm laser with different-irradiation levels was linearly mediated corresponding to the laser-induced PE.

  7. A self-adaptive method for creating high efficiency communication channels through random scattering media.

    PubMed

    Hao, Xiang; Martin-Rouault, Laure; Cui, Meng

    2014-07-29

    Controlling the propagation of electromagnetic waves is important to a broad range of applications. Recent advances in controlling wave propagation in random scattering media have enabled optical focusing and imaging inside random scattering media. In this work, we propose and demonstrate a new method to deliver optical power more efficiently through scattering media. Drastically different from the random matrix characterization approach, our method can rapidly establish high efficiency communication channels using just a few measurements, regardless of the number of optical modes, and provides a practical and robust solution to boost the signal levels in optical or short wave communications. We experimentally demonstrated analog and digital signal transmission through highly scattering media with greatly improved performance. Besides scattering, our method can also reduce the loss of signal due to absorption. Experimentally, we observed that our method forced light to go around absorbers, leading to even higher signal improvement than in the case of purely scattering media. Interestingly, the resulting signal improvement is highly directional, which provides a new means against eavesdropping.

  8. A self-adaptive method for creating high efficiency communication channels through random scattering media

    PubMed Central

    Hao, Xiang; Martin-Rouault, Laure; Cui, Meng

    2014-01-01

    Controlling the propagation of electromagnetic waves is important to a broad range of applications. Recent advances in controlling wave propagation in random scattering media have enabled optical focusing and imaging inside random scattering media. In this work, we propose and demonstrate a new method to deliver optical power more efficiently through scattering media. Drastically different from the random matrix characterization approach, our method can rapidly establish high efficiency communication channels using just a few measurements, regardless of the number of optical modes, and provides a practical and robust solution to boost the signal levels in optical or short wave communications. We experimentally demonstrated analog and digital signal transmission through highly scattering media with greatly improved performance. Besides scattering, our method can also reduce the loss of signal due to absorption. Experimentally, we observed that our method forced light to go around absorbers, leading to even higher signal improvement than in the case of purely scattering media. Interestingly, the resulting signal improvement is highly directional, which provides a new means against eavesdropping. PMID:25070592

  9. The mechanism of inward rectification in Kir channels: A novel kinetic model with non-equilibrium thermodynamics approach.

    PubMed

    Hsieh, Chi-Pan; Chiang, Cheng-Chin; Huang, Chiung-Wei

    2016-05-01

    The mechanisms of the strong inward rectification in inward rectifier K(+) (Kir) channels are controversial because the drop in electrical potential due to the movement of the blocker and coupling ions is insufficient to explain the steep voltage-dependent block near the equilibrium potential. Here, we study the "driving force"-dependent block in Kir channels with a novel approach incorporating concepts from the non-equilibrium thermodynamics of small systems, and computer kinetic simulations based on the experimental data of internal Ba(2+) block on Kir2.1 channels. The steep exponential increase in the apparent binding rate near the equilibrium potential is explained, when the encounter frequency is construed as the likelihood of transfer events down or against the electrochemical potential gradient. The exponent of flux ratio, nf=2.62, implies that the blockage of the internal blocker may be coupled with the outward transport of 2 to 3K(+) ions. The flux-coupled block in the single-file multi-ion pore can be demonstrated by the concentration gradient alone, as well as when the driving force is the electrochemical potential difference across the membrane. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Kinetic model of Nav1.5 channel provides a subtle insight into slow inactivation associated excitability in cardiac cells.

    PubMed

    Zhang, Zheng; Zhao, Zhiwen; Liu, Yongfeng; Wang, Wei; Wu, Ying; Ding, Jiuping

    2013-01-01

    Voltage-gated sodium channel Nav1.5 has been linked to the cardiac cell excitability and a variety of arrhythmic syndromes including long QT, Brugada, and conduction abnormalities. Nav1.5 exhibits a slow inactivation, corresponding to a duration-dependent bi-exponential recovery, which is often associated with various arrhythmia syndromes. However, the gating mechanism of Nav1.5 and the physiological role of slow inactivation in cardiac cells remain elusive. Here a 12-state two-step inactivation Markov model was successfully developed to depict the gating kinetics of Nav1.5. This model can simulate the Nav1.5 channel in not only steady state processes, but also various transient processes. Compared with the simpler 8-state model, this 12-state model is well-behaved in simulating and explaining the processes of slow inactivation and slow recovery. This model provides a good framework for further studying the gating mechanism and physiological role of sodium channel in excitable cells.

  11. Ion conduction in the KcsA potassium channel analyzed with a minimal kinetic model.

    PubMed

    Mafé, Salvador; Pellicer, Julio

    2005-02-01

    We use a model by Nelson to study the current-voltage and conductance-concentration curves of bacterial potassium channel KcsA without assuming rapid ion translocation. Ion association to the channel filter is rate controlling at low concentrations, but dissociation and transport in the filter can limit conduction at high concentration for ions other than K+. The absolute values of the effective rate constants are tentative but the relative changes in these constants needed to qualitatively explain the experiments should be of significance.

  12. Activation of α7 nicotinic receptors by orthosteric and allosteric agonists: influence on single-channel kinetics and conductance.

    PubMed

    Pałczyńska, Magda M; Jindrichova, Marie; Gibb, Alasdair J; Millar, Neil S

    2012-11-01

    Nicotinic acetylcholine receptors (nAChRs) are oligomeric transmembrane proteins in which five subunits coassemble to form a central ion channel pore. Conventional agonists, such as acetylcholine (ACh), bind to an orthosteric site, located at subunit interfaces in the extracellular domain. More recently, it has been demonstrated that nAChRs can also be activated by ligands binding to an allosteric transmembrane site. In the case of α7 nAChRs, ACh causes rapid activation and almost complete desensitization. In contrast, allosteric agonists such as 4-(4-bromophenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c] quin oline-8-sulfonamide (4BP-TQS) activate α7 nAChRs more slowly and cause only low levels of apparent desensitization. In the present study, single-channel patch-clamp recording has been used to investigate differences in the mechanism of activation of α7 nAChRs by ACh and 4BP-TQS. The most striking difference between activation by ACh and 4BP-TQS is in single-channel kinetics. In comparison with activation by ACh, single-channel open times and burst lengths are substantially longer (~160-800-fold, respectively), and shut times are shorter (~8-fold) when activated by 4BP-TQS. In addition, coapplication of ACh and 4BP-TQS results in a further increase in single-channel burst lengths. Mean burst lengths seen when the two agonists are coapplied (3099 ± 754 ms) are ~2.5-fold longer than with 4BP-TQS alone and ∼370-fold longer than with ACh alone. Intriguingly, the main single-channel conductance of α7 nAChRs, was significantly larger when activated by 4BP-TQS (100.3 ± 2.4 pS) than when activated by ACh (90.0 ± 2.7 pS), providing evidence that activation by allosteric and orthosteric agonists results in different α7 nAChRs open-channel conformations.

  13. Activation of α7 Nicotinic Receptors by Orthosteric and Allosteric Agonists: Influence on Single-Channel Kinetics and Conductance

    PubMed Central

    Pałczyńska, Magda M.; Jindrichova, Marie; Gibb, Alasdair J.

    2012-01-01

    Nicotinic acetylcholine receptors (nAChRs) are oligomeric transmembrane proteins in which five subunits coassemble to form a central ion channel pore. Conventional agonists, such as acetylcholine (ACh), bind to an orthosteric site, located at subunit interfaces in the extracellular domain. More recently, it has been demonstrated that nAChRs can also be activated by ligands binding to an allosteric transmembrane site. In the case of α7 nAChRs, ACh causes rapid activation and almost complete desensitization. In contrast, allosteric agonists such as 4-(4-bromophenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c] quin oline-8-sulfonamide (4BP-TQS) activate α7 nAChRs more slowly and cause only low levels of apparent desensitization. In the present study, single-channel patch-clamp recording has been used to investigate differences in the mechanism of activation of α7 nAChRs by ACh and 4BP-TQS. The most striking difference between activation by ACh and 4BP-TQS is in single-channel kinetics. In comparison with activation by ACh, single-channel open times and burst lengths are substantially longer (∼160–800-fold, respectively), and shut times are shorter (∼8-fold) when activated by 4BP-TQS. In addition, coapplication of ACh and 4BP-TQS results in a further increase in single-channel burst lengths. Mean burst lengths seen when the two agonists are coapplied (3099 ± 754 ms) are ∼2.5-fold longer than with 4BP-TQS alone and ∼370-fold longer than with ACh alone. Intriguingly, the main single-channel conductance of α7 nAChRs, was significantly larger when activated by 4BP-TQS (100.3 ± 2.4 pS) than when activated by ACh (90.0 ± 2.7 pS), providing evidence that activation by allosteric and orthosteric agonists results in different α7 nAChRs open-channel conformations. PMID:22874415

  14. Ion-polycyclic aromatic hydrocarbon collisions: kinetic energy releases for specific fragmentation channels

    NASA Astrophysics Data System (ADS)

    Reitsma, G.; Zettergren, H.; Boschman, L.; Bodewits, E.; Hoekstra, R.; Schlathölter, T.

    2013-12-01

    We report on 30 keV He2 + collisions with naphthalene (C10H8) molecules, which leads to very extensive fragmentation. To unravel such complex fragmentation patterns, we designed and constructed an experimental setup, which allows for the determination of the full momentum vector by measuring charged collision products in coincidence in a recoil ion momentum spectrometer type of detection scheme. The determination of fragment kinetic energies is found to be considerably more accurate than for the case of mere coincidence time-of-flight spectrometers. In fission reactions involving two cationic fragments, typically kinetic energy releases of 2-3 eV are observed. The results are interpreted by means of density functional theory calculations of the reverse barriers. It is concluded that naphthalene fragmentation by collisions with keV ions clearly is much more violent than the corresponding photofragmentation with energetic photons. The ion-induced naphthalene fragmentation provides a feedstock of various small hydrocarbonic species of different charge states and kinetic energy, which could influence several molecule formation processes in the cold interstellar medium and facilitates growth of small hydrocarbon species on pre-existing polycyclic aromatic hydrocarbons.

  15. Kinetic Structure of Large-Conductance Ca2+-activated K+ Channels Suggests that the Gating Includes Transitions through Intermediate or Secondary States

    PubMed Central

    Rothberg, Brad S.; Magleby, Karl L.

    1998-01-01

    Mechanisms for the Ca2+-dependent gating of single large-conductance Ca2+-activated K+ channels from cultured rat skeletal muscle were developed using two-dimensional analysis of single-channel currents recorded with the patch clamp technique. To extract and display the essential kinetic information, the kinetic structure, from the single channel currents, adjacent open and closed intervals were binned as pairs and plotted as two-dimensional dwell-time distributions, and the excesses and deficits of the interval pairs over that expected for independent pairing were plotted as dependency plots. The basic features of the kinetic structure were generally the same among single large-conductance Ca2+-activated K+ channels, but channel-specific differences were readily apparent, suggesting heterogeneities in the gating. Simple gating schemes drawn from the Monod- Wyman-Changeux (MWC) model for allosteric proteins could approximate the basic features of the Ca2+ dependence of the kinetic structure. However, consistent differences between the observed and predicted dependency plots suggested that additional brief lifetime closed states not included in MWC-type models were involved in the gating. Adding these additional brief closed states to the MWC-type models, either beyond the activation pathway (secondary closed states) or within the activation pathway (intermediate closed states), improved the description of the Ca2+ dependence of the kinetic structure. Secondary closed states are consistent with the closing of secondary gates or channel block. Intermediate closed states are consistent with mechanisms in which the channel activates by passing through a series of intermediate conformations between the more stable open and closed states. It is the added secondary or intermediate closed states that give rise to the majority of the brief closings (flickers) in the gating. PMID:9607935

  16. Osmotic stress regulates the strength and kinetics of sugar binding to the maltoporin channel.

    PubMed

    Gurnev, Philip A; Harries, Daniel; Parsegian, V Adrian; Bezrukov, Sergey M

    2010-11-17

    We study the effect of osmotic stress, exerted by salts, on carbohydrate binding to the sugar-specific bacterial channel maltoporin. When the channel is reconstituted into planar lipid bilayers, single events of its occlusion by sugar are seen as transient interruptions in the flow of small ions. We find that, for most salts, changes in the free energy of maltoporin-sugar binding vary linearly with solution osmotic pressure. Such a change in binding with solution osmolarity indicates that for each salt a constant number of salt-excluding water molecules is released upon sugar-maltoporin association at all salt concentrations. We find that larger numbers of water molecules are released upon binding of the cyclic carbohydrate β-cyclodextrin (CD) than upon binding of the corresponding linear homologue maltoheptaose (m7). Remarkably, the extent to which salts affect the binding constants and rates depends sensitively on the type of salt; dehydration in solutions of different anions corresponds to the Hofmeister series. In sodium sulfate solutions, CD and m7 respectively release about 120 and 35 salt-excluding water molecules; in sodium chloride solutions, 35 and 15 waters. No water release is observed with sodium bromide. Finally, by adding adamantane, known to form an inclusion complex with CD, we can infer that CD not only dehydrates but also undergoes a conformational change upon binding to the channel. As a practical outcome, our results also demonstrate how osmotic stress can improve single-molecule detection of different solutes using protein-based nanopores.

  17. Nanopore-based kinetics analysis of individual antibody-channel and antibody-antigen interactions

    PubMed Central

    Winters-Hilt, Stephen; Morales, Eric; Amin, Iftekhar; Stoyanov, Alexander

    2007-01-01

    Background The UNO/RIC Nanopore Detector provides a new way to study the binding and conformational changes of individual antibodies. Many critical questions regarding antibody function are still unresolved, questions that can be approached in a new way with the nanopore detector. Results We present evidence that different forms of channel blockade can be associated with the same antibody, we associate these different blockades with different orientations of "capture" of an antibody in the detector's nanometer-scale channel. We directly detect the presence of antibodies via reductions in channel current. Changes to blockade patterns upon addition of antigen suggest indirect detection of antibody/antigen binding. Similarly, DNA-hairpin anchored antibodies have been studied, where the DNA linkage is to the carboxy-terminus at the base of the antibody's Fc region, with significantly fewer types of (lengthy) capture blockades than was observed for free (un-bound) IgG antibody. The introduction of chaotropic agents and its effects on protein-protein interactions have also been observed. Conclusion Nanopore-based approaches may eventually provide a direct analysis of the complex conformational "negotiations" that occur upon binding between proteins. PMID:18047720

  18. Osmotic stress regulates the strength and kinetics of sugar binding to the maltoporin channel

    NASA Astrophysics Data System (ADS)

    Gurnev, Philip A.; Harries, Daniel; Parsegian, V. Adrian; Bezrukov, Sergey M.

    2010-11-01

    We study the effect of osmotic stress, exerted by salts, on carbohydrate binding to the sugar-specific bacterial channel maltoporin. When the channel is reconstituted into planar lipid bilayers, single events of its occlusion by sugar are seen as transient interruptions in the flow of small ions. We find that, for most salts, changes in the free energy of maltoporin-sugar binding vary linearly with solution osmotic pressure. Such a change in binding with solution osmolarity indicates that for each salt a constant number of salt-excluding water molecules is released upon sugar-maltoporin association at all salt concentrations. We find that larger numbers of water molecules are released upon binding of the cyclic carbohydrate β-cyclodextrin (CD) than upon binding of the corresponding linear homologue maltoheptaose (m7). Remarkably, the extent to which salts affect the binding constants and rates depends sensitively on the type of salt; dehydration in solutions of different anions corresponds to the Hofmeister series. In sodium sulfate solutions, CD and m7 respectively release about 120 and 35 salt-excluding water molecules; in sodium chloride solutions, 35 and 15 waters. No water release is observed with sodium bromide. Finally, by adding adamantane, known to form an inclusion complex with CD, we can infer that CD not only dehydrates but also undergoes a conformational change upon binding to the channel. As a practical outcome, our results also demonstrate how osmotic stress can improve single-molecule detection of different solutes using protein-based nanopores.

  19. Osmotic Stress Regulates the Strength and Kinetics of Sugar Binding to Maltoporin Channel

    PubMed Central

    Gurnev, Philip A; Harries, Daniel; Parsegian, V Adrian; Bezrukov, Sergey M

    2011-01-01

    We study the effect of osmotic stress, exerted by salts, on carbohydrate binding to the sugar-specific bacterial channel maltoporin. When the channel is reconstituted into planar lipid bilayers, single events of its occlusion by sugar are seen as transient interruptions in the flow of small ions. We find that, for most salts, changes in the free energy of maltoporin-sugar binding vary linearly with solution osmotic pressure. Such a change in binding with solution osmolarity indicates that for each salt a constant number of salt-excluding water molecules is released upon sugar-maltoporin association at all salt concentrations. We find that larger numbers of water molecules are released upon binding of the cyclic carbohydrate β-cyclodextrin (CD) than upon binding of the corresponding linear homologue maltoheptaose (m7). Remarkably, the extent to which salts affect the binding constant depends sensitively on the type of salt; dehydration in solutions of different anions corresponds to the Hofmeister series. In sodium sulfate solutions, CD and m7 respectively release about 120 and 35 water molecules; in sodium chloride solutions, 35 and 15 waters. No water release is observed with sodium bromide. Finally, by adding adamantane, known to form an inclusion complex with CD, we can infer that CD not only dehydrates but also undergoes a conformational change upon binding to the channel. Our results demonstrate how osmotic stress can improve single-molecule detection of different solutes using protein-based nanopores. PMID:21339598

  20. A prospective randomized comparison of early embryo cleavage kinetics between two media culture systems

    PubMed Central

    Zhang, Huan; Zheng, Yi; Wu, Yonggen; Ye, Danna; Huang, Xuefeng

    2016-01-01

    Objective: To investigate whether early embryo cleavage kinetics were affected by type of culture media. Methods: In this prospective sibling-split study, 620 oocytes from 37 patients were randomly allocated into two groups: Cook group and Vitrolife group. Oocytes/embryos in Cook group, would be cultured with Cook sequential culture medium, while oocytes/embryos in Vitrolife group, would be cultured with Vitrolife sequential culture medium. Time-lapse imaging technology was used to calculate exact timing of early embryo cleavage events which included time to 2PN breakdown, cleavage to 2-, 3-, 4-, 5- cell and the time duration in the 2-,3-cell stage. Then these timing of early embryo cleavage events were compared between Cook group and Vitrolife group. Moreover, fertilization rate, cleavage rate, high quality embryo rate, usable blastocyst rate, pregnancy rate and implantation rate of these two groups were also analyzed. Results: The results showed there were no differences in all timing of early embryo cleavage events between the two groups. In addition, the two groups were similar in fertilization rate (Cook 71.0% vs. Vitrolife 71.3%, P>0.05), cleavage rate (Cook 98.1% vs. Vitrolife 98.2%, P>0.05), high quality embryo rate (Cook 52.1% vs. Vitrolife 52.7%, P>0.05), usable blastocyst rate (Cook 29.7% vs. Vitrolife 28.0%, P>0.05), pregnancy rate (Cook 46.7% VS. Vitrolife 50.0%, P>0.05) and implantation rate (Cook 30.3% VS. Vitrolife 29.0%, P>0.05). Conclusions: Morphokinetics used for embryo selection are not affected by the two different culture media. PMID:28083029

  1. A prospective randomized comparison of early embryo cleavage kinetics between two media culture systems.

    PubMed

    Zhang, Huan; Zheng, Yi; Wu, Yonggen; Ye, Danna; Huang, Xuefeng

    2016-01-01

    To investigate whether early embryo cleavage kinetics were affected by type of culture media. In this prospective sibling-split study, 620 oocytes from 37 patients were randomly allocated into two groups: Cook group and Vitrolife group. Oocytes/embryos in Cook group, would be cultured with Cook sequential culture medium, while oocytes/embryos in Vitrolife group, would be cultured with Vitrolife sequential culture medium. Time-lapse imaging technology was used to calculate exact timing of early embryo cleavage events which included time to 2PN breakdown, cleavage to 2-, 3-, 4-, 5- cell and the time duration in the 2-,3-cell stage. Then these timing of early embryo cleavage events were compared between Cook group and Vitrolife group. Moreover, fertilization rate, cleavage rate, high quality embryo rate, usable blastocyst rate, pregnancy rate and implantation rate of these two groups were also analyzed. The results showed there were no differences in all timing of early embryo cleavage events between the two groups. In addition, the two groups were similar in fertilization rate (Cook 71.0% vs. Vitrolife 71.3%, P>0.05), cleavage rate (Cook 98.1% vs. Vitrolife 98.2%, P>0.05), high quality embryo rate (Cook 52.1% vs. Vitrolife 52.7%, P>0.05), usable blastocyst rate (Cook 29.7% vs. Vitrolife 28.0%, P>0.05), pregnancy rate (Cook 46.7% VS. Vitrolife 50.0%, P>0.05) and implantation rate (Cook 30.3% VS. Vitrolife 29.0%, P>0.05). Morphokinetics used for embryo selection are not affected by the two different culture media.

  2. Kinetic analysis of strontium and potassium sorption onto sands and gravels in a natural channel.

    USGS Publications Warehouse

    Bencala, K.E.; Jackman, A.P.; Kennedy, V.C.; Avanzino, R.J.; Zellweger, G.W.

    1983-01-01

    A kinetic, first-order mass transfer model was used to describe the sorption of strontium onto sand-and gravel-sized streambed sediments. Rate parameters, empirically determined for strontium, allowed for the prediction of potassium sorption with moderate success. The model parameters varied significantly with particle size. The sorption data were collected during an experimental injection of several elements into a small mountain pool-and- riffle stream. The sorption process onto sand- and gravel-sized sediment was relatively slow compared to changes in the dissolved concentrations. -Authors

  3. Real-time reliable determination of binding kinetics of DNA hybridization using a multi-channel graphene biosensor

    PubMed Central

    Xu, Shicai; Zhan, Jian; Man, Baoyuan; Jiang, Shouzhen; Yue, Weiwei; Gao, Shoubao; Guo, Chengang; Liu, Hanping; Li, Zhenhua; Wang, Jihua; Zhou, Yaoqi

    2017-01-01

    Reliable determination of binding kinetics and affinity of DNA hybridization and single-base mismatches plays an essential role in systems biology, personalized and precision medicine. The standard tools are optical-based sensors that are difficult to operate in low cost and to miniaturize for high-throughput measurement. Biosensors based on nanowire field-effect transistors have been developed, but reliable and cost-effective fabrication remains a challenge. Here, we demonstrate that a graphene single-crystal domain patterned into multiple channels can measure time- and concentration-dependent DNA hybridization kinetics and affinity reliably and sensitively, with a detection limit of 10 pM for DNA. It can distinguish single-base mutations quantitatively in real time. An analytical model is developed to estimate probe density, efficiency of hybridization and the maximum sensor response. The results suggest a promising future for cost-effective, high-throughput screening of drug candidates, genetic variations and disease biomarkers by using an integrated, miniaturized, all-electrical multiplexed, graphene-based DNA array. PMID:28322227

  4. Real-time reliable determination of binding kinetics of DNA hybridization using a multi-channel graphene biosensor

    NASA Astrophysics Data System (ADS)

    Xu, Shicai; Zhan, Jian; Man, Baoyuan; Jiang, Shouzhen; Yue, Weiwei; Gao, Shoubao; Guo, Chengang; Liu, Hanping; Li, Zhenhua; Wang, Jihua; Zhou, Yaoqi

    2017-03-01

    Reliable determination of binding kinetics and affinity of DNA hybridization and single-base mismatches plays an essential role in systems biology, personalized and precision medicine. The standard tools are optical-based sensors that are difficult to operate in low cost and to miniaturize for high-throughput measurement. Biosensors based on nanowire field-effect transistors have been developed, but reliable and cost-effective fabrication remains a challenge. Here, we demonstrate that a graphene single-crystal domain patterned into multiple channels can measure time- and concentration-dependent DNA hybridization kinetics and affinity reliably and sensitively, with a detection limit of 10 pM for DNA. It can distinguish single-base mutations quantitatively in real time. An analytical model is developed to estimate probe density, efficiency of hybridization and the maximum sensor response. The results suggest a promising future for cost-effective, high-throughput screening of drug candidates, genetic variations and disease biomarkers by using an integrated, miniaturized, all-electrical multiplexed, graphene-based DNA array.

  5. Slag condensation kinetics in the channel of an MHD generator: Explosive condensation

    SciTech Connect

    Zhukhovitskii, D.I.; Khrapak, A.G.; Yakubov, I.T.

    1983-09-01

    A study has been made of the bulk condensation of the inorganic part of combustion products in the channel of an MHD generator. An analytic solution has been obtained to the equations describing the process. A physical interpretation is given for the various stages. It is known that the condensation consists of several slightly overlapping stages. First there is the explosive formation of nuclei, which then grow rapidly, and a quasistationary stage of condensation sets in. A calculation is performed for particular conditions in an MHD generator.

  6. Distinct kinetics of cloned T-type Ca2 + channels lead to differential Ca2 + entry and frequency-dependence during mock action potentials.

    PubMed

    Kozlov, A S; McKenna, F; Lee, J H; Cribbs, L L; Perez-Reyes, E; Feltz, A; Lambert, R C

    1999-12-01

    Voltage-dependent activity around the resting potential is determinant in neuronal physiology and participates in the definition of the firing pattern. Low-voltage-activated T-type Ca2 + channels directly affect the membrane potential and control a number of secondary Ca2 + -dependent permeabilities. We have studied the ability of the cloned T-type channels (alpha1G,H,I) to carry Ca2 + currents in response to mock action potentials. The relationship between the spike duration and the current amplitude is specific for each of the T-type channels, reflecting their individual kinetic properties. Typically the charge transfer increases with spike broadening, but the total Ca2 + entry saturates at different spike durations according to the channel type: 4 ms for alpha1G; 7 ms for alpha1H; and > 10 ms for alpha1I channels. During bursts, currents are inhibited and/or transiently potentiated according to the alpha1 channel type, with larger effects at higher frequency. The inhibition may be induced by voltage-independent transitions toward inactivated states and/or channel inactivation through intermediate closed states. The potentiation is explained by an acceleration in the channel activation kinetics. Relatively fast inactivation and slow recovery limit the ability of alpha1G and alpha1H channels to respond to high frequency stimulation ( > 20 Hz). In contrast, the slow inactivation of alpha1I subunits allows these channels to continue participating in high frequency bursts (100 Hz). The biophysical properties of alpha1G, H and I channels will therefore dramatically modulate the effect of neuronal activities on Ca2 + signalling.

  7. Kinetic approach with ab initio MO method on ionic selectivity and size in sodium channel.

    PubMed

    Tani, S; Imamura, A; Kanda, K

    1989-10-23

    Three kinds of models for ionic selectivity and size of the filter in sodium channel have been treated by using ab initio molecular orbital (MO) calculations with MINI-3 and MIDI-3* basis sets. A three-components system, HCO2M-H2O (M = Li+, Na+ or K+), is acceptable for describing experimental facts well. Thermochemical parameters obtained from harmonic vibrational analysis with MINI-3 basis sets, for the translocation of the permeant metal cations in the HCO2M-H2O system, are that the activation enthalpies for Li+, Na+ and K+ are 7.0, 6.4 and 23.4 kJ/mol, and also the free energies of activation are 10.6, 1.5 and 19.0 kJ/mol, respectively. These results are qualitatively in good correspondence with experimental facts of the ion selectivity of the channel. One of water molecule was found to have a key role in the translocation of the permeant cations.

  8. Carvacrol modulates voltage-gated sodium channels kinetics in dorsal root ganglia.

    PubMed

    Joca, Humberto Cavalcante; Vieira, Daiana Cardoso Oliveira; Vasconcelos, Aliny Perreira; Araújo, Demetrius Antônio Machado; Cruz, Jader Santos

    2015-06-05

    Recent studies have shown that many of plant-derived compounds interact with specific ion channels and thereby modulate many sensing mechanisms, such as nociception. The monoterpenoid carvacrol (5-isopropyl-2-methylphenol) has an anti-nociceptive effect related to a reduction in neuronal excitability and voltage-gated Na(+) channels (NaV) inhibition in peripheral neurons. However, the detailed mechanisms of carvacrol-induced inhibition of neuronal NaV remain elusive. This study explores the interaction between carvacrol and NaV in isolated dorsal root ganglia neurons. Carvacrol reduced the total voltage-gated Na(+) current and tetrodotoxin-resistant (TTX-R) Na(+) current component in a concentration-dependent manner. Carvacrol accelerates current inactivation and induced a negative-shift in voltage-dependence of steady-state fast inactivation in total and TTX-R Na(+) current. Furthermore, carvacrol slowed the recovery from inactivation. Carvacrol provoked a leftward shift in both the voltage-dependence of steady-state inactivation and activation of the TTX-R Na(+) current component. In addition, carvacrol-induced inhibition of TTX-R Na(+) current was enhanced by an increase in stimulation frequency and when neurons were pre-conditioned with long depolarization pulse (5s at -50 mV). Taken all results together, we herein demonstrated that carvacrol affects NaV gating properties. The present findings would help to explain the mechanisms underlying the analgesic activity of carvacrol.

  9. Luminescent oxygen channeling immunoassay: measurement of particle binding kinetics by chemiluminescence.

    PubMed Central

    Ullman, E F; Kirakossian, H; Singh, S; Wu, Z P; Irvin, B R; Pease, J S; Switchenko, A C; Irvine, J D; Dafforn, A; Skold, C N

    1994-01-01

    A method for monitoring formation of latex particle pairs by chemiluminescence is described. Molecular oxygen is excited by a photosensitizer and an antenna dye that are dissolved in one of the particles. 1 delta gO2 diffuses to the second particle and initiates a high quantum yield chemiluminescent reaction of an olefin that is dissolved in it. The efficiency of 1 delta gO2 transfer between particles is approximately 3.5%. The technique permits real-time measurement of particle binding kinetics. Second-order rate constants increase with the number of receptor binding sites on the particles and approach diffusion control. By using antibody-coated particles, a homogeneous immunoassay capable of detecting approximately 4 amol of thyroid-stimulating hormone in 12 min was demonstrated. Single molecules of analyte produce particle heterodimers that are detected even when no larger aggregates are formed. PMID:8202502

  10. Kinetics and Mechanism of the CIO + CIO Reaction: Pressure and Temperature Dependences of the Bimolecular and Termolecular Channels andThermal Decomposition of Chlorine Peroxide, CIOOCI

    NASA Technical Reports Server (NTRS)

    Nickolaisen, Scott L.; Friedl, Randall R.; Sander, Stanley P.

    1993-01-01

    The kinetics and mechanism of the CIO + CIO reaction and the thermal decomposition of CIOOCI were studied using the flash photolysis/long path ultraviolet absorption technique. Pressure and temperature dependences were determined for the rate coefficients for the bimolecular and termolecular reaction channels, and for the thermal decompositon of CIOOCI.

  11. Kinetics and Mechanism of the CIO + CIO Reaction: Pressure and Temperature Dependences of the Bimolecular and Termolecular Channels andThermal Decomposition of Chlorine Peroxide, CIOOCI

    NASA Technical Reports Server (NTRS)

    Nickolaisen, Scott L.; Friedl, Randall R.; Sander, Stanley P.

    1993-01-01

    The kinetics and mechanism of the CIO + CIO reaction and the thermal decomposition of CIOOCI were studied using the flash photolysis/long path ultraviolet absorption technique. Pressure and temperature dependences were determined for the rate coefficients for the bimolecular and termolecular reaction channels, and for the thermal decompositon of CIOOCI.

  12. Channels

    NASA Image and Video Library

    2015-11-20

    Today's VIS image shows a number of unnamed channels located on the northeastern margin of Terra Sabaea. Orbit Number: 61049 Latitude: 33.5036 Longitude: 58.6967 Instrument: VIS Captured: 2015-09-18 12:54 http://photojournal.jpl.nasa.gov/catalog/PIA20097

  13. Scaling of flow distance in random self-similar channel networks

    USGS Publications Warehouse

    Troutman, B.M.

    2005-01-01

    Natural river channel networks have been shown in empirical studies to exhibit power-law scaling behavior characteristic of self-similar and self-affine structures. Of particular interest is to describe how the distribution of distance to the outlet changes as a function of network size. In this paper, networks are modeled as random self-similar rooted tree graphs and scaling of distance to the root is studied using methods in stochastic branching theory. In particular, the asymptotic expectation of the width function (number of nodes as a function of distance to the outlet) is derived under conditions on the replacement generators. It is demonstrated further that the branching number describing rate of growth of node distance to the outlet is identical to the length ratio under a Horton-Strahler ordering scheme as order gets large, again under certain restrictions on the generators. These results are discussed in relation to drainage basin allometry and an application to an actual drainage network is presented. ?? World Scientific Publishing Company.

  14. Connectivity, permeability, and channeling in randomly distributed and kinematically defined discrete fracture network models

    NASA Astrophysics Data System (ADS)

    Maillot, J.; Davy, P.; Le Goc, R.; Darcel, C.; de Dreuzy, J. R.

    2016-11-01

    A major use of DFN models for industrial applications is to evaluate permeability and flow structure in hardrock aquifers from geological observations of fracture networks. The relationship between the statistical fracture density distributions and permeability has been extensively studied, but there has been little interest in the spatial structure of DFN models, which is generally assumed to be spatially random (i.e., Poisson). In this paper, we compare the predictions of Poisson DFNs to new DFN models where fractures result from a growth process defined by simplified kinematic rules for nucleation, growth, and fracture arrest. This so-called "kinematic fracture model" is characterized by a large proportion of T intersections, and a smaller number of intersections per fracture. Several kinematic models were tested and compared with Poisson DFN models with the same density, length, and orientation distributions. Connectivity, permeability, and flow distribution were calculated for 3-D networks with a self-similar power law fracture length distribution. For the same statistical properties in orientation and density, the permeability is systematically and significantly smaller by a factor of 1.5-10 for kinematic than for Poisson models. In both cases, the permeability is well described by a linear relationship with the areal density p32, but the threshold of kinematic models is 50% larger than of Poisson models. Flow channeling is also enhanced in kinematic DFN models. This analysis demonstrates the importance of choosing an appropriate DFN organization for predicting flow properties from fracture network parameters.

  15. Silicide/Silicon Heterointerfaces, Reaction Kinetics and Ultra-short Channel Devices

    NASA Astrophysics Data System (ADS)

    Tang, Wei

    Nickel silicide is one of the electrical contact materials widely used on very large scale integration (VLSI) of Si devices in microelectronic industry. This is because the silicide/silicon interface can be formed in a highly controlled manner to ensure reproducibility of optimal structural and electrical properties of the metal-Si contacts. These advantages can be inherited to Si nanowire (NW) field-effect transistors (FET) device. Due to the technological importance of nickel silicides, fundamental materials science of nickel silicides formation (Ni-Si reaction), especially in nanoscale, has raised wide interest and stimulate new insights and understandings. In this dissertation, in-situ transmission electron microscopy (TEM) in combination with FET device characterization will be demonstrated as useful tools in nano-device fabrication as well as in gaining insights into the process of nickel silicide formation. The shortest transistor channel length (17 nm) fabricated on a vapor-liquid-solid (VLS) grown silicon nanowire (NW) has been demonstrated by controlled reaction with Ni leads on an in-situ transmission electron microscope (TEM) heating stage at a moderate temperature of 400 ºC. NiSi2 is the leading phase, and the silicide-silicon interface is an atomically sharp type-A interface. At such channel lengths, high maximum on-currents of 890 (microA/microm) and a maximum transconductance of 430 (microS/microm) were obtained, which pushes forward the performance of bottom-up Si NW Schottky barrier field-effect transistors (SB-FETs). Through accurate control over the silicidation reaction, we provide a systematic study of channel length dependent carrier transport in a large number of SB-FETs with channel lengths in the range of (17 nm -- 3.6 microm). Our device results corroborate with our transport simulations and reveal a characteristic type of short channel effects in SB-FETs, both in on- and off-state, which is different from that in conventional MOSFETs

  16. Kinetics of water filling the hydrophobic channels of narrow carbon nanotubes studied by molecular dynamics simulations.

    PubMed

    Wu, Kefei; Zhou, Bo; Xiu, Peng; Qi, Wenpeng; Wan, Rongzheng; Fang, Haiping

    2010-11-28

    The kinetics of water filling narrow single-walled carbon nanotubes was studied using molecular dynamics simulations. The time required to fully fill a nanotube was linear with respect to the tube length. We observed that water molecules could enter into nanotubes of different lengths, either from one end or from both ends. The probability of having a nanotube filled completely from both ends increased exponentially with the tube length. For short tubes, filling usually proceeded from only one end. For long tubes, filling generally proceeded from both tube ends over three stages, i.e., filling from one end, filling from both ends, and filling from both ends with the dipole reorientation of water molecules to give a concerted ordering within the fully filled tube. The water molecules in the partially filled nanotube were hydrogen bonded similarly to those in the fully filled nanotube. Simulations for the reference Lennard-Jones fluid without hydrogen bonds were also performed and showed that the filling behavior of water molecules can be attributed to strong intermolecular hydrogen bonding.

  17. Kinetics of water filling the hydrophobic channels of narrow carbon nanotubes studied by molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Wu, Kefei; Zhou, Bo; Xiu, Peng; Qi, Wenpeng; Wan, Rongzheng; Fang, Haiping

    2010-11-01

    The kinetics of water filling narrow single-walled carbon nanotubes was studied using molecular dynamics simulations. The time required to fully fill a nanotube was linear with respect to the tube length. We observed that water molecules could enter into nanotubes of different lengths, either from one end or from both ends. The probability of having a nanotube filled completely from both ends increased exponentially with the tube length. For short tubes, filling usually proceeded from only one end. For long tubes, filling generally proceeded from both tube ends over three stages, i.e., filling from one end, filling from both ends, and filling from both ends with the dipole reorientation of water molecules to give a concerted ordering within the fully filled tube. The water molecules in the partially filled nanotube were hydrogen bonded similarly to those in the fully filled nanotube. Simulations for the reference Lennard-Jones fluid without hydrogen bonds were also performed and showed that the filling behavior of water molecules can be attributed to strong intermolecular hydrogen bonding.

  18. Whole cell and single channel analysis of the kinetics of glycine-sensitive N-methyl-D-aspartate receptor desensitization.

    PubMed Central

    Parsons, C. G.; Zong, X.; Lux, H. D.

    1993-01-01

    1. The kinetics of glycine-sensitive, N-methyl-D-aspartate (NMDA) receptor desensitization were investigated in cultured neurones with the patch clamp technique. 2. The degree of fast NMDA-receptor desensitization was inversely related to glycine concentration. Thus, increasing concentrations of glycine from 30 nM to 2.5 microM potentiated desensitized NMDA responses (873% +/- 101%) to a greater degree than peak responses (260% +/- 27%). 3. The desensitization was due to a decrease in the affinity of glycine for the strychnine-insensitive, glycine modulatory site (glycineB site) following activation of the NMDA-receptor complex. Thus, the A50 for glycine in potentiating peak responses (77 nM, 95% confidence limited 58-104 nM) was five fold lower than that for plateau responses (399 nM, 340-468 nM). 4. The rate of desensitization was related to glycine concentration such that a reciprocal plot of desensitization rate (1/tau S-1) against glycine concentration had a slope of 9.5* 10(6) M-1 S-1. 5. Recovery from desensitization following step increases in glycine or L-alanine concentration in the continuous presence of NMDA (200 microM) reflected the association kinetics of the glycineB agonist used. 6. The rate and degree of NMDA receptor desensitization was independent of holding potential. 7. NMDA receptor desensitization was also evident at the single channel level. 8. The glycineB antagonist 7-chlorokynurenic acid (7-Chl-Kyn 3 and 10 microM) concentration-dependently induced an identical form of desensitization in the presence of 1 microM glycine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8098640

  19. Hydrogen peroxide release kinetics into saliva from different whitening products: a double-blind, randomized clinical trial.

    PubMed

    Marques, Duarte Nuno da Silva; da Mata, António Duarte Sola Pereira; Silveira, João Miguel Lourenço; Marques, Joana Rita Oliveira Faria; Amaral, João Pedro de Almeida Rato; Guilherme, Nuno Filipe Rito Parada Marques

    2012-02-01

    The objective of this study is to compare salivary hydrogen peroxide (HP) release kinetics and potential toxicity of systemic exposure of four different whitening products. A double-blind, randomized controlled trial was conducted in a Portuguese dental faculty clinic. Two hundred forty volunteers were randomized to eight intervention groups. Participants were randomly assigned to receive active or placebo applications of one of four different products: Opalescence 10% PF™ (OPL), Vivastyle® 10%™ (VS10%), Vivadent Paint On Plus™ (PO+), and Trés White Supreme™ (TWS). Saliva collection was obtained by established methods at different times. The HP salivary content was determined by a photometric method. Salivary HP variations, total amount of salivary HP, and counts of subjects above the safe daily HP dose were the main outcome measures. All whitening systems significantly released HP to the saliva when compared to placebo, and all showed different release kinetics. The adaptable tray system (TWS) presented a risk increase of 37% [20-54%, 95% confidence interval] when compared to the other systems. The use of an adaptable tray whitening system with higher concentration of HP increases the toxicity potential.

  20. Automated evolutionary optimization of ion channel conductances and kinetics in models of young and aged rhesus monkey pyramidal neurons.

    PubMed

    Rumbell, Timothy H; Draguljić, Danel; Yadav, Aniruddha; Hof, Patrick R; Luebke, Jennifer I; Weaver, Christina M

    2016-08-01

    Conductance-based compartment modeling requires tuning of many parameters to fit the neuron model to target electrophysiological data. Automated parameter optimization via evolutionary algorithms (EAs) is a common approach to accomplish this task, using error functions to quantify differences between model and target. We present a three-stage EA optimization protocol for tuning ion channel conductances and kinetics in a generic neuron model with minimal manual intervention. We use the technique of Latin hypercube sampling in a new way, to choose weights for error functions automatically so that each function influences the parameter search to a similar degree. This protocol requires no specialized physiological data collection and is applicable to commonly-collected current clamp data and either single- or multi-objective optimization. We applied the protocol to two representative pyramidal neurons from layer 3 of the prefrontal cortex of rhesus monkeys, in which action potential firing rates are significantly higher in aged compared to young animals. Using an idealized dendritic topology and models with either 4 or 8 ion channels (10 or 23 free parameters respectively), we produced populations of parameter combinations fitting the target datasets in less than 80 hours of optimization each. Passive parameter differences between young and aged models were consistent with our prior results using simpler models and hand tuning. We analyzed parameter values among fits to a single neuron to facilitate refinement of the underlying model, and across fits to multiple neurons to show how our protocol will lead to predictions of parameter differences with aging in these neurons.

  1. Theoretical and kinetic study of the reactions of ketones with HO2 radicals. Part I: abstraction reaction channels.

    PubMed

    Mendes, Jorge; Zhou, Chong-Wen; Curran, Henry J

    2013-06-06

    This work presents an ab initio and chemical kinetic study of the reaction mechanisms of hydrogen atom abstraction by the HO2 radical on five ketones: dimethyl, ethyl methyl, n-propyl methyl, iso-propyl methyl, and iso-butyl methyl ketones. The Møller-Plesset method using the 6-311G(d,p) basis set has been used in the geometry optimization and the frequency calculation for all the species involved in the reactions, as well as the hindrance potential description for reactants and transition states. Intrinsic reaction coordinate calculations were carried out to validate all the connections between transition states and local minima. Energies are reported at the CCSD(T)/cc-pVTZ//MP2/6-311G(d,p) level of theory. The CCSD(T)/cc-pVXZ method (X = D, T, Q) was used for the reaction mechanism of dimethyl ketone + HO2 radical in order to benchmark the computationally less expensive method of CCSD(T)/cc-pVTZ//MP2/6-311G(d,p). High-pressure limit rate constants have been calculated for all the reaction channels by conventional transition state theory with asymmetric Eckart tunneling corrections and 1-D hindered rotor approximations in the temperature range 500-2000 K.

  2. H∞ state estimation for discrete-time neural networks with distributed delays and randomly occurring uncertainties through Fading channels.

    PubMed

    Hou, Nan; Dong, Hongli; Wang, Zidong; Ren, Weijian; Alsaadi, Fuad E

    2017-05-01

    In this paper, the H∞ state estimation problem is investigated for a class of uncertain discrete-time neural networks subject to infinitely distributed delays and fading channels. Randomly occurring uncertainties (ROUs) are introduced to reflect the random nature of the network condition fluctuations, and the channel fading phenomenon is considered to account for the possibly unreliable network medium on which the measurement signal is transmitted. A set of Bernoulli-distributed white sequences are employed to govern the ROUs and the L-th Rice fading model is utilized where channel coefficients are mutually independent random variables with certain probability density function on [0,1]. We aim to design a state estimator such that the dynamics of the estimation error is asymptotically stable while satisfying the prescribed H∞ performance constraint. By adopting the Lyapunov-Krasovskii functional and the stochastic analysis theory, sufficient conditions are established to ensure the existence of the desired state estimators and the explicit expression of such estimators is acquired. A simulation example is provided to verify the usefulness of the proposed approach. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Physical-layer security analysis of a quantum-noise randomized cipher based on the wire-tap channel model.

    PubMed

    Jiao, Haisong; Pu, Tao; Zheng, Jilin; Xiang, Peng; Fang, Tao

    2017-05-15

    The physical-layer security of a quantum-noise randomized cipher (QNRC) system is, for the first time, quantitatively evaluated with secrecy capacity employed as the performance metric. Considering quantum noise as a channel advantage for legitimate parties over eavesdroppers, the specific wire-tap models for both channels of the key and data are built with channel outputs yielded by quantum heterodyne measurement; the general expressions of secrecy capacities for both channels are derived, where the matching codes are proved to be uniformly distributed. The maximal achievable secrecy rate of the system is proposed, under which secrecy of both the key and data is guaranteed. The influences of various system parameters on secrecy capacities are assessed in detail. The results indicate that QNRC combined with proper channel codes is a promising framework of secure communication for long distance with high speed, which can be orders of magnitude higher than the perfect secrecy rates of other encryption systems. Even if the eavesdropper intercepts more signal power than the legitimate receiver, secure communication (up to Gb/s) can still be achievable. Moreover, the secrecy of running key is found to be the main constraint to the systemic maximal secrecy rate.

  4. Dielectric function beyond the random-phase approximation: kinetic theory versus linear response theory.

    PubMed

    Reinholz, H; Röpke, G

    2012-03-01

    Calculating the frequency-dependent dielectric function for strongly coupled plasmas, the relations within kinetic theory and linear response theory are derived and discussed in comparison. In this context, we give a proof that the Kohler variational principle can be extended to arbitrary frequencies. It is shown to be a special case of the Zubarev method for the construction of a nonequilibrium statistical operator from the principle of the extremum of entropy production. Within kinetic theory, the commonly used energy-dependent relaxation time approach is strictly valid only for the Lorentz plasma in the static case. It is compared with the result from linear response theory that includes electron-electron interactions and applies for arbitrary frequencies, including bremsstrahlung emission. It is shown how a general approach to linear response encompasses the different approximations and opens options for systematic improvements.

  5. Long-term adsorption kinetics of asphaltenes at the oil-water interface: a random sequential adsorption perspective.

    PubMed

    Pauchard, Vincent; Rane, Jayant P; Zarkar, Sharli; Couzis, Alexander; Banerjee, Sanjoy

    2014-07-22

    Previous studies indicated that asphaltenes adsorbed as monomers on oil-water interfaces and the early stage kinetics of the process was controlled by diffusion and hence dependent on oil viscosity. By measuring interfacial tension (IFT) as a function of surface coverage during droplet expansions in pendant drop experiments, it was also concluded that the IFT data could be interpreted with a Langmuir equation of state (EoS), which was independent of oil viscosity, time of adsorption, and bulk asphaltenes concentration. The surface excess coverage was calculated to be ∼0.3 nm(2)/molecule, which suggested adsorption in face-on configuration of asphaltenes monomers at the interface and average PAH core per molecule of about 6 for the asphaltenes investigated, consistent with the Yen-Mullins model. The current study focuses on the kinetics of asphaltenes adsorption at longer times and higher interfacial coverage. Long-term IFT data have been measured by the pendant drop method for different asphaltenes concentrations and for different bulk viscosities of the oil phase (0.5-28 cP). The data indicate that when coverage reaches 35-40%, the adsorption rates slow down considerably compared to the diffusion-controlled rates at the very early stages. The surface pressure increase rate (or IFT decrease rate) at these higher coverages is now independent of oil viscosity but dependent upon both surface pressure itself and asphaltene monomer concentration. The long-term asymptotic behavior of surface coverage is found to be consistent with the predictions from surface diffusion-mediated random sequential adsorption (RSA) theory which indicates a linear dependency of surface coverage on 1/√t and an asymptotic limit very close to 2D random close packing of polydispersed disks (85%). From these observations RSA theory parameters were extracted that enabled description of adsorption kinetics for the range of conditions above surface coverage of 35%.

  6. Integration of biological kinetics and computational fluid dynamics to model the growth of Nannochloropsis salina in an open channel raceway.

    PubMed

    Park, Stephen; Li, Yebo

    2015-05-01

    Microalgal growth and systemic productivity is not only affected by environmental conditions such as temperature, irradiance, and nutrient concentrations, but also by physical processes such as fluid flow and particulate sedimentation. Modeling and simulating the system is a cost-effective way to predict the growth behavior under various environmental and physical conditions while determining effective engineering approaches to maximize productivity. Many mathematical models have been proposed to describe microalgal growth, while computational fluid dynamics (CFD) have been used to model the behavior of many fluid systems. Integrating the growth kinetics into a CFD model can help researchers understand the impact of a variety of parameters and determine what measures can be taken to overcome some obstacles in the aquaculture industry--self-shading, biomass sedimentation, and contamination--which prevent the production of high biomass yields. The aim of this study was to integrate physical and environmental effects to predict space- and time-dependent algal growth in industrial scale raceways. A commercial CFD software, ANSYS-Fluent 14.5, was used to solve the proposed models in regards to fluid flow, heat transfer, and nutrient balance. User-defined functions written in C language were used to incorporate the kinetic equations into a three-dimensional standard k-ε turbulence model of an open channel raceway system driven by a single paddlewheel. Simulated results were compared with light intensity, temperature, nutrient concentration, and algal biomass data acquired for 56 day from an industrial scale raceway pond constructed for the growth of Nannochloropsis salina and were observed to be in good agreement with one another. There was up to a 17.6% increase in simulated productivity when the incoming CO2 concentration was increased from 0.0006 to 0.150 g L(-1), while the effect of paddlewheel velocity was not significant. Sensitivity analysis showed that the model

  7. Development of rat chorda tympani sodium responses: evidence for age-dependent changes in global amiloride-sensitive Na(+) channel kinetics.

    PubMed

    Hendricks, S J; Stewart, R E; Heck, G L; DeSimone, J A; Hill, D L

    2000-09-01

    In rat, chorda tympani nerve taste responses to Na(+) salts increase between roughly 10 and 45 days of age to reach stable, mature magnitudes. Previous evidence from in vitro preparations and from taste nerve responses using Na(+) channel blockers suggests that the physiological basis for this developmental increase in gustatory Na(+) sensitivity is the progressive addition of functional, Na(+) transduction elements (i.e., amiloride-sensitive Na(+) channels) to the apical membranes of fungiform papilla taste receptor cells. To avoid potential confounding effects of pharmacological interventions and to permit quantification of aggregate Na(+) channel behavior using a kinetic model, we obtained chorda tympani nerve responses to NaCl and sodium gluconate (NaGlu) during receptive field voltage clamp in rats aged from 12-14 to 60 days and older (60+ days). Significant, age-dependent increases in chorda tympani responses to these stimuli occurred as expected. Importantly, apical Na(+) channel density, estimated from an apical Na(+) channel kinetic model, increased monotonically with age. The maximum rate of Na(+) response increase occurred between postnatal days 12-14 and 29-31. In addition, estimated Na(+) channel affinity increased between 12-14 and 19-23 days of age, i.e., on a time course distinct from that of the maximum rate of Na(+) response increase. Finally, estimates of the fraction of clamp voltage dropped across taste receptor apical membranes decreased between 19-23 and 29-31 days of age for NaCl but remained stable for NaGlu. The stimulus dependence of this change is consistent with a developmental increase in taste bud tight junctional Cl(-) ion permeability that lags behind the developmental increase in apical Na(+) channel density. A significant, indirect anion influence on apical Na(+) channel properties was present at all ages tested. This influence was evident in the higher apparent apical Na(+) channel affinities obtained for NaCl relative to Na

  8. Four-Channel Current-Biased Kinetic Inductance Detectors Using MgB $_2$ 2 Nanowires for Sensing Pulsed Laser Irradiation

    NASA Astrophysics Data System (ADS)

    Yoshioka, N.; Narukami, Y.; Miyajima, S.; Shishido, H.; Fujimaki, A.; Miki, S.; Wang, Z.; Ishida, T.

    2014-08-01

    We recently proposed the idea of a novel sort of superconducting detector, i.e., a current-biased kinetic inductance detector (CB-KID). This detector is different from a current-biased transition edge detector studied previously, and is able to sense a change in kinetic inductance given by (; kinetic inductivity, ; mass of Cooper pair, ; density of Cooper pairs, ; charge of Cooper pair, ; length of device, ; cross sectional area) under a constant dc bias current . In the present work, we first extend this idea to construct a multi-channel CB-KIDs array made of 200-nm-thick MgB thin-film meanderline with 3-m thin wire. We succeeded in observing clear signals for imaging from the four-channel CB-KIDs at 4 K by irradiating focused pulsed laser. A scanning laser spot can be achieved by an XYZ piezo-driven stage and an optical fiber with an aspheric focused lens. We can see typical signals from all 4 channels at 4 K, and obtain the positional dependence of the signal as the contour in XY plane. Our CB-KIDs can be used as neutron detectors by utilizing energy released from a nuclear reaction between B and cold neutron.

  9. The classical-quantum channel with random state parameters known to the sender

    NASA Astrophysics Data System (ADS)

    Boche, Holger; Cai, Ning; Nötzel, Janis

    2016-05-01

    We study an analog of the well-known Gel’fand Pinsker channel which uses quantum states for the transmission of the data. We consider the case where both the sender’s inputs to the channel and the channel states are to be taken from a finite set (the cq-channel with state information at the sender). We distinguish between causal and non-causal channel state information input by the sender. The receiver remains ignorant, throughout. We give a single-letter description of the capacity in the first case. In the second case we present two different regularized expressions for the capacity. It is an astonishing and unexpected result of our work that a simple change from causal to non-causal channel state information by the encoder causes the complexity of a numerical computation of the capacity formula to change from trivial to seemingly difficult. Still, even the non-single letter formula allows one to draw nontrivial conclusions, for example regarding the continuity of the capacity with respect to changes in the system parameters. The direct parts of both coding theorems are based on a special class of positive operator valued measurements (POVMs) which are derived from orthogonal projections onto certain representations of the symmetric groups. This approach supports a reasoning that is inspired by the classical method of types. In combination with the non-commutative union bound these POVMs yield an elegant method of proof for the direct part of the coding theorem in the first case.

  10. Kinetic study of the heterogeneous photocatalysis of porous nanocrystalline TiO₂ assemblies using a continuous random walk simulation.

    PubMed

    Liu, Baoshun; Zhao, Xiujian

    2014-10-28

    The continuous time random walk (CTRW) simulation was used to study the photocatalytic kinetics of nanocrystalline (nc)-TiO2 assemblies in this research. nc-TiO2 assemblies, such as nc-TiO2 porous films and nc-TiO2 hierarchical structures, are now widely used in photocatalysis. The nc-TiO2 assemblies have quasi-disordered networks consisting of many tiny nanoparticles, so the charge transport within them can be studied by CTRW simulation. We considered the experimental facts that the holes can be quickly trapped and transferred to organic species just after photogeneration, and the electrons transfer to O2 slowly and accumulate in the conduction band of TiO2, which is believed to be the rate-limiting process of the photocatalysis under low light intensity and low organic concentration. Due to the existence of numerous traps, the electron transport within the nc-TiO2 assemblies follows a multi-trapping (MT) mechanism, which significantly limits the electron diffusion speed. The electrons need to undergo several steps of MT transport before transferring to oxygen, so it is highly important that the electron transport in nc-TiO2 networks is determined for standard photocatalytic reactions. Based on the MT transport model, the transient decays of photocurrents during the photocatalytic oxidation of formic acid were studied by CTRW simulation, and are in good accordance with experiments. The steady state photocatalysis was also simulated. The effects of organic concentration, light intensity, temperature, and nc-TiO2 crystallinity on the photocatalytic kinetics were investigated, and were also consistent with the experimental results. Due to the agreement between the simulation and the experiments for both the transient and the steady state photocatalysis, the MT charge transport should be an important mechanism that controls the kinetics of recombination and photocatalysis in nc-TiO2 assemblies. Also, our research provides a new methodology to study the photocatalytic

  11. Determining hillslope-channel connectivity in an agricultural catchment using rare-earth oxide tracers and random forests.

    NASA Astrophysics Data System (ADS)

    Masselink, Rens; Temme, Arnaud; Giménez, Rafael; Casalí, Javier; Keesstra, Saskia

    2017-04-01

    Soil erosion from agricultural areas is a large problem, because of off-site effects like the rapid filling of reservoirs. To mitigate the problem of sediments from agricultural areas reaching the channel, reservoirs and other surface waters, it is important to understand hillslope-channel connectivity and catchment connectivity. To determine the functioning of hillslope-channel connectivity and the continuation of transport of these sediments in the channel, it is necessary to obtain data on sediment transport from the hillslopes to the channels. Simultaneously, the factors that influence sediment export out of the catchment need to be studied. For measuring hillslope-channel sediment connectivity, Rare-Earth Oxide (REO) tracers were applied to a hillslope in an agricultural catchment in Navarre, Spain, preceding the winter of 2014-2015. The results showed that during the winter there was no sediment transport from the hillslope to the channel. Analysis of precipitation data showed that total precipitation quantities did not differ much from the mean. However, precipitation intensities were low, causing little sediment mobilisation. To test the implication of the REO results at the catchment scale, two conceptual models for sediment connectivity were assessed using a Random Forest (RF) machine learning method. One model proposes that small events provide sediment for large events, while the other proposes that only large events cause sediment detachment and small events subsequently remove these sediments from near and in the channel. The RF method was applied to a daily dataset of sediment yield from the catchment (N=2451 days), and two subsets of the whole dataset: small events (N=2319) and large events (N=132). For sediment yield prediction of small events, variables related to large preceding events were the most important. The model for large events underperformed and, therefore, we could not draw any immediate conclusions whether small events influence the

  12. Capacity of Multi-Channel Wireless Networks with Random (c,f) Assignment

    DTIC Science & Technology

    2007-06-01

    flow traversing a sequence of cells D1, D2 , .... Then if the representative of Bp(x) (let us call it qx) in Di can communicate (directly or indirectly...Load: Lemma 25: The number of flows that enter any cell on a given channel is O( n √ a(n) c ) w.h.p. Proof: A flow on route D1, D2 , ...,D j−1,D j.... may...H. Vaidya, “Connectivity and Capacity of Multichannel Wireless Networks with Channel Switching Constraints,” Technical Report, CSL , UIUC, January 2007

  13. Kinetics of Hypotension during 50 Sessions of Resistance and Aerobic Training in Hypertensive Patients: a Randomized Clinical Trial

    PubMed Central

    Damorim, Igor Rodrigues; Santos, Tony Meireles; Barros, Gustavo Willames Pimentel; Carvalho, Paulo Roberto Cavalcanti

    2017-01-01

    Background Resistance and aerobic training are recommended as an adjunctive treatment for hypertension. However, the number of sessions required until the hypotensive effect of the exercise has stabilized has not been clearly established. Objective To establish the adaptive kinetics of the blood pressure (BP) responses as a function of time and type of training in hypertensive patients. Methods We recruited 69 patients with a mean age of 63.4 ± 2.1 years, randomized into one group of resistance training (n = 32) and another of aerobic training (n = 32). Anthropometric measurements were obtained, and one repetition maximum (1RM) testing was performed. BP was measured before each training session with a digital BP arm monitor. The 50 training sessions were categorized into quintiles. To compare the effect of BP reduction with both training methods, we used two-way analysis of covariance (ANCOVA) adjusted for the BP values obtained before the interventions. The differences between the moments were established by one-way analysis of variance (ANOVA). Results The reductions in systolic (SBP) and diastolic BP (DBP) were 6.9 mmHg and 5.3 mmHg, respectively, with resistance training and 16.5 mmHg and 11.6 mmHg, respectively, with aerobic training. The kinetics of the hypotensive response of the SBP showed significant reductions until the 20th session in both groups. Stabilization of the DBP occurred in the 20th session of resistance training and in the 10th session of aerobic training. Conclusion A total of 20 sessions of resistance or aerobic training are required to achieve the maximum benefits of BP reduction. The methods investigated yielded distinct adaptive kinetic patterns along the 50 sessions. PMID:28380132

  14. Analysis of a Coded, M-ary Orthogonal Input Optical Channel with Random-gain Photomultiplier Detection

    NASA Technical Reports Server (NTRS)

    Lee, P. J.

    1984-01-01

    Performance of two coding systems is analyzed for a noisy optical channel with M(=2(L)-ary orthogonal signaling and random gain photomultiplier detection. The considered coding systems are the Reed Solomon (RS) coding with error only correction decoding and the interleaved binary convolutional system with soft decision Viterbi decoding. The required average number of received signal photons per information bit, N sub b, for a desired bit error of 0.000001 is found for a set of commonly used parameters and with a high background noise level. We find that the interleaved binary convolutional coding system is preferable to the RS coding system in performance complexity tradeoffs.

  15. Random dimer filling of lattices: Three-dimensional application to free radical recombination kinetics

    SciTech Connect

    Evans, J.W.; Nord, R.S.

    1985-02-01

    The recombination of nearest neighbors in a condensed matrix of free radicals was modeled by Jackson and Montroll as irreversible, sequential, random dimer filling of nearest-neighbor sites on an infinite, three-dimensional lattice. Here we analyze the master equations for random dimer filling recast as an infinite hierarchy of rate equations for subconfiguration probabilities using techniques involving truncation, formal density expansions (coupled with resummation), and spectral theory. A detailed analysis for the cubic lattice case produces, e.g., estimates for the fraction of isolated empty sites (i.e., free radicals) at saturation. We also consider the effect of a stochastically specified distribution of nonadsorptive sites (i.e., inert dilutents).

  16. Kinetic Ising models with various single-spin-flip dynamics on quenched and annealed random regular graphs

    NASA Astrophysics Data System (ADS)

    Jedrzejewski, Arkadiusz; Chmiel, Anna; Sznajd-Weron, Katarzyna

    2017-07-01

    We investigate a kinetic Ising model with several single-spin-flip dynamics (including Metropolis and heat bath) on quenched and annealed random regular graphs. As expected, on the quenched structures all proposed algorithms reproduce the same results since the conditions for the detailed balance and the Boltzmann distribution in an equilibrium are satisfied. However, on the annealed graphs the situation is far less clear—the network annealing disturbs the equilibrium moving the system away from it. Consequently, distinct dynamics lead to different steady states. We show that some algorithms are more resistant to the annealed disorder, which causes only small quantitative changes in the model behavior. On the other hand, there are dynamics for which the influence of annealing on the system is significant, and qualitative changes arise like switching the type of phase transition from a continuous to a discontinuous one. We try to identify features of the proposed dynamics which are responsible for the above phenomenon.

  17. Channel-opening kinetic mechanism for human wild-type GluK2 and the M867I mutant kainate receptor.

    PubMed

    Han, Yan; Wang, Congzhou; Park, Jae Seon; Niu, Li

    2010-11-02

    GluK2 is a kainate receptor subunit that is alternatively spliced at the C-terminus. Previous studies implicated GluK2 in autism. In particular, the methionine-to-isoleucine replacement at amino acid residue 867 (M867I) that can only occur in the longest isoform of the human GluK2 (hGluK2), as the disease (autism) mutation, is thought to cause gain-of-function. However, the kinetic properties of the wild-type hGluK2 and the functional consequence of this gain-of-function mutation at the molecular level are not well understood. To investigate whether the M867I mutation affects the channel properties of the human GluK2 kainate receptor, we have systematically characterized the rate and the equilibrium constants pertinent to channel opening and channel desensitization for this mutant and the wild-type hGluK2 receptor, along with the wild-type rat GluK2 kainate receptor (rGluK2) as the control. Our results show that the M867I mutation does not affect either the rate or the equilibrium constants of the channel opening but does slow down the channel desensitization rate by ~1.6-fold at saturating glutamate concentrations. It is possible that a consequence of this mutation on the desensitization rate is linked to facilitating the receptor trafficking and membrane expression, given the close proximity of M867 to the forward trafficking motif in the C-terminal sequence. By comparing the kinetic data of the wild-type human and rat GluK2 receptors, we also find that the human GluK2 has a ~3-fold smaller channel-opening rate constant but an identical channel-closing rate constant and thus a channel-opening probability of 0.85 vs 0.96 for rGluK2. Furthermore, the intrinsic equilibrium dissociation constant K(1) for hGluK2, like the EC(50) value, is ~2-fold lower than rGluK2. Our results therefore suggest that the human GluK2 is relatively a slowly activating channel but more sensitive to glutamate, as compared to the rat ortholog, despite the fact that the human and rat forms

  18. Kinetic bottleneck to the self-organization of bidisperse hard disk monolayers formed by random sequential adsorption.

    PubMed

    Doty, R Christopher; Bonnecaze, Roger T; Korgel, Brian A

    2002-06-01

    We study the self-organization of bidisperse mixtures of hard spheres in two dimensions by simulating random sequential adsorption (RSA) of tethered hard disks that undergo limited Monte Carlo surface diffusion. The tethers place a control on the local entropy of the disks by constraining their movement within a specified distance from their original adsorption positions. By tuning the tether length, from zero (the pure RSA process) to infinity (near-equilibrium conditions), the kinetic pathway to monolayer formation can be varied. Previously [J. J. Gray et al., Phys. Rev. Lett. 85, 4430 (2000); Langmuir 17, 2317 (2001)], we generated nonequilibrium phase diagrams for size-monodisperse and size-polydisperse hard disks as a function of surface coverage, size distribution, and tether length to reveal the occurrence of hexagonal close-packed, hexatic, and disordered phases. Bidisperse hard disks potentially offer increasingly diverse phase diagrams, with the possible occurrence of spatially and compositionally organized superlattices. Geometric packing calculations anticipate the formation of close-packed lattices in two dimensions for particle size ratios sigma=R(S)/R(L)=0.53, 0.414, and 0.155. The simulations of these systems presented here, however, reveal that RSA kinetics frustrate superlattice ordering, even for infinite tethers. The calculated jamming limits fall well below the minimum surface coverages necessary for stable ordering, as determined by melting simulations.

  19. Modification of light transmission channels by inhomogeneous absorption in random media.

    PubMed

    Liew, Seng Fatt; Cao, Hui

    2015-05-04

    Optical absorption is omnipresent and often distributed non-uniformly in space. We present a numerical study on the effects of inhomogeneous absorption on transmission eigenchannels of light in highly scattering media. In the weak absorption regime, the spatial profile of a transmission channel remains similar to that without absorption, and the effect of inhomogeneous absorption can be stronger or weaker than homogeneous absorption depending on the spatial overlap of the localized absorbing region with the field intensity maximum of the channel. In the strong absorption regime, the high transmission channels redirect the energy flows to circumvent the absorbing regions to minimize loss. The attenuation of high transmission channels by inhomogeneous absorption is lower than that by homogeneous absorption, regardless of the location of the absorbing region. The statistical distribution of transmission eigenvalues in the former becomes broader than that in the latter, due to a longer tail at high transmission. The maximum enhancement factor of total transmission increases with absorption, eventually exceeds that without absorption.

  20. Conformational Changes in Alamethicin Associated with Substitution of Its α-Methylalanines with Leucines: A FTIR Spectroscopic Analysis and Correlation with Channel Kinetics

    PubMed Central

    Haris, Parvez I.; Molle, Gérard; Duclohier, Hervé

    2004-01-01

    Alamethicin, a 20 residue-long peptaibol remains a favorite high voltage-dependent channel-forming peptide. However, the structural significance of its abundant noncoded residues (α-methylalanine or Aib) for its ion channel activity remains unknown, although a previous study showed that replacement of all Aib residues with leucines preserved the essential channel behavior except for much faster single-channel events. To correlate these functional properties with structural data, here we compare the secondary structures of an alamethicin derivative where all the eight Aibs were replaced by leucines and the native alamethicin. Fourier transform infrared (FTIR) spectra of these peptides were recorded in methanol and in aqueous phospholipid membranes. Results obtained show a significant conformational change in alamethicin upon substitution of its Aib residues with Leu. The amide I band occurs at a lower frequency for the Leu-derivative indicating that its α-helices are involved in stronger hydrogen-bonding. In addition, the structure of the Leu-derivative is quite sensitive to membrane fluidity changes. The amide I band shifts to higher frequencies when the lipids are in the fluid phase. This indicates either a decreased solvation due to a more complete peptide insertion or a peptide stretching to match the full thickness of the bilayer. These results contribute to explain the fast single-channel kinetics displayed by the Leu-derivative. PMID:14695266

  1. Modulation of human Kv4.3/KChIP2 channel inactivation kinetics by cytoplasmic Ca²⁺.

    PubMed

    Groen, Christiane; Bähring, Robert

    2017-07-22

    The transient outward current (I to) in the human heart is mediated by Kv4.3 channels complexed with Kv channel interacting protein (KChIP) 2, a cytoplasmic Ca(2+)-binding EF-hand protein known to modulate Kv4.3 inactivation gating upon heterologous co-expression. We studied Kv4.3 channels co-expressed with wild-type (wt) or EF-hand-mutated (?EF) KChIP2 in human embryonic kidney (HEK) 293 cells. Co-expression took place in the absence or presence of BAPTA-AM, and macroscopic currents were recorded in the whole-cell patch-clamp configuration with different free Ca(2+) concentrations in the patch-pipette. Our data indicate that Ca(2+) is not necessary for Kv4.3/KChIP2 complex formation. The Kv4.3/KChIP2-mediated current decay was faster and the recovery of Kv4.3/KChIP2 channels from inactivation slower with 50 µM Ca(2+) than with BAPTA (nominal Ca(2+)-free) in the patch-pipette. The apparent Ca(2+)-mediated slowing of recovery kinetics was still observed when EF-hand 4 of KChIP2 was mutated (?EF4) but not when EF-hand 2 (?EF2) was mutated, and turned into a Ca(2+)-mediated acceleration of recovery kinetics when EF-hand 3 (?EF3) was mutated. In the presence of the Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) inhibitor KN-93 cytoplasmic Ca(2+) (50 µM) induced an acceleration of Kv4.3/KChIP2 recovery kinetics, which was still observed when EF-hand 2 was mutated (?EF2) but not when EF-hand 3 (?EF3) or EF-hand 4 (?EF4) was mutated. Our results support the notion that binding of Ca(2+) to KChIP2 EF-hands can acutely modulate Kv4.3/KChIP2 channel inactivation gating, but the Ca(2+)-dependent gating modulation depends on CaMKII action. Our findings speak for an acute modulation of I to kinetics and frequency-dependent I to availability in cardiomyocytes under conditions with elevated Ca(2+) levels and CaMKII activity.

  2. Nonconservative kinetic exchange model of opinion dynamics with randomness and bounded confidence.

    PubMed

    Sen, Parongama

    2012-07-01

    The concept of a bounded confidence level is incorporated in a nonconservative kinetic exchange model of opinion dynamics model where opinions have continuous values ∈[-1,1]. The characteristics of the unrestricted model, which has one parameter λ representing conviction, undergo drastic changes with the introduction of bounded confidence parametrized by δ. Three distinct regions are identified in the phase diagram in the δ-λ plane and the evidences of a first order phase transition for δ ≥ 0.3 are presented. A neutral state with all opinions equal to zero occurs for λ ≤ λ(c1) ≃ 2/3, independent of δ, while for λ(c(1)) ≤ λ ≤ λ(c(2))(δ), an ordered region is seen to exist where opinions of only one sign prevail. At λ(c(2))(δ), a transition to a disordered state is observed, where individual opinions of both signs coexist and move closer to the extreme values (±1) as λ is increased. For confidence level δ < 0.3, the ordered phase exists for a narrow range of λ only. The line δ = 0 is apparently a line of discontinuity, and this limit is discussed in some detail.

  3. Phase transitions in a two-parameter model of opinion dynamics with random kinetic exchanges.

    PubMed

    Sen, Parongama

    2011-01-01

    Recently, a model of opinion formation with kinetic exchanges has been proposed in which a spontaneous symmetry-breaking transition was reported [M. Lallouache, A. S. Chakrabarti, A. Chakraborti, and B. K. Chakrabarti, Phys. Rev. E 82, 056112 (2010)]. We generalize the model to incorporate two parameters: λ, to represent conviction, and μ, to represent the influencing ability of individuals. A phase boundary given by λ=1-μ/2 is obtained separating the symmetric and symmetry broken phases: The effect of the influencing term enhances the possibility of reaching a consensus in the society. The time scale diverges near the phase boundary in a power-law manner. The order parameter and the condensate also show power-law growth close to the phase boundary albeit with different exponents. The exponents in general change along the phase boundary, indicating a nonuniversality. The relaxation times, however, become constant with increasing system size near the phase boundary, indicating the absence of any diverging length scale. Consistently, the fluctuations remain finite but show strong dependence on the trajectory along which it is estimated.

  4. Propagation of Sobolev regularity for a class of random kinetic models on the real line

    NASA Astrophysics Data System (ADS)

    Matthes, Daniel; Toscani, Giuseppe

    2010-09-01

    A class of Kac-like kinetic equations on the real line is considered, with general smoothing transforms as collisional kernels. These equations have been introduced recently e.g. in the context of econophysics (Cordier et al 2005 J. Stat. Phys. 120 253-77) or as models for granular gases with a background heat bath (Carrillo et al 2009 Discrete Contin. Dyn. Syst. 24 59-81). We show that the stationary solutions to these equations are not smooth in general, and we characterize their (finite) Sobolev regularity in dependence of the properties of the collisional kernel. Moreover, we prove that any initial Sobolev regularity below a well-defined threshold is uniformly propagated in time by the transient weak solutions, implying their strong convergence to the steady state. The applied techniques differ from the classical ones developed for the Kac equation as the models at hand neither dissipate the entropy nor the Fisher information. Instead, the proof relies on direct estimates on the collisional operator.

  5. Kinetics of PIP2 metabolism and KCNQ2/3 channel regulation studied with a voltage-sensitive phosphatase in living cells

    PubMed Central

    Falkenburger, Björn H.; Jensen, Jill B.

    2010-01-01

    The signaling phosphoinositide phosphatidylinositol 4,5-bisphosphate (PIP2) is synthesized in two steps from phosphatidylinositol by lipid kinases. It then interacts with KCNQ channels and with pleckstrin homology (PH) domains among many other physiological protein targets. We measured and developed a quantitative description of these metabolic and protein interaction steps by perturbing the PIP2 pool with a voltage-sensitive phosphatase (VSP). VSP can remove the 5-phosphate of PIP2 with a time constant of τ <300 ms and fully inhibits KCNQ currents in a similar time. PIP2 was then resynthesized from phosphatidylinositol 4-phosphate (PIP) quickly, τ = 11 s. In contrast, resynthesis of PIP2 after activation of phospholipase C by muscarinic receptors took ∼130 s. These kinetic experiments showed that (1) PIP2 activation of KCNQ channels obeys a cooperative square law, (2) the PIP2 residence time on channels is <10 ms and the exchange time on PH domains is similarly fast, and (3) the step synthesizing PIP2 by PIP 5-kinase is fast and limited primarily by a step(s) that replenishes the pool of plasma membrane PI(4)P. We extend the kinetic model for signaling from M1 muscarinic receptors, presented in our companion paper in this issue (Falkenburger et al. 2010. J. Gen. Physiol. doi:10.1085/jgp.200910344), with this new information on PIP2 synthesis and KCNQ interaction. PMID:20100891

  6. Gβ₂ mimics activation kinetic slowing of CaV2.2 channels by noradrenaline in rat sympathetic neurons.

    PubMed

    Hernández-Castellanos, Juan M; Vivas, Oscar; Garduño, Julieta; De la Cruz, Lizbeth; Arenas, Isabel; Elías-Viñas, David; Mackie, Ken; García, David E

    2014-02-28

    Several neurotransmitters and hormones acting through G protein-coupled receptors elicit a voltage-dependent regulation of CaV2.2 channels, having profound effects on cell function and the organism. It has been hypothesized that protein-protein interactions define specificity in signal transduction. Yet it is unknown how the molecular interactions in an intracellular signaling cascade determine the specificity of the voltage-dependent regulation induced by a specific neurotransmitter. It has been suspected that specific effector regions on the Gβ subunits of the G proteins are responsible for voltage-dependent regulation. The present study examines whether a neurotransmitter's specificity can be revealed by simple ion-current kinetic analysis likely resulting from interactions between Gβ subunits and the channel-molecule. Noradrenaline is a neurotransmitter that induces voltage-dependent regulation. By using biochemical and patch-clamp methods in rat sympathetic neurons we examined calcium current modulation induced by each of the five Gβ subunits and found that Gβ2 mimics activation kinetic slowing of CaV2.2 channels by noradrenaline. Furthermore, overexpression of the Gβ2 isoform reproduces the effect of noradrenaline in the willing-reluctant model. These results advance our understanding on the mechanisms by which signals conveying from a variety of membrane receptors are able to display precise homeostatic responses.

  7. A single Markov-type kinetic model accounting for the macroscopic currents of all human voltage-gated sodium channel isoforms.

    PubMed

    Balbi, Pietro; Massobrio, Paolo; Hellgren Kotaleski, Jeanette

    2017-09-01

    Modelling ionic channels represents a fundamental step towards developing biologically detailed neuron models. Until recently, the voltage-gated ion channels have been mainly modelled according to the formalism introduced by the seminal works of Hodgkin and Huxley (HH). However, following the continuing achievements in the biophysical and molecular comprehension of these pore-forming transmembrane proteins, the HH formalism turned out to carry limitations and inconsistencies in reproducing the ion-channels electrophysiological behaviour. At the same time, Markov-type kinetic models have been increasingly proven to successfully replicate both the electrophysiological and biophysical features of different ion channels. However, in order to model even the finest non-conducting molecular conformational change, they are often equipped with a considerable number of states and related transitions, which make them computationally heavy and less suitable for implementation in conductance-based neurons and large networks of those. In this purely modelling study we develop a Markov-type kinetic model for all human voltage-gated sodium channels (VGSCs). The model framework is detailed, unifying (i.e., it accounts for all ion-channel isoforms) and computationally efficient (i.e. with a minimal set of states and transitions). The electrophysiological data to be modelled are gathered from previously published studies on whole-cell patch-clamp experiments in mammalian cell lines heterologously expressing the human VGSC subtypes (from NaV1.1 to NaV1.9). By adopting a minimum sequence of states, and using the same state diagram for all the distinct isoforms, the model ensures the lightest computational load when used in neuron models and neural networks of increasing complexity. The transitions between the states are described by original ordinary differential equations, which represent the rate of the state transitions as a function of voltage (i.e., membrane potential). The

  8. The Kinetics of Integrilin Limited by Obesity (KILO): A Multicenter Randomized Pharmacokinetic and Pharmacodynamic Clinical Trial

    PubMed Central

    Vavalle, John P.; Stevens, Susanna R.; Hassinger, Nancy; Cohen, Mauricio G.; Arnold, Anita; Kandzari, David E.; Aguirre, Frank V.; Gretler, Daniel D.; Alexander, John H.

    2013-01-01

    Background KILO tested 2 novel weight-based eptifibatide dosing strategies compared with standard dosing in obese patients undergoing elective percutaneous coronary intervention (PCI). Eptifibatide dosing is weight-adjusted for patients up to 121 kg. Patients above this weight receive the same maximal dose, although it is unknown if this provides adequate eptifibatide concentration or platelet inhibition. Methods Sixty-seven patients weighing ≥125 kg undergoing elective PCI were randomized to 1 of 3 eptifibatide dosing regimens: standard dosing using a weight of 121 kg, actual body weight-based (ABW) dosing with no upper limit, or ideal body weight-based (IBW) dosing. Boluses of 180 μg/kg were given 10 minutes apart, followed by a 2.0 μg/kg/min infusion. Plasma eptifibatide concentrations were drawn at 12–18 hours after initiating the infusion. Platelet aggregation was assessed at baseline and 10 minutes after the second bolus. Results Sixty-seven patients were randomized to standard (n=22), ABW (n=23), or IBW (n=22) dosing. The median (25th, 75th) steady-state plasma eptifibatide concentrations were 1740 ng/mL (1350, 2350), 1780 ng/mL (1510, 2350), and 1055 ng/mL (738, 1405), respectively (P<0.001). Ten-minute median (25th, 75th) platelet aggregation units were 7 (0, 21), 2 (0, 8), and 14 (8, 20), respectively, (P=0.001). Conclusions ABW eptifibatide dosing leads to higher plasma concentrations and greater platelet inhibition than standard or IBW dosing in obese patients undergoing PCI. Current recommendations for eptifibatide dosing may be inadequate in patients >121 kg. Further study is warranted to define the optimal dosing of eptifibatide and other medications in obese patients. PMID:22137072

  9. The kinetics of integrilin limited by obesity: a multicenter randomized pharmacokinetic and pharmacodynamic clinical trial.

    PubMed

    Vavalle, John P; Stevens, Susanna R; Hassinger, Nancy; Cohen, Mauricio G; Arnold, Anita; Kandzari, David E; Aguirre, Frank V; Gretler, Daniel D; Alexander, John H

    2011-12-01

    KILO tested 2 novel weight-based eptifibatide dosing strategies compared with standard dosing in obese patients undergoing elective percutaneous coronary intervention (PCI). Eptifibatide dosing is weight adjusted for patients up to 121 kg. Patients above this weight receive the same maximal dose, although it is unknown if this provides adequate eptifibatide concentration or platelet inhibition. Sixty-seven patients weighing ≥125 kg undergoing elective PCI were randomized to 1 of 3 eptifibatide dosing regimens: standard dosing using a weight of 121 kg, actual body weight (ABW)-based dosing with no upper limit, or ideal body weight (IBW)-based dosing. Boluses of 180 μg/kg were given 10 minutes apart, followed by a 2.0 μg/kg per minute infusion. Plasma eptifibatide concentrations were drawn at 12 to 18 hours after initiating the infusion. Platelet aggregation was assessed at baseline and 10 minutes after the second bolus. Sixty-seven patients were randomized to standard (n = 22), ABW (n = 23), or IBW (n = 22) dosing. The median (25th, 75th) steady-state plasma eptifibatide concentrations were 1,740 ng/mL (1,350, 2,350), 1,780 ng/mL (1,510, 2,350), and 1,055 ng/mL (738, 1,405), respectively (P < .001). Ten-minute median (25th, 75th) platelet aggregation units were 7 (0, 21), 2 (0, 8), and 14 (8, 20), respectively (P = .001). Actual body weight eptifibatide dosing leads to higher plasma concentrations and greater platelet inhibition than standard or IBW dosing in obese patients undergoing PCI. Current recommendations for eptifibatide dosing may be inadequate in patients >121 kg. Further study is warranted to define the optimal dosing of eptifibatide and other medications in obese patients. Copyright © 2011 Mosby, Inc. All rights reserved.

  10. Flow-Induced New Channels of Energy Exchange in Multi-Scale Plasma Dynamics - Revisiting Perturbative Hybrid Kinetic-MHD Theory.

    PubMed

    Shiraishi, Junya; Miyato, Naoaki; Matsunaga, Go

    2016-05-10

    It is found that new channels of energy exchange between macro- and microscopic dynamics exist in plasmas. They are induced by macroscopic plasma flow. This finding is based on the kinetic-magnetohydrodynamic (MHD) theory, which analyses interaction between macroscopic (MHD-scale) motion and microscopic (particle-scale) dynamics. The kinetic-MHD theory is extended to include effects of macroscopic plasma flow self-consistently. The extension is realised by generalising an energy exchange term due to wave-particle resonance, denoted by δ WK. The first extension is generalisation of the particle's Lagrangian, and the second one stems from modification to the particle distribution function due to flow. These extensions lead to a generalised expression of δ WK, which affects the MHD stability of plasmas.

  11. Flow-Induced New Channels of Energy Exchange in Multi-Scale Plasma Dynamics – Revisiting Perturbative Hybrid Kinetic-MHD Theory

    PubMed Central

    Shiraishi, Junya; Miyato, Naoaki; Matsunaga, Go

    2016-01-01

    It is found that new channels of energy exchange between macro- and microscopic dynamics exist in plasmas. They are induced by macroscopic plasma flow. This finding is based on the kinetic-magnetohydrodynamic (MHD) theory, which analyses interaction between macroscopic (MHD-scale) motion and microscopic (particle-scale) dynamics. The kinetic-MHD theory is extended to include effects of macroscopic plasma flow self-consistently. The extension is realised by generalising an energy exchange term due to wave-particle resonance, denoted by δ WK. The first extension is generalisation of the particle’s Lagrangian, and the second one stems from modification to the particle distribution function due to flow. These extensions lead to a generalised expression of δ WK, which affects the MHD stability of plasmas. PMID:27160346

  12. Two distinct voltage-sensing domains control voltage sensitivity and kinetics of current activation in CaV1.1 calcium channels

    PubMed Central

    Tuluc, Petronel; Benedetti, Bruno; Coste de Bagneaux, Pierre; Grabner, Manfred

    2016-01-01

    Alternative splicing of the skeletal muscle CaV1.1 voltage-gated calcium channel gives rise to two channel variants with very different gating properties. The currents of both channels activate slowly; however, insertion of exon 29 in the adult splice variant CaV1.1a causes an ∼30-mV right shift in the voltage dependence of activation. Existing evidence suggests that the S3–S4 linker in repeat IV (containing exon 29) regulates voltage sensitivity in this voltage-sensing domain (VSD) by modulating interactions between the adjacent transmembrane segments IVS3 and IVS4. However, activation kinetics are thought to be determined by corresponding structures in repeat I. Here, we use patch-clamp analysis of dysgenic (CaV1.1 null) myotubes reconstituted with CaV1.1 mutants and chimeras to identify the specific roles of these regions in regulating channel gating properties. Using site-directed mutagenesis, we demonstrate that the structure and/or hydrophobicity of the IVS3–S4 linker is critical for regulating voltage sensitivity in the IV VSD, but by itself cannot modulate voltage sensitivity in the I VSD. Swapping sequence domains between the I and the IV VSDs reveals that IVS4 plus the IVS3–S4 linker is sufficient to confer CaV1.1a-like voltage dependence to the I VSD and that the IS3–S4 linker plus IS4 is sufficient to transfer CaV1.1e-like voltage dependence to the IV VSD. Any mismatch of transmembrane helices S3 and S4 from the I and IV VSDs causes a right shift of voltage sensitivity, indicating that regulation of voltage sensitivity by the IVS3–S4 linker requires specific interaction of IVS4 with its corresponding IVS3 segment. In contrast, slow current kinetics are perturbed by any heterologous sequences inserted into the I VSD and cannot be transferred by moving VSD I sequences to VSD IV. Thus, CaV1.1 calcium channels are organized in a modular manner, and control of voltage sensitivity and activation kinetics is accomplished by specific molecular

  13. Two distinct voltage-sensing domains control voltage sensitivity and kinetics of current activation in CaV1.1 calcium channels.

    PubMed

    Tuluc, Petronel; Benedetti, Bruno; Coste de Bagneaux, Pierre; Grabner, Manfred; Flucher, Bernhard E

    2016-06-01

    Alternative splicing of the skeletal muscle CaV1.1 voltage-gated calcium channel gives rise to two channel variants with very different gating properties. The currents of both channels activate slowly; however, insertion of exon 29 in the adult splice variant CaV1.1a causes an ∼30-mV right shift in the voltage dependence of activation. Existing evidence suggests that the S3-S4 linker in repeat IV (containing exon 29) regulates voltage sensitivity in this voltage-sensing domain (VSD) by modulating interactions between the adjacent transmembrane segments IVS3 and IVS4. However, activation kinetics are thought to be determined by corresponding structures in repeat I. Here, we use patch-clamp analysis of dysgenic (CaV1.1 null) myotubes reconstituted with CaV1.1 mutants and chimeras to identify the specific roles of these regions in regulating channel gating properties. Using site-directed mutagenesis, we demonstrate that the structure and/or hydrophobicity of the IVS3-S4 linker is critical for regulating voltage sensitivity in the IV VSD, but by itself cannot modulate voltage sensitivity in the I VSD. Swapping sequence domains between the I and the IV VSDs reveals that IVS4 plus the IVS3-S4 linker is sufficient to confer CaV1.1a-like voltage dependence to the I VSD and that the IS3-S4 linker plus IS4 is sufficient to transfer CaV1.1e-like voltage dependence to the IV VSD. Any mismatch of transmembrane helices S3 and S4 from the I and IV VSDs causes a right shift of voltage sensitivity, indicating that regulation of voltage sensitivity by the IVS3-S4 linker requires specific interaction of IVS4 with its corresponding IVS3 segment. In contrast, slow current kinetics are perturbed by any heterologous sequences inserted into the I VSD and cannot be transferred by moving VSD I sequences to VSD IV. Thus, CaV1.1 calcium channels are organized in a modular manner, and control of voltage sensitivity and activation kinetics is accomplished by specific molecular mechanisms

  14. Periodic forcing of a K+ channel at various temperatures.

    PubMed Central

    Petracchi, D; Pellegrini, M; Pellegrino, M; Barbi, M; Moss, F

    1994-01-01

    The random sequence of openings and closings of single ion channels and the channel conductances have been the object of intense study over the past two decades with a view toward illuminating the underlying kinetics of the channel protein molecules. Channels that are sensitive to voltage, such as many K(+)-selective channels, have been particularly useful, because the kinetic rates can be manipulated by changing the membrane voltage. Most such studies have been performed under stationary conditions and usually at a single temperature. Here we report the results of experiments with sinusoidal modulation of the membrane potential performed at several temperatures. Dwell time and cycle histograms, objects not normally associated with ion channel experiments, are herein reported. From the last, the transition probability densities for channel opening and closing events are obtained. A new and unusual phase anticipation is observed in the cycle histograms, and its temperature dependence is measured. PMID:8075322

  15. Variational perturbation and extended Plefka approaches to dynamics on random networks: the case of the kinetic Ising model

    NASA Astrophysics Data System (ADS)

    Bachschmid-Romano, L.; Battistin, C.; Opper, M.; Roudi, Y.

    2016-10-01

    We describe and analyze some novel approaches for studying the dynamics of Ising spin glass models. We first briefly consider the variational approach based on minimizing the Kullback-Leibler divergence between independent trajectories and the real ones and note that this approach only coincides with the mean field equations from the saddle point approximation to the generating functional when the dynamics is defined through a logistic link function, which is the case for the kinetic Ising model with parallel update. We then spend the rest of the paper developing two ways of going beyond the saddle point approximation to the generating functional. In the first one, we develop a variational perturbative approximation to the generating functional by expanding the action around a quadratic function of the local fields and conjugate local fields whose parameters are optimized. We derive analytical expressions for the optimal parameters and show that when the optimization is suitably restricted, we recover the mean field equations that are exact for the fully asymmetric random couplings (Mézard and Sakellariou 2011 J. Stat. Mech. 2011 L07001). However, without this restriction the results are different. We also describe an extended Plefka expansion in which in addition to the magnetization, we also fix the correlation and response functions. Finally, we numerically study the performance of these approximations for Sherrington-Kirkpatrick type couplings for various coupling strengths and the degrees of coupling symmetry, for both temporally constant but random, as well as time varying external fields. We show that the dynamical equations derived from the extended Plefka expansion outperform the others in all regimes, although it is computationally more demanding. The unconstrained variational approach does not perform well in the small coupling regime, while it approaches dynamical TAP equations of (Roudi and Hertz 2011 J. Stat. Mech. 2011 P03031) for strong couplings.

  16. Kinetic aspects of ion transport through neural membrane

    NASA Astrophysics Data System (ADS)

    Clay, John R.; Shlesinger, Michael F.

    1984-02-01

    The Hodgkin-Huxley model for the nerve membrane action potential is reviewed. The model can be described in terms of channels and gates. That is, ions permeate the nerve membrane through narrow ion specific pores, or channels, which are modulated by a voltage dependent gating process. The Hodgkin-Huxley model provides a detailed kinetic scheme for channel gating, but not for channel permeation. Radioactive tracer flux experiments suggest that permeation occurs via single file motion of ions through a channel. We have modeled this process as a random walk with internal states. The theory leads to expressions for one way fluxes which can be compared with experimental tracer flux data. Recent experiments on channel gating have indicated that the Hodgkin-Huxley model of the gating process requires certain modifications. We present a class of modifications involving temporal memory of gating and interactions between gating particles of any single channel. Thses models can also be described in terms of random walks.

  17. Groundwater cleanup by in-situ sparging. XIII. Random air channels for sparing of dissolved and nonaqueous phase volatiles

    SciTech Connect

    Wilson, D.J.; Clarke, A.N.; Kaminski, K.M.; Chang, E.Y.

    1997-12-01

    A mathematical model is developed to simulate the sparging of dissolved volatile organic compounds (VOCs) and nonaqueous phase liquid (NAPL) from contaminated aquifers. The sparging air moves through the aquifer in persistent, random channels, to which VOC must move by diffusion/dispersion to be removed. The dependence of the rate of remediation on the various model parameters is investigated and some practical conclusions are reached regarding the operation of air sparging wells for aquifer remediation. VOCs of low water solubility (such as alkanes) and present as NAPL are found to be removed by air sparging much more slowly than VOCs of higher water solubility (such as benzene, toluene, ethylbenzene and xylenes) and present as NAPL, due to the very small maximum concentration gradients which can be maintained around droplets of the former. These small concentration gradients result in very slow rates of NAPL solution.

  18. Witnessing random unitary and projective quantum channels: Complementarity between separable and maximally entangled states

    NASA Astrophysics Data System (ADS)

    Bruns, D.; Sperling, J.; Scheel, S.

    2016-03-01

    Modern applications in quantum computation and quantum communication require the precise characterization of quantum states and quantum channels. In practice, this means that one has to determine the quantum capacity of a physical system in terms of measurable quantities. Witnesses, if properly constructed, succeed in performing this task. We derive a method that is capable to compute witnesses for identifying deterministic evolutions and measurement-induced collapse processes. At the same time, applying the Choi-Jamiołkowski isomorphism, it uncovers the entanglement characteristics of bipartite quantum states. Remarkably, a statistical mixture of unitary evolutions is mapped onto mixtures of maximally entangled states, and classical separable states originate from genuine quantum-state reduction maps. Based on our treatment, we are able to witness these opposing attributes at once and, furthermore, obtain an insight into their different geometric structures. The complementarity is further underpinned by formulating a complementary Schmidt decomposition of a state in terms of maximally entangled states and discrete Fourier-transformed Schmidt coefficients.

  19. Kv3.1/Kv3.2 channel positive modulators enable faster activating kinetics and increase firing frequency in fast-spiking GABAergic interneurons.

    PubMed

    Boddum, Kim; Hougaard, Charlotte; Xiao-Ying Lin, Julie; von Schoubye, Nadia Lybøl; Jensen, Henrik Sindal; Grunnet, Morten; Jespersen, Thomas

    2017-02-24

    Due to their fast kinetic properties, Kv3.1 voltage gated potassium channels are important in setting and controlling firing frequency in neurons and pivotal in generating high frequency firing of interneurons. Pharmacological activation of Kv3.1 channels may possess therapeutic potential for treatment of epilepsy, hearing disorders, schizophrenia and cognitive impairments. Here we thoroughly investigate the selectivity and positive modulation of the two small molecules, EX15 and RE01, on Kv3 channels. Selectivity studies, conducted in Xenopus laevis oocytes confirmed a positive modulatory effect of the two compounds on Kv3.1 and to a minor extent on Kv3.2 channels. RE01 had no effect on the Kv3.3 and Kv3.4 channels, whereas EX15 had an inhibitory impact on the Kv3.4 mediated current. Voltage-clamp experiments in monoclonal hKv3.1b/HEK293 cells (34 °C) revealed that the two compounds indeed induced larger currents and faster activation kinetics. They also decrease the speed of deactivation and shifted the voltage dependence of activation, to a more negative activation threshold. Application of action potential clamping and repetitive stimulation protocols of hKv3.1b expressing HEK293 cells revealed that EX15 and RE01 significantly increased peak amplitude, half width and decay time of Kv3.1 mediated currents, even during high-frequency action potential clamping (250 Hz). In rat hippocampal slices, EX15 and RE01 increased neuronal excitability in fast-spiking interneurons in dentate gyrus. Action potential frequency was prominently increased at minor depolarizing steps, whereas more marginal effects of EX15 and RE01 were observed after stronger depolarizations. In conclusion, our results suggest that EX15 and RE01 positive modulation of Kv3.1 and Kv3.2 currents facilitate increased firing frequency in fast-spiking GABAergic interneurons.

  20. A tapered channel microfluidic device for comprehensive cell adhesion analysis, using measurements of detachment kinetics and shear stress-dependent motion.

    PubMed

    Rupprecht, Peter; Golé, Laurent; Rieu, Jean-Paul; Vézy, Cyrille; Ferrigno, Rosaria; Mertani, Hichem C; Rivière, Charlotte

    2012-03-01

    We have developed a method for studying cellular adhesion by using a custom-designed microfluidic device with parallel non-connected tapered channels. The design enables investigation of cellular responses to a large range of shear stress (ratio of 25) with a single input flow-rate. For each shear stress, a large number of cells are analyzed (500-1500 cells), providing statistically relevant data within a single experiment. Besides adhesion strength measurements, the microsystem presented in this paper enables in-depth analysis of cell detachment kinetics by real-time videomicroscopy. It offers the possibility to analyze adhesion-associated processes, such as migration or cell shape change, within the same experiment. To show the versatility of our device, we examined quantitatively cell adhesion by analyzing kinetics, adhesive strength and migration behaviour or cell shape modifications of the unicellular model cell organism Dictyostelium discoideum at 21 °C and of the human breast cancer cell line MDA-MB-231 at 37 °C. For both cell types, we found that the threshold stresses, which are necessary to detach the cells, follow lognormal distributions, and that the detachment process follows first order kinetics. In addition, for particular conditions' cells are found to exhibit similar adhesion threshold stresses, but very different detachment kinetics, revealing the importance of dynamics analysis to fully describe cell adhesion. With its rapid implementation and potential for parallel sample processing, such microsystem offers a highly controllable platform for exploring cell adhesion characteristics in a large set of environmental conditions and cell types, and could have wide applications across cell biology, tissue engineering, and cell screening.

  1. A randomized trial of a low-trapping nonselective N-methyl-D-aspartate channel blocker in major depression.

    PubMed

    Zarate, Carlos A; Mathews, Daniel; Ibrahim, Lobna; Chaves, Jose Franco; Marquardt, Craig; Ukoh, Immaculata; Jolkovsky, Libby; Brutsche, Nancy E; Smith, Mark A; Luckenbaugh, David A

    2013-08-15

    The high-affinity N-methyl-D-aspartate (NMDA) antagonist ketamine exerts rapid antidepressant effects but has psychotomimetic properties. AZD6765 is a low-trapping NMDA channel blocker with low rates of associated psychotomimetic effects. This study investigated whether AZD6765 could produce rapid antidepressant effects in subjects with treatment-resistant major depressive disorder (MDD). In this double-blind, randomized, crossover, placebo-controlled study, 22 subjects with DSM-IV treatment-resistant MDD received a single infusion of either AZD6765 (150 mg) or placebo on 2 test days 1 week apart. The primary outcome measure was the Montgomery-Åsberg Depression Rating Scale, which was used to rate overall depressive symptoms at baseline and 60, 80, 110, and 230 min postinfusion and on Days 1, 2, 3, and 7 postinfusion. Several secondary outcome measures were also used, including the Hamilton Depression Rating Scale. Within 80 min, Montgomery-Åsberg Depression Rating Scale scores significantly improved in subjects receiving AZD6765 compared with placebo; this improvement remained significant only through 110 min (d = .40). On the Hamilton Depression Rating Scale, a drug difference was found at 80 and 110 min and at Day 2 (d = .49). Overall, 32% of subjects responded to AZD6765, and 15% responded to placebo at some point during the trial. No difference was observed between the groups with regard to psychotomimetic or dissociative adverse effects. In patients with treatment-resistant MDD, a single intravenous dose of the low-trapping NMDA channel blocker AZD6765 was associated with rapid but short-lived antidepressant effects; no psychotomimetic effects were observed. Published by Elsevier Inc.

  2. Effects of aerobic exercise training on variability and heart rate kinetic during submaximal exercise after gastric bypass surgery--a randomized controlled trial.

    PubMed

    Castello-Simões, Viviane; Polaquini Simões, Rodrigo; Beltrame, Thomas; Bassi, Daniela; Maria Catai, Aparecida; Arena, Ross; Azambuja, Noé Carvalho; do Nascimento Ortega, João; Borghi-Silva, Audrey

    2013-02-01

    This study aimed to determine whether morbidly obese women have an alteration of heart rate (HR) kinetics and HR variability (HRV) during the 6-min walk test (6MWT) and if an aerobic exercise training can modify these indexes after gastric bypass surgery (GBS). Nineteen morbidly obese women were randomized to a trained (TG) or control group and 12 women of eutrophic group (EG) were also evaluated. The obese women were tested on two occasions: 1 week before and 4 months after GBS through record of HR and R-R intervals during 6MWT for analysis HR kinetics. The TG underwent an aerobic exercise training program on a treadmill (1-h session, totaling 36 sessions over 12-week). Both obese groups demonstrated a significant reduction of rMSSD and slower HR kinetics during the 6MWT when compared to the EG. In addition, only the TG demonstrated a significant improvement in HRV indexes, walking distance, faster time constant and mean response time of HR during 6MWT after training (p < 0.05). Morbidly obese women have slower HR kinetics and altered cardiac modulation during submaximal exercise. However, aerobic exercise training can produce beneficial adaptations in HRV and faster HR kinetics following GBS.

  3. Kinetics of binding of dihydropyridine calcium channel ligands to skeletal muscle membranes: Evidence for low-affinity sites and for the involvement of G proteins

    SciTech Connect

    Dunn, S.M.J.; Bladen, C. )

    1991-06-11

    Detailed kinetic studies of the binding of the calcium channel antagonist (+)-({sup 3}H)PN200-110 to membrane preparations form rabbit skeletal muscle have demonstrated that, in addition to the high-affinity sites that are readily measured in equilibrium and kinetic experiments, there are also dihydropyridine binding sites with much lower affinities. These sites were detected by the ability of micromolar concentrations of several dihydropyridines to accelerate the rate of dissociation of (+)-({sup 3}H)PN200-110 from its high-affinity sites. The observed increase in rate was dependent on the concentration of competing ligand, and half-maximal effects occurred at approximately 10 {mu}M for the agonist ({plus minus})-Bay K8644 and for the antagonists nifedipine, ({plus minus})-nitrendipine, and (+)-PN200-110. The low-affinity sites appear to be stereospecific since ({minus})-PN200-110 (1-200 {mu}M) did not affect the dissociation rate. The possible involvement of guanine nucleotide binding proteins in dihydropyridine binding has been investigated by studying the effects of guanosine 5'-O-(3-thiotriphosphate) (GTP{gamma}S) and guanosine 5'-O-(2-thiodiphosphate) (GDP{beta}S) on binding parameters. GTP{gamma}S did increase the ability of ({plus minus})-({sup 3}H)PN200-110. These results suggest that skeletal muscle dihydropyridine receptors have low-affinity binding sites that may be involved in the regulation of calcium channel function and that activation of a guanine nucleotide binding protein may modulate the binding of agonists but not of antagonists to these sites.

  4. Transcranial random noise stimulation-induced plasticity is NMDA-receptor independent but sodium-channel blocker and benzodiazepines sensitive

    PubMed Central

    Chaieb, Leila; Antal, Andrea; Paulus, Walter

    2015-01-01

    Background: Application of transcranial random noise stimulation (tRNS) between 0.1 and 640 Hz of the primary motor cortex (M1) for 10 min induces a persistent excitability increase lasting for at least 60 min. However, the mechanism of tRNS-induced cortical excitability alterations is not yet fully understood. Objective: The main aim of this study was to get first efficacy data with regard to the possible neuronal effect of tRNS. Methods: Single-pulse transcranial magnetic stimulation (TMS) was used to measure levels of cortical excitability before and after combined application of tRNS at an intensity of 1 mA for 10 min stimulation duration and a pharmacological agent (or sham) on eight healthy male participants. Results: The sodium channel blocker carbamazepine showed a tendency toward inhibiting MEPs 5–60 min poststimulation. The GABAA agonist lorazepam suppressed tRNS-induced cortical excitability increases at 0–20 and 60 min time points. The partial NMDA receptor agonist D-cycloserine, the NMDA receptor antagonist dextromethorphan and the D2/D3 receptor agonist ropinirole had no significant effects on the excitability increases seen with tRNS. Conclusions: In contrast to transcranial direct current stimulation (tDCS), aftereffects of tRNS are seem to be not NMDA receptor dependent and can be suppressed by benzodiazepines suggesting that tDCS and tRNS depend upon different mechanisms. PMID:25914617

  5. Mechanistic insights from resolving ligand-dependent kinetics of conformational changes at ATP-gated P2X1R ion channels

    PubMed Central

    Fryatt, Alistair G.; Dayl, Sudad; Cullis, Paul M.; Schmid, Ralf; Evans, Richard J.

    2016-01-01

    Structural studies of P2X receptors show a novel U shaped ATP orientation following binding. We used voltage clamp fluorometry (VCF) and molecular dynamics (MD) simulations to investigate agonist action. For VCF the P2X1 receptor (P2X1R) K190C mutant (adjacent to the agonist binding pocket) was labelled with the fluorophore MTS-TAMRA and changes in fluorescence on agonist treatment provided a real time measure of conformational changes. Studies with heteromeric channels incorporating a key lysine mutation (K68A) in the ATP binding site demonstrate that normally three molecules of ATP activate the receptor. The time-course of VCF responses to ATP, 2′-deoxy ATP, 3′-deoxy ATP, Ap5A and αβmeATP were agonist dependent. Comparing the properties of the deoxy forms of ATP demonstrated the importance of the 2′ hydroxyl group on the ribose ring in determining agonist efficacy consistent with MD simulations showing that it forms a hydrogen bond with the γ-phosphate oxygen stabilizing the U-shaped conformation. Comparison of the recovery of fluorescence on agonist washout, with channel activation to a second agonist application for the partial agonists Ap5A and αβmeATP, showed a complex relationship between conformational change and desensitization. These results highlight that different agonists induce distinct conformational changes, kinetics and recovery from desensitization at P2X1Rs. PMID:27616669

  6. Fluorescence changes reveal kinetic steps of muscarinic receptor–mediated modulation of phosphoinositides and Kv7.2/7.3 K+ channels

    PubMed Central

    Jensen, Jill B.; Lyssand, John S.; Hague, Chris

    2009-01-01

    G protein–coupled receptors initiate signaling cascades. M1 muscarinic receptor (M1R) activation couples through Gαq to stimulate phospholipase C (PLC), which cleaves phosphatidylinositol 4,5-bisphosphate (PIP2). Depletion of PIP2 closes PIP2-requiring Kv7.2/7.3 potassium channels (M current), thereby increasing neuronal excitability. This modulation of M current is relatively slow (6.4 s to reach within 1/e of the steady-state value). To identify the rate-limiting steps, we investigated the kinetics of each step using pairwise optical interactions likely to represent fluorescence resonance energy transfer for M1R activation, M1R/Gβ interaction, Gαq/Gβ separation, Gαq/PLC interaction, and PIP2 hydrolysis. Electrophysiology was used to monitor channel closure. Time constants for M1R activation (<100 ms) and M1R/Gβ interaction (200 ms) are both fast, suggesting that neither of them is rate limiting during muscarinic suppression of M current. Gαq/Gβ separation and Gαq/PLC interaction have intermediate 1/e times (2.9 and 1.7 s, respectively), and PIP2 hydrolysis (6.7 s) occurs on the timescale of M current suppression. Overexpression of PLC accelerates the rate of M current suppression threefold (to 2.0 s) to become nearly contemporaneous with Gαq/PLC interaction. Evidently, channel release of PIP2 and closure are rapid, and the availability of active PLC limits the rate of M current suppression. PMID:19332618

  7. An ab initio/rice--Ramsperger--Kassel--Marcus study of the reactions of propenols with OH. Mechanism and kinetics of H abstraction channels.

    PubMed

    Zhou, Chong-Wen; Mebel, Alexander M; Li, Xiang-Yuan

    2009-10-08

    Propenols have been found to be common intermediates in the hydrocarbon combustion and they are present in substantial concentrations in a wide range of flames. However, the kinetics properties of these species in combustion flames have not received much attention. In this work, the mechanism and kinetics of the OH hydrogen abstraction from propenols are investigated. Three stable conformations of propenols, (E)-1-propenol, (Z)-1-propenol, and syn-propen-2-ol, are taken into consideration. The potential energy profiles for the three reaction systems have been first investigated by the CCSD(T) method. The geometric parameters and relative energies of the reactants, reactant complexes, transition states, product complexes, and products have been investigated theoretically. The rate constants are calculated in the temperature range of 200-3000 K by the Variflex code based on the weak collision master equation/microcanonical variational RRKM theory. For all considered reactions, our results support a stepwise mechanism involving the formation of a reactant complex in the entrance channel and a product complex in the exit channel. In the reaction of OH with (E)-1-propenol, the hydrogen abstractions from the -CH(3) and -OH sites are dominant and competitive with each other in the temperature range from 500 to 2000 K. Above 2000 K, the hydrogen abstraction from the -CH group bonded to O atom becomes dominant with a relative yield of 51.1% at 3000 K. In the reaction of OH with (Z)-1-propenol, the hydrogen abstractions from -CH(3), -CH bonded to O atom, and -OH are preferable in the temperature range from 500 to 1800 K, with the first two channels being competitive with each other. Above 1800 K, the hydrogen abstraction reaction from the CH group bonded to the CH(3) group becomes dominant with the branching ratio of 90.3% at 3000 K. In the reaction of OH with syn-propen-2-ol, the abstractions from the -CH(3) and -OH sites are competitive with each other when the temperature

  8. PKA phosphorylation reshapes the pharmacological kinetics of BmK AS, a unique site-4 sodium channel-specific modulator

    PubMed Central

    Liu, Z. R.; Zhang, H.; Wu, J. Q.; Zhou, J. J.; Ji, Y. H.

    2014-01-01

    Although modulation of the activity of voltage-gated sodium channels (VGSCs) by protein kinase A (PKA) phosphorylation has been investigated in multiple preparations, the pharmacological sensitivity of VGSCs to scorpion toxins after PKA phosphorylation has rarely been approached. In this study, the effects of BmK AS, a sodium channel-specific modulator from Chinese scorpion Buthus martensi Karsch, on the voltage-dependent activation and inactivation of Nav1.2 were examined before and after PKA activation. After PKA phosphorylation, the pattern of dose-dependent modulation of BmK AS, on both Nav1.2α and Nav1.2 (α + β1) was reshaped. Meanwhile, the shifts in voltage-dependency of activation and inactivation induced by BmK AS were attenuated. The results suggested that PKA might play a role in different patterns how β-like toxins such as BmK AS modulate gating properties and peak currents of VGSCs. PMID:24430351

  9. Kinetics of Hypotension during 50 Sessions of Resistance and Aerobic Training in Hypertensive Patients: a Randomized Clinical Trial.

    PubMed

    Damorim, Igor Rodrigues; Santos, Tony Meireles; Barros, Gustavo Willames Pimentel; Carvalho, Paulo Roberto Cavalcanti

    2017-04-01

    Resistance and aerobic training are recommended as an adjunctive treatment for hypertension. However, the number of sessions required until the hypotensive effect of the exercise has stabilized has not been clearly established. To establish the adaptive kinetics of the blood pressure (BP) responses as a function of time and type of training in hypertensive patients. We recruited 69 patients with a mean age of 63.4 ± 2.1 years, randomized into one group of resistance training (n = 32) and another of aerobic training (n = 32). Anthropometric measurements were obtained, and one repetition maximum (1RM) testing was performed. BP was measured before each training session with a digital BP arm monitor. The 50 training sessions were categorized into quintiles. To compare the effect of BP reduction with both training methods, we used two-way analysis of covariance (ANCOVA) adjusted for the BP values obtained before the interventions. The differences between the moments were established by one-way analysis of variance (ANOVA). The reductions in systolic (SBP) and diastolic BP (DBP) were 6.9 mmHg and 5.3 mmHg, respectively, with resistance training and 16.5 mmHg and 11.6 mmHg, respectively, with aerobic training. The kinetics of the hypotensive response of the SBP showed significant reductions until the 20th session in both groups. Stabilization of the DBP occurred in the 20th session of resistance training and in the 10th session of aerobic training. A total of 20 sessions of resistance or aerobic training are required to achieve the maximum benefits of BP reduction. The methods investigated yielded distinct adaptive kinetic patterns along the 50 sessions. Os treinamentos de força e aeróbio são indicados para o tratamento adjuvante da hipertensão. Entretanto, o número de sessões necessárias até estabilização do efeito hipotensor com o exercício ainda não está claramente estabelecido. Estabelecer a cinética adaptativa das respostas tensionais em função do

  10. Combinations of olmesartan and a calcium channel blocker or a diuretic in elderly hypertensive patients: a randomized, controlled trial.

    PubMed

    Ogihara, Toshio; Saruta, Takao; Rakugi, Hiromi; Saito, Ikuo; Shimamoto, Kazuaki; Matsuoka, Hiroaki; Shimada, Kazuyuki; Ito, Sadayoshi; Horiuchi, Masatsugu; Imaizumi, Tsutomu; Takishita, Shuichi; Higaki, Jitsuo; Katayama, Shigehiro; Kimura, Genjiroh; Umemura, Satoshi; Ura, Nobuyuki; Hayashi, Koichi; Odawara, Masato; Tanahashi, Norio; Ishimitsu, Toshihiko; Kashihara, Naoki; Morita, Satoshi; Teramukai, Satoshi

    2014-10-01

    The aim of the present study was to compare the cardiovascular effects of olmesartan, an angiotensin II receptor blocker, combined with a calcium channel blocker (CCB) or a diuretic, in a prospective, randomized, open-label, blinded endpoint trial. Japanese hypertensive patients aged at least 65 to less than 85 years with SBP at least 140 mmHg and/or DBP at least 90 mmHg with antihypertensive treatment, or SBP at least 160 mmHg and/or DBP at least 100 mmHg without antihypertensive treatment were randomized to receive olmesartan with either a dihydropyridine CCB or a low-dose diuretic. If SBP and/or DBP remained at least 140 and/or at least 90 mmHg, the other antihypertensive drug was added. The primary endpoint was a composite of fatal and nonfatal cardiovascular events. The median follow-up time was 3.3 years. Blood pressure decreased similarly in both groups. The primary endpoint occurred in 116/2568 patients (4.5%) in the olmesartan plus CCB group and in 135/2573 patients (5.3%) in the olmesartan plus diuretic group [hazard ratio 0.83, 95% confidence interval (CI) 0.65-1.07, P = 0.16]. Rates of all-cause death and cardiovascular deaths were similar. Among patients aged at least 75 years, the incidence of stroke tended to be lower in the olmesartan plus CCB group than in the olmesartan plus diuretic group (hazard ratio 0.63, 95% CI 0.38-1.02, P = 0.059, interaction P = 0.019). Fewer patients in the olmesartan plus CCB group (8.2%, 211/2568) than in the olmesartan plus diuretic group (9.8%, 253/2573; P = 0.046) experienced serious adverse events. Despite no significant difference in cardiovascular events, the different safety profiles suggest that the combination of olmesartan and CCB may be preferable to that of olmesartan and diuretic.

  11. Combinations of olmesartan and a calcium channel blocker or a diuretic in elderly hypertensive patients: a randomized, controlled trial1

    PubMed Central

    Ogihara, Toshio; Saruta, Takao; Rakugi, Hiromi; Saito, Ikuo; Shimamoto, Kazuaki; Matsuoka, Hiroaki; Shimada, Kazuyuki; Ito, Sadayoshi; Horiuchi, Masatsugu; Imaizumi, Tsutomu; Takishita, Shuichi; Higaki, Jitsuo; Katayama, Shigehiro; Kimura, Genjiroh; Umemura, Satoshi; Ura, Nobuyuki; Hayashi, Koichi; Odawara, Masato; Tanahashi, Norio; Ishimitsu, Toshihiko; Kashihara, Naoki; Morita, Satoshi; Teramukai, Satoshi

    2014-01-01

    Objective: The aim of the present study was to compare the cardiovascular effects of olmesartan, an angiotensin II receptor blocker, combined with a calcium channel blocker (CCB) or a diuretic, in a prospective, randomized, open-label, blinded endpoint trial. Methods: Japanese hypertensive patients aged at least 65 to less than 85 years with SBP at least 140 mmHg and/or DBP at least 90 mmHg with antihypertensive treatment, or SBP at least 160 mmHg and/or DBP at least 100 mmHg without antihypertensive treatment were randomized to receive olmesartan with either a dihydropyridine CCB or a low-dose diuretic. If SBP and/or DBP remained at least 140 and/or at least 90 mmHg, the other antihypertensive drug was added. The primary endpoint was a composite of fatal and nonfatal cardiovascular events. The median follow-up time was 3.3 years. Results: Blood pressure decreased similarly in both groups. The primary endpoint occurred in 116/2568 patients (4.5%) in the olmesartan plus CCB group and in 135/2573 patients (5.3%) in the olmesartan plus diuretic group [hazard ratio 0.83, 95% confidence interval (CI) 0.65–1.07, P = 0.16]. Rates of all-cause death and cardiovascular deaths were similar. Among patients aged at least 75 years, the incidence of stroke tended to be lower in the olmesartan plus CCB group than in the olmesartan plus diuretic group (hazard ratio 0.63, 95% CI 0.38–1.02, P = 0.059, interaction P = 0.019). Fewer patients in the olmesartan plus CCB group (8.2%, 211/2568) than in the olmesartan plus diuretic group (9.8%, 253/2573; P = 0.046) experienced serious adverse events. Conclusion: Despite no significant difference in cardiovascular events, the different safety profiles suggest that the combination of olmesartan and CCB may be preferable to that of olmesartan and diuretic. PMID:24999799

  12. Impact of Junction Nonabruptness on Random-Discrete-Dopant Induced Variability in Intrinsic Channel Trigate Metal-Oxide-Semiconductor Field-Effect Transistors

    NASA Astrophysics Data System (ADS)

    Wei, Kang Liang; Liu, Xiao Yan; Du, Gang

    2013-04-01

    Using full three-dimensional (3D) technology computer-aided design (TCAD) simulations, we present a comprehensive statistical study on the random discrete dopant (RDD) induced variability in state-of-the-art intrinsic channel trigate MOSFETs. This paper is focused on the RDD variability sources that are introduced by dopant diffusion from highly doped source/drain (S/D) regions into the undoped channel region, which is referred to as junction nonabruptness (JNA). By considering a realistic lateral doping profile in the channel and evaluating the impact of JNA on the variability of performance parameters such as threshold voltage (Vth), subthreshold slope (SS), drain-induced barrier lowering (DIBL), on current (Ion), and off current (Ioff), we show that the effect of JNA can lead to substantial device variations. The nonnegligible influence of JNA puts limitations on device scaling, which is also investigated in this paper.

  13. Fuzzy [Formula: see text] output-feedback control for the discrete-time system with channel fadings, sector nonlinearities, and randomly occurring interval delays and nonlinearities.

    PubMed

    Fan, Xiaozheng; Wang, Yan; Hu, Manfeng

    2016-01-01

    In this paper, the fuzzy [Formula: see text] output-feedback control problem is investigated for a class of discrete-time T-S fuzzy systems with channel fadings, sector nonlinearities, randomly occurring interval delays (ROIDs) and randomly occurring nonlinearities (RONs). A series of variables of the randomly occurring phenomena obeying the Bernoulli distribution is used to govern ROIDs and RONs. Meanwhile, the measurement outputs are subject to the sector nonlinearities (i.e. the sensor saturations) and we assume the system output is [Formula: see text], [Formula: see text]. The Lth-order Rice model is utilized to describe the phenomenon of channel fadings by setting different values of the channel coefficients. The aim of this work is to deal with the problem of designing a full-order dynamic fuzzy [Formula: see text] output-feedback controller such that the fuzzy closed-loop system is exponentially mean-square stable and the [Formula: see text] performance constraint is satisfied, by means of a combination of Lyapunov stability theory and stochastic analysis along with LMI methods. The proposed fuzzy controller parameters are derived by solving a convex optimization problem via the semidefinite programming technique. Finally, a numerical simulation is given to illustrate the feasibility and effectiveness of the proposed design technique.

  14. A stochastic study of electron transfer kinetics in nano-particulate photocatalysis: a comparison of the quasi-equilibrium approximation with a random walking model.

    PubMed

    Liu, Baoshun; Zhao, Xiujian; Yu, Jiaguo; Fujishima, Akira; Nakata, Kazuya

    2016-11-23

    In the photocatalysis of porous nano-crystalline materials, the transfer of electrons to O2 plays an important role, which includes the electron transport to photocatalytic active centers and successive interfacial transfer to O2. The slowest of them will determine the overall speed of electron transfer in the photocatalysis reaction. Considering the photocatalysis of porous nano-crystalline TiO2 as an example, although some experimental results have shown that the electron kinetics are limited by the interfacial transfer, we still lack the depth of understanding the microscopic mechanism from a theoretical viewpoint. In the present research, a stochastic quasi-equilibrium (QE) theoretical model and a stochastic random walking (RW) model were established to discuss the electron transport and electron interfacial transfer by taking the electron multi-trapping transport and electron interfacial transfer from the photocatalytic active centers to O2 into consideration. By carefully investigating the effect of the electron Fermi level (EF) and the photocatalytic center number on electron transport, we showed that the time taken for an electron to transport to a photocatalytic center predicated by the stochastic RW model was much lower than that predicted by the stochastic QE model, indicating that the electrons cannot reach a QE state during their transport to photocatalytic centers. The stochastic QE model predicted that the electron kinetics of a real photocatalysis for porous nano-crystalline TiO2 should be limited by electron transport, whereas the stochastic RW model showed that the electron kinetics of a real photocatalysis can be limited by the interfacial transfer. Our simulation results show that the stochastic RW model was more in line with the real electron kinetics that have been observed in experiments, therefore it is concluded that the photoinduced electrons cannot reach a QE state before transferring to O2.

  15. Multiple inhibition of glutathione S-transferase A from rat liver by glutathione derivatives: kinetic analysis supporting a steady-state random sequential mechanism.

    PubMed Central

    Jakobson, I; Warholm, M; Mannervik, B

    1979-01-01

    Glutathione derivatives inhibit glutathione S-transferase A [cf. Biochem. J. (1975) 147, 513--522]. The steady-state kinetics of this inhibition have been investigated in detail by using S-octyglutathione, glutathione disulphide and S-(2-chloro-4-nitrophenyl)glutathione: the last compound is a product of the enzyme-catalused reaction. Interpreted in terms of generalized denotations of inhibition patterns, the compounds were found to be competitive with the substrate glutathione. Double-inhibition experiments involving simultaneous use of two inhibitors indicated exclusive binding of the inhibitors to the enzyme. The discrimination between alternative rate equations has been based on the results of weighted non-linear regression analysis. The experimental error was determined by replicate measurements and was found to increase with velocity. The established error structure was used as a basis for weighting in the regression and to construct confidence levels for the judgement of goodness-of-fit of rate equations fitted to experimental data. The results obtained support a steady-state random model for the mechanism of action of glutathione S-transferase A and exclude a number of simple kinetic models. PMID:444209

  16. Microwell devices with finger-like channels for long-term imaging of HIV-1 expression kinetics in primary human lymphocytes.

    PubMed

    Razooky, Brandon S; Gutierrez, Edgar; Terry, Valeri H; Spina, Celsa A; Groisman, Alex; Weinberger, Leor S

    2012-11-07

    A major obstacle in the treatment of human immunodeficiency virus type 1 (HIV-1) is a sub-population of latently infected CD4(+) T lymphocytes. The cellular and viral mechanisms regulating HIV-1 latency are not completely understood, and a promising technique for probing the regulation of HIV-1 latency is single-cell time-lapse microscopy. Unfortunately, CD4(+) T lymphocytes rapidly migrate on substrates and spontaneously detach, making them exceedingly difficult to track, hampering single-cell level studies. To overcome these problems, we built microdevices with a three-level architecture. The devices contain arrays of finger-like microchannels to "corral" T-lymphocyte migration, round wells that are accessible to pipetting, and microwells connecting the microchannels with the round wells. T lymphocytes that are loaded into a well first settle into the microwells and then to microchannels by gravity. Within the microchannels, T lymphocytes are in favorable culture conditions because they are in physical contact with each other, under no mechanical stress, and fed from a large reservoir of fresh medium. Most importantly, T lymphocytes in the microchannels are not exposed to any flow and their random migration is restricted to a nearly one-dimensional region, greatly facilitating long-term tracking of multiple cells in time-lapse microscopy. The devices have up to nine separate round wells, making it possible to test up to nine different cell lines or medium conditions in a single experiment. Activated primary CD4(+) T lymphocytes, resting primary CD4(+) T lymphocytes, and THP-1 monocytic leukemia cells loaded into the devices maintained viability over multiple days. The devices were used to track the fluorescence level of individual primary CD4(+) T lymphocytes expressing green fluorescent protein (GFP) for up to 60 hours (h) and to quantify single-cell gene-expression kinetics of four different HIV-1 variants. The kinetics of GFP expression from the lentiviruses

  17. How helix-coil transition influences translocation of a single-stranded DNA and kinetics of its fluctuation inside the channel

    NASA Astrophysics Data System (ADS)

    Singh, Kulveer; Sain, Anirban

    2013-10-01

    Many biopolymers like proteins, RNA, single-stranded DNA form secondary structures, namely helices and loops. These polymers often get transported from one compartment of the cell to another through narrow protein channels. Motivated by recent experimental results on translocation of polymers through channels and helix-coil transition inside the channel, we have constructed a two-dimensional toy model to study how secondary structures influence such processes. Through a Langevin dynamics simulation we investigated the statistics of translocation as well as how channel width, force and temperature affect the helix-coil transition inside a channel. Our results are in qualitative agreement with experimental data.

  18. Isotope partitioning for NAD-malic enzyme from Ascaris suum confirms a steady-state random kinetic mechanism

    SciTech Connect

    Chen, C.Y.; Harris, B.G.; Cook, P.F.

    1988-01-12

    Isotope partitioning studies beginning with E-(/sup 14/C)NAD, E-(/sup 14/C) malate, E-(/sup 14/C) NAD-Mg/sup 2 +/, and E-Mg-(/sup 14/C)malate suggest a steady-state random mechanism for the NAD-malic enzyme. Isotope trapping beginning with E-(/sup 14/C)NAD and with varying concentrations of Mg/sup 2 +/ and malate in the chase solution indicates that Mg/sup 2 +/ is added in rapid equilibrium and must be added prior to malate for productive ternary complex formation. Equal percentage trapping from E-(/sup 14/C)NAD-Mg and E-Mg-(/sup 14/C) malate indicates the mechanism is steady-state random with equal off-rates for NAD and malate from E-NAD-Mg-malate. The off-rates for both do not change significantly in the ternary E-Mg-malate and E-NAD-Mg complexes, nor does the off-rate change for NAD from E-NAD. No trapping of malate was obtained from E-(/sup 14/C) malate, suggesting that this complex is nonproductive. A quantitative analysis of the data allows an estimation of values for a number of the rate constants along the reaction pathway.

  19. Effects of a T-type calcium channel blocker, ABT-639, on spontaneous activity in C-nociceptors in patients with painful diabetic neuropathy: a randomized controlled trial.

    PubMed

    Serra, Jordi; Duan, W Rachel; Locke, Charles; Solà, Romà; Liu, Wei; Nothaft, Wolfram

    2015-11-01

    T-type calcium channels are a potential novel target for treatment of neuropathic pain such as painful diabetic neuropathy. ABT-639 is a peripherally acting highly selective T-type Ca(v)3.2 calcium channel blocker that has demonstrated analgesic efficacy in preclinical models and may have the potential to reduce spontaneous fiber activity. Microneurography is a unique technique that directly assesses the function of peripheral sensory afferents and measures abnormal spontaneous activity in single peripheral nociceptive C fibers. Abnormal spontaneous activity in C-nociceptors functions as a marker for spontaneous pain, as reduction of this activity could indicate analgesic efficacy. This randomized, double-blind controlled study evaluated the effects of a single 100-mg oral dose of ABT-639, compared with placebo, on abnormal spontaneous activity in peripheral C-nociceptors, measured for the first time by microneurography in adult patients with painful diabetic neuropathy. Lidocaine was included in this study and compared with placebo. Pharmacokinetics and safety of ABT-639 were evaluated. Thirty-nine patients were randomized, and a total of 56 analyzable C-nociceptors with spontaneous activity were identified in 34 patients. There were no significant differences in C-nociceptor activities after ABT-639 treatment vs placebo. Similar findings were observed for lidocaine vs placebo. There were no clinically significant findings in the safety of ABT-639. Further research of T-type Ca(v)3.2 calcium channels as potential treatment targets for painful diabetic neuropathy is warranted. The utilization of microneurography as a means to measure abnormal activity in C-nociceptors in human clinical studies opens new possibilities for future studies of compounds targeting peripheral nerve hyperexcitability. ClinicalTrials.gov identifier: NCT01589432.

  20. A randomized double-blind, placebo-, and active-controlled study of T-type calcium channel blocker ABT-639 in patients with diabetic peripheral neuropathic pain

    PubMed Central

    Ziegler, Dan; Duan, W. Rachel; An, Guohua; Thomas, James W.; Nothaft, Wolfram

    2015-01-01

    Abstract T-type Cav3.2 calcium channels represent a novel target for neuropathic pain modulation. Preclinical studies with ABT-639, a peripherally acting highly selective T-type Cav3.2 calcium channel blocker, showed dose-dependent reduction of pain in multiple pain models. ABT-639 also demonstrated an acceptable safety profile at single- and multiple-dose levels evaluated in a clinical phase 1 study in healthy volunteers. The primary objective of this phase 2, multicenter, randomized, double-blind, placebo-controlled, and active-controlled study was to compare the analgesic efficacy and safety of ABT-639 with placebo in the treatment of diabetic neuropathic pain. Pregabalin, an approved treatment for painful diabetic neuropathy, was included as a positive control. A total of 194 patients were randomized and treated for 6 weeks; 62 patients received ABT-639 (100 mg twice daily), 70 patients received pregabalin (150 mg twice daily), and 62 patients received placebo. When assessing the mean changes from baseline in patient-recorded pain scores at the end of week 6, there was no significant difference observed for ABT-639 compared with placebo (−2.28 vs −2.36; P = 0.582). Pregabalin treatment resulted in a transient improvement in pain compared with placebo, which did not persist throughout the study. There were no significant safety issues identified with ABT-639. A majority of adverse events were considered mild to moderate in intensity. In conclusion, treatment with the highly selective T-type Cav3.2 calcium channel blocker ABT-639 100 mg twice daily for 6 weeks showed no safety signals that would preclude further investigation but did not reduce neuropathic pain in patients with diabetes (ClinicalTrials.gov identifier: NCT01345045). PMID:26067585

  1. Random Dopant Threshold Voltage Fluctuations in 50 nm Epitaxial Channel MOSFETs: A 3D 'Atomoc' Simulation Study

    NASA Technical Reports Server (NTRS)

    Asenov, Asen

    2000-01-01

    3D 'atomistic' simulations are used to study random dopant related threshold voltage fluctuations in 50 nm MOSFETs. Comparisons are made between conventionally doped transistors and transistors with thin epitaxial silicon layers on heavily doped silicon. Issues related to both the optimum threshold voltage control and the suppression of the threshold voltage dispersion are addressed.

  2. Random field Ising model with conserved kinetics: Super-universality violation, logarithmic growth law and the generalized Tomita sum rule

    NASA Astrophysics Data System (ADS)

    Kumar, Manoj; Banerjee, Varsha; Puri, Sanjay

    2017-01-01

    We perform comprehensive Monte Carlo (MC) simulations to study ordering dynamics in the random field Ising model with conserved order parameter (C-RFIM) in d=2,3 . The observations from this study are: a) For a fixed value of the disorder Δ, the correlation function C(r,t;Δ) exhibits dynamical scaling. b) The scaling function is not robust with respect to Δ, i.e., super-universality (SU) is violated by C(r,t;Δ) . c) At early times, the domains follow the algebraic growth with a disorder-dependent exponent: L(t,Δ)∼ t1/\\bar{z(Δ)} . At late times, there is a crossover to logarithmic growth: L(t,Δ) ∼ (\\ln t)1/\\varphi , where φ is a disorder-independent exponent. d) The small-r behavior of the correlation function exhibits a cusp singularity: 1-C(r) ∼ rα(Δ) , where α is the cusp exponent signifying rough fractal interfaces. e) The corresponding structure factor exhibits a non-Porod tail: S(k,t;Δ)∼ k-(d+α) , and obeys a generalized Tomita sum rule \\int_0^∞ {d}p p1-α≤ft[pd+αf(p)-C\\right]=0 , where f(p) is the appropriate scaling function, and C is a constant.

  3. Directional random laser source consisting of a HC-ARROW reservoir connected to channels for spectroscopic analysis in microfluidic devices.

    PubMed

    Jorge, K C; Alvarado, M A; Melo, E G; Carreño, M N P; Alayo, M I; Wetter, N U

    2016-07-10

    Light sources are used in optofluidic devices for real-time system control and quantitative analysis of important process parameters. In this work, we present a random laser source using a hollow-core antiresonant reflecting optical waveguide (HC-ARROW) containing the gain media inside a reservoir to reduce dye bleaching, which is connected to microchannel waveguides to increase beam directionality. The device is pumped externally and emits a highly coherent and collimated laser beam.

  4. Effects of negative air ions on oxygen uptake kinetics, recovery and performance in exercise: a randomized, double-blinded study

    NASA Astrophysics Data System (ADS)

    Nimmerichter, Alfred; Holdhaus, Johann; Mehnen, Lars; Vidotto, Claudia; Loidl, Markus; Barker, Alan R.

    2014-09-01

    Limited research has suggested that acute exposure to negatively charged ions may enhance cardio-respiratory function, aerobic metabolism and recovery following exercise. To test the physiological effects of negatively charged air ions, 14 trained males (age: 32 ± 7 years; : 57 ± 7 mL min-1 kg-1) were exposed for 20 min to either a high-concentration of air ions (ION: 220 ± 30 × 103 ions cm-3) or normal room conditions (PLA: 0.1 ± 0.06 × 103 ions cm-3) in an ionization chamber in a double-blinded, randomized order, prior to performing: (1) a bout of severe-intensity cycling exercise for determining the time constant of the phase II response ( τ) and the magnitude of the slow component (SC); and (2) a 30-s Wingate test that was preceded by three 30-s Wingate tests to measure plasma [adrenaline] (ADR), [nor-adrenaline] (N-ADR) and blood [lactate] (BLac) over 20 min during recovery in the ionization chamber. There was no difference between ION and PLA for the phase II τ (32 ± 14 s vs. 32 ± 14 s; P = 0.7) or SC (404 ± 214 mL vs 482 ± 217 mL; P = 0.17). No differences between ION and PLA were observed at any time-point for ADR, N-ADR and BLac as well as on peak and mean power output during the Wingate tests (all P > 0.05). A high-concentration of negatively charged air ions had no effect on aerobic metabolism during severe-intensity exercise or on performance or the recovery of the adrenergic and metabolic responses after repeated-sprint exercise in trained athletes.

  5. Energy transfer, pressure tensor, and heating of kinetic plasma

    NASA Astrophysics Data System (ADS)

    Yang, Yan; Matthaeus, William H.; Parashar, Tulasi N.; Haggerty, Colby C.; Roytershteyn, Vadim; Daughton, William; Wan, Minping; Shi, Yipeng; Chen, Shiyi

    2017-07-01

    Kinetic plasma turbulence cascade spans multiple scales ranging from macroscopic fluid flow to sub-electron scales. Mechanisms that dissipate large scale energy, terminate the inertial range cascade, and convert kinetic energy into heat are hotly debated. Here, we revisit these puzzles using fully kinetic simulation. By performing scale-dependent spatial filtering on the Vlasov equation, we extract information at prescribed scales and introduce several energy transfer functions. This approach allows highly inhomogeneous energy cascade to be quantified as it proceeds down to kinetic scales. The pressure work, - ( P . ∇ ) . u , can trigger a channel of the energy conversion between fluid flow and random motions, which contains a collision-free generalization of the viscous dissipation in collisional fluid. Both the energy transfer and the pressure work are strongly correlated with velocity gradients.

  6. Network-Based Robust H₂/H∞ Control for Linear Systems With Two-Channel Random Packet Dropouts and Time Delays.

    PubMed

    Qiu, Li; Shi, Yang; Yao, Fengqi; Xu, Gang; Xu, Bugong

    2015-08-01

    This paper focuses on the robust output feedback H₂/H∞ control issue for a class of discrete-time networked control systems with uncertain parameters and external disturbance. Sensor-to-controller and controller-to-actuator packet dropouts and time delays are considered simultaneously. According to the stochastic characteristic of the packet dropouts and time delays, a model based on a Markov jump system framework is proposed to randomly compensate for the adverse effect of the two-channel packet dropouts and time delays. To analyze the robust stability of the resulting closed-loop system, a Lyapunov function is proposed, based on which sufficient conditions for the existence of the H₂/H∞ controller are derived in terms of linear matrix inequalities, ensuring robust stochastic stability as well as the prescribed H₂ and H∞ performance. Finally, an angular positioning system is exploited to demonstrate the effectiveness and applicability of the proposed design strategy.

  7. Phase transitions in a three-dimensional kinetic spin-1/2 Ising model with random field: effective-field-theory study.

    PubMed

    Costabile, Emanuel; de Sousa, J Ricardo

    2012-01-01

    The dynamical phase transitions of the kinetic Ising model in the presence of a random magnetic field with a bimodal probability distribution is studied by using effective-field theory (EFT) with correlations. We have used a Glauber-type stochastic dynamic to describe the time evolution of the system, where the system strongly depends on the H≡√(c) root mean square deviation of the magnetic field. The EFT dynamic equation is given for the simple cubic lattice (z=6), and the dynamic order parameter is calculated. The system presents ferromagnetic and paramagnetic states for low and high temperatures, respectively. Our results predict first-order transitions at low temperatures and large disorder strengths, which corresponds to the existence of a nonequilibrium tricritical point (TCP) in a phase diagram in the T-H plane. We compare the results with the equilibrium phase diagram, where only the first-order line is different. Our qualitative results are compatible with recent Monte Carlo simulations. © 2012 American Physical Society

  8. Transient protein-protein interactions and a random-ordered kinetic mechanism for the phosphorylation of a transcription factor by extracellular-regulated protein kinase 2.

    PubMed

    Waas, William F; Dalby, Kevin N

    2002-04-12

    No thorough mechanistic study of extracellular signal-regulated protein kinase 2 (ERK2) has appeared in the literature. A recombinant protein termed EtsDelta138, which comprises of residues 1-138 of the transcription factor Ets-1 is an excellent substrate of ERK2 (Waas W. F., and Dalby, K. N. (2001) Protein Exp. Purif. 23, 191-197). The kinetic mechanism of ERK2 was examined, with excess magnesium, by initial velocity measurements, both in the absence and presence of products at 27 degrees C, pH 7.5, and ionic strength 0.1 m (KCl). The velocity data are consistent with a steady-state random-ordered ternary complex mechanism, where both substrates have unhindered access to binding sites on the enzyme. The mechanism and magnitude of product inhibition by monophosphorylated EtsDelta138 is consistent with, but does not prove, the notion that ERK2 forms a discrete interaction with EtsDelta138 in the absence of active site interactions, and that this "docking complex" facilitates intramolecular phosphorylation of the substrate. The approximation of the steady-state data to a rapid equilibrium model strongly suggests that the formation of ERK2.Ets138 complexes are transient in nature with dissociation constants of greater magnitude than the catalytic constant, of k(cat) = 17 s(-1).

  9. Gait training assisted by multi-channel functional electrical stimulation early after stroke: study protocol for a randomized controlled trial.

    PubMed

    van Bloemendaal, Maijke; Bus, Sicco A; de Boer, Charlotte E; Nollet, Frans; Geurts, Alexander C H; Beelen, Anita

    2016-10-01

    Many stroke survivors suffer from paresis of lower limb muscles, resulting in compensatory gait patterns characterised by asymmetries in spatial and temporal parameters and reduced walking capacity. Functional electrical stimulation has been used to improve walking capacity, but evidence is mostly limited to the orthotic effects of peroneal functional electrical stimulation in the chronic phase after stroke. The aim of this study is to investigate the therapeutic effects of up to 10 weeks of multi-channel functional electrical stimulation (MFES)-assisted gait training on the restoration of spatiotemporal gait symmetry and walking capacity in subacute stroke patients. In a proof-of-principle study with a randomised controlled design, 40 adult patients with walking deficits who are admitted for inpatient rehabilitation within 31 days since the onset of stroke are randomised to either MFES-assisted gait training or conventional gait training. Gait training is delivered in 30-minute sessions each workday for up to 10 weeks. The step length symmetry ratio is the primary outcome. Blinded assessors conduct outcome assessments at baseline, every 2 weeks during the intervention period, immediately post intervention and at 3-month follow-up. This study aims to provide preliminary evidence for the feasibility and effectiveness of MFES-assisted gait rehabilitation early after stroke. Results will inform the design of a larger multi-centre trial. This trial is registered at the Netherlands Trial Register (number NTR4762 , registered 28 August 2014).

  10. Prospective, randomized comparison of a prototype endoscope with deflecting working channels versus a conventional double-channel endoscope for rectal endoscopic submucosal dissection in an established experimental simulation model (with video).

    PubMed

    Jung, Yunho; Kato, Masayuki; Lee, Jongchan; Gromski, Mark A; Chuttani, Ram; Matthes, Kai

    2013-11-01

    A prototype endoscope was designed to improve visualization and dissection of tissue with the use of 2 working channels with different deflections. To evaluate the efficacy and operability of a prototype endoscope in comparison with a conventional double-channel endoscope for rectal endoscopic submucosal dissection (ESD). Randomized, prospective, controlled, ex vivo study. Academic medical center. A total of 80 standardized artificial lesions measuring 3 × 3 cm were created approximately 5 cm from the anal verge in fresh ex vivo porcine colorectal specimens. Two endoscopists each completed 20 cases with the prototype endoscope and 20 cases with the conventional endoscope. An independent observer recorded procedure time, specimen size, en bloc resection, and perforation rate. For the ESD novice, the mean submucosal dissection time (10.5 ± 3.8 vs 14.9 ± 7.3 minutes; P = .024) and total procedure time (18.1 ± 5.2 vs 23.6 ± 8.2 minutes; P = .015) were significantly shorter in the prototype group in comparison with the conventional group. For the ESD expert, there was no significant difference between the mean circumferential resection, submucosal dissection, and total procedure time (prototype group 14.2 ± 6.0 minutes, conventional group 14.2 ± 8.8 minutes; P = .992). The overall perforation and en bloc resection rates were not significantly different between groups. Ex vivo study. In this ex vivo prospective comparison study, there was a technical advantage for the ESD novice with the prototype endoscope that resulted in a shorter procedure time, which was not observed for cases performed by the ESD expert. Copyright © 2013 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

  11. Effects of TRP channel agonist ingestion on metabolism and autonomic nervous system in a randomized clinical trial of healthy subjects

    PubMed Central

    Michlig, Stéphanie; Merlini, Jenny Meylan; Beaumont, Maurice; Ledda, Mirko; Tavenard, Aude; Mukherjee, Rajat; Camacho, Susana; le Coutre, Johannes

    2016-01-01

    Various lines of published evidence have already demonstrated the impact of TRPV1 agonists on energetic metabolism through the stimulation of the sympathetic nervous system (SNS). This study presents a trial investigating if stimulation of the two related sensory receptors TRPA1 and TRPM8 could also stimulate the SNS and impact the energetic metabolism of healthy subjects. The trial was designed to be double-blinded, randomized, cross-over, placebo-controlled with healthy subjects and the impact on the energetic metabolism and the autonomic nervous system (ANS) of cinnamaldehyde, capsaicin and a cooling flavor was measured during the 90 min after ingestion. Energy expenditure and substrate oxidation were measured by indirect calorimetry. An exploratory method to measure ANS activity was by facial thermography and power spectral analysis of heart rate variability using ECG was also used. Following cinnamaldehyde ingestion, energy expenditure was increased as compared to placebo. Furthermore, postprandial fat oxidation was maintained higher compared to placebo after cinnamaldehyde and capsaicin ingestion. Similar peripheral thermoregulation was observed after capsaicin and cinnamaldehyde ingestion. Unlike capsaicin, the dose of cinnamaldehyde was not judged to be sensorially ‘too intense’ by participants suggesting that Cinnamaldehyde would be a more tolerable solution to improve thermogenesis via spicy ingredients as compared to capsaicin. PMID:26883089

  12. Effects of TRP channel agonist ingestion on metabolism and autonomic nervous system in a randomized clinical trial of healthy subjects.

    PubMed

    Michlig, Stéphanie; Merlini, Jenny Meylan; Beaumont, Maurice; Ledda, Mirko; Tavenard, Aude; Mukherjee, Rajat; Camacho, Susana; le Coutre, Johannes

    2016-02-17

    Various lines of published evidence have already demonstrated the impact of TRPV1 agonists on energetic metabolism through the stimulation of the sympathetic nervous system (SNS). This study presents a trial investigating if stimulation of the two related sensory receptors TRPA1 and TRPM8 could also stimulate the SNS and impact the energetic metabolism of healthy subjects. The trial was designed to be double-blinded, randomized, cross-over, placebo-controlled with healthy subjects and the impact on the energetic metabolism and the autonomic nervous system (ANS) of cinnamaldehyde, capsaicin and a cooling flavor was measured during the 90 min after ingestion. Energy expenditure and substrate oxidation were measured by indirect calorimetry. An exploratory method to measure ANS activity was by facial thermography and power spectral analysis of heart rate variability using ECG was also used. Following cinnamaldehyde ingestion, energy expenditure was increased as compared to placebo. Furthermore, postprandial fat oxidation was maintained higher compared to placebo after cinnamaldehyde and capsaicin ingestion. Similar peripheral thermoregulation was observed after capsaicin and cinnamaldehyde ingestion. Unlike capsaicin, the dose of cinnamaldehyde was not judged to be sensorially 'too intense' by participants suggesting that Cinnamaldehyde would be a more tolerable solution to improve thermogenesis via spicy ingredients as compared to capsaicin.

  13. Sigma-1 receptor alters the kinetics of Kv1.3 voltage gated potassium channels but not the sensitivity to receptor ligands.

    PubMed

    Kinoshita, Maho; Matsuoka, Yoshikazu; Suzuki, Takeshi; Mirrielees, Jennifer; Yang, Jay

    2012-05-03

    Sigma1 receptors (Sigma1R) are intracellular chaperone proteins that bind psychotropic drugs and also clinically used drugs such as ketamine and haloperidol. Co-expression of the Sigma1R has been reported to enhance the sensitivity of several voltage-gated ion channels to Sigma1R ligands. Kv1.3 is the predominant voltage-gated potassium channel expressed in T lymphocytes with a documented role in immune activation. To gain a better understanding of Sigma1R modulation of Kv ion channels, we investigated the effects of Sigma1R co-expression on Kv1.3 physiology and pharmacology in ion channels expressed in Xenopus oocytes. We also explored the protein domains of Kv1.3 necessary for protein:protein interaction between Kv1.3 and Sigma1R through co-immunoprecipitation studies. Slowly inactivating outward-going currents consistent with Kv1.3 expression were elicited on step depolarizations. The current characterized by E(rev), V(1/2), and slope factor remained unchanged when co-expressed with Sigma1R. Analysis of inactivation time constant revealed a faster Kv1.3 current decay when co-expressed with Sigma1R. However the sensitivity to Sigma1R ligands remained unaltered when co-expressed with the Sigma1R in contrast to the previously reported modulation of ligand sensitivity in closely related Kv1.4 and Kv1.5 voltage gated potassium channels. Co-immunoprecipitation assays of various Kv1.3 truncation constructs indicated that the transmembrane domain of the Kv1.3 protein was responsible for the protein:protein interaction with the Sigma1R. Sigma1R likely interacts with different domains of Kv ion channel family proteins resulting in distinct modulation of different channels.

  14. A Randomized Trial of a Low Trapping Non-Selective N-methyl-D-aspartate (NMDA) Channel Blocker in Major Depression

    PubMed Central

    Zarate, Carlos A; Mathews, Daniel; Ibrahim, Lobna; Chaves, Jose Franco; Marquardt, Craig; Ukoh, Immaculata; Jolkovsky, Libby; Brutsche, Nancy E; Smith, Mark A.; Luckenbaugh, David A

    2012-01-01

    Background The high-affinity N-methyl-D-aspartate (NMDA) antagonist ketamine exerts rapid antidepressant effects, but has psychotomimetic properties. AZD6765 is a low-trapping NMDA channel blocker with low rates of associated psychotomimetic effects. This study investigated whether AZD6765 could produce rapid antidepressant effects in subjects with treatment-resistant major depressive disorder (MDD). Methods In this double-blind, randomized, crossover, placebo-controlled study, 22 subjects with DSM-IV treatment-resistant MDD received a single infusion of either AZD6765 (150 mg) or placebo on two test days one week apart. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale (MADRS), which was used to rate overall depressive symptoms at baseline; at 60, 80, 110, and 230 minutes post-infusion; and on Days 1, 2, 3, and 7 post-infusion. Several secondary outcome measures were also used, including the Hamilton Depression Rating Scale (HDRS). Results Within 80 minutes, MADRS scores significantly improved in subjects receiving AZD6765 compared to placebo; this improvement remained significant only through 110 minutes (d=0.40). On the HDRS, a drug difference was found at 80 and 110 minutes and at Day 2 (d=0.49). Overall, 32% of subjects responded to AZD6765 and 15% responded to placebo at some point during the trial. No difference was observed between the groups with regard to psychotomimetic or dissociative adverse effects. Conclusions In patients with treatment-resistant MDD, a single intravenous dose of the low trapping NMDA channel blockerAZD6765 was associated with rapid but short-lived antidepressant effects; no psychotomimetic effects were observed. PMID:23206319

  15. Theoretical and kinetic study of the reaction of ethyl methyl ketone with HO2 for T = 600-1600 K. Part II: addition reaction channels.

    PubMed

    Zhou, Chong-Wen; Mendes, Jorge; Curran, Henry J

    2013-06-06

    The temperature and pressure dependence of the addition reaction of ethyl methyl ketone (EMK) with HO2 radical has been calculated using the master equation method employing conventional transition state theory estimates for the microcanonical rate coefficients in the temperature range of 600-1600 K. Geometries, frequencies, and hindrance potentials were obtained at the B3LYP/6-311G(d,p) level of theory. A modified G3(MP2,CC) method has been used to calculate accurate electronic energies for all of the species involved in the reactions. The rigid-rotor harmonic oscillator approximation has been used for all of the vibrations except for the torsional degrees of freedom which are being treated as 1D hindered rotors. Asymmetric Eckart barriers were used to model tunneling effect in a one-dimensional reaction coordinate through saddle points. Our calculated results show that the four reaction channels forming 1-buten-2-ol + HO2 radical (R5), 2-buten-2-ol + HO2 radical (R10), acetic acid + ethylene + OH radical (R13), and 2-methyl-2-oxetanol + OH radical (R15) are the dominant channels. When the temperature is below 1000 K, the reaction R15 forming the cyclic ether, 2-methyl-2-oxetanol, is dominant while the reaction R13 forming acetic acid + ethylene + OH radical becomes increasingly dominant at temperatures above 1000 K. The other two channels forming 1-buten-2-ol, 2-buten-2-ol, and HO2 radical are not dominant but are still important product channels over the whole temperature range investigated here. No pressure dependence has been found for the reaction channels forming 2-methyl-2-oxetanol + OH radical and acetic acid + ethylene + OH radical. A slightly negative pressure dependence has been found for the reaction channels producing the two butenols. Rate constants for the four important reaction channels at 1 atm (in cm(3) mol(-1) s(-1)) are k(R5) = 2.67 × 10(15) × T(-1.32)exp(-16637/T), k(R10) = 1.62 × 10(8) × T(0.57)exp(-13142/T), k(R13) = 2.29 × 10(17) × T

  16. Generation of multi-channel high-speed physical random numbers originated from two chaotic signals of mutually coupled semiconductor lasers

    NASA Astrophysics Data System (ADS)

    Tang, X.; Wu, Z. M.; Wu, J. G.; Deng, T.; Fan, L.; Zhong, Z. Q.; Chen, J. J.; Xia, G. Q.

    2015-01-01

    We propose and experimentally demonstrate a novel technique to generate multi-channel high-speed physical random numbers (PRNs) by taking two chaotic signal outputs from mutually coupled semiconductor lasers (MC-SLs) as entropy sources. First, through controlling the operation parameters of the MC-SL system, two time-delay signature (TDS) suppressed chaotic signals can be obtained. Next, each of these two chaotic signals is sampled by an 8 bit analog-to-digital converter (ADC) with a sampling rate of 10 GHz, and then a bitwise exclusive-OR (XOR) operation on the corresponding bits in samples of the chaotic signal and its time delayed signal is implemented to obtain 8 bit XOR data. Furthermore, through selecting the five least significant bits (LSBs) of 8 bit XOR data to form 5 bit Boolean sequences, two sets of PRN streams with a rate up to 50 Gbits s-1 are generated and successfully pass the NIST statistical tests. Finally, merging these two sets of 50 Gbits s-1 PRN streams by an interleaving operation, another set of the 100 Gbits s-1 PRN stream, which meets all the quality criteria of NIST statistical tests, is also acquired.

  17. Renoprotective effect of calcium channel blockers in combination with an angiotensin receptor blocker in elderly patients with hypertension. A randomized crossover trial between benidipine and amlodipine.

    PubMed

    Miyagawa, Koichi; Dohi, Yasuaki; Nakazawa, Ai; Sugiura, Tomonori; Yamashita, Sumiyo; Sato, Koichi; Kimura, Genjiro

    2010-01-01

    Anti-hypertensive medication with an angiotensin II receptor blocker (ARB) is effective in slowing the progression of chronic kidney disease. The present study was designed to investigate whether calcium channel blockers (CCBs) in combination with an ARB differentially affect kidney function. Elderly hypertensive patients with chronic kidney disease (n = 17, 72 +/- 6 years old) were instructed to self-measure blood pressure. They were randomly assigned to receive either benidipine (4-8 mg/day) or amlodipine (5-10 mg/day) combined with olmesartan (10 mg/day). After 3 months, CCBs were switched in each patient and the same protocol was applied for another 3 months. At baseline, significant correlation was obtained between urine albumin (22.8 +/- 16.7 (median +/- median absolute deviation) mg/g creatinine) and self-measured blood pressure (170 +/- 23/87 +/- 10 (mean +/- SD) mmHg, r = 0.65, p < 0.01). Both regimens reduced blood pressure to a similar extent (139 +/- 22/75 +/- 11 mmHg and 133 +/- 17/72 +/- 10 mmHg, respectively; both p < 0.001), while urine albumin decreased only after combination therapy including benidipine (11.7 +/- 6.1 mg/g creatinine, p < 0.05). Benidipine, but not amlodipine, in combination with olmesartan, reduced urinary albumin excretion in elderly hypertensive patients with chronic kidney disease. The results suggest the importance of selecting medications used in combination with ARB in hypertensive patients with chronic kidney disease.

  18. Oral versus topical calcium channel blockers for chronic anal fissure-a systematic review and meta-analysis of randomized controlled trials.

    PubMed

    Sahebally, Shaheel M; Ahmed, Khalid; Cerneveciute, Raminta; Iqbal, Asif; Walsh, Stewart R; Joyce, Myles R

    2017-08-01

    Chemical sphincterotomy with pharmacological agents is recommended as first line therapy for chronic anal fissures (CAF). Calcium channel blockers (CCB) are associated with similar efficacy but fewer side effects compared to nitrates. However, the optimal formulation (oral versus topical) is unknown. We aimed to perform a systematic review and meta-analysis to compare the effectiveness of oral and topical CCB in the treatment of CAF. PubMed and Embase online databases were searched for relevant articles. Two independent reviewers performed methodological assessment and data extraction. Random effects models were used to calculate pooled effect size estimates. A sensitivity analysis was also carried out. Four randomized controlled trials describing 279 patients (138 in oral, 141 in topical group) were examined. There was significant heterogeneity among studies. On random effects analysis, topical CCB were associated with a significantly lower rate of unhealed fissure (21.3% vs. 38.4%; OR = 2.65, 95% CI = 1.50 to 4.69, p = 0.0008) when compared to oral therapy. However, there were no significant differences in fissure recurrence (5.4% vs. 5.5%; OR = 1.01, 95% CI = 0.31 to 3.33, p = 0.98) or side effects (15.6% vs. 39.1%; OR = 4.54, 95% CI = 0.46 to 44.3, p = 0.19) between topical and oral CCB. On sensitivity analysis, having excluded the most heavily biased trial, topical CCB were associated with significantly fewer side effects compared to oral therapy (4.3% vs. 38.0%; OR = 13.16, 95% CI = 5.05 to 34.3, p < 0.00001). Topical CCB are associated with better healing and fewer side effects when compared to oral therapy but there is no difference in recurrence rates. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  19. Biochemical engineering of the N-acyl side chain of sialic acids alters the kinetics of a glycosylated potassium channel Kv3.1.

    PubMed

    Hall, M Kristen; Reutter, Werner; Lindhorst, Thisbe; Schwalbe, Ruth A

    2011-10-20

    The sialic acid of complex N-glycans can be biochemically engineered by substituting the physiological precursor N-acetylmannosamine with non-natural N-acylmannosamines. The Kv3.1 glycoprotein, a neuronal voltage-gated potassium channel, contains sialic acid. Western blots of the Kv3.1 glycoprotein isolated from transfected B35 neuroblastoma cells incubated with N-acylmannosamines verified sialylated N-glycans attached to the Kv3.1 glycoprotein. Outward ionic currents of Kv3.1 transfected B35 cells treated with N-pentanoylmannosamine or N-propanoylmannosamine had slower activation and inactivation rates than those of untreated cells. Therefore, the N-acyl side chain of sialic acid is intimately connected with the activation and inactivation rates of this glycosylated potassium channel.

  20. Cholesterol and Ion Channels

    PubMed Central

    Levitan, Irena; Fang, Yun; Rosenhouse-Dantsker, Avia; Romanenko, Victor

    2010-01-01

    A variety of ion channels, including members of all major ion channel families, have been shown to be regulated by changes in the level of membrane cholesterol and partition into cholesterol-rich membrane domains. In general, several types of cholesterol effects have been described. The most common effect is suppression of channel activity by an increase in membrane cholesterol, an effect that was described for several types of inwardly-rectifying K+ channels, voltage-gated K+ channels, Ca+2 sensitive K+ channels, voltage-gated Na+ channels, N-type voltage-gated Ca+2 channels and volume-regulated anion channels. In contrast, several types of ion channels, such as epithelial amiloride-sensitive Na+ channels and Transient Receptor Potential channels, as well as some of the types of inwardly-rectifying and voltage-gated K+ channels were shown to be inhibited by cholesterol depletion. Cholesterol was also shown to alter the kinetic properties and current-voltage dependence of several voltage-gated channels. Finally, maintaining membrane cholesterol level is required for coupling ion channels to signalling cascades. In terms of the mechanisms, three general mechanisms have been proposed: (i) specific interactions between cholesterol and the channel protein, (ii) changes in the physical properties of the membrane bilayer and (iii) maintaining the scaffolds for protein-protein interactions. The goal of this review is to describe systematically the role of cholesterol in regulation of the major types of ion channels and to discuss these effects in the context of the models proposed. PMID:20213557

  1. Anthrax Toxin Protective Antigen: Inhibition of Channel Function by Chloroquine and Related Compounds and Study of Binding Kinetics Using the Current Noise Analysis

    PubMed Central

    Orlik, Frank; Schiffler, Bettina; Benz, Roland

    2005-01-01

    Protective antigen (PA) of the tripartite anthrax toxin binds to a cell surface receptor and mediates the transport of two enzymatic components, edema factor and lethal factor, into the cytosol of host cells. Here recombinant PA63 from Bacillus anthracis was reconstituted into artificial lipid bilayer membranes and formed ion permeable channels. The heptameric PA63-channel contains a binding site for 4-aminoquinolones, which block ion transport through PA in vitro. This result allowed a detailed investigation of ligand binding and the stability constants for the binding of chloroquine, fluphenazine, and quinacrine to the binding site inside the PA63-channel were determined using titration experiments. Open PA63-channels exhibit 1/f noise in the frequency range between 1 and 100 Hz, whereas the spectral density of the ligand-induced current noise was of Lorentzian type. The analysis of the power density spectra allowed the evaluation of the on- and off-rate constants (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} \\begin{equation*}k_{1}\\end{equation*}\\end{document} and \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} \\begin{equation*}k_{-1}\\end{equation*}\\end{document}) of ligand binding. The on-rate constants of ligand binding were between 106 and 108 M−1 s−1 and were dependent on the ionic strength of the aqueous phase, sidedness of ligand addition, as well as the orientation and intensity of the applied electric field. The off-rates varied between ∼10 s−1 and 2600 s−1 and depended mainly on the structure of the ligand. PMID:15596516

  2. Effect of mastication on lipid bioaccessibility of almonds in a randomized human study and its implications for digestion kinetics, metabolizable energy, and postprandial lipemia1234

    PubMed Central

    Grundy, Myriam ML; Grassby, Terri; Mandalari, Giuseppina; Waldron, Keith W; Butterworth, Peter J; Berry, Sarah EE

    2015-01-01

    Background: The particle size and structure of masticated almonds have a significant impact on nutrient release (bioaccessibility) and digestion kinetics. Objectives: The goals of this study were to quantify the effects of mastication on the bioaccessibility of intracellular lipid of almond tissue and examine microstructural characteristics of masticated almonds. Design: In a randomized, subject-blind, crossover trial, 17 healthy subjects chewed natural almonds (NAs) or roasted almonds (RAs) in 4 separate mastication sessions. Particle size distributions (PSDs) of the expectorated boluses were measured by using mechanical sieving and laser diffraction (primary outcome). The microstructure of masticated almonds, including the structural integrity of the cell walls (i.e., dietary fiber), was examined with microscopy. Lipid bioaccessibility was predicted by using a theoretical model, based on almond particle size and cell dimensions, and then compared with empirically derived release data. Results: Intersubject variations (n = 15; 2 subjects withdrew) in PSDs of both NA and RA samples were small (e.g., laser diffraction; CV: 12% and 9%, respectively). Significant differences in PSDs were found between these 2 almond forms (P < 0.05). A small proportion of lipid was released from ruptured cells on fractured surfaces of masticated particles, as predicted by using the mathematical model (8.5% and 11.3% for NAs and RAs, respectively). This low percentage of lipid bioaccessibility is attributable to the high proportion (35–40%) of large particles (>500 μm) in masticated almonds. Microstructural examination of the almonds indicated that most intracellular lipid remained undisturbed in intact cells after mastication. No adverse events were recorded. Conclusions: Following mastication, most of the almond cells remained intact with lipid encapsulated by cell walls. Thus, most of the lipid in masticated almonds is not immediately bioaccessible and remains unavailable for

  3. Kinetic description of a free electron laser with an electromagnetic-wave wiggler and ion-channel guiding by using the Einstein coefficient technique

    NASA Astrophysics Data System (ADS)

    Mehdian, H.; AbasiRostami, S.; Hasanbeigi, A.

    2016-04-01

    A theoretical study of electron trajectories and gain in a free electron laser (FEL) with an electromagnetic-wave wiggler and ion-channel guiding is presented based on the Einstein coefficient method. The laser gain in the low-gain regime is obtained for the case of a cold tenuous relativistic electron beam, where the beam plasma frequency is much less than the radiation frequency propagating in this configuration. The resulting gain equation is analyzed numerically over a wide range of system parameters.

  4. Rainwater Channelization and Infiltration in Granular Media

    NASA Astrophysics Data System (ADS)

    Cejas, Cesare; Wei, Yuli; Barrois, Remi; Durian, Douglas; Dreyfus, Remi; Compass Team

    2013-03-01

    We investigate the formation of fingered flow in dry granular media under simulated rainfall using a quasi-2D experimental set-up composed of a random close packing of mono-disperse glass beads. We determine effects of grain diameter and surface wetting properties on the formation and infiltration of water channels. For hydrophilic granular media, rainwater initially infiltrates a shallow top layer of soil creating a uniform horizontal wetting front before instabilities occur and grow to form water channels. For hydrophobic media, rainwater ponds on the soil surface rather than infiltrates and water channels may still occur at a later time when the hydraulic pressure of the ponding water exceeds the capillary repellency of the soil. We probe the kinetics of the fingering instabilities that serve as precursors for the growth and drainage of water channels. We also examine the effects of several different methods on improving rainwater channelization such as varying the level of pre-saturation, modifying the soil surface flatness, and adding superabsorbent hydrogel particles.

  5. Kinetics of xylem loading, membrane potential maintenance, and sensitivity of K(+) -permeable channels to reactive oxygen species: physiological traits that differentiate salinity tolerance between pea and barley.

    PubMed

    Bose, Jayakumar; Shabala, Lana; Pottosin, Igor; Zeng, Fanrong; Velarde-Buendía, Ana-Maria; Massart, Amandine; Poschenrieder, Charlotte; Hariadi, Yuda; Shabala, Sergey

    2014-03-01

    Salt sensitive (pea) and salt tolerant (barley) species were used to understand the physiological basis of differential salinity tolerance in crops. Pea plants were much more efficient in restoring otherwise depolarized membrane potential thereby effectively decreasing K(+) efflux through depolarization-activated outward rectifying potassium channels. At the same time, pea root apex was 10-fold more sensitive to physiologically relevant H2 O2 concentration and accumulated larger amounts of H2 O2 under saline conditions. This resulted in a rapid loss of cell viability in the pea root apex. Barley plants rapidly loaded Na(+) into the xylem; this increase was only transient, and xylem and leaf Na(+) concentration remained at a steady level for weeks. On the contrary, pea plants restricted xylem Na(+) loading during the first few days of treatment but failed to prevent shoot Na(+) elevation in the long term. It is concluded that superior salinity tolerance of barley plants compared with pea is conferred by at least three different mechanisms: (1) efficient control of xylem Na(+) loading; (2) efficient control of H2 O2 accumulation and reduced sensitivity of non-selective cation channels to H2 O2 in the root apex; and (3) higher energy saving efficiency, with less ATP spent to maintain membrane potential under saline conditions. © 2013 John Wiley & Sons Ltd.

  6. Accuracy of enthalpy and entropy determination using the kinetic method: are we approaching a consensus?

    PubMed

    Drahos, László; Peltz, Csaba; Vékey, Károly

    2004-09-01

    There is an emerging consensus regarding the applicability of the kinetic method. All parties acknowledge that it is an approximate quantitative technique, capable of yielding not only enthalpy, but also entropy values. Opinions differ mainly on the accuracy of the results but it is agreed that the energy (effective temperature) dependence of kinetic method plots needs to be checked in all but the simplest of cases. When the 'apparent basicity' is found to depend on collision energy (and hence effective temperature), the extended kinetic method must be used. We have performed a large-scale modeling study, involving thousands of randomly selected molecular systems and a variety of experimental conditions, using exact calculations and realistic data sets. The results show that when the measured entropy difference between the two competing reaction channels is less than approximately 35 J mol(-1) K(-1), overall errors (standard deviations) of DeltaH(298) determined by the kinetic method are +/-5 kJ mol(-1); those of DeltaS(298) are +/-10 J mol(-1) K(-1). These include not only inherent errors of the kinetic method, but also errors in ion abundance measurement (5%) and inaccurate knowledge of reference compound thermochemistry (+/-2 kJ mol(-1), on average). We recommend, in general, that these errors be reported in kinetic method studies. When the measured entropy difference between the two competing fragmentation channels is large (>35 J mol(-1) K(-1)), it is likely to be significantly underestimated and errors of the kinetic method increase significantly.

  7. 2,2,2-Trifluoroethanol changes the transition kinetics and subunit interactions in the small bacterial mechanosensitive channel MscS.

    PubMed

    Akitake, Bradley; Spelbrink, Robin E J; Anishkin, Andriy; Killian, J Antoinette; de Kruijff, Ben; Sukharev, Sergei

    2007-04-15

    2,2,2-Trifluoroethanol (TFE), a low-dielectric solvent, has recently been used as a promising tool to probe the strength of intersubunit interactions in membrane proteins. An analysis of inner membrane proteins of Escherichia coli has identified several SDS-resistant protein complexes that separate into subunits upon exposure to TFE. One of these was the homo-heptameric stretch-activated mechanosensitive channel of small conductance (MscS), a ubiquitous component of the bacterial turgor-regulation system. Here we show that a substantial fraction of MscS retains its oligomeric state in cold lithium-dodecyl-sulfate gel electrophoresis. Exposure of MscS complexes to 10-15 vol % TFE in native membranes or nonionic detergent micelles before lithium-dodecyl-sulfate electrophoresis results in a complete dissociation into monomers, suggesting that at these concentrations TFE by itself disrupts or critically compromises intersubunit interactions. Patch-clamp analysis of giant E. coli spheroplasts expressing MscS shows that exposure to TFE in lower concentrations (0.5-5.0 vol %) causes leftward shifts of the dose-response curves when applied extracellularly, and rightward shifts when added from the cytoplasmic side. In the latter case, TFE increases the rate of tension-dependent inactivation and lengthens the process of recovery to the resting state. MscS responses to pressure ramps of different speeds indicate that in the presence of TFE most channels reside in the resting state and only at tensions near the activation threshold does TFE dramatically speed up inactivation. The effect of TFE is reversible as normal channel activity returns 15-30 min after a TFE washout. We interpret the observed midpoint shifts in terms of asymmetric partitioning of TFE into the membrane and distortion of the bilayer lateral pressure profile. We also relate the increased rate of inactivation and subunit separation with the capacity of TFE to perturb buried interhelical contacts in proteins

  8. Kinetic Analysis of Membrane Potential Dye Response to NaV1.7 Channel Activation Identifies Antagonists with Pharmacological Selectivity against NaV1.5.

    PubMed

    Finley, Michael; Cassaday, Jason; Kreamer, Tony; Li, Xinnian; Solly, Kelli; O'Donnell, Greg; Clements, Michelle; Converso, Antonella; Cook, Sean; Daley, Chris; Kraus, Richard; Lai, Ming-Tain; Layton, Mark; Lemaire, Wei; Staas, Donnette; Wang, Jixin

    2016-06-01

    The NaV1.7 voltage-gated sodium channel is a highly valued target for the treatment of neuropathic pain due to its expression in pain-sensing neurons and human genetic mutations in the gene encoding NaV1.7, resulting in either loss-of-function (e.g., congenital analgesia) or gain-of-function (e.g., paroxysmal extreme pain disorder) pain phenotypes. We exploited existing technologies in a novel manner to identify selective antagonists of NaV1.7. A full-deck high-throughput screen was developed for both NaV1.7 and cardiac NaV1.5 channels using a cell-based membrane potential dye FLIPR assay. In assay development, known local anesthetic site inhibitors produced a decrease in maximal response; however, a subset of compounds exhibited a concentration-dependent delay in the onset of the response with little change in the peak of the response at any concentration. Therefore, two methods of analysis were employed for the screen: one to measure peak response and another to measure area under the curve, which would capture the delay-to-onset phenotype. Although a number of compounds were identified by a selective reduction in peak response in NaV1.7 relative to 1.5, the AUC measurement and a subsequent refinement of this measurement were able to differentiate compounds with NaV1.7 pharmacological selectivity over NaV1.5 as confirmed in electrophysiology.

  9. Transition event statistics in genetics and disordered kinetics. Theoretical approaches for extracting rate distributions from experimental data.

    PubMed

    Vlad, Marcel O; Oefner, Peter; Ross, John

    2006-09-28

    We study the analogies between the theory of rate processes in disordered systems and the overdispersed molecular clocks in evolutionary biology. A biological "molecular clock" expresses the statistics of the number of amino acid or nucleotide substitutions during evolution. Random variations of the evolution rates lead to statistical (overdispersed) molecular clocks which are described by random point processes with random substitution rates. We find that the models for overdispersed molecular clocks are equivalent to those of the random-rate or random channel models used in disordered kinetics. The number of transport (reaction) events in disordered kinetics plays the same role as the number of substitution events in molecular biology. We study the connections between the (observed) statistics of the transition events and the statistics of random rate coefficients and random channels; a unified approach is developed which is valid both in molecular biology and in disordered kinetics. We develop methods for extracting statistical information about the variations of rate coefficients from experimental or observed data regarding the fluctuations of the numbers of substitution, reaction, or transport events. For systems with static disorder, the observed statistics of the number of reaction events, expressed in terms of probabilities at a given time or by the cumulants of the number of transition events at a given time, contains the information necessary for evaluating the cumulants or the probability density of the rate coefficients or the density of states for random channel kinetics. For dynamic disorder this is not possible; further information about multitime probability distributions of the reaction events is needed.

  10. Early versus late start of open kinetic chain quadriceps exercises after ACL reconstruction with patellar tendon or hamstring grafts: a prospective randomized outcome study.

    PubMed

    Heijne, Annette; Werner, Suzanne

    2007-04-01

    The purpose of the present investigation was to evaluate physical outcome after anterior cruciate ligament (ACL) reconstruction with early versus late initiation of open kinetic chain (OKC) exercises for the quadriceps in patients operated on either patellar tendon or hamstring grafts. Sixty-eight patients, 36 males and 32 females, with either patellar tendon graft (34 patients) or hamstring graft (34 patients) were enrolled in this study. All patients were randomly allocated to either early (the 4th postoperative week) or late (the 12th postoperative week) start of OKC exercises for the quadriceps, resulting in four subgroups: patellar tendon reconstruction, early start (P4) or late start (P12) of OKC quadriceps exercises, hamstring tendon reconstruction, early start (H4) or late start (H12) of quadriceps OKC exercises. Prior to surgery and 3, 5 and 7 months later, assessments of range of motion (goniometer), anterior knee laxity (KT-1000), postural sway (KAT 2000), thigh muscle torques (Kin-Com dynamometer) and anterior knee pain (anterior knee pain score) were evaluated. No significant group differences were found in terms of range of motion 3, 5 and 7 months postoperatively. The H4 group showed a significantly higher mean difference of laxity over time of 1.0 mm (CI: 0.18-1.86) than the P4 group (P=0.04). Within the same type of surgery, the H4 against the H12, the mean difference over time was 1.2 mm (0.37-2.1) higher in the H4 group than in the H12 group (P=0.01). There were no significant group differences in terms of postural sway or anterior knee pain at the different test occasions. Significant differences in trends (changes over time) were found when comparing the four groups, for both quadriceps muscle torques (P<0.001) and hamstring muscle torques (P<0.001). All groups, except the P4 group, reached preoperative values of quadriceps muscle torques at the 7 months follow-up. In the H4 and the H12 groups, significantly lower hamstring muscle torques at

  11. Dynamic State Transitions in the Nervous System: From Ion Channels to Neurons to Networks

    NASA Astrophysics Data System (ADS)

    Århem, Peter; Braun, Hans A.; Huber, Martin T.; Liljenström, Hans

    The following sections are included: * Introduction * Ion channels: The microscopic scale * The variety of ion channels * Channel kinetics * Neurons: The mesoscopic scale * The feedback loops between membrane potential and ion currents * Neuron models: Concepts and examples * Impulse pattern modulation by ion channel densities * Oscillatory patterns * Irregular patterns * Impulse pattern modulation by subthreshold oscillations * The cold receptor model * Deterministic patterns and noise induced state-transitions on temperature scaling * Neuronal networks: The oscopic scale * Random channel events cause network state transitions * A hippocampal neural network model * Simulating noise-induced state transitions * Functional significance of oscopic neurodynamics * Conclusions * Appendix A: Computation of the neuron models * Hippocampal neuron model * The cold receptor model * Appendix B: Neural network model * References

  12. Channel Flow Cell Studies of the Inhibiting Action of Gypsum on the Dissolution Kinetics of Calcite: A Laboratory Approach with Implications for Field Monitoring.

    PubMed

    Wilkins, Shelley J.; Compton, Richard G.; Taylor, Mark A.; Viles, Heather A.

    2001-04-15

    The rate of dissolution of surface-treated calcite crystals in aqueous acidic solution has been studied using an adaptation of the channel flow cell method with microdisc electrode detection. Surface treatments of calcite with sulfuric acid lead to the nucleation of gypsum overgrowths, which reduce the rate of dissolution of calcite. Rate constants for untreated calcite and calcite pretreated with sulfuric acid conditions of 0.01 M for 1 h, 0.05 M for 5 h, and 0.1 M for 21 h are found to be 0.035, 0.018, 0.006, and 0.004 cm s(-1), respectively. Deterioration of calcite materials caused by acid deposition was investigated by field exposure of untreated and sulfate pretreated calcite rocks under urban conditions for 12 months. The rate constant for both pretreated and untreated calcite exposed to weathering is 0.003 cm s(-1). This suggests that calcite self-passivates the surface from further reaction when exposed to acid deposition. However, surface studies indicate that the surface undergoes erosion and dissolution before passivation. Pretreatment of the surface with sulfate protects the surface from acid deposition so it remains less reactive toward acid compared with untreated calcite. Copyright 2001 Academic Press.

  13. Biased Brownian motion in narrow channels with asymmetry and anisotropy

    NASA Astrophysics Data System (ADS)

    Peng, Zheng; To, Kiwing

    2016-08-01

    We study Brownian motion of a single millimeter size bead confined in a quasi-two-dimensional horizontal channel with built-in anisotropy and asymmetry. Channel asymmetry is implemented by ratchet walls while anisotropy is introduced using a channel base that is grooved along the channel axis so that a bead can acquire a horizontal impulse perpendicular to the longitudinal direction when it collides with the base. When energy is injected to the channel by vertical vibration, the combination of asymmetric walls and anisotropic base induces an effective force which drives the bead into biased diffusive motion along the channel axis with diffusivity and drift velocity increase with vibration strength. The magnitude of this driving force, which can be measured in experiments on a tilted channel, is found to be consistent with those obtained from dynamic mobility and position probability distribution measurements. These results are explained by a simple collision model that suggests the random kinetic energy transfer between different translational degrees of freedom may be turned into useful work in the presence of asymmetry and anisotropy.

  14. Biased Brownian motion in narrow channels with asymmetry and anisotropy

    NASA Astrophysics Data System (ADS)

    To, Kiwing; Peng, Zheng

    2016-11-01

    We study Brownian motion of a single millimeter size bead confined in a quasi-two-dimensional horizontal channel with built-in anisotropy and asymmetry. Channel asymmetry is implemented by ratchet walls while anisotropy is introduced using a channel base that is grooved along the channel axis so that a bead can acquire a horizontal impulse perpendicular to the longitudinal direction when it collides with the base. When energy is injected to the channel by vertical vibration, the combination of asymmetric walls and anisotropic base induces an effective force which drives the bead into biased diffusive motion along the channel axis with diffusivity and drift velocity increase with vibration strength. The magnitude of this driving force, which can be measured in experiments of tilted channel, is found to be consistent to those obtained from dynamic mobility and position probability distribution measurements. These results are explained by a simple collision model that suggests the random kinetic energies transfer between different translational degrees of freedom may be turned into useful work in the presence of asymmetry and anisotropy.

  15. Kinetic Atom.

    ERIC Educational Resources Information Center

    Wilson, David B.

    1981-01-01

    Surveys the research of scientists like Joule, Kelvin, Maxwell, Clausius, and Boltzmann as it comments on the basic conceptual issues involved in the development of a more precise kinetic theory and the idea of a kinetic atom. (Author/SK)

  16. Kinetic Atom.

    ERIC Educational Resources Information Center

    Wilson, David B.

    1981-01-01

    Surveys the research of scientists like Joule, Kelvin, Maxwell, Clausius, and Boltzmann as it comments on the basic conceptual issues involved in the development of a more precise kinetic theory and the idea of a kinetic atom. (Author/SK)

  17. Interaction of tetanus toxin with lipid vesicles. Effects of pH, surface charge, and transmembrane potential on the kinetics of channel formation.

    PubMed Central

    Menestrina, G; Forti, S; Gambale, F

    1989-01-01

    We investigated the interaction of tetanus toxin with small unilamellar vesicles composed of different phospholipids as a function of pH, toxin concentration, temperature, and ionic strength of the solution. Tetanus toxin increased the permeability of the vesicles to fluorescent markers of molecular weight up to 700. The time course of the permeabilization was described as the sum of two exponential components of which the faster accounts for more than 70% of the total effect. Both time constants decreased when the pH of the solution was lowered and when vesicles contained negative lipids. These results can be explained in terms of a phenomenological model based on reaction rate theory. The model assumes that tetanus toxin, after equilibrating with the local pH existing at the surface of the vesicles, inserts into the lipid bilayer forming an ionic channel through which solutes can diffuse. Trigger event for the insertion of the toxin is the protonation, and consequent neutralization of one charged group which makes the molecule more hydrophobic. The intrinsic pK of this group was found to be 3.4 +/- 0.2, suggesting that it may be a carboxyl group. Since the toxin equilibrates with the local pH, the enhancing effect of acidic phospholipids is merely explained by the creation of a negative surface potential which increases the local proton concentration. This was confirmed by the inhibitory effect of high Na+ concentration which reduced the surface charge by screening and specific binding. We found still small differences between the lipids tested and the following order of sensitivity to the action of the toxin: phosphatidylinositol greater than phosphatidylserine greater than phosphatidylcholine approximately cholesterol. The activation energy for the two time constants was found to be 19.8 and 14.8 kcal/mol, fast and slow component, respectively, i.e., slightly larger than that for pure diffusion through the bilayer. The permeabilization induced by tetanus toxin

  18. Enzyme Kinetics.

    ERIC Educational Resources Information Center

    Moe, Owen; Cornelius, Richard

    1988-01-01

    Conveys an appreciation of enzyme kinetic analysis by using a practical and intuitive approach. Discusses enzyme assays, kinetic models and rate laws, the kinetic constants (V, velocity, and Km, Michaels constant), evaluation of V and Km from experimental data, and enzyme inhibition. (CW)

  19. Enzyme Kinetics.

    ERIC Educational Resources Information Center

    Moe, Owen; Cornelius, Richard

    1988-01-01

    Conveys an appreciation of enzyme kinetic analysis by using a practical and intuitive approach. Discusses enzyme assays, kinetic models and rate laws, the kinetic constants (V, velocity, and Km, Michaels constant), evaluation of V and Km from experimental data, and enzyme inhibition. (CW)

  20. The second law of thermodynamics for high-energy channeled particles

    NASA Astrophysics Data System (ADS)

    Kashlev, Yu. A.

    2010-02-01

    In microscopic theory, the number of kinetic equations underlying the proof of the second law of thermodynamics is quite restricted. We explicitly prove that the second law of thermodynamics is satisfied for high-energy particles moving in a crystal in the channeling regime. The proof involves a local Boltzmann equation for the distribution function of the particles written in the Bogoliubov form. In this, we take one statistical mechanism into account: the scattering of channeled particles on lattice atoms randomly displaced from the crystal sites.

  1. The Impact of Classroom Physical Activity Breaks on Middle School Students' Health-Related Fitness: An Xbox One Kinetic Delivered 4-Week Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Yli-Piipari, S.; Layne, T.; McCollins, T.; Knox, T.

    2016-01-01

    The aim of the study was to examine the effect of a 4-week classroom physical activity break intervention on middle school students' health-related physical fitness. The study was a randomized controlled trial with students assigned to the experiment and control conditions. A convenience sample comprised 94 adolescents (experiment group n = 52;…

  2. On the Evolution of Voltage Gated Ion Channels

    NASA Astrophysics Data System (ADS)

    Brenner, Michael

    2006-03-01

    This talk summarizes some ideas, calculations and data analysis/collection surrounding the structure and evolution of ion channels, in particular voltage gated sodium channels. The great advantage of ion channels is that they are individual proteins whose function has long been known and is readily inferred through voltage measurements. Their evolution can be tracked through the growing data base of sequences. Kinetic data is readily available, showing important differences between nearly identical channels. I will discuss our efforts to collate available functional data on voltage gated sodium channels into an 'ion channel property space' . We then use this dataset to infer underlying kinetic models, and to create evolutionary trees based on the function of the channels. Finally, I will discuss our endeavors to how ion channels evolved to be the way they are: Examples of questions we would like to answer include: to what extent do design principles dictate the details of the kinetic schemes of ion channels, such as (a) the symmetry of the sodium and potassium channels (or lack thereof), as reflected in their kinetic schemes ; (b) the coupling of sodium channel kinetics to potassium channel kinetics; or (c) activation/inactivation of the channels themselves.

  3. Binding and dissociation kinetics using fractals: an analysis of electrostatic effects and randomly coupled and oriented coupled receptors on biosensor surfaces.

    PubMed

    Butala, Harshala D; Sadana, Ajit

    2004-03-15

    A fractal analysis is used to analyze the influence of: (a) electrostatic interactions on binding and dissociation rate coefficients for antibodies HH8, HH10, and HH26 in solution to hen egg-white lysozyme (HEL) immobilized on a sensor chip surface [Biophys. J. 83 (2002) 2946]; and (b) the binding and dissociation of recombinant Fab in solution to random NHS-coupled Cys-HEL and oriented thiol-coupled Cys-HEL immobilized on a sensor chip surface [Methods 20 (2000) 310]. Single- and dual-fractal models were employed to fit the data. Values of the binding and the dissociation rate coefficient(s) and the fractal dimensions were obtained from a regression analysis provided by Corel Quattro Pro 8.0 (Corel Corporation Limited, Ottawa, Canada. 1997). The binding rate coefficients are quite sensitive to the degree of heterogeneity on the sensor chip surface. It is of interest to compare the results obtained by the fractal analysis with that of the original analysis [Biophys. J. 83 (2002) 2946]. For example, as one goes from the binding of 21 nM HH10/HEL to the binding of 640 nM HH10/HEL(K97A), Sinha et al. [Biophys. J. 83 (2002) 29461 indicate that the enhancement of diffusional encounter rates may be due to 'electrostatic steering' (a long-range interaction). Our analysis indicates that there is an increase in the value of the fractal dimension, Df1 by a factor of 1.12 from a value of 2.133-2.385. This increase in the degree of heterogeneity on the surface leads to an increase in the binding rate coefficient, k1 by a factor of 1.59 from 12.92 to 20.57. The fractal analysis of binding and dissociation of recombinant Fab in solution to random NHS-coupled Cys-HEL and oriented thiol-coupled Cys-HEL immobilized on a sensor chip [Methods 20 (2000) 310] surface are consistent with the degree of heterogeneity present on the sensor chip surface for the random and the oriented case. As expected, the random case will exhibit a higher degree of heterogeneity than the oriented case

  4. Full kinetic chain manual and manipulative therapy plus exercise compared with targeted manual and manipulative therapy plus exercise for symptomatic osteoarthritis of the hip: a randomized controlled trial.

    PubMed

    Brantingham, James W; Parkin-Smith, Gregory; Cassa, Tammy Kay; Globe, Gary A; Globe, Denise; Pollard, Henry; deLuca, Katie; Jensen, Muffit; Mayer, Stephan; Korporaal, Charmaine

    2012-02-01

    To determine the short-term effectiveness of full kinematic chain manual and manipulative therapy (MMT) plus exercise compared with targeted hip MMT plus exercise for symptomatic mild to moderate hip osteoarthritis (OA). Parallel-group randomized trial with 3-month follow-up. Two chiropractic outpatient teaching clinics. Convenience sample of eligible participants (N=111) with symptomatic hip OA were consented and randomly allocated to receive either the experimental or comparison treatment, respectively. Participants in the experimental group received full kinematic chain MMT plus exercise while those in the comparison group received targeted hip MMT plus exercise. Participants in both groups received 9 treatments over a 5-week period. Western Ontario and McMasters Osteoarthritis Index (WOMAC), Harris hip score (HHS), and Overall Therapy Effectiveness, alongside estimation of clinically meaningful outcomes. Total dropout was 9% (n=10) with 7% of total data missing, replaced using a multiple imputation method. No statistically significant differences were found between the 2 groups for any of the outcome measures (analysis of covariance, P=.45 and P=.79 for the WOMAC and HHS, respectively). There were no statistically significant differences in the primary or secondary outcome scores when comparing full kinematic chain MMT plus exercise with targeted hip MMT plus exercise for mild to moderate symptomatic hip OA. Consequently, the nonsignificant findings suggest that there would also be no clinically meaningful difference between the 2 groups. The results of this study provides guidance to musculoskeletal practitioners who regularly use MMT that the full kinematic chain approach does not appear to have any benefit over targeted treatment. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  5. Two classes of alamethicin transmembrane channels: molecular models from single-channel properties.

    PubMed

    Mak, D O; Webb, W W

    1995-12-01

    Molecular structures of transmembrane channels formed by alamethicin polypeptide aggregates were analyzed by measuring open-channel conductances and state-transition kinetics using voltage-clamp technique with artificial phospholipid bilayers isolated onto micropipettes by a novel solvent-free tip-dip method. Two distinct classes of alamethicin channels, each with a unique set of conductance states and kinetic properties, were identified. Alamethicin Rf50 at low temperatures forms mostly nonpersistent channels with lifetimes of < 1 min. Long-lasting persistent channels are formed by alamethicin Rf30 at all temperatures and by alamethicin Rf50 at room temperature. In the "modified barrel-stave" model for persistent channels based on the crystalline alamethicin secondary structure, the aqueous pore of the channel surrounded by parallel alamethicin monomers has a constriction generated by amino acid side chains protruding from the alamethicin helices into the pore. The model explains quantitatively the nonohmic channel conductance at high applied voltages and the conductance values and ion selectivities of various persistent channel states. The kinetic properties of nonpersistent channels are explained qualitatively by the "reversed-molecule" model in which nonpersistent channels differ from persistent channels by having one of the channel-forming alamethicin monomers oriented antiparallel to the others.

  6. Two classes of alamethicin transmembrane channels: molecular models from single-channel properties.

    PubMed Central

    Mak, D O; Webb, W W

    1995-01-01

    Molecular structures of transmembrane channels formed by alamethicin polypeptide aggregates were analyzed by measuring open-channel conductances and state-transition kinetics using voltage-clamp technique with artificial phospholipid bilayers isolated onto micropipettes by a novel solvent-free tip-dip method. Two distinct classes of alamethicin channels, each with a unique set of conductance states and kinetic properties, were identified. Alamethicin Rf50 at low temperatures forms mostly nonpersistent channels with lifetimes of < 1 min. Long-lasting persistent channels are formed by alamethicin Rf30 at all temperatures and by alamethicin Rf50 at room temperature. In the "modified barrel-stave" model for persistent channels based on the crystalline alamethicin secondary structure, the aqueous pore of the channel surrounded by parallel alamethicin monomers has a constriction generated by amino acid side chains protruding from the alamethicin helices into the pore. The model explains quantitatively the nonohmic channel conductance at high applied voltages and the conductance values and ion selectivities of various persistent channel states. The kinetic properties of nonpersistent channels are explained qualitatively by the "reversed-molecule" model in which nonpersistent channels differ from persistent channels by having one of the channel-forming alamethicin monomers oriented antiparallel to the others. PMID:8599639

  7. Lava Channels

    NASA Image and Video Library

    2013-12-03

    The channels and linear depression in this image captured by NASA 2001 Mars Odyssey spacecraft are located on the western margin of the Elysium Volcanic complex. The channels were created by lava flow.

  8. An open-label, randomized, controlled, 4-week comparative clinical trial of barnidipine hydrochloride, a calcium-channel blocker, and benazepril, an angiotensin-converting enzyme inhibitor, in Chinese patients with renal parenchymal hypertension.

    PubMed

    Chen, X; Zheng, F; Chen, P; Tang, L; Wei, R; Yu, Y; Su, Y; Kikkawa, T; Yamamoto, M

    2006-01-01

    This study compared barnidipine, a calcium-channel blocker, and benazepril, an angiotensin-converting enzyme inhibitor, in 85 Chinese patients with renal parenchymal hypertension (diastolic blood pressure range 95 - 110 mmHg). Patients were randomly assigned to receive either 10 mg barnidipine or 10 mg benazepril orally daily for 4 weeks. In patients with diastolic blood pressure > 90 mmHg after 2 weeks of treatment, the dose of barnidipine or benazepril was increased by 5 or 10 mg, respectively. Both the barnidipine-treated group (n = 43) and the benazepril-treated group (n = 42) showed significant mean reductions from baseline in sitting systolic and diastolic blood pressures. The decrease in diastolic blood pressure with benazepril was significantly greater than with barnidipine treatment. Sitting heart rate was not changed by either drug. There was no significant difference in adverse events between the two groups. Barnidipine is similar to benazepril for the treatment of renal parenchymal hypertension.

  9. Local dynamic subgrid-scale models in channel flow

    NASA Technical Reports Server (NTRS)

    Cabot, William H.

    1994-01-01

    The dynamic subgrid-scale (SGS) model has given good results in the large-eddy simulation (LES) of homogeneous isotropic or shear flow, and in the LES of channel flow, using averaging in two or three homogeneous directions (the DA model). In order to simulate flows in general, complex geometries (with few or no homogeneous directions), the dynamic SGS model needs to be applied at a local level in a numerically stable way. Channel flow, which is inhomogeneous and wall-bounded flow in only one direction, provides a good initial test for local SGS models. Tests of the dynamic localization model were performed previously in channel flow using a pseudospectral code and good results were obtained. Numerical instability due to persistently negative eddy viscosity was avoided by either constraining the eddy viscosity to be positive or by limiting the time that eddy viscosities could remain negative by co-evolving the SGS kinetic energy (the DLk model). The DLk model, however, was too expensive to run in the pseudospectral code due to a large near-wall term in the auxiliary SGS kinetic energy (k) equation. One objective was then to implement the DLk model in a second-order central finite difference channel code, in which the auxiliary k equation could be integrated implicitly in time at great reduction in cost, and to assess its performance in comparison with the plane-averaged dynamic model or with no model at all, and with direct numerical simulation (DNS) and/or experimental data. Other local dynamic SGS models have been proposed recently, e.g., constrained dynamic models with random backscatter, and with eddy viscosity terms that are averaged in time over material path lines rather than in space. Another objective was to incorporate and test these models in channel flow.

  10. On anti-portfolio effects in science and technology with application to reaction kinetics, chemical synthesis, and molecular biology

    PubMed Central

    Vlad, Marcel O.; Corlan, Alexandru Dan; Popa, Vlad T.; Ross, John

    2007-01-01

    The portfolio effect is the increase of the stability of a system to random fluctuations with the increase of the number of random state variables due to spreading the risk among these variables; many examples exist in various areas of science and technology. We report the existence of an opposite effect, the decrease of stability to random fluctuations due to an increase of the number of random state variables. For successive industrial or biochemical processes of independent, random efficiencies, the stability of the total efficiency decreases with the increase of the number of processes. Depending on the variables considered, the same process may display both a portfolio as well as an anti-portfolio behavior. In disordered kinetics, the activation energy of a reaction or transport process is the result of a sum of random components. Although the total activation energy displays a portfolio effect, the rate coefficient displays an anti-portfolio effect. For random-channel kinetics, the stability of the total rate coefficient increases with the average number of reaction pathways, whereas the stability of the survival function has an opposite behavior: it decreases exponentially with the increase of the average number of reaction pathways (anti-portfolio effect). In molecular biology, the total rate of a nucleotide substitution displays a portfolio effect, whereas the probability that no substitutions occur displays an anti-portfolio effect, resulting in faster evolutionary processes due to fluctuations. The anti-portfolio effect emerges for products of random variables or equations involving multiplicative convolution products. PMID:18003905

  11. On anti-portfolio effects in science and technology with application to reaction kinetics, chemical synthesis, and molecular biology.

    PubMed

    Vlad, Marcel O; Corlan, Alexandru Dan; Popa, Vlad T; Ross, John

    2007-11-20

    The portfolio effect is the increase of the stability of a system to random fluctuations with the increase of the number of random state variables due to spreading the risk among these variables; many examples exist in various areas of science and technology. We report the existence of an opposite effect, the decrease of stability to random fluctuations due to an increase of the number of random state variables. For successive industrial or biochemical processes of independent, random efficiencies, the stability of the total efficiency decreases with the increase of the number of processes. Depending on the variables considered, the same process may display both a portfolio as well as an anti-portfolio behavior. In disordered kinetics, the activation energy of a reaction or transport process is the result of a sum of random components. Although the total activation energy displays a portfolio effect, the rate coefficient displays an anti-portfolio effect. For random-channel kinetics, the stability of the total rate coefficient increases with the average number of reaction pathways, whereas the stability of the survival function has an opposite behavior: it decreases exponentially with the increase of the average number of reaction pathways (anti-portfolio effect). In molecular biology, the total rate of a nucleotide substitution displays a portfolio effect, whereas the probability that no substitutions occur displays an anti-portfolio effect, resulting in faster evolutionary processes due to fluctuations. The anti-portfolio effect emerges for products of random variables or equations involving multiplicative convolution products.

  12. TRP Channels

    PubMed Central

    Venkatachalam, Kartik; Montell, Craig

    2011-01-01

    The TRP (Transient Receptor Potential) superfamily of cation channels is remarkable in that it displays greater diversity in activation mechanisms and selectivities than any other group of ion channels. The domain organizations of some TRP proteins are also unusual, as they consist of linked channel and enzyme domains. A unifying theme in this group is that TRP proteins play critical roles in sensory physiology, which include contributions to vision, taste, olfaction, hearing, touch, and thermo- and osmosensation. In addition, TRP channels enable individual cells to sense changes in their local environment. Many TRP channels are activated by a variety of different stimuli and function as signal integrators. The TRP superfamily is divided into seven subfamilies: the five group 1 TRPs (TRPC, TRPV, TRPM, TRPN, and TRPA) and two group 2 subfamilies (TRPP and TRPML). TRP channels are important for human health as mutations in at least four TRP channels underlie disease. PMID:17579562

  13. Improving the In Silico Assessment of Proarrhythmia Risk by Combining hERG (Human Ether-à-go-go-Related Gene) Channel-Drug Binding Kinetics and Multichannel Pharmacology.

    PubMed

    Li, Zhihua; Dutta, Sara; Sheng, Jiansong; Tran, Phu N; Wu, Wendy; Chang, Kelly; Mdluli, Thembi; Strauss, David G; Colatsky, Thomas

    2017-02-01

    The current proarrhythmia safety testing paradigm, although highly efficient in preventing new torsadogenic drugs from entering the market, has important limitations that can restrict the development and use of valuable new therapeutics. The CiPA (Comprehensive in vitro Proarrhythmia Assay) proposes to overcome these limitations by evaluating drug effects on multiple cardiac ion channels in vitro and using these data in a predictive in silico model of the adult human ventricular myocyte. A set of drugs with known clinical torsade de pointes risk was selected to develop and calibrate the in silico model. Manual patch-clamp data assessing drug effects on expressed cardiac ion channels were integrated into the O'Hara-Rudy myocyte model modified to include dynamic drug-hERG channel (human Ether-à-go-go-Related Gene) interactions. Together with multichannel pharmacology data, this model predicts that compounds with high torsadogenic risk are more likely to be trapped within the hERG channel and show stronger reverse use dependency of action potential prolongation. Furthermore, drug-induced changes in the amount of electronic charge carried by the late sodium and L-type calcium currents was evaluated as a potential metric for assigning torsadogenic risk. Modeling dynamic drug-hERG channel interactions and multi-ion channel pharmacology improves the prediction of torsadogenic risk. With further development, these methods have the potential to improve the regulatory assessment of drug safety models under the CiPA paradigm. © 2017 American Heart Association, Inc.

  14. Effect of If-channel inhibition on hemodynamic status and exercise tolerance in heart failure with preserved ejection fraction: a randomized trial.

    PubMed

    Kosmala, Wojciech; Holland, David J; Rojek, Aleksandra; Wright, Leah; Przewlocka-Kosmala, Monika; Marwick, Thomas H

    2013-10-08

    The aim of this study was to test the effects of treatment with ivabradine on exercise capacity and left ventricular filling in patients with heart failure with preserved ejection fraction (HFpEF). Because symptoms of HFpEF are typically exertional, optimization of diastolic filling time by controlling heart rate may delay the onset of symptoms. Sixty-one patients with HFpEF were randomly assigned to ivabradine 5 mg twice daily (n = 30) or placebo (n = 31) for 7 days in this double-blind trial. Cardiopulmonary exercise testing with echocardiographic assessment of myocardial function and left ventricular filling were undertaken at rest and after exercise. The ivabradine group demonstrated significant improvement between baseline and follow-up exercise capacity (4.2 ± 1.8 METs vs. 5.7 ± 1.9 METs, p = 0.001) and peak oxygen uptake (14.0 ± 6.1 ml/min/kg vs. 17.0 ± 3.3 ml/min/kg, p = 0.001), with simultaneous reduction in exercise-induced increase in the ratio of peak early diastolic mitral flow velocity to peak early diastolic mitral annular velocity (3.1 ± 2.7 vs. 1.3 ± 2.0, p = 0.004). Work load-corrected chronotropic response (the difference in heart rate at the same exercise time at the baseline and follow-up tests) showed a slower increase in heart rate during exercise than in the placebo-treated group. Therapy with ivabradine (β = 0.34, p = 0.04) and change with treatment in exertional increase in the ratio of peak early diastolic mitral flow velocity to peak early diastolic mitral annular velocity (β = -0.30, p = 0.02) were independent correlates of increase in exercise capacity, and therapy with ivabradine (β = 0.32, p = 0.007) was independently correlated with increase in peak oxygen uptake. In patients with HFpEF, short-term treatment with ivabradine increased exercise capacity, with a contribution from improved left ventricular filling pressure response to exercise as reflected by the ratio of peak early diastolic mitral flow velocity to peak early

  15. 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.

  16. Kinetic percolation

    NASA Astrophysics Data System (ADS)

    Heinson, W. R.; Chakrabarti, A.; Sorensen, C. M.

    2017-05-01

    We demonstrate that kinetic aggregation forms superaggregates that have structures identical to static percolation aggregates, and these superaggregates appear as a separate phase in the size distribution. Diffusion limited cluster-cluster aggregation (DLCA) simulations were performed to yield fractal aggregates with a fractal dimension of 1.8 and superaggregates with a fractal dimension of D = 2.5 composed of these DLCA supermonomers. When properly normalized to account for the DLCA fractal nature of their supermonomers, these superaggregates have the exact same monomer packing fraction, scaling law prefactor, and scaling law exponent (the fractal dimension) as percolation aggregates; these are necessary and sufficient conditions for same structure. The size distribution remains monomodal until these superaggregates form to alter the distribution. Thus the static percolation and the kinetic descriptions of gelation are now unified.

  17. Rippley Channel

    NASA Technical Reports Server (NTRS)

    2006-01-01

    18 September 2006 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a narrow channel on the upper east flank of the martian volcano, Hadriaca Patera. Because it is located on a volcano, most likely this channel was formed by lava, perhaps as a lava tube at which the thin roof later collapsed. Large ripples of windblown sediment now occur on the channel floor; their crests are generally perpendicular to the channel walls, suggesting that winds blow up and down through this channel.

    Location near: 30.5oS, 266.2oW Image width: 3 km (1.9 mi) Illumination from: upper left Season: Southern Autumn

  18. Rippley Channel

    NASA Technical Reports Server (NTRS)

    2006-01-01

    18 September 2006 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a narrow channel on the upper east flank of the martian volcano, Hadriaca Patera. Because it is located on a volcano, most likely this channel was formed by lava, perhaps as a lava tube at which the thin roof later collapsed. Large ripples of windblown sediment now occur on the channel floor; their crests are generally perpendicular to the channel walls, suggesting that winds blow up and down through this channel.

    Location near: 30.5oS, 266.2oW Image width: 3 km (1.9 mi) Illumination from: upper left Season: Southern Autumn

  19. Ionic Channels in Thunderclouds

    NASA Astrophysics Data System (ADS)

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

    2007-12-01

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

  20. [Amphotericin B channel conductance inactivation].

    PubMed

    Ibragimova, V Kh; Alieva, I N; Aliev, D I

    2003-01-01

    Effects induced in bilayer lipid membranes by amphotericin B and its alkyl derivatives was analysed. Inactivation of the antibiotic-dependent multichannel membrane conductance was discovered. Kinetics of membrane conductivity was shown to depend on the antibiotic concentration in the membrane. At concentrations between 10(-8) and 10(-7) M, the resulting conductance appeared to the transient. We suggest that the phenomenon of biphasic kinetics of membrane conductance is the result of a consecutive transformation of polyene channels in the membrane: half-pores are assembled on either side of membrane-nonconducting 1; two half-pores combine to build up a conducting channels-conducting 2, and the conducting channels are disassemled to monomers and nonconducting self-associated forms inside the membrane-disassembled state (nonconducting 3). To explain the transient characteristics of the induced conductance, it is proposed that the antibiotic, present in the solution under self-associated form, binds the membrane and forms pores, then dissociates in the bilayer in a non-active monomeric form. The existence of definite monomers and nonconducting self-associated forms of amphotericin B molecules inside the membrane was estimated from the dependence of kinetic conductance of lipid membranes of amphotericin B and its alkyl derivatives, when the antibiotics are washed out from aqueous medium. Equilibrium between different antibiotic assemblies inside the membrane was demonstrated by the kinetics of conductance decrease following washing the antibiotic. Using circular dichroism measurements, we observed that amphotericin B alkyl derivatives were in self-associated form being susceptible to form pores across cholesterol-containing membranes. The phenomenon of biophasic kinetics was observed only in the cholesterol-containing membrane. The substitution of membrane cholesterol for ergosterol provides monotonic kinetics of membrane conductance at any antibiotic concentration.

  1. Mechanosensitive Channels

    NASA Astrophysics Data System (ADS)

    Martinac, Boris

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

  2. Channel catfish

    USDA-ARS?s Scientific Manuscript database

    This book chapter provides a comprehensive overview of channel catfish aquaculture. Sections include fish biology; commercial culture; culture facilities; production practices; water quality management; nutrition, feeding and feed formulation; infectious diseases; harvesting and processing; and the...

  3. Tolrestat kinetics

    SciTech Connect

    Hicks, D.R.; Kraml, M.; Cayen, M.N.; Dubuc, J.; Ryder, S.; Dvornik, D.

    1984-10-01

    The kinetics of tolrestat, a potent inhibitor of aldose reductase, were examined. Serum concentrations of tolrestat and of total /sup 14/C were measured after dosing normal subjects and subjects with diabetes with /sup 14/C-labeled tolrestat. In normal subjects, tolrestat was rapidly absorbed and disappearance from serum was biphasic. Distribution and elimination t 1/2s were approximately 2 and 10 to 12 hr, respectively, after single and multiple doses. Unchanged tolrestat accounted for the major portion of /sup 14/C in serum. Radioactivity was rapidly and completely excreted in urine and feces in an approximate ratio of 2:1. Findings were much the same in subjects with diabetes. In normal subjects, the kinetics of oral tolrestat were independent of dose in the 10 to 800 mg range. Repetitive dosing did not result in unexpected cumulation. Tolrestat was more than 99% bound to serum protein; it did not compete with warfarin for binding sites but was displaced to some extent by high concentrations of tolbutamide or salicylate.

  4. Growth of channel catfish and channel x blue hybrid catfish in ponds at restricted or satiate feeding rate

    USDA-ARS?s Scientific Manuscript database

    Growth and yield of channel catfish Ictalurus punctatus and channel x blue hybrid catfish I. punctatus x I. furcatus were evaluated in a completely randomized design study in 2 x 2 factorial arrangement that was conducted in 16 0.25-ac earthen ponds. Factor 1 was strain (channel or channel x blue hy...

  5. Substrate channeling in proline metabolism

    PubMed Central

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

    2012-01-01

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

  6. Random matrix techniques in quantum information theory

    SciTech Connect

    Collins, Benoît; Nechita, Ion

    2016-01-15

    The purpose of this review is to present some of the latest developments using random techniques, and in particular, random matrix techniques in quantum information theory. Our review is a blend of a rather exhaustive review and of more detailed examples—coming mainly from research projects in which the authors were involved. We focus on two main topics, random quantum states and random quantum channels. We present results related to entropic quantities, entanglement of typical states, entanglement thresholds, the output set of quantum channels, and violations of the minimum output entropy of random channels.

  7. Random matrix techniques in quantum information theory

    NASA Astrophysics Data System (ADS)

    Collins, Benoît; Nechita, Ion

    2016-01-01

    The purpose of this review is to present some of the latest developments using random techniques, and in particular, random matrix techniques in quantum information theory. Our review is a blend of a rather exhaustive review and of more detailed examples—coming mainly from research projects in which the authors were involved. We focus on two main topics, random quantum states and random quantum channels. We present results related to entropic quantities, entanglement of typical states, entanglement thresholds, the output set of quantum channels, and violations of the minimum output entropy of random channels.

  8. Kinetic buffers.

    PubMed

    Alibrandi, Giuseppe; Fabbrizzi, Luigi; Licchelli, Maurizio; Puglisi, Antonio

    2015-01-12

    This paper proposes a new type of molecular device that is able to act as an inverse proton sponge to slowly decrease the pH inside a reaction vessel. This makes the automatic monitoring of the concentration of pH-sensitive systems possible. The device is a composite formed of an alkyl chloride, which kinetically produces acidity, and a buffer that thermodynamically modulates the variation in pH value. Profiles of pH versus time (pH-t plots) have been generated under various experimental conditions by computer simulation, and the device has been tested by carrying out automatic spectrophotometric titrations, without using an autoburette. To underline the wide variety of possible applications, this new system has been used to realize and monitor HCl uptake by a di-copper(II) bistren complex in a single run, in a completely automatic experiment. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. English Channel

    NASA Technical Reports Server (NTRS)

    1984-01-01

    The cloud covered earthscape of Northern Europe demonstrates the difficulty of photographing this elusive subject from space. The English Channel (51.0N, 1.5E) separating the British Islands from Europe is in the center of the scene. The white cliffs of Dover on the SE coast of the UK, the Thames River estuary and a partial view of the city of London can be seen on the north side of the Channel while the Normandy coast of France is to the south.

  10. English Channel

    NASA Technical Reports Server (NTRS)

    1984-01-01

    The cloud covered earthscape of Northern Europe demonstrates the difficulty of photographing this elusive subject from space. The English Channel (51.0N, 1.5E) separating the British Islands from Europe is in the center of the scene. The white cliffs of Dover on the SE coast of the UK, the Thames River estuary and a partial view of the city of London can be seen on the north side of the Channel while the Normandy coast of France is to the south.

  11. Integral kinetic equation in dechanneling problem

    NASA Astrophysics Data System (ADS)

    Ryabov, V.

    1989-11-01

    A version of dechanneling theory, based on using an integral kinetic equation in both the phase and transverse energy space, is described. It is derived from the binary collision model and it takes into account consistently the thermal multiple and single scattering of axial and planar channeled particles. The connection between the method developed and that of Oshiyama and of Gartner is discussed.

  12. Enhancing conjugation rate of antibodies to carboxylates: Numerical modeling of conjugation kinetics in microfluidic channels and characterization of chemical over-exposure in conventional protocols by quartz crystal microbalance

    PubMed Central

    Asiaei, Sasan; Smith, Brendan

    2015-01-01

    This research reports an improved conjugation process for immobilization of antibodies on carboxyl ended self-assembled monolayers (SAMs). The kinetics of antibody/SAM binding in microfluidic heterogeneous immunoassays has been studied through numerical simulation and experiments. Through numerical simulations, the mass transport of reacting species, namely, antibodies and crosslinking reagent, is related to the available surface concentration of carboxyl ended SAMs in a microchannel. In the bulk flow, the mass transport equation (diffusion and convection) is coupled to the surface reaction between the antibodies and SAM. The model developed is employed to study the effect of the flow rate, conjugating reagents concentration, and height of the microchannel. Dimensionless groups, such as the Damköhler number, are used to compare the reaction and fluidic phenomena present and justify the kinetic trends observed. Based on the model predictions, the conventional conjugation protocol is modified to increase the yield of conjugation reaction. A quartz crystal microbalance device is implemented to examine the resulting surface density of antibodies. As a result, an increase in surface density from 321 ng/cm2, in the conventional protocol, to 617 ng/cm2 in the modified protocol is observed, which is quite promising for (bio-) sensing applications. PMID:26697125

  13. Optofluidic random laser

    NASA Astrophysics Data System (ADS)

    Shivakiran Bhaktha, B. N.; Bachelard, Nicolas; Noblin, Xavier; Sebbah, Patrick

    2012-10-01

    Random lasing is reported in a dye-circulated structured polymeric microfluidic channel. The role of disorder, which results from limited accuracy of photolithographic process, is demonstrated by the variation of the emission spectrum with local-pump position and by the extreme sensitivity to a local perturbation of the structure. Thresholds comparable to those of conventional microfluidic lasers are achieved, without the hurdle of state-of-the-art cavity fabrication. Potential applications of optofluidic random lasers for on-chip sensors are discussed. Introduction of random lasers in the field of optofluidics is a promising alternative to on-chip laser integration with light and fluidic functionalities.

  14. Slow inactivation in human cardiac sodium channels.

    PubMed Central

    Richmond, J E; Featherstone, D E; Hartmann, H A; Ruben, P C

    1998-01-01

    The available pool of sodium channels, and thus cell excitability, is regulated by both fast and slow inactivation. In cardiac tissue, the requirement for sustained firing of long-duration action potentials suggests that slow inactivation in cardiac sodium channels may differ from slow inactivation in skeletal muscle sodium channels. To test this hypothesis, we used the macropatch technique to characterize slow inactivation in human cardiac sodium channels heterologously expressed in Xenopus oocytes. Slow inactivation was isolated from fast inactivation kinetically (by selectively recovering channels from fast inactivation before measurement of slow inactivation) and structurally (by modification of fast inactivation by mutation of IFM1488QQQ). Time constants of slow inactivation in cardiac sodium channels were larger than previously reported for skeletal muscle sodium channels. In addition, steady-state slow inactivation was only 40% complete in cardiac sodium channels, compared to 80% in skeletal muscle channels. These results suggest that cardiac sodium channel slow inactivation is adapted for the sustained depolarizations found in normally functioning cardiac tissue. Complete slow inactivation in the fast inactivation modified IFM1488QQQ cardiac channel mutant suggests that this impairment of slow inactivation may result from an interaction between fast and slow inactivation. PMID:9635748

  15. Chromatic effects in long periodic transport channels

    SciTech Connect

    Litvinenko V. N.; Hao, Y.; Jing, Y.

    2015-05-03

    Long periodic transport channels are frequently used in accelerator complexes and suggested for using in high-energy ERLs for electron-hadron colliders. Without proper chromaticity compensation, such transport channels exhibit high sensitivity to the random orbit errors causing significant emittance growth. Such emittance growth can come from both the correlated and the uncorrelated energy spread. In this paper we present results of our theoretical and numerical studies of such effects and develop a criteria for acceptable chromaticity in such channels.

  16. The channels of Mars

    NASA Technical Reports Server (NTRS)

    Baker, Victor R.

    1988-01-01

    The geomorphology of Mars is discussed, focusing on the Martian channels. The great flood channels of Mars, the processes of channel erosion, and dendritic channel networks, are examined. The topography of the Channeled Scabland region of the northwestern U.S. is described and compared to the Martian channels. The importance of water in the evolution of the channel systems is considered.

  17. The channels of Mars

    NASA Technical Reports Server (NTRS)

    Baker, Victor R.

    1988-01-01

    The geomorphology of Mars is discussed, focusing on the Martian channels. The great flood channels of Mars, the processes of channel erosion, and dendritic channel networks, are examined. The topography of the Channeled Scabland region of the northwestern U.S. is described and compared to the Martian channels. The importance of water in the evolution of the channel systems is considered.

  18. Reconstruction of Cell Surface Densities of Ion Pumps, Exchangers, and Channels from mRNA Expression, Conductance Kinetics, Whole-Cell Calcium, and Current-Clamp Voltage Recordings, with an Application to Human Uterine Smooth Muscle Cells

    PubMed Central

    Atia, Jolene; McCloskey, Conor; Shmygol, Anatoly S.; Rand, David A.; van den Berg, Hugo A.; Blanks, Andrew M.

    2016-01-01

    Uterine smooth muscle cells remain quiescent throughout most of gestation, only generating spontaneous action potentials immediately prior to, and during, labor. This study presents a method that combines transcriptomics with biophysical recordings to characterise the conductance repertoire of these cells, the ‘conductance repertoire’ being the total complement of ion channels and transporters expressed by an electrically active cell. Transcriptomic analysis provides a set of potential electrogenic entities, of which the conductance repertoire is a subset. Each entity within the conductance repertoire was modeled independently and its gating parameter values were fixed using the available biophysical data. The only remaining free parameters were the surface densities for each entity. We characterise the space of combinations of surface densities (density vectors) consistent with experimentally observed membrane potential and calcium waveforms. This yields insights on the functional redundancy of the system as well as its behavioral versatility. Our approach couples high-throughput transcriptomic data with physiological behaviors in health and disease, and provides a formal method to link genotype to phenotype in excitable systems. We accurately predict current densities and chart functional redundancy. For example, we find that to evoke the observed voltage waveform, the BK channel is functionally redundant whereas hERG is essential. Furthermore, our analysis suggests that activation of calcium-activated chloride conductances by intracellular calcium release is the key factor underlying spontaneous depolarisations. PMID:27105427

  19. Modeling interactions between voltage-gated Ca2+ channels and KCa1.1 channels

    PubMed Central

    Engbers, Jordan DT; Zamponi, Gerald W; Turner, Ray W

    2013-01-01

    High voltage-activated (HVA) Cav channels form complexes with KCa1.1 channels, allowing reliable activation of KCa1.1 current through a nanodomain interaction. We recently found that low voltage-activated Cav3 calcium channels also create KCa1.1-Cav3 complexes. While coimmunoprecipitation studies again supported a nanodomain interaction, the sensitivity to calcium chelating agents was instead consistent with a microdomain interaction. A computational model of the KCa1.1-Cav3 complex suggested that multiple Cav3 channels were necessary to activate KCa1.1 channels, potentially causing the KCa1.1-Cav3 complex to be more susceptible to calcium chelators. Here, we expanded the model and compared it to a KCa1.1-Cav2.2 model to examine the role of Cav channel conductance and kinetics on KCa1.1 activation. As found for direct recordings, the voltage-dependent and kinetic properties of Cav3 channels were reflected in the activation of KCa1.1 current, including transient activation from lower voltages than other KCa1.1-Cav complexes. Substantial activation of KCa1.1 channels required the concerted activity of several Cav3.2 channels. Combined with the effect of EGTA, these results suggest that the Ca2+ domains of several KCa1.1-Cav3 complexes need to cooperate to generate sufficient [Ca2+]i, despite the physical association between KCa1.1 and Cav3 channels. By comparison, Cav2.2 channels were twice as effective at activating KCa1.1 channels and a single KCa1.1-Cav2.2 complex would be self-sufficient. However, even though Cav3 channels generate small, transient currents, the regulation of KCa1.1 activity by Cav3 channels is possible if multiple complexes cooperate through microdomain interactions. PMID:23928916

  20. Use of drug therapy in the management of symptomatic ureteric stones in hospitalized adults (SUSPEND), a multicentre, placebo-controlled, randomized trial of a calcium-channel blocker (nifedipine) and an α-blocker (tamsulosin): study protocol for a randomized controlled trial

    PubMed Central

    2014-01-01

    Background Urinary stone disease is common, with an estimated prevalence among the general population of 2% to 3%. Ureteric stones can cause severe pain and have a significant impact on quality of life, accounting for over 15,000 hospital admissions in England annually. Uncomplicated cases of smaller stones in the lower ureter are traditionally treated expectantly. Those who fail standard care or develop complications undergo active treatment, such as extracorporeal shock wave lithotripsy or ureteroscopy with stone retrieval. Such interventions are expensive, require urological expertise and carry a risk of complications. Growing understanding of ureteric function and pathophysiology has led to the hypothesis that drugs causing relaxation of ureteric smooth muscle, such as the selective α-blocker tamsulosin and the calcium-channel blocker nifedipine, can enhance the spontaneous passage of ureteric stones. The use of drugs in augmenting stone passage, reducing the morbidity and costs associated with ureteric stone disease, is promising. However, the majority of clinical trials conducted to date have been small, poor to moderate quality and lacking in comprehensive economic evaluation. This trial aims to determine the clinical and cost-effectiveness of tamsulosin and nifedipine in the management of symptomatic urinary stones. Methods/design The SUSPEND (Spontaneous Urinary Stone Passage ENabled by Drugs) trial is a multicentre, double-blind, randomized controlled trial evaluating two medical expulsive therapy strategies (nifedipine or tamsulosin) versus placebo. Patients aged 18 to 65 with a ureteric stone confirmed by non-contrast computed tomography of the kidney, ureter and bladder will be randomized to receive nifedipine, tamsulosin or placebo (400 participants per arm) for a maximum of 28 days. The primary clinical outcome is spontaneous passage of ureteric stones at 4 weeks (defined as no further intervention required to facilitate stone passage). The

  1. Use of drug therapy in the management of symptomatic ureteric stones in hospitalized adults (SUSPEND), a multicentre, placebo-controlled, randomized trial of a calcium-channel blocker (nifedipine) and an α-blocker (tamsulosin): study protocol for a randomized controlled trial.

    PubMed

    McClinton, Sam; Starr, Kathryn; Thomas, Ruth; McLennan, Graeme; McPherson, Gladys; McDonald, Alison; Lam, Thomas; N'Dow, James; Kilonzo, Mary; Pickard, Robert; Anson, Ken; Burr, Jennifer

    2014-06-20

    Urinary stone disease is common, with an estimated prevalence among the general population of 2% to 3%. Ureteric stones can cause severe pain and have a significant impact on quality of life, accounting for over 15,000 hospital admissions in England annually. Uncomplicated cases of smaller stones in the lower ureter are traditionally treated expectantly. Those who fail standard care or develop complications undergo active treatment, such as extracorporeal shock wave lithotripsy or ureteroscopy with stone retrieval. Such interventions are expensive, require urological expertise and carry a risk of complications.Growing understanding of ureteric function and pathophysiology has led to the hypothesis that drugs causing relaxation of ureteric smooth muscle, such as the selective α-blocker tamsulosin and the calcium-channel blocker nifedipine, can enhance the spontaneous passage of ureteric stones. The use of drugs in augmenting stone passage, reducing the morbidity and costs associated with ureteric stone disease, is promising. However, the majority of clinical trials conducted to date have been small, poor to moderate quality and lacking in comprehensive economic evaluation.This trial aims to determine the clinical and cost-effectiveness of tamsulosin and nifedipine in the management of symptomatic urinary stones. The SUSPEND (Spontaneous Urinary Stone Passage ENabled by Drugs) trial is a multicentre, double-blind, randomized controlled trial evaluating two medical expulsive therapy strategies (nifedipine or tamsulosin) versus placebo.Patients aged 18 to 65 with a ureteric stone confirmed by non-contrast computed tomography of the kidney, ureter and bladder will be randomized to receive nifedipine, tamsulosin or placebo (400 participants per arm) for a maximum of 28 days. The primary clinical outcome is spontaneous passage of ureteric stones at 4 weeks (defined as no further intervention required to facilitate stone passage). The primary economic outcome is a

  2. Inverted Channels

    NASA Technical Reports Server (NTRS)

    2006-01-01

    23 June 2006 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows sinuous ridges and other landforms exposed by erosion in the Aeolis region of Mars. The ridges in this scene indicate the locations of ancient channels in a fan of sediment deposited in this region. Over time, wind erosion has removed surrounding materials and left the channels, which had been filled by sediment, standing as ridges.

    Location near: 4.5oS, 205.2oW Image width: 2 km (1.2 mi) Illumination from: upper left Season: Southern Autumn

  3. Starburst Channels

    NASA Technical Reports Server (NTRS)

    2007-01-01

    [figure removed for brevity, see original site] Figure 1

    Translucent carbon dioxide ice covers the polar regions of Mars seasonally. It is warmed and sublimates (evaporates) from below, and escaping gas carves a numerous channel morphologies.

    In this example (figure 1) the channels form a 'starburst' pattern, radiating out into feathery extensions. The center of the pattern is being buried with dust and new darker dust fans ring the outer edges. This may be an example of an expanding morphology, where new channels are formed as the older ones fill and are no longer efficiently channeling the subliming gas out.

    Observation Geometry Image PSP_003443_0980 was taken by the High Resolution Imaging Science Experiment (HiRISE) camera onboard the Mars Reconnaissance Orbiter spacecraft on 21-Apr-2007. The complete image is centered at -81.8 degrees latitude, 76.2 degrees East longitude. The range to the target site was 247.1 km (154.4 miles). At this distance the image scale is 24.7 cm/pixel (with 1 x 1 binning) so objects 74 cm across are resolved. The image shown here has been map-projected to 25 cm/pixel. The image was taken at a local Mars time of 04:52 PM and the scene is illuminated from the west with a solar incidence angle of 71 degrees, thus the sun was about 19 degrees above the horizon. At a solar longitude of 223.4 degrees, the season on Mars is Northern Autumn.

  4. Starburst Channels

    NASA Technical Reports Server (NTRS)

    2007-01-01

    [figure removed for brevity, see original site] Figure 1

    Translucent carbon dioxide ice covers the polar regions of Mars seasonally. It is warmed and sublimates (evaporates) from below, and escaping gas carves a numerous channel morphologies.

    In this example (figure 1) the channels form a 'starburst' pattern, radiating out into feathery extensions. The center of the pattern is being buried with dust and new darker dust fans ring the outer edges. This may be an example of an expanding morphology, where new channels are formed as the older ones fill and are no longer efficiently channeling the subliming gas out.

    Observation Geometry Image PSP_003443_0980 was taken by the High Resolution Imaging Science Experiment (HiRISE) camera onboard the Mars Reconnaissance Orbiter spacecraft on 21-Apr-2007. The complete image is centered at -81.8 degrees latitude, 76.2 degrees East longitude. The range to the target site was 247.1 km (154.4 miles). At this distance the image scale is 24.7 cm/pixel (with 1 x 1 binning) so objects 74 cm across are resolved. The image shown here has been map-projected to 25 cm/pixel. The image was taken at a local Mars time of 04:52 PM and the scene is illuminated from the west with a solar incidence angle of 71 degrees, thus the sun was about 19 degrees above the horizon. At a solar longitude of 223.4 degrees, the season on Mars is Northern Autumn.

  5. Nonlinear channelizer.

    PubMed

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

    2012-12-01

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

  6. Nonlinear channelizer

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

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

  7. Clinical events in high-risk hypertensive patients randomly assigned to calcium channel blocker versus angiotensin-converting enzyme inhibitor in the antihypertensive and lipid-lowering treatment to prevent heart attack trial.

    PubMed

    Leenen, Frans H H; Nwachuku, Chuke E; Black, Henry R; Cushman, William C; Davis, Barry R; Simpson, Lara M; Alderman, Michael H; Atlas, Steven A; Basile, Jan N; Cuyjet, Aloysius B; Dart, Richard; Felicetta, James V; Grimm, Richard H; Haywood, L Julian; Jafri, Syed Z A; Proschan, Michael A; Thadani, Udho; Whelton, Paul K; Wright, Jackson T

    2006-09-01

    The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT) provides a unique opportunity to compare the long-term relative safety and efficacy of angiotensin-converting enzyme inhibitor and calcium channel blocker-initiated therapy in older hypertensive individuals. Patients were randomized to amlodipine (n=9048) or lisinopril (n=9054). The primary outcome was combined fatal coronary heart disease or nonfatal myocardial infarction, analyzed by intention-to-treat. Secondary outcomes included all-cause mortality, stroke, combined cardiovascular disease (CVD), end-stage renal disease (ESRD), cancer, and gastrointestinal bleeding. Mean follow-up was 4.9 years. Blood pressure control was similar in nonblacks, but not in blacks. No significant differences were found between treatment groups for the primary outcome, all-cause mortality, ESRD, or cancer. Stroke rates were higher on lisinopril in blacks (RR=1.51, 95% CI 1.22 to 1.86) but not in nonblacks (RR=1.07, 95% CI 0.89 to 1.28), and in women (RR=1.45, 95% CI 1.17 to 1.79), but not in men (RR=1.10, 95% CI 0.92 to 1.31). Rates of combined CVD were higher (RR=1.06, 95% CI 1.00 to 1.12) because of higher rates for strokes, peripheral arterial disease, and angina, which were partly offset by lower rates for heart failure (RR=0.87, 95% CI 0.78 to 0.96) on lisinopril compared with amlodipine. Gastrointestinal bleeds and angioedema were higher on lisinopril. Patients with and without baseline coronary heart disease showed similar outcome patterns. We conclude that in hypertensive patients, the risks for coronary events are similar, but for stroke, combined CVD, gastrointestinal bleeding, and angioedema are higher and for heart failure are lower for lisinopril-based compared with amlodipine-based therapy. Some, but not all, of these differences may be explained by less effective blood pressure control in the lisinopril arm.

  8. The Effects of Calcium Channel Blockers in the Prevention of Stroke in Adults with Hypertension: A Meta-Analysis of Data from 273,543 Participants in 31 Randomized Controlled Trials

    PubMed Central

    Chen, Gui Jv; Yang, Mao Sheng

    2013-01-01

    Background Hypertension is a major risk factor for the development of stroke. It is well known that lowering blood pressure decreases the risk of stroke in people with moderate to severe hypertension. However, the specific effects of calcium channel blockers (CCBs) against stroke in patients with hypertension as compared to no treatment and other antihypertensive drug classes are not known. Methods and Findings This systematic review and meta-analysis of randomized controlled trials (RCTs) evaluated CCBs effect on stroke in patients with hypertension in studies of CCBs versus placebo, angiotensin-converting-enzyme inhibitors (ACEIs), β-adrenergic blockers, and diuretics. The PUBMED, MEDLINE, EMBASE, OVID, CNKI, MEDCH, and WANFANG databases were searched for trials published in English or Chinese during the period January 1, 1996 to July 31, 2012. A total of 177 reports were collected, among them 31 RCTs with 273,543 participants (including 130,466 experimental subjects and 143,077 controls) met the inclusion criteria. In these trials a total of 9,550 stroke events (4,145 in experimental group and 5,405 in control group) were reported. CCBs significantly decreased the incidence of stroke compared with placebo (OR = 0.68, 95% CI 0.61–0.75, p<1×10−5), β-adrenergic blockers combined with diuretics (OR = 0.89, 95% CI 0.83–0.95, p = 7×10−5) and β-adrenergic blockers (OR = 0.79, 95% CI 0.72–0.87, p<1×10−5), statistically significant difference was not found between CCBs and ACEIs (OR = 0.92, 95% CI 0.8–1.02, p = 0.12) or diuretics (OR = 0.95, 95% CI 0.84–1.07, p = 0.39). Conclusion In a pooled analysis of data of 31 RCTs measuring the effect of CCBs on stroke, CCBs reduced stroke more than placebo and β-adrenergic blockers, but were not different than ACEIs and diuretics. More head to head RCTs are warranted. PMID:23483932

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

    PubMed

    Chang, Xi-Lang

    2008-10-01

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

  10. Diffusion in random networks

    DOE PAGES

    Zhang, Duan Z.; Padrino, Juan C.

    2017-06-01

    The ensemble averaging technique is applied to model mass transport by diffusion in random networks. The system consists of an ensemble of random networks, where each network is made of pockets connected by tortuous channels. Inside a channel, fluid transport is assumed to be governed by the one-dimensional diffusion equation. Mass balance leads to an integro-differential equation for the pocket mass density. The so-called dual-porosity model is found to be equivalent to the leading order approximation of the integration kernel when the diffusion time scale inside the channels is small compared to the macroscopic time scale. As a test problem,more » we consider the one-dimensional mass diffusion in a semi-infinite domain. Because of the required time to establish the linear concentration profile inside a channel, for early times the similarity variable is xt$-$1/4 rather than xt$-$1/2 as in the traditional theory. We found this early time similarity can be explained by random walk theory through the network.« less

  11. Superposition properties of interacting ion channels.

    PubMed Central

    Keleshian, A M; Yeo, G F; Edeson, R O; Madsen, B W

    1994-01-01

    Quantitative analysis of patch clamp data is widely based on stochastic models of single-channel kinetics. Membrane patches often contain more than one active channel of a given type, and it is usually assumed that these behave independently in order to interpret the record and infer individual channel properties. However, recent studies suggest there are significant channel interactions in some systems. We examine a model of dependence in a system of two identical channels, each modeled by a continuous-time Markov chain in which specified transition rates are dependent on the conductance state of the other channel, changing instantaneously when the other channel opens or closes. Each channel then has, e.g., a closed time density that is conditional on the other channel being open or closed, these being identical under independence. We relate the two densities by a convolution function that embodies information about, and serves to quantify, dependence in the closed class. Distributions of observable (superposition) sojourn times are given in terms of these conditional densities. The behavior of two channel systems based on two- and three-state Markov models is examined by simulation. Optimized fitting of simulated data using reasonable parameters values and sample size indicates that both positive and negative cooperativity can be distinguished from independence. PMID:7524711

  12. Dynamic Channel Allocation

    DTIC Science & Technology

    2003-09-01

    7 1 . Fixed Channel Allocation (FCA) ........................................................7 2. Dynamic Channel ...19 7. CSMA/CD-Based Multiple Network Lines .....................................20 8. Hybrid Channel Allocation in Wireless Networks...28 1 . Channel Allocation

  13. Ion channeling revisited

    SciTech Connect

    Doyle, Barney Lee; Corona, Aldo; Nguyen, Anh

    2014-09-01

    A MS Excel program has been written that calculates accidental, or unintentional, ion channeling in cubic bcc, fcc and diamond lattice crystals or polycrystalline materials. This becomes an important issue when simulating the creation by energetic neutrons of point displacement damage and extended defects using beams of ions. All of the tables and graphs in the three Ion Beam Analysis Handbooks that previously had to be manually looked up and read from were programed into Excel in handy lookup tables, or parameterized, for the case of the graphs, using rather simple exponential functions with different powers of the argument. The program then offers an extremely convenient way to calculate axial and planar half-angles and minimum yield or dechanneling probabilities, effects on half-angles of amorphous overlayers, accidental channeling probabilities for randomly oriented crystals or crystallites, and finally a way to automatically generate stereographic projections of axial and planar channeling half-angles. The program can generate these projections and calculate these probabilities for axes and [hkl] planes up to (555).

  14. Modeling ion channels: Past, present, and future

    PubMed Central

    2014-01-01

    Ion channels are membrane-bound enzymes whose catalytic sites are ion-conducting pores that open and close (gate) in response to specific environmental stimuli. Ion channels are important contributors to cell signaling and homeostasis. Our current understanding of gating is the product of 60 plus years of voltage-clamp recording augmented by intervention in the form of environmental, chemical, and mutational perturbations. The need for good phenomenological models of gating has evolved in parallel with the sophistication of experimental technique. The goal of modeling is to develop realistic schemes that not only describe data, but also accurately reflect mechanisms of action. This review covers three areas that have contributed to the understanding of ion channels: traditional Eyring kinetic theory, molecular dynamics analysis, and statistical thermodynamics. Although the primary emphasis is on voltage-dependent channels, the methods discussed here are easily generalized to other stimuli and could be applied to any ion channel and indeed any macromolecule. PMID:24935742

  15. Kinetics of Propargyl Radical Dissociation.

    PubMed

    Klippenstein, Stephen J; Miller, James A; Jasper, Ahren W

    2015-07-16

    Due to the prominent role of the propargyl radical for hydrocarbon growth within combustion environments, it is important to understand the kinetics of its formation and loss. The ab initio transition state theory-based master equation method is used to obtain theoretical kinetic predictions for the temperature and pressure dependence of the thermal decomposition of propargyl, which may be its primary loss channel under some conditions. The potential energy surface for the decomposition of propargyl is first mapped at a high level of theory with a combination of coupled cluster and multireference perturbation calculations. Variational transition state theory is then used to predict the microcanonical rate coefficients, which are subsequently implemented within the multiple-well multiple-channel master equation. A variety of energy transfer parameters are considered, and the sensitivity of the thermal rate predictions to these parameters is explored. The predictions for the thermal decomposition rate coefficient are found to be in good agreement with the limited experimental data. Modified Arrhenius representations of the rate constants are reported for utility in combustion modeling.

  16. Mitigation of Control Channel Jamming under Node Capture Attacks

    DTIC Science & Technology

    2008-01-01

    9] to randomly hop away from jammed channels and re-synchronize on available channels and the use of wormholes [10] to create a channel for reports or...Apr. 2007, pp. 499–508. [10] M. C̆agalj, S. C̆apkun, and J.-P. Hubaux, “ Wormhole -based an- tijamming techniques in sensor networks,” IEEE Transactions

  17. Kinetics of Deliquescence

    NASA Astrophysics Data System (ADS)

    McGraw, R. L.; Lewis, E.

    2009-12-01

    We examine deliquescence phase transformation for inorganic salt particles ranging from bulk down to several nanometers in size. Thermodynamic properties of the particles, coated with aqueous solution layers of varying thickness and surrounded by vapor, are analyzed. A thin layer criterion is introduced to define a limiting deliquescence relative humidity (DRH). Nano-size particles are predicted to deliquesce at relative humidity just below the DRH on crossing a nucleation barrier, located at a critical solution layer thickness. This barrier vanishes precisely at the DRH defined by the criterion. For a population of particles, the inherent random nature of the nucleation process is predicted to result in a distribution of RH values over which deliquescence will be seen to occur. Measurement of this (apparent) non-abrupt deliquescence of the population should provide both a validation of the nucleation mechanism and a quantitative determination of nucleation rate. This paper presents calculations of crossing (i.e. deliquescence) rate using the theory of mean first passage times (MFPT). MFPT theory is shown to provide a generalization of Becker-Döring nucleation kinetics especially useful for barrier heights much lower than those typically encountered in vapor-liquid nucleation. Barrier heights for deliquescence depend on the concentration of pre-deliquesced particles and observation time, but are typically in the 5-15kT range. Calculations use the tandem nano-differential mobility analyzer setup of Biskos et al. [1] as a model framework. In their experiment, a concentration of dry salt particles is subject to a higher RH for some observation time, after which is measured the (well-separated) populations of un-deliquesced particles and those that have deliquesced. Theoretical estimates for the conversion kinetics are presented as a function of dry particle size, DRH, and salt properties. [1] G. Biskos, A. Malinowski, L. M. Russell, P. R. Buseck, and S. T. Martin

  18. Chemical and Biological Kinetics

    NASA Astrophysics Data System (ADS)

    Emanuel', N. M.

    1981-10-01

    Examples of the application of the methods and ideas of chemical kinetics in various branches of chemistry and biology are considered and the results of studies on the kinetics and mechanisms of autoxidation and inhibited and catalysed oxidation of organic substances in the liquid phase are surveyed. Problems of the kinetics of the ageing of polymers and the principles of their stabilisation are discussed and certain trends in biological kinetics (kinetics of tumour growth, kinetic criteria of the effectiveness of chemotherapy, problems of gerontology, etc.) are considered. The bibliography includes 281 references.

  19. Cesium removal and kinetics equilibrium: Precipitation kinetics

    SciTech Connect

    Barnes, M.J.

    1999-12-17

    This task consisted of both non-radioactive and radioactive (tracer) tests examining the influence of potentially significant variables on cesium tetraphenylborate precipitation kinetics. The work investigated the time required to reach cesium decontamination and the conditions that affect the cesium precipitation kinetics.

  20. Production characteristics of channel catfish and channel x blue catfish in earthen ponds

    USDA-ARS?s Scientific Manuscript database

    The channel (female) x blue (male) hybrid catfish increasingly is being selected by catfish farmers in the United States as their culture fish. This completely randomized design study in 2 x 2 factorial arrangement was conducted to compare production traits in earthen ponds of the channel x blue hyb...

  1. Yeast screens show aromatic residues at the end of the sixth helix anchor transient receptor potential channel gate.

    PubMed

    Zhou, Xinliang; Su, Zhenwei; Anishkin, Andriy; Haynes, W John; Friske, Eric M; Loukin, Stephen H; Kung, Ching; Saimi, Yoshiro

    2007-09-25

    Transient receptor potential (TRP) channels are first elements in sensing chemicals, heat, and force and are widespread among protists and fungi as well as animals. Despite their importance, the arrangement and roles of the amino acids that constitute the TRP channel gate are unknown. The yeast TRPY1 is activated in vivo by osmotically induced vacuolar membrane deformation and by cytoplasmic Ca(2+). After a random mutagenesis, we isolated TRPY1 mutants that responded more strongly to mild osmotic upshocks. One such gain-of-function mutant has a Y458H substitution at the C terminus of the predicted sixth transmembrane helix. Direct patch-clamp examination of vacuolar membranes showed that Y458H channels were already active with little stimulus and showed marked flickers between the open and intraburst closed states. They remained responsive to membrane stretch force and to Ca(2+), indicating primary defects in the gate region but not in the sensing of gating principles. None of the other 18 amino acid replacements engineered here showed normal channel kinetics except the two aromatic substitutions, Y458F and Y458W. The Y458 of TRPY1 has its aromatic counterpart in mammalian TRPM. Furthermore, conserved aromatics one alpha-helical turn downstream from this point are also found in animal TRPC, TRPN, TRPP, and TRPML, suggesting that gate anchoring with aromatics may be common among many TRP channels. The possible roles of aromatics at the end of the sixth transmembrane helix are discussed.

  2. Fractal analysis of a voltage-dependent potassium channel from cultured mouse hippocampal neurons.

    PubMed Central

    Liebovitch, L S; Sullivan, J M

    1987-01-01

    The kinetics of ion channels have been widely modeled as a Markov process. In these models it is assumed that the channel protein has a small number of discrete conformational states and the kinetic rate constants connecting these states are constant. In the alternative fractal model the spontaneous fluctuations of the channel protein at many different time scales are represented by a kinetic rate constant k = At1-D, where A is the kinetic setpoint and D the fractal dimension. Single-channel currents were recorded at 146 mM external K+ from an inwardly rectifying, 120 pS, K+ selective, voltage-sensitive channel in cultured mouse hippocampal neurons. The kinetics of these channels were found to be statistically self-similar at different time scales as predicted by the fractal model. The fractal dimensions were approximately 2 for the closed times and approximately 1 for the open times and did not depend on voltage. For both the open and closed times the logarithm of the kinetic setpoint was found to be proportional to the applied voltage, which indicates that the gating of this channel involves the net inward movement of approximately one negative charge when this channel opens. Thus, the open and closed times and the voltage dependence of the gating of this channel are well described by the fractal model. PMID:2447974

  3. Hippocampal hypoglycaemia-activated K+ channels: single-channel analysis of glucose and voltage dependence.

    PubMed

    Tromba, C; Salvaggio, A; Racagni, G; Volterra, A

    1994-11-01

    The effect of glucose on kinetics and the voltage-dependent characteristics of glucose-sensitive channels in hippocampal neurons were examined with the cell-attached mode of the patch-clamp technique. Recordings of a 100-pS K+ channel in the presence or absence of glucose demonstrate that the increase in channel open state probability (Po) induced by glucose deprivation (40- to 400-times the control in high-glucose medium) was largely due to a decrease in the global amount of time spent by the channel in a long-lived closed state. The Po value of the same 100-pS channel was also found to increase (by approx. 80-times) following a depolarization of 40 mV from rest, the main factor responsible for this being a dramatic shortening of the long closed-times on depolarization. Another glucose-sensitive channel of smaller conductance (approx. 10 pS) showed a similar dependence of Po on glucose, but different dependence on voltage, with long openings at the same hyperpolarized potentials where the 100-pS channel was almost always closed. Our results indicate that the action of glucose on the kinetics of hippocampal channels closely resembles that of ATP-sensitive channels in pancreatic beta-cells. Furthermore, they indicate that the two types of glucose-sensitive channels found in hippocampal neurons, differing not only in their single-channel conductance but also in the dependence on voltage, could play different roles in the responses of these cells to modified energetic supply.

  4. Casimir rack and pinion as a miniaturized kinetic energy harvester.

    PubMed

    Miri, MirFaez; Etesami, Zahra

    2016-08-01

    We study a nanoscale machine composed of a rack and a pinion with no contact, but intermeshed via the lateral Casimir force. We adopt a simple model for the random velocity of the rack subject to external random forces, namely, a dichotomous noise with zero mean value. We show that the pinion, even when it experiences random thermal torque, can do work against a load. The device thus converts the kinetic energy of the random motions of the rack into useful work.

  5. Eukaryotic mechanosensitive channels.

    PubMed

    Arnadóttir, Jóhanna; Chalfie, Martin

    2010-01-01

    Mechanosensitive ion channels are gated directly by physical stimuli and transduce these stimuli into electrical signals. Several criteria must apply for a channel to be considered mechanically gated. Mechanosensitive channels from bacterial systems have met these criteria, but few eukaryotic channels have been confirmed by the same standards. Recent work has suggested or confirmed that diverse types of channels, including TRP channels, K(2P) channels, MscS-like proteins, and DEG/ENaC channels, are mechanically gated. Several studies point to the importance of the plasma membrane for channel gating, but intracellular and/or extracellular structures may also be required.

  6. Kinetic Transport in Crystals

    NASA Astrophysics Data System (ADS)

    Marklof, Jens

    2010-03-01

    One of the central challenges in kinetic theory is the derivation of macroscopic evolution equations--describing, for example, the dynamics of an electron gas--from the underlying fundamental microscopic laws of classical or quantum mechanics. An iconic mathematical model in this research area is the Lorentz gas, which describes an ensemble of non-interacting point particles in an infinite array of spherical scatterers. In the case of a disordered scatterer configuration, the classical results by Gallavotti, Spohn and Boldrighini-Bunimovich-Sinai show that the time evolution of a macroscopic particle cloud is governed, in the limit of small scatterer density (Boltzmann-Grad limit), by the linear Boltzmann equation. In this lecture I will discuss the recent discovery that for a periodic configuration of scatterers the linear Boltzmann equation fails, and the random flight process that emerges in the Boltzmann-Grad limit is substantially more complicated. The key ingredient in the description of the limiting stochastic process is the renormalization dynamics on the space of lattices, a powerful technique that has recently been successfully applied also to other open problems in mathematical physics, including KAM theory and quantum chaos. This lecture is based on joint work with Andreas Strömbergsson, Uppsala.

  7. Random potentials and cosmological attractors

    NASA Astrophysics Data System (ADS)

    Linde, Andrei

    2017-02-01

    I show that the problem of realizing inflation in theories with random potentials of a limited number of fields can be solved, and agreement with the observational data can be naturally achieved if at least one of these fields has a non-minimal kinetic term of the type used in the theory of cosmological α-attractors.

  8. Fiber channel services

    NASA Astrophysics Data System (ADS)

    Malavalli, Kumar

    1993-02-01

    There exists an increasing need, in the user environment, for a computer interconnect scheme with higher speed, higher performance and longer reach than the presently available alternatives. There is also a great demand for a multidirectional networking to provide high bandwidth on demand, high distribution capability, random access and high transport flexibility. The users expect low access delay, low transfer delay, high data integrity and a definable quality of service from their networks. All these requirements, however, have to be met with the preservation of the existing software in which a lot of user investment has already been made. In answer to the demands, there has been an emergence of a new network to interconnect heterogeneous systems at very high cost performance ratio. This new network is based on Fiber Channel Standard, blessed by the American National Standards Institute (ANSI).

  9. Tortuosity of lightning return stroke channels

    NASA Technical Reports Server (NTRS)

    Levine, D. M.; Gilson, B.

    1984-01-01

    Data obtained from photographs of lightning are presented on the tortuosity of return stroke channels. The data were obtained by making piecewise linear fits to the channels, and recording the cartesian coordinates of the ends of each linear segment. The mean change between ends of the segments was nearly zero in the horizontal direction and was about eight meters in the vertical direction. Histograms of these changes are presented. These data were used to create model lightning channels and to predict the electric fields radiated during return strokes. This was done using a computer generated random walk in which linear segments were placed end-to-end to form a piecewise linear representation of the channel. The computer selected random numbers for the ends of the segments assuming a normal distribution with the measured statistics. Once the channels were simulated, the electric fields radiated during a return stroke were predicted using a transmission line model on each segment. It was found that realistic channels are obtained with this procedure, but only if the model includes two scales of tortuosity: fine scale irregularities corresponding to the local channel tortuosity which are superimposed on large scale horizontal drifts. The two scales of tortuosity are also necessary to obtain agreement between the electric fields computed mathematically from the simulated channels and the electric fields radiated from real return strokes. Without large scale drifts, the computed electric fields do not have the undulations characteristics of the data.

  10. Random sequential adsorption on fractals.

    PubMed

    Ciesla, Michal; Barbasz, Jakub

    2012-07-28

    Irreversible adsorption of spheres on flat collectors having dimension d < 2 is studied. Molecules are adsorbed on Sierpinski's triangle and carpet-like fractals (1 < d < 2), and on general Cantor set (d < 1). Adsorption process is modeled numerically using random sequential adsorption (RSA) algorithm. The paper concentrates on measurement of fundamental properties of coverages, i.e., maximal random coverage ratio and density autocorrelation function, as well as RSA kinetics. Obtained results allow to improve phenomenological relation between maximal random coverage ratio and collector dimension. Moreover, simulations show that, in general, most of known dimensional properties of adsorbed monolayers are valid for non-integer dimensions.

  11. Improvements in haemolysis and indicators of erythrocyte survival do not correlate with acute vaso-occlusive crises in patients with sickle cell disease: a phase III randomized, placebo-controlled, double-blind study of the Gardos channel blocker senicapoc (ICA-17043).

    PubMed

    Ataga, Kenneth I; Reid, Marvin; Ballas, Samir K; Yasin, Zahida; Bigelow, Carolyn; James, Luther St; Smith, Wally R; Galacteros, Frederic; Kutlar, Abdullah; Hull, James H; Stocker, Jonathan W

    2011-04-01

    Red blood cell (RBC) hydration is regulated in part by the Ca(2+) -activated K(+) efflux (Gardos) channel. Senicapoc selectively blocks potassium efflux through the Gardos channel, reducing RBC dehydration and haemolysis, and increasing haemoglobin levels in sickle cell disease (SCD). This randomized, placebo-controlled trial was designed to determine the safety and clinical efficacy of senicapoc in SCD patients. One hundred and forty-five patients were randomized to receive senicapoc and 144 patients to receive placebo for 52 weeks. Consistent with a previous study, patients in the senicapoc group had significantly increased haematocrit, haemoglobin, and decreased numbers of both dense erythrocytes and reticulocytes when compared to the placebo group. The unblinded Data Monitoring Committee terminated this study early due to a lack of efficacy when it determined that, despite improvements in anaemia and haemolysis, no significant improvement in the rate of sickle cell painful crises was observed in patients treated with senicapoc compared to those on placebo (0·38 vs. 0·31, respectively). Comparisons of the times to first, second and third crises between the senicapoc and placebo groups were not statistically significant. Nausea and urinary tract infections occurred more frequently in the senicapoc group than placebo. Serious adverse events were similar in the two groups.

  12. Pair creation in heavy ion channeling

    NASA Astrophysics Data System (ADS)

    Belov, N. A.; Harman, Z.

    2016-04-01

    Heavy ions channeled through crystals with multi-GeV kinetic energies can create electron-positron pairs. In the framework of the ion, the energy of virtual photons arising from the periodic crystal potential may exceed the threshold 2mec2. The repeated periodic collisions with the crystal ions yield high pair production rates. When the virtual photon frequency matches a nuclear transition in the ion, the production rate can be resonantly increased. In this two-step excitation-pair conversion scheme, the excitation rates are coherently enhanced, and scale approximately quadratically with the number of crystal sites along the channel.

  13. Probability density functions in turbulent channel flow

    NASA Technical Reports Server (NTRS)

    Dinavahi, Surya P. G.

    1992-01-01

    The probability density functions (pdf's) of the fluctuating velocity components, as well as their first and second derivatives, are calculated using data from the direct numerical simulations (DNS) of fully developed turbulent channel flow. It is observed that, beyond the buffer region, the pdf of each of these quantities is independent of the distance from the channel wall. It is further observed that, beyond the buffer region, the pdf's for all the first derivatives collapse onto a single universal curve and those of the second derivatives also collapse onto another universal curve, irrespective of the distance from the wall. The kinetic-energy dissipation rate exhibits log normal behavior.

  14. Low and moderate-fat plant sterol fortified soymilk in modulation of plasma lipids and cholesterol kinetics in subjects with normal to high cholesterol concentrations: report on two randomized crossover studies

    PubMed Central

    Rideout, Todd C; Chan, Yen-Ming; Harding, Scott V; Jones, Peter JH

    2009-01-01

    Background Although consumption of various plant sterol (PS)-enriched beverages is effective in lowering plasma cholesterol, the lipid-lowering potential of PS in a soymilk format has not been investigated thoroughly. Therefore, to evaluate the efficacy of PS-enriched soy beverages on plasma lipids and cholesterol kinetics, we conducted two separate 28 d dietary controlled cross-over studies. In study 1, the cholesterol-lowering efficacy of a low-fat (2 g/serving) PS enriched soy beverage was examined in 33 normal cholesterolemic subjects in comparison with 1% dairy milk. In study 2, we investigated the efficacy of a moderate-fat (3.5 g/serving) PS-enriched soy beverage on plasma cholesterol concentrations and cholesterol kinetic responses in 23 hypercholesterolemic subjects compared with 1% dairy milk. Both the low and moderate-fat PS-enriched soymilk varieties provided 1.95 g PS/d. Endpoint plasma variables were analyzed by repeated-measures ANOVA using baseline values as covariates for plasma lipid measurements. Results In comparison with the 1% dairy milk control, the low-fat soy beverage reduced (P < 0.05) total and LDL-cholesterol by 10 and 13%, respectively. Consumption of the moderate-fat PS-enriched soy beverage reduced (P < 0.05) plasma total and LDL-cholesterol by 12 and 15% respectively. Fasting triglycerides were reduced by 9.4% following consumption of the moderate-fat soy beverage in comparison with the 1% dairy milk. Both low and moderate-fat PS-enriched soy varieties reduced (P < 0.05) LDL:HDL and TC:HDL ratios compared with the 1% dairy milk control. Consumption of the moderate-fat PS-enriched soymilk reduced (P < 0.05) cholesterol absorption by 27%, but did not alter cholesterol synthesis in comparison with 1% dairy milk. Conclusion We conclude that, compared to 1% dairy milk, consumption of low and moderate-fat PS-enriched soy beverages represents an effective dietary strategy to reduce circulating lipid concentrations in normal to

  15. Sediment Transport of Vegetated Channel Flow

    NASA Astrophysics Data System (ADS)

    Chen, Y.; Chan, H.; Hsieh, P.

    2012-12-01

    Sediment transport is one of the points of river management. Since the reservoir is usually dredged by hydro-flushing, the river morphology, hydraulic constructions and aquatic habitats are changed by the flow full of sediment which is discharged from the reservoir. These phenomena are more complex for vegetated channels. The flow and streambed affected by the variation of water level in the vegetated channel are simulated by a numerical method. The Navier-Stokes equations which are taken Reynolds average and depth average into 2-D associated with the governing equation of sediment transport are solved by the finite volume method. The k-ɛ model is applied in the process, and the resistance is considered due to the vegetation in the channel. In the vegetated channel, the turbulent kinetic energy at the vegetation zone is reduced and it is rising at the non-vegetated flow zone from the interface between two zones. The flow at the vegetation zone becomes uniform when the upstream water depth increases. Similar situation of the bed shear stress is also found. The phenomenon becomes more apparent when the upstream water depth gets deeper. The channel bed is protected by planting vegetation, but the capability of erosion also increases in the same channel without vegetation. Besides, the model is verified to be well by employing the experimental data presented by Tsujimoto and Kitamura (1995). It is good for predicting the velocity distribution of corss-section in the vegetated channel.; ;

  16. Digital data communications over microwave radio channels

    NASA Astrophysics Data System (ADS)

    Salz, J.

    1984-10-01

    A major contribution to system outage in a terrestrial digital radio channel is deep fading of the frequency transfer characteristic, which in addition to causing a precipitous drop in received signal-to-noise ratio also causes signal dispersion that can result in severe intersymbol interference. Because the temporal variation of the channel is slow compared to the signaling rate, the information theoretic channel capacity and the efficiency index in bits/cycle can be viewed as random processes. Based on an established mathematical model for fading channels, the probability distribution of channel capacity and the distribution of efficiency indices for different communications techniques are estimated. A crucial obstacle to achieving these rates is the nonlinear distortion introduced by power amplifiers. A method for coping with this nonlinear distortion is also described.

  17. Modeling a Ca2+ Channel/BKCa Channel Complex at the Single-Complex Level

    PubMed Central

    Cox, Daniel H.

    2014-01-01

    BKCa-channel activity often affects the firing properties of neurons, the shapes of neuronal action potentials (APs), and in some cases the extent of neurotransmitter release. It has become clear that BKCa channels often form complexes with voltage-gated Ca2+ channels (CaV channels) such that when a CaV channel is activated, the ensuing influx of Ca2+ activates its closely associated BKCa channel. Thus, in modeling the electrical properties of neurons, it would be useful to have quantitative models of CaV/BKCa complexes. Furthermore, in a population of CaV/BKCa complexes, all BKCa channels are not exposed to the same Ca2+ concentration at the same time. Thus, stochastic rather than deterministic models are required. To date, however, no such models have been described. Here, however, I present a stochastic model of a CaV2.1/BKCa(α-only) complex, as might be found in a central nerve terminal. The CaV2.1/BKCa model is based on kinetic modeling of its two component channels at physiological temperature. Surprisingly, The CaV2.1/BKCa model predicts that although the CaV channel will open nearly every time during a typical cortical AP, its associated BKCa channel is expected to open in only 30% of trials, and this percentage is very sensitive to the duration of the AP, the distance between the two channels in the complex, and the presence of fast internal Ca2+ buffers. Also, the model predicts that the kinetics of the BKCa currents of a population of CaV2.1/BKCa complexes will not be limited by the kinetics of the CaV2.1 channel, and during a train of APs, the current response of the complex is expected to faithfully follow even very rapid trains. Aside from providing insight into how these complexes are likely to behave in vivo, the models presented here could also be of use more generally as components of higher-level models of neural function. PMID:25517147

  18. The Psychology of Channeling.

    ERIC Educational Resources Information Center

    Corey, Michael A.

    1988-01-01

    Theoretically analyzes phenomenon of channeling from perspective of C. G. Jung's analytic psychology. Hypothesizes that contact with otherworldly spiritual beings claimed by channelers is actually projected contact with contents of channeler's own unconscious mind. Suggests that channelers seek more constructive ways of contacting their…

  19. Tetrodotoxin block of sodium channels in rabbit Purkinje fibers. Interactions between toxin binding and channel gating

    PubMed Central

    1981-01-01

    Tetrodotoxin (TTX) block of cardiac sodium channels was studied in rabbit Purkinje fibers using a two-microelectrode voltage clamp to measure sodium current. INa decreases with TTX as if one toxin molecule blocks one channel with a dissociation constant KD approximately equal to 1 microM. KD remains unchanged when INa is partially inactivated by steady depolarization. Thus, TTX binding and channel inactivation are independent at equilibrium. Interactions between toxin binding and gating were revealed, however, by kinetic behavior that depends on rates of equilibration. For example, frequent suprathreshold pulses produce extra use-dependent block beyond the tonic block seen with widely spaced stimuli. Such lingering aftereffects of depolarization were characterized by double-pulse experiments. The extra block decays slowly enough (tau approximately equal to 5 s) to be easily separated from normal recovery from inactivation (tau less than 0.2 s at 18 degrees C). The amount of extra block increases to a saturating level with conditioning depolarizations that produce inactivation without detectable activation. Stronger depolarizations that clearly open channels give the same final level of extra block, but its development includes a fast phase whose voltage- and time-dependence resemble channel activation. Thus, TTX block and channel gating are not independent, as believed for nerve. Kinetically, TTX resembles local anesthetics, but its affinity remains unchanged during maintained depolarization. On this last point, comparison of our INa results and earlier upstroke velocity (Vmax) measurements illustrates how much these approaches can differ. PMID:6270235

  20. Signal detection in multiaccess quantum channels

    NASA Astrophysics Data System (ADS)

    Concha, Julio Ignacio

    Quantum channels are communication channels in which quantum effects are important, e.g. low-power optical links. While a "classical" channel is a mapping between probability distributions, a quantum channel is a mapping between quantum states. Among quantum channels, multiple-access channels (MACS) are interesting because of some conceptual differences with their classical counterparts. In a classical MAC, the receiver can make several copies of the incoming signal, and then process each copy in a different way so as to demodulate specific users. In contrast, the celebrated no-cloning theorem of quantum mechanics implies that a quantum signal cannot be perfectly copied, so that joint demodulation of all users is necessary. This thesis studies the detection of multiple users in a quantum channel. The most important contribution is a mathematical model of a quantum MAC, analogous to the "linear superposition plus Gaussian noise" model prevalent in classical communications. The model determines the output of a photon channel given the inputs from several users, and is derived from first principles by solving a Fokker-Planck equation for the system state. It accounts for multiple access interference, signal attenuation, and random noise, and reduces to the classical superposition model when quantum effects are negligible. Information can be extracted from the quantum channel output by measuring a (generalized) observable, which yields a random variable from the quantum state. A fundamental problem is to find the observable that minimizes the probability of decision error. By exploiting the structure of the multiaccess problem, we show that the optimal observable for an interference-free channel is robust in the presence of small interference, and compute the variation in the error probability via a perturbation technique. We also extend previously known quantum detection methods, in particular the square-root measurement, and introduce a novel detector. We show by

  1. Mitochondrial chloride channels: electrophysiological characterization and pH induction of channel pore dilation.

    PubMed

    Misak, Anton; Grman, Marian; Malekova, Lubica; Novotova, Marta; Markova, Jana; Krizanova, Olga; Ondrias, Karol; Tomaskova, Zuzana

    2013-09-01

    Physiological and pathological functions of mitochondria are highly dependent on the properties and regulation of mitochondrial ion channels. There is still no clear understanding of the molecular identity, regulation, and properties of anion mitochondrial channels. The inner membrane anion channel (IMAC) was assumed to be equivalent to mitochondrial centum picosiemens (mCS). However, the different properties of IMAC and mCS channels challenges this opinion. In our study, we characterized the single-channel anion selectivity and pH regulation of chloride channels from purified cardiac mitochondria. We observed that channel conductance decreased in the order: Cl⁻ > Br⁻ > I⁻ > chlorate ≈ formate > acetate, and that gluconate did not permeate under control conditions. The selectivity sequence was Br⁻ ≥ chlorate ≥ I⁻ ≥ Cl⁻ ≥ formate ≈ acetate. Measurement of the concentration dependence of chloride conductance revealed altered channel gating kinetics, which was demonstrated by prolonged mean open time value with increasing chloride concentration. The observed mitochondrial chloride channels were in many respects similar to those of mCS, but not those of IMAC. Surprisingly, we observed that acidic pH increased channel conductance and that an increase of pH from 7.4 to 8.5 reduced it. The gluconate current appeared and gradually increased when pH decreased from pH 7.0 to 5.6. Our results indicate that pH regulates the channel pore diameter in such a way that dilation increases with more acidic pH. We assume this newly observed pH-dependent anion channel property may be involved in pH regulation of anion distribution in different mitochondrial compartments.

  2. Channel nut tool

    DOEpatents

    Olson, Marvin

    2016-01-12

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

  3. Comparison of modal test results - Multipoint sine versus single-point random. [for Mariner Jupiter/Saturn spacecraft

    NASA Technical Reports Server (NTRS)

    Leppert, E. L.; Lee, S. H.; Day, F. D.; Chapman, P. C.; Wada, B. K.

    1976-01-01

    The Mariner Jupiter/Saturn (MJS) spacecraft was subjected to the traditional multipoint sine dwell (MPSD) modal test using 111 accelerometer channels, and also to single-point random (SPR) testing using 26 accelerometer channels, and the two methods are compared according to cost, schedule, and technical criteria. A measure of comparison between the systems was devised in terms of the cumulative difference in the kinetic energy distribution of the common accelerometers. The SPR and MPSD method show acceptable agreement with respect to frequencies and mode damping. The merit of the SPR method is that the excitation points are minimized and the test article can be committed to other uses while data analysis is performed. The MPSD approach allows validity of the data to be determined as the test progresses. Costs are about the same for the two methods.

  4. Simulation methods with extended stability for stiff biochemical Kinetics.

    PubMed

    Rué, Pau; Villà-Freixa, Jordi; Burrage, Kevin

    2010-08-11

    With increasing computer power, simulating the dynamics of complex systems in chemistry and biology is becoming increasingly routine. The modelling of individual reactions in (bio)chemical systems involves a large number of random events that can be simulated by the stochastic simulation algorithm (SSA). The key quantity is the step size, or waiting time, tau, whose value inversely depends on the size of the propensities of the different channel reactions and which needs to be re-evaluated after every firing event. Such a discrete event simulation may be extremely expensive, in particular for stiff systems where tau can be very short due to the fast kinetics of some of the channel reactions. Several alternative methods have been put forward to increase the integration step size. The so-called tau-leap approach takes a larger step size by allowing all the reactions to fire, from a Poisson or Binomial distribution, within that step. Although the expected value for the different species in the reactive system is maintained with respect to more precise methods, the variance at steady state can suffer from large errors as tau grows. In this paper we extend Poisson tau-leap methods to a general class of Runge-Kutta (RK) tau-leap methods. We show that with the proper selection of the coefficients, the variance of the extended tau-leap can be well-behaved, leading to significantly larger step sizes. The benefit of adapting the extended method to the use of RK frameworks is clear in terms of speed of calculation, as the number of evaluations of the Poisson distribution is still one set per time step, as in the original tau-leap method. The approach paves the way to explore new multiscale methods to simulate (bio)chemical systems.

  5. Simulation methods with extended stability for stiff biochemical Kinetics

    PubMed Central

    2010-01-01

    Background With increasing computer power, simulating the dynamics of complex systems in chemistry and biology is becoming increasingly routine. The modelling of individual reactions in (bio)chemical systems involves a large number of random events that can be simulated by the stochastic simulation algorithm (SSA). The key quantity is the step size, or waiting time, τ, whose value inversely depends on the size of the propensities of the different channel reactions and which needs to be re-evaluated after every firing event. Such a discrete event simulation may be extremely expensive, in particular for stiff systems where τ can be very short due to the fast kinetics of some of the channel reactions. Several alternative methods have been put forward to increase the integration step size. The so-called τ-leap approach takes a larger step size by allowing all the reactions to fire, from a Poisson or Binomial distribution, within that step. Although the expected value for the different species in the reactive system is maintained with respect to more precise methods, the variance at steady state can suffer from large errors as τ grows. Results In this paper we extend Poisson τ-leap methods to a general class of Runge-Kutta (RK) τ-leap methods. We show that with the proper selection of the coefficients, the variance of the extended τ-leap can be well-behaved, leading to significantly larger step sizes. Conclusions The benefit of adapting the extended method to the use of RK frameworks is clear in terms of speed of calculation, as the number of evaluations of the Poisson distribution is still one set per time step, as in the original τ-leap method. The approach paves the way to explore new multiscale methods to simulate (bio)chemical systems. PMID:20701766

  6. Src Tyrosine Kinase Alters Gating of Hyperpolarization-Activated HCN4 Pacemaker Channel through Tyr531

    PubMed Central

    Li, Chen-Hong; Zhang, Qi; Teng, Bunyen; Mustafa, S. Jamal; Huang, Jian-Ying; Yu, Han-Gang

    2009-01-01

    We recently discovered that the constitutively active Src tyrosine kinase can enhance the HCN4 channel activity by binding to the channel protein. To investigate the mechanism of modulation by Src of HCN channels, we studied the effects of a selective inhibitor of Src tyrosine kinase, PP2, on HCN4 and its mutant channels ex pressed in HEK293 cells using whole-cell patch clamp technique. We found that PP2 can inhibit HCN4 currents by negatively shifting the voltage dependence of channel activation, decreasing the whole-cell channel conductance, and slowing activation and deactivation kinetics. Screening putative tyrosine residues subject to phosphorylation yielded two candidates: Tyr531 and Tyr554. Substituting HCN4-Tyr531 with phenylalanine largely abolished the effects of PP2 on HCN4 channels. Replacing HCN4-Tyr554 by phenylalanine did not abolish the effects of PP2 on voltage-dependent activation, but did eliminate PP2-induced slowing of channel kinetics. The inhibitory effects of HCN channels associated with reduced Src tyrosine activity is confirmed in HL-1 cardiomyocytes. Finally, we found that PP2 can decrease the heart rate in a mouse model. These results demonstrate that Src tyrosine kinase enhances HCN4 currents by shifting their activation to more positive potentials and increasing the whole-cell channel conductance as well as speeding the channel kinetics. The tyrosine residue that mediates most of Src actions on HCN4 channels is Tyr531. PMID:17977941

  7. Evaluation of acute effect of light-emitting diode (LED) phototherapy on muscle deoxygenation and pulmonary oxygen uptake kinetics in patients with diabetes mellitus: study protocol for a randomized controlled trial.

    PubMed

    Francisco, Cristina de Oliveira; Beltrame, Thomas; Ferraresi, Cleber; Parizotto, Nivaldo Antonio; Bagnato, Vanderlei Salvador; Borghi Silva, Audrey; Benze, Benedito Galvão; Porta, Alberto; Catai, Aparecida Maria

    2015-12-15

    Type 2 diabetes mellitus (DM) is responsible for a significant reduction in the quality of life due to its negative impact on functional capacity. Cardiopulmonary fitness impairment in DM patients has been associated with limited tissue oxygenation. Phototherapy is widely utilized to treat several disorders due to expected light-tissue interaction. This type of therapy may help to improve muscular oxygenation, thereby increasing aerobic fitness and functional capacity. This study is a randomized, double-blind, placebo-controlled crossover trial approved by the Ethics Committee of the Federal University of São Carlos and registered at ClinicalTrials.gov. Four separate tests will be performed to evaluate the acute effect of phototherapy. All participants will receive both interventions in random order: light-emitting diode therapy (LEDT) and placebo, with a minimum 14-day interval between sessions (washout period). Immediately after the intervention, participants will perform moderate constant workload cycling exercise corresponding to 80 % of the pulmonary oxygen uptake [Formula: see text] during the gas exchange threshold (GET). LEDT will be administered with a multidiode cluster probe (50 GaAIA LEDs, 850 ηm, 75 mW each diode, and 3 J per point) before each exercise session. Pulmonary oxygen uptake, muscle oxygenation, heart rate, and arterial pressure will be measured using a computerized metabolic cart, a near-infrared spectrometer, an electrocardiogram, and a photoplethysmography system, respectively. The main objective of this study is to evaluate the acute effects of muscular pre-conditioning using LED phototherapy on pulmonary oxygen uptake, muscle oxygenation, heart rate, and arterial pressure dynamics during dynamic moderate exercise. We hypothesize that phototherapy may be beneficial to optimize aerobic fitness in the DM population. Data will be published after the study is completed. Registered at ClinicalTrials.gov under trial number NCT01889784 (date

  8. Microfluidic channel fabrication method

    DOEpatents

    Arnold, Don W.; Schoeniger, Joseph S.; Cardinale, Gregory F.

    2001-01-01

    A new channel structure for microfluidic systems and process for fabricating this structure. In contrast to the conventional practice of fabricating fluid channels as trenches or grooves in a substrate, fluid channels are fabricated as thin walled raised structures on a substrate. Microfluidic devices produced in accordance with the invention are a hybrid assembly generally consisting of three layers: 1) a substrate that can or cannot be an electrical insulator; 2) a middle layer, that is an electrically conducting material and preferably silicon, forms the channel walls whose height defines the channel height, joined to and extending from the substrate; and 3) a top layer, joined to the top of the channels, that forms a cover for the channels. The channels can be defined by photolithographic techniques and are produced by etching away the material around the channel walls.

  9. Capillary wave measurements on helically-supported capillary channels

    NASA Astrophysics Data System (ADS)

    Chandurwala, Fahim; Thiessen, David

    2010-10-01

    NASA is considering power generation by the Rankine cycle to save weight on long-duration manned missions to the moon or Mars. Phase separation technology is critical to this process in microgravity. Arrays of capillary channels might be useful for filtering liquid drops from a flowing vapor. The efficiency of droplet capture by a helically-supported capillary channel is being studied. A droplet impinging on the channel launches capillary waves that propagate down the channel helping to dissipate some of the drop's kinetic energy. High-speed video of the channel combined with image processing allows for measurement of the amplitude and speed of the wave packets. Increasing the pitch of the support structure decreases the wave speed. An understanding of the dynamic response of the channel to drop impact is a first step in predicting drop-capture efficiency.

  10. Studying mechanosensitive ion channels with an automated patch clamp.

    PubMed

    Barthmes, Maria; Jose, Mac Donald F; Birkner, Jan Peter; Brüggemann, Andrea; Wahl-Schott, Christian; Koçer, Armağan

    2014-03-01

    Patch clamp electrophysiology is the main technique to study mechanosensitive ion channels (MSCs), however, conventional patch clamping is laborious and success and output depends on the skills of the operator. Even though automated patch systems solve these problems for other ion channels, they could not be applied to MSCs. Here, we report on activation and single channel analysis of a bacterial mechanosensitive ion channel using an automated patch clamp system. With the automated system, we could patch not only giant unilamellar liposomes but also giant Escherichia coli (E. coli) spheroplasts. The tension sensitivity and channel kinetics data obtained in the automated system were in good agreement with that obtained from the conventional patch clamp. The findings will pave the way to high throughput fundamental and drug screening studies on mechanosensitive ion channels.

  11. Fast activation of dihydropyridine-sensitive calcium channels of skeletal muscle. Multiple pathways of channel gating

    PubMed Central

    1996-01-01

    Dihydropyridine (DHP) receptors of the transverse tubule membrane play two roles in excitation-contraction coupling in skeletal muscle: (a) they function as the voltage sensor which undergoes fast transition to control release of calcium from sarcoplasmic reticulum, and (b) they provide the conducting unit of a slowly activating L-type calcium channel. To understand this dual function of the DHP receptor, we studied the effect of depolarizing conditioning pulse on the activation kinetics of the skeletal muscle DHP-sensitive calcium channels reconstituted into lipid bilayer membranes. Activation of the incorporated calcium channel was imposed by depolarizing test pulses from a holding potential of -80 mV. The gating kinetics of the channel was studied with ensemble averages of repeated episodes. Based on a first latency analysis, two distinct classes of channel openings occurred after depolarization: most had delayed latencies, distributed with a mode of 70 ms (slow gating); a small number of openings had short first latencies, < 12 ms (fast gating). A depolarizing conditioning pulse to +20 mV placed 200 ms before the test pulse (-10 mV), led to a significant increase in the activation rate of the ensemble averaged-current; the time constant of activation went from tau m = 110 ms (reference) to tau m = 45 ms after conditioning. This enhanced activation by the conditioning pulse was due to the increase in frequency of fast open events, which was a steep function of the intermediate voltage and the interval between the conditioning pulse and the test pulse. Additional analysis demonstrated that fast gating is the property of the same individual channels that normally gate slowly and that the channels adopt this property after a sojourn in the open state. The rapid secondary activation seen after depolarizing prepulses is not compatible with a linear activation model for the calcium channel, but is highly consistent with a cyclical model. A six- state cyclical model is

  12. Experimental quantum channel simulation

    NASA Astrophysics Data System (ADS)

    Lu, He; Liu, Chang; Wang, Dong-Sheng; Chen, Luo-Kan; Li, Zheng-Da; Yao, Xing-Can; Li, Li; Liu, Nai-Le; Peng, Cheng-Zhi; Sanders, Barry C.; Chen, Yu-Ao; Pan, Jian-Wei

    2017-04-01

    Quantum simulation is of great importance in quantum information science. Here, we report an experimental quantum channel simulator imbued with an algorithm for imitating the behavior of a general class of quantum systems. The reported quantum channel simulator consists of four single-qubit gates and one controlled-not gate. All types of quantum channels can be decomposed by the algorithm and implemented on this device. We deploy our system to simulate various quantum channels, such as quantum-noise channels and weak quantum measurement. Our results advance experimental quantum channel simulation, which is integral to the goal of quantum information processing.

  13. Kinetic properties of fractal stellar media

    NASA Astrophysics Data System (ADS)

    Chumak, O. V.; Rastorguev, A. S.

    2017-01-01

    Kinetic processes in fractal stellar media are analysed in terms of the approach developed in our earlier paper involving a generalization of the nearest neighbour and random force distributions to fractal media. Diffusion is investigated in the approximation of scale-dependent conditional density based on an analysis of the solutions of the corresponding Langevin equations. It is shown that kinetic parameters (time-scales, coefficients of dynamic friction, diffusion, etc.) for fractal stellar media can differ significantly both qualitatively and quantitatively from the corresponding parameters for a quasi-uniform random media with limited fluctuations. The most important difference is that in the fractal case, kinetic parameters depend on spatial scalelength and fractal dimension of the medium studied. A generalized kinetic equation for stellar media (fundamental equation of stellar dynamics) is derived in the Fokker-Planck approximation with the allowance for the fractal properties of the spatial stellar density distribution. Also derived are its limit forms that can be used to describe small departures of fractal gravitating medium from equilibrium.

  14. Hadamard quantum broadcast channels

    NASA Astrophysics Data System (ADS)

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

    2017-10-01

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

  15. Fading channel simulator

    SciTech Connect

    Argo, P.E.; Fitzgerald, T.J.

    1991-12-31

    This invention relates to high frequency (HF) radio signal propagation through fading channels and, more particularly, to simulation of fading channels in order to characterize HF radio system performance in transmitting and receiving signals through such fading channels. Fading channel effects on a transmitted communication signal are simulated with both frequency and time variations using a channel scattering function to affect the transmitted signal. A conventional channel scattering function is converted to a series of channel realizations by multiplying the square root of the channel scattering function by a complex number of which the real and imaginary parts are each independent variables. The two-dimensional inverse-FFT of this complex-valued channel realization yields a matrix of channel coefficients that provide a complete frequency-time description of the channel. The transmitted radio signal is segmented to provide a series of transmitted signal and each segment is subject to FFT to generate a series of signal coefficient matrices. The channel coefficient matrices and signal coefficient matrices are then multiplied and subjected to inverse-FFT to output a signal representing the received affected radio signal. A variety of channel scattering functions can be used to characterize the response of a transmitter-receiver system to such atmospheric effects.

  16. Spatial organization of RYRs and BK channels underlying the activation of STOCs by Ca2+ sparks in airway myocytes

    PubMed Central

    Lifshitz, Lawrence M.; Carmichael, Jeffrey D.; Lai, F. Anthony; Sorrentino, Vincenzo; Bellvé, Karl; Fogarty, Kevin E.

    2011-01-01

    Short-lived, localized Ca2+ events mediate Ca2+ signaling with high efficiency and great fidelity largely as a result of the close proximity between Ca2+-permeable ion channels and their molecular targets. However, in most cases, direct evidence of the spatial relationship between these two types of molecules is lacking, and, thus, mechanistic understanding of local Ca2+ signaling is incomplete. In this study, we use an integrated approach to tackling this issue on a prototypical local Ca2+ signaling system composed of Ca2+ sparks resulting from the opening of ryanodine receptors (RYRs) and spontaneous transient outward currents (STOCs) caused by the opening of Ca2+-activated K+ (BK) channels in airway smooth muscle. Biophysical analyses of STOCs and Ca2+ sparks acquired at 333 Hz demonstrate that these two events are associated closely in time, and approximately eight RYRs open to give rise to a Ca2+ spark, which activates ∼15 BK channels to generate a STOC at 0 mV. Dual immunocytochemistry and 3-D deconvolution at high spatial resolution reveal that both RYRs and BK channels form clusters and RYR1 and RYR2 (but not RYR3) localize near the membrane. Using the spatial relationship between RYRs and BK channels, the spatial-temporal profile of [Ca2+] resulting from Ca2+ sparks, and the kinetic model of BK channels, we estimate that an average Ca2+ spark caused by the opening of a cluster of RYR1 or RYR2 acts on BK channels from two to three clusters that are randomly distributed within an ∼600-nm radius of RYRs. With this spatial organization of RYRs and BK channels, we are able to model BK channel currents with the same salient features as those observed in STOCs across a range of physiological membrane potentials. Thus, this study provides a mechanistic understanding of the activation of STOCs by Ca2+ sparks using explicit knowledge of the spatial relationship between RYRs (the Ca2+ source) and BK channels (the Ca2+ target). PMID:21746845

  17. Multiple channel programmable coincidence counter

    DOEpatents

    Arnone, Gaetano J.

    1990-01-01

    A programmable digital coincidence counter having multiple channels and featuring minimal dead time. Neutron detectors supply electrical pulses to a synchronizing circuit which in turn inputs derandomized pulses to an adding circuit. A random access memory circuit connected as a programmable length shift register receives and shifts the sum of the pulses, and outputs to a serializer. A counter is input by the adding circuit and downcounted by the seralizer, one pulse at a time. The decoded contents of the counter after each decrement is output to scalers.

  18. Mechanochemical Kinetics in Elastomeric Polymer Networks: Heterogeneity of Local Forces Results in Nonexponential Kinetics.

    PubMed

    Adhikari, Ramesh; Makarov, Dmitrii E

    2017-03-16

    A common approach to inducing selective mechanochemical transformations relies on embedding the target molecules (called mechanophores) within elastomeric polymer networks. Mechanical properties of such elastomers can also be modulated through the mechanochemical response of the constituent polymer chains. The inherent randomness in the molecular structure of such materials leads to heterogeneity of the local forces exerted on individual mechanophores. Here we use coarse-grained simulations to study the force distributions within random elastomeric networks and show that those distributions are close to exponential regardless of the applied macroscopic load, entanglement effects, or network parameters. Exponential form of the distribution allows one to completely characterize the mechanophore kinetics in terms of the mean value of the force. At the same time, heterogeneity of the local force affects the kinetics qualitatively: While a narrow force distribution around the mean would lead to exponential kinetics, exponential force distribution results in highly nonexponential kinetics, with a fast kinetic phase involving highly loaded molecules, followed by a slow phase dominated by unloaded molecules.

  19. Single Na+ channels activated by veratridine and batrachotoxin

    PubMed Central

    1987-01-01

    Voltage-sensitive Na+ channels from rat skeletal muscle plasma membrane vesicles were inserted into planar lipid bilayers in the presence of either of the alkaloid toxins veratridine (VT) or batrachotoxin (BTX). Both of these toxins are known to cause persistent activation of Na+ channels. With BTX as the channel activator, single channels remain open nearly all the time. Channels activated with VT open and close on a time scale of 1-10 s. Increasing the VT concentration enhances the probability of channel opening, primarily by increasing the rate constant of opening. The kinetics and voltage dependence of channel block by 21-sulfo-11-alpha-hydroxysaxitoxin are identical for VT and BTX, as is the ionic selectivity sequence determined by bi-ionic reversal potential (Na+ approximately Li+ greater than K+ greater than Rb+ greater than Cs+). However, there are striking quantitative differences in open channel conduction for channels in the presence of the two activators. Under symmetrical solution conditions, the single channel conductance for Na+ is about twice as high with BTX as with VT. Furthermore, the symmetrical solution single channel conductances show a different selectivity for BTX (Na+ greater than Li+ greater than K+) than for VT (Na+ greater than K+ greater than Li+). Open channel current-voltage curves in symmetrical Na+ and Li+ are roughly linear, while those in symmetrical K+ are inwardly rectifying. Na+ currents are blocked asymmetrically by K+ with both BTX and VT, but the voltage dependence of K+ block is stronger with BTX than with VT. The results show that the alkaloid neurotoxins not only alter the gating process of the Na+ channel, but also affect the structure of the open channel. We further conclude that the rate-determining step for conduction by Na+ does not occur at the channel's "selectivity filter," where poorly permeating ions like K+ are excluded. PMID:2435846

  20. The Channel Tunnel

    NASA Image and Video Library

    2006-08-11

    The Channel Tunnel is a 50.5 km-long rail tunnel beneath the English Channel at the Straits of Dover. It connects Dover, Kent in England with Calais, northern France. This image was acquired by NASA Terra spacecraft.

  1. Bayesian sparse channel estimation

    NASA Astrophysics Data System (ADS)

    Chen, Chulong; Zoltowski, Michael D.

    2012-05-01

    In Orthogonal Frequency Division Multiplexing (OFDM) systems, the technique used to estimate and track the time-varying multipath channel is critical to ensure reliable, high data rate communications. It is recognized that wireless channels often exhibit a sparse structure, especially for wideband and ultra-wideband systems. In order to exploit this sparse structure to reduce the number of pilot tones and increase the channel estimation quality, the application of compressed sensing to channel estimation is proposed. In this article, to make the compressed channel estimation more feasible for practical applications, it is investigated from a perspective of Bayesian learning. Under the Bayesian learning framework, the large-scale compressed sensing problem, as well as large time delay for the estimation of the doubly selective channel over multiple consecutive OFDM symbols, can be avoided. Simulation studies show a significant improvement in channel estimation MSE and less computing time compared to the conventional compressed channel estimation techniques.

  2. Kinetics of proton release and uptake by channelrhodopsin-2.

    PubMed

    Nack, Melanie; Radu, Ionela; Schultz, Bernd-Joachim; Resler, Tom; Schlesinger, Ramona; Bondar, Ana-Nicoleta; del Val, Coral; Abbruzzetti, Stefania; Viappiani, Cristiano; Bamann, Christian; Bamberg, Ernst; Heberle, Joachim

    2012-05-07

    Electrophysiological experiments showed that the light-activated cation channel channelrhodopsin-2 (ChR2) pumps protons in the absence of a membrane potential. We determined here the kinetics of transient pH change using a water-soluble pH-indicator. It is shown that ChR2 released protons prior to uptake with a stoichiometry of 0.3 protons per ChR2. Comparison to the photocycle kinetics revealed that proton release and uptake match rise and decay of the P(3)(520) intermediate. As the P(3)(520) state also represents the conductive state of cation channeling, the concurrence of proton pumping and channel gating implies an intimate mechanistic link of the two functional modes. Studies on the E123T and S245E mutants show that these residues are not critically involved in proton translocation.

  3. Chemical Kinetic Characterization of Combustion Toluene

    SciTech Connect

    Pitz, W J; Seiser, R; Bozzelli, J W; Da Costa, I; Fournet, R; Billaud, F; Battin-Leclerc, F; Seshadri, K; Westbrook, C K

    2001-03-20

    A study is performed to elucidate the chemical kinetic mechanism of combustion of toluene. A detailed chemical kinetic mechanism for toluene was improved by adding a more accurate description of the phenyl + O{sub 2} reaction channels. Results of the chemical kinetic mechanism are compared with experimental data obtained from premixed and nonpremixed systems. Under premixed conditions, predicted ignition delay times are compared with new experimental data obtained in shock tube. Also, calculated species concentration histories are compared to experimental flow reactor data from the literature. Critical conditions of extinction and ignition were measured in strained laminar flows under nonpremixed conditions in the counterflow configuration. Numerical calculations are performed using the chemical kinetic mechanism at conditions corresponding to those in the experiments. Critical conditions of extinction and ignition are predicted and compared with the experimental data. For both premixed and nonpremixed systems, sensitivity analysis was used to identify the reaction rate constants that control the overall rate of oxidation in each of the systems considered.

  4. Randomization Strategies.

    PubMed

    Kepler, Christopher K

    2017-04-01

    An understanding of randomization is important both for study design and to assist medical professionals in evaluating the medical literature. Simple randomization can be done through a variety of techniques, but carries a risk of unequal distribution of subjects into treatment groups. Block randomization can be used to overcome this limitation by ensuring that small subgroups are distributed evenly between treatment groups. Finally, techniques can be used to evenly distribute subjects between treatment groups while accounting for confounding variables, so as to not skew results when there is a high index of suspicion that a particular variable will influence outcome.

  5. Message passing with queues and channels

    DOEpatents

    Dozsa, Gabor J; Heidelberger, Philip; Kumar, Sameer; Ratterman, Joseph D; Steinmacher-Burow, Burkhard; Wisniewski, Robert W

    2013-09-24

    In an embodiment, a send thread receives an identifier that identifies a destination node and a pointer to data. The send thread creates a first send request in response to the receipt of the identifier and the data pointer. The send thread selects a selected channel from among a plurality of channels. The selected channel comprises a selected hand-off queue and an identification of a selected message unit. Each of the channels identifies a different message unit. The selected hand-off queue is randomly accessible. If the selected hand-off queue contains an available entry, the send thread adds the first send request to the selected hand-off queue. If the selected hand-off queue does not contain an available entry, the send thread removes a second send request from the selected hand-off queue and sends the second send request to the selected message unit.

  6. Quasi-Anonymous Channels

    DTIC Science & Technology

    2003-01-01

    QUASI- ANONYMOUS CHANNELS Ira S. Moskowitz Center for High Assurance Computer Systems - Code 5540 Naval Research Laboratory, Washington, DC...Assurance Computer Systems - Code 5540 Naval Research Laboratory, Washington, DC 20375, USA Abstract Although both anonymity and covert...channels are part of the larger topic of information hiding, there also exists an intrinsic linkage between anonymity and covert channels. This linkage

  7. Channel morphology [Chapter 5

    Treesearch

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

    2012-01-01

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

  8. Spectroscopy and reaction kinetics of HCO

    SciTech Connect

    Guo, Yili

    1989-01-01

    The high-resolution infrared spectrum of the C-H stretching fundamental of HCO has been studied by means of infrared flash kinetic spectroscopy. HCO was generated by flash photolysis of acetaldehyde or formaldehyde using a 308 nm (XeCl) excimer laser. The transient absorption was probed with an infrared difference frequency laser system. The high resolution spectra obtained were assigned and fitted with rotational, spin-rotational, and centrifugal distortion constants. The ..nu../sub 1/ band origin is 2434.48 cm/sup /minus/1/. New ground state constants have been derived from a least-squares fit combining the ..nu../sub 1/ data with previous microwave and FIR LMR measurements. A new set of spectroscopic constants for the (1, 0, 0) state, the equilibrium rotational constants, and the orientation of the transition dipole moment are also reported. The kinetics and product branching ratios of the HCO + NO/sub 2/ reaction have been studied using visible and infrared laser flash kinetic spectroscopy. The rate constant for the disappearance of HCO radical at 296 K is (5.7 +- 0.9) /times/ 10/sup /minus/11/ cm/sup 3/ molec/sup /minus/1/ sec/sup /minus/1/, and it is independent of the pressure of SF/sub 6/ buffer gas up to 700 torr. Less than 10% of the reaction goes through the most exothermic product channel, HNO + CO/sub 2/. The product channel, H + CO/sub 2/ + NO, is responsible for 52% of the reaction. HONO has been observed, though not quantitatively, as a reaction product corresponding to the HONO + CO channel. 51 refs., 21 figs., 8 tabs.

  9. Characteristic eddy decomposition of turbulence in a channel

    NASA Technical Reports Server (NTRS)

    Moin, Parviz; Moser, Robert D.

    1991-01-01

    The proper orthogonal decomposition technique (Lumley's decomposition) is applied to the turbulent flow in a channel to extract coherent structures by decomposing the velocity field into characteristic eddies with random coefficients. In the homogeneous spatial directions, a generaliztion of the shot-noise expansion is used to determine the characteristic eddies. In this expansion, the Fourier coefficients of the characteristic eddy cannot be obtained from the second-order statistics. Three different techniques are used to determine the phases of these coefficients. They are based on: (1) the bispectrum, (2) a spatial compactness requirement, and (3) a functional continuity argument. Results from these three techniques are found to be similar in most respects. The implications of these techniques and the shot-noise expansion are discussed. The dominant eddy is found to contribute as much as 76 percent to the turbulent kinetic energy. In both 2D and 3D, the characteristic eddies consist of an ejection region straddled by streamwise vortices that leave the wall in the very short streamwise distance of about 100 wall units.

  10. A "Stationery" Kinetics Experiment.

    ERIC Educational Resources Information Center

    Hall, L.; Goberdhansingh, A.

    1988-01-01

    Describes a simple redox reaction that occurs between potassium permanganate and oxalic acid that can be used to prepare an interesting disappearing ink for demonstrating kinetics for introductory chemistry. Discusses laboratory procedures and factors that influence disappearance times. (CW)

  11. Chemical Kinetics Database

    National Institute of Standards and Technology Data Gateway

    SRD 17 NIST Chemical Kinetics Database (Web, free access)   The NIST Chemical Kinetics Database includes essentially all reported kinetics results for thermal gas-phase chemical reactions. The database is designed to be searched for kinetics data based on the specific reactants involved, for reactions resulting in specified products, for all the reactions of a particular species, or for various combinations of these. In addition, the bibliography can be searched by author name or combination of names. The database contains in excess of 38,000 separate reaction records for over 11,700 distinct reactant pairs. These data have been abstracted from over 12,000 papers with literature coverage through early 2000.

  12. Adequacy of kinetic models

    SciTech Connect

    Kiperman, S.L.

    1995-01-01

    The problems associated with the accuracy of kinetic models in heterogeneous catalysis and their adequacy to experimental data and reaction mechanisms are considered. The prospects for the further improvement and use of these models is also explored.

  13. A "Stationery" Kinetics Experiment.

    ERIC Educational Resources Information Center

    Hall, L.; Goberdhansingh, A.

    1988-01-01

    Describes a simple redox reaction that occurs between potassium permanganate and oxalic acid that can be used to prepare an interesting disappearing ink for demonstrating kinetics for introductory chemistry. Discusses laboratory procedures and factors that influence disappearance times. (CW)

  14. Thermal kinetic inductance detector

    DOEpatents

    Cecil, Thomas; Gades, Lisa; Miceli, Antonio; Quaranta, Orlando

    2016-12-20

    A microcalorimeter for radiation detection that uses superconducting kinetic inductance resonators as the thermometers. The detector is frequency-multiplexed which enables detector systems with a large number of pixels.

  15. Fundamentals of enzyme kinetics.

    PubMed

    Seibert, Eleanore; Tracy, Timothy S

    2014-01-01

    This chapter provides a general introduction to the kinetics of enzyme-catalyzed reactions, with a focus on drug-metabolizing enzymes. A prerequisite to understanding enzyme kinetics is having a clear grasp of the meanings of "enzyme" and "catalysis." Catalysts are reagents that can increase the rate of a chemical reaction without being consumed in the reaction. Enzymes are proteins that form a subset of catalysts. These concepts are further explored below.

  16. Random thoughts

    NASA Astrophysics Data System (ADS)

    ajansen; kwhitefoot; panteltje1; edprochak; sudhakar, the

    2014-07-01

    In reply to the physicsworld.com news story “How to make a quantum random-number generator from a mobile phone” (16 May, http://ow.ly/xFiYc, see also p5), which describes a way of delivering random numbers by counting the number of photons that impinge on each of the individual pixels in the camera of a Nokia N9 smartphone.

  17. Epithelial Sodium and Chloride Channels and Asthma

    PubMed Central

    Wang, Wen; Ji, Hong-Long

    2015-01-01

    Objective: To focus on the asthmatic pathogenesis and clinical manifestations related to epithelial sodium channel (ENaC)/chlorine ion channel. Data Sources: The data analyzed in this review were the English articles from 1980 to 2015 from journal databases, primarily PubMed and Google Scholar. The terms used in the literature search were: (1) ENaCs; cystic fibrosis (CF) transmembrane conductance regulator (CFTR); asthma/asthmatic, (2) ENaC/sodium salt; CF; asthma/asthmatic, (3) CFTR/chlorine ion channels; asthma/asthmatic, (4) ENaC/sodium channel/scnn1a/scnn1b/scnn1g/scnn1d/amiloride-sensitive/amiloride-inhibtable sodium channels/sodium salt; asthma/asthmatic, lung/pulmonary/respiratory/tracheal/alveolar, and (5) CFTR; CF; asthma/asthmatic (ti). Study Selection: These studies included randomized controlled trials or studies covering asthma pathogenesis and clinical manifestations related to ENaC/chlorine ion channels within the last 25 years (from 1990 to 2015). The data involving chronic obstructive pulmonary disease and CF obtained from individual studies were also reviewed by the authors. Results: Airway surface liquid dehydration can cause airway inflammation and obstruction. ENaC and CFTR are closely related to the airway mucociliary clearance. Ion transporters may play a critical role in pathogenesis of asthmatic exacerbations. Conclusions: Ion channels have been the center of many studies aiming to understand asthmatic pathophysiological mechanisms or to identify therapeutic targets for better control of the disease. PMID:26265620

  18. Low voltage activated calcium channels: from genes to function.

    PubMed

    Lacinová, L; Klugbauer, N; Hofmann, F

    2000-06-01

    Cloning of three members of low-voltage-activated (LVA) calcium channel family, predominantly neuronal alpha1G and alpha1I, and ubiquitous alpha1H, enabled to investigate directly their electrophysiological and pharmacological profile as well as their putative subunit composition. All the three channels are half-activated at membrane potential about -40 mV and half-inactivated at about -70 mV. Kinetics of alpha1G and alpha1H channels activation and inactivation are similar and faster than that of alpha1I channel. All the three channels are blocked with high affinity by the organic blocker mibefradil. Another high affinity blocker is kurtoxin. Cloned LVA channels are relatively insensitive to antiepileptics, dihydropyridines and omega-conotoxins. Ni2+ is high affinity blocker of alpha1H channel only. Amiloride inhibits the alpha1H channel. The subunit composition of LVA channel remains unclear. Out of known high-voltage-activated calcium channel subunits, alpha2delta-2 and gamma-5 subunits significantly and systematically modified activation and/or inactivation of the current. In contrast, alpha2delta-1, alpha2delta-3, gamma-2 and gamma-4 subunits failed to modulate the current or had only minor effects.

  19. On 1-qubit channels

    NASA Astrophysics Data System (ADS)

    Uhlmann, Armin

    2001-09-01

    The entropy HT (ρ) of a state with respect to a channel T and the Holevo capacity of the channel require the solution of difficult variational problems. For a class of 1-qubit channels, which contains all the extremal ones, the problem can be significantly simplified by attaching a unique Hermitian antilinear operator ϑ to every channel of the considered class. The channel's concurrence CT can be expressed by ϑ and turns out to be a flat roof. This allows to write down an explicit expression for HT. Its maximum would give the Holevo (one-shot) capacity.

  20. Incompatibility of quantum channels

    NASA Astrophysics Data System (ADS)

    Heinosaari, Teiko; Miyadera, Takayuki

    2017-03-01

    Two quantum channels are called compatible if they can be obtained as marginals from a single broadcasting channel; otherwise they are incompatible. We derive a characterization of the compatibility relation in terms of concatenation and conjugation, and we show that all pairs of sufficiently noisy quantum channels are compatible. The complement relation of incompatibility can be seen as a unifying aspect for several important quantum features, such as impossibility of universal broadcasting and unavoidable measurement disturbance. We show that the concepts of entanglement breaking channel and antidegradable channel can be completely characterized in terms compatibility.

  1. Cardiac ion channels

    PubMed Central

    Priest, Birgit T; McDermott, Jeff S

    2015-01-01

    Ion channels are critical for all aspects of cardiac function, including rhythmicity and contractility. Consequently, ion channels are key targets for therapeutics aimed at cardiac pathophysiologies such as atrial fibrillation or angina. At the same time, off-target interactions of drugs with cardiac ion channels can be the cause of unwanted side effects. This manuscript aims to review the physiology and pharmacology of key cardiac ion channels. The intent is to highlight recent developments for therapeutic development, as well as elucidate potential mechanisms for drug-induced cardiac side effects, rather than present an in-depth review of each channel subtype. PMID:26556552

  2. Ion channels in plants

    PubMed Central

    Baluška, František; Mancuso, Stefano

    2013-01-01

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

  3. Kinetic energy distribution of OH+ from water fragmentation by electron impact

    NASA Astrophysics Data System (ADS)

    Ferreira, Natalia; Sigaud, L.; Montenegro, E. C.

    2017-07-01

    The release of the highly reactive radical OH+ from the fragmentation of water by electron impact is made mostly through the OH++H0 channel. This channel ejects suprathermal OH+ ions with a kinetic energy distribution whose details are unexplored so far due to the difficulty in experimentally characterizing ions ejected with very low kinetic energy without another charged partner. These ions are studied here using the delayed extraction time-of-flight technique (DETOF). The structures and substructures in the kinetic energy distribution of OH+ associated with both single and double ionization are identified qualitatively and quantitatively. A comparison with the kinetic energy distribution of the complementary channel OH0+H+ , also originating from vacancies in the 1 b2 orbital, shows marked differences between the two, mainly regarding the relative role between the fragmentation involving the H2O+ ground state or via transitions to repulsive states.

  4. Kinetics of geminate recombination of aromatic free radicals

    NASA Astrophysics Data System (ADS)

    Khudyakov, I. V.; Kiryukhin, Yu. I.; Yasmenko, A. I.

    1980-09-01

    Nanosecond laser flash photolysis techniques were used to observe the geminate recombination kinetics of 2-(4'-diphenylaminophenyl)-indandione-1,3-yl radicals (R) in vaseline oil at 0°C. The kinetics are closely described by the Kofman-Burshtein model. The rate of diffusion-controlled recombination of R by random encounters in the bulk was also measured. The kinetics of geminate recombination and recombination in the bulk are described by the same parameters (diffusion coefficient (1.8 ± O.6) × 10 -8 cm 2/s and reaction radius 13.2Å).

  5. Nested Channels near Hellas

    NASA Image and Video Library

    2015-09-30

    This image from NASA Mars Reconnaissance Orbiter spacecraft shows a channel system flowing to the southwest toward the huge Hellas impact basin. We're not sure if this channel-inside-a-channel was carved by flowing water or lava. Flowing water erodes channels, and flowing lava both erodes and melts surrounding rock to form channels. It's not clear whether a huge surge of water or lava first formed the wide channel and then subsided into a trickle to form this narrow, inner channel, or if a trickle formed the inner channel and a subsequent surge formed the wider one. Detailed analysis of the shape could reveal which scenario is most likely, as well as whether water or lava is responsible. Relevant observations for such a determination would include, for example, the facts that the channels lack levees (ridges along the banks) and that the inner channel diverts around a mound, which at one time was an island. This channel system flowed to the southwest toward the huge Hellas impact basin.

  6. Random packing of spheres in Menger sponge.

    PubMed

    Cieśla, Michał; Barbasz, Jakub

    2013-06-07

    Random packing of spheres inside fractal collectors of dimension 2 < d < 3 is studied numerically using Random Sequential Adsorption (RSA) algorithm. The paper focuses mainly on the measurement of random packing saturation limit. Additionally, scaling properties of density autocorrelations in the obtained packing are analyzed. The RSA kinetics coefficients are also measured. Obtained results allow to test phenomenological relation between random packing saturation density and collector dimension. Additionally, performed simulations together with previously obtained results confirm that, in general, the known dimensional relations are obeyed by systems having non-integer dimension, at least for d < 3.

  7. Mechanically Activated Ion Channels.

    PubMed

    Ranade, Sanjeev S; Syeda, Ruhma; Patapoutian, Ardem

    2015-09-23

    Mechanotransduction, the conversion of physical forces into biochemical signals, is essential for various physiological processes such as the conscious sensations of touch and hearing, and the unconscious sensation of blood flow. Mechanically activated (MA) ion channels have been proposed as sensors of physical force, but the identity of these channels and an understanding of how mechanical force is transduced has remained elusive. A number of recent studies on previously known ion channels along with the identification of novel MA ion channels have greatly transformed our understanding of touch and hearing in both vertebrates and invertebrates. Here, we present an updated review of eukaryotic ion channel families that have been implicated in mechanotransduction processes and evaluate the qualifications of the candidate genes according to specified criteria. We then discuss the proposed gating models for MA ion channels and highlight recent structural studies of mechanosensitive potassium channels.

  8. Mechanically Activated Ion Channels

    PubMed Central

    Ranade, Sanjeev S.; Syeda, Ruhma; Patapoutian, Ardem

    2015-01-01

    Mechanotransduction, the conversion of physical forces into biochemical signals, is an essential component of numerous physiological processes including not only conscious senses of touch and hearing, but also unconscious senses such as blood pressure regulation. Mechanically activated (MA) ion channels have been proposed as sensors of physical force, but the identity of these channels and an understanding of how mechanical force is transduced has remained elusive. A number of recent studies on previously known ion channels along with the identification of novel MA ion channels have greatly transformed our understanding of touch and hearing in both vertebrates and invertebrates. Here, we present an updated review of eukaryotic ion channel families that have been implicated in mechanotransduction processes and evaluate the qualifications of the candidate genes according to specified criteria. We then discuss the proposed gating models for MA ion channels and highlight recent structural studies of mechanosensitive potassium channels. PMID:26402601

  9. Single Channel Properties and Regulated Expression of Ca2+ Release-Activated Ca2+ (Crac) Channels in Human T Cells

    PubMed Central

    Fomina, Alla F.; Fanger, Christopher M.; Kozak, J. Ashot; Cahalan, Michael D.

    2000-01-01

    Although the crucial role of Ca2+ influx in lymphocyte activation has been well documented, little is known about the properties or expression levels of Ca2+ channels in normal human T lymphocytes. The use of Na+ as the permeant ion in divalent-free solution permitted Ca2+ release-activated Ca2+ (CRAC) channel activation, kinetic properties, and functional expression levels to be investigated with single channel resolution in resting and phytohemagglutinin (PHA)-activated human T cells. Passive Ca2+ store depletion resulted in the opening of 41-pS CRAC channels characterized by high open probabilities, voltage-dependent block by extracellular Ca2+ in the micromolar range, selective Ca2+ permeation in the millimolar range, and inactivation that depended upon intracellular Mg2+ ions. The number of CRAC channels per cell increased greatly from ∼15 in resting T cells to ∼140 in activated T cells. Treatment with the phorbol ester PMA also increased CRAC channel expression to ∼60 channels per cell, whereas the immunosuppressive drug cyclosporin A (1 μM) suppressed the PHA-induced increase in functional channel expression. Capacitative Ca2+ influx induced by thapsigargin was also significantly enhanced in activated T cells. We conclude that a surprisingly low number of CRAC channels are sufficient to mediate Ca2+ influx in human resting T cells, and that the expression of CRAC channels increases ∼10-fold during activation, resulting in enhanced Ca2+ signaling. PMID:10995447

  10. Kinetic Damage from Meteorites

    NASA Technical Reports Server (NTRS)

    Cooke, William; Brown, Peter; Matney, Mark

    2017-01-01

    A Near Earth object impacting into Earth's atmosphere may produce damaging effects at the surface due to airblast, thermal pulse, or kinetic impact in the form of meteorites. At large sizes (greater than many tens of meters), the damage is amplified by the hypersonic impact of these large projectiles moving with cosmic velocity, leaving explosively produced craters. However, much more common is simple "kinetic" damage caused by the impact of smaller meteorites moving at terminal speeds. As of this date a handful of instances are definitively known of people or structures being directly hit and/or damaged by the kinetic impact of meteorites. Meteorites known to have struck humans include the Sylacauga, Alabama fall (1954) and the Mbale meteorite fall (1992). Much more common is kinetic meteorite damage to cars, buildings, and even a post box (Claxton, Georgia - 1984). Historical accounts indicate that direct kinetic damage by meteorites may be more common than recent accounts suggest (Yau et al., 1994). In this talk we will examine the contemporary meteorite flux and estimate the frequency of kinetic damage to various structures, as well as how the meteorite flux might affect the rate of human casualties. This will update an earlier study by Halliday et al (1985), adding variations expected in meteorite flux with latitude (Le Feuvre and Wieczorek, 2008) and validating these model predictions of speed and entry angle with observations from the NASA and SOMN fireball networks. In particular, we explore the physical characteristics of bright meteors which may be used as a diagnostic for estimating which fireballs produce meteorites and hence how early warning of such kinetic damage may be estimated in advance through observations and modeling.

  11. Kinetic Damage from Meteorites

    NASA Technical Reports Server (NTRS)

    Cooke, William; Brown, Peter; Matney, Mark

    2017-01-01

    A Near Earth object impacting into Earth's atmosphere may produce damaging effects at the surface due to airblast, thermal pulse, or kinetic impact in the form of meteorites. At large sizes (>many tens of meters), the damage is amplified by the hypersonic impact of these large projectiles moving with cosmic velocity, leaving explosively produced craters. However, much more common is simple "kinetic" damage caused by the impact of smaller meteorites moving at terminal speeds. As of this date a handful of instances are definitively known of people or structures being directly hit and/or damaged by the kinetic impact of meteorites. Meteorites known to have struck humans include the Sylacauga, Alabama fall (1954) and the Mbale meteorite fall (1992). Much more common is kinetic meteorite damage to cars, buildings, and even a post box (Claxton, Georgia - 1984). Historical accounts indicate that direct kinetic damage by meteorites may be more common than recent accounts suggest (Yau et al., 1994). In this talk we will examine the contemporary meteorite flux and estimate the frequency of kinetic damage to various structures, as well as how the meteorite flux might affect the rate of human casualties. This will update an earlier study by Halliday et al (1985), adding variations expected in meteorite flux with latitude (Le Feuvre and Wieczorek, 2008) and validating these model predictions of speed and entry angle with observations from the NASA and SOMN fireball networks. In particular, we explore the physical characteristics of bright meteors which may be used as a diagnostic for estimating which fireballs produce meteorites and hence how early warning of such kinetic damage may be estimated in advance through observations and modelling.

  12. Modeling the Influence of Ion Channels on Neuron Dynamics in Drosophila

    PubMed Central

    Berger, Sandra D.; Crook, Sharon M.

    2015-01-01

    Voltage gated ion channels play a major role in determining a neuron's firing behavior, resulting in the specific processing of synaptic input patterns. Drosophila and other invertebrates provide valuable model systems for investigating ion channel kinetics and their impact on firing properties. Despite the increasing importance of Drosophila as a model system, few computational models of its ion channel kinetics have been developed. In this study, experimentally observed biophysical properties of voltage gated ion channels from the fruitfly Drosophila melanogaster are used to develop a minimal, conductance based neuron model. We investigate the impact of the densities of these channels on the excitability of the model neuron. Changing the channel densities reproduces different in situ observed firing patterns and induces a switch from integrator to resonator properties. Further, we analyze the preference to input frequency and how it depends on the channel densities and the resulting bifurcation type the system undergoes. An extension to a three dimensional model demonstrates that the inactivation kinetics of the sodium channels play an important role, allowing for firing patterns with a delayed first spike and subsequent high frequency firing as often observed in invertebrates, without altering the kinetics of the delayed rectifier current. PMID:26635592

  13. Modeling the Influence of Ion Channels on Neuron Dynamics in Drosophila.

    PubMed

    Berger, Sandra D; Crook, Sharon M

    2015-01-01

    Voltage gated ion channels play a major role in determining a neuron's firing behavior, resulting in the specific processing of synaptic input patterns. Drosophila and other invertebrates provide valuable model systems for investigating ion channel kinetics and their impact on firing properties. Despite the increasing importance of Drosophila as a model system, few computational models of its ion channel kinetics have been developed. In this study, experimentally observed biophysical properties of voltage gated ion channels from the fruitfly Drosophila melanogaster are used to develop a minimal, conductance based neuron model. We investigate the impact of the densities of these channels on the excitability of the model neuron. Changing the channel densities reproduces different in situ observed firing patterns and induces a switch from integrator to resonator properties. Further, we analyze the preference to input frequency and how it depends on the channel densities and the resulting bifurcation type the system undergoes. An extension to a three dimensional model demonstrates that the inactivation kinetics of the sodium channels play an important role, allowing for firing patterns with a delayed first spike and subsequent high frequency firing as often observed in invertebrates, without altering the kinetics of the delayed rectifier current.

  14. Quantum steganography with noisy quantum channels

    SciTech Connect

    Shaw, Bilal A.; Brun, Todd A.

    2011-02-15

    Steganography is the technique of hiding secret information by embedding it in a seemingly ''innocent'' message. We present protocols for hiding quantum information by disguising it as noise in a codeword of a quantum error-correcting code. The sender (Alice) swaps quantum information into the codeword and applies a random choice of unitary operation, drawing on a secret random key she shares with the receiver (Bob). Using the key, Bob can retrieve the information, but an eavesdropper (Eve) with the power to monitor the channel, but without the secret key, cannot distinguish the message from channel noise. We consider two types of protocols: one in which the hidden quantum information is stored locally in the codeword, and another in which it is embedded in the space of error syndromes. We analyze how difficult it is for Eve to detect the presence of secret messages, and estimate rates of steganographic communication and secret key consumption for specific protocols and examples of error channels. We consider both the case where there is no actual noise in the channel (so that all errors in the codeword result from the deliberate actions of Alice), and the case where the channel is noisy and not controlled by Alice and Bob.

  15. Quantum steganography with noisy quantum channels

    NASA Astrophysics Data System (ADS)

    Shaw, Bilal A.; Brun, Todd A.

    2011-02-01

    Steganography is the technique of hiding secret information by embedding it in a seemingly “innocent” message. We present protocols for hiding quantum information by disguising it as noise in a codeword of a quantum error-correcting code. The sender (Alice) swaps quantum information into the codeword and applies a random choice of unitary operation, drawing on a secret random key she shares with the receiver (Bob). Using the key, Bob can retrieve the information, but an eavesdropper (Eve) with the power to monitor the channel, but without the secret key, cannot distinguish the message from channel noise. We consider two types of protocols: one in which the hidden quantum information is stored locally in the codeword, and another in which it is embedded in the space of error syndromes. We analyze how difficult it is for Eve to detect the presence of secret messages, and estimate rates of steganographic communication and secret key consumption for specific protocols and examples of error channels. We consider both the case where there is no actual noise in the channel (so that all errors in the codeword result from the deliberate actions of Alice), and the case where the channel is noisy and not controlled by Alice and Bob.

  16. Large fraction of crystal directions leads to ion channeling

    NASA Astrophysics Data System (ADS)

    Nordlund, K.; Djurabekova, F.; Hobler, G.

    2016-12-01

    It is well established that when energetic ions are moving in crystals, they may penetrate much deeper if they happen to be directed in some specific crystal directions. This `channeling' effect is utilized for instance in certain ion beam analysis methods and has been described by analytical theories and atomistic computer simulations. However, there have been very few systematic studies of channeling in directions other than the principal low-index ones. We present here a molecular dynamics-based approach to calculate ion channeling systematically over all crystal directions, providing ion `channeling maps' that easily show in which directions channeling is expected. The results show that channeling effects can be quite significant even at energies below 1 keV, and that in many cases, significant planar channeling occurs also in a wide range of crystal directions between the low-index principal ones. In all of the cases studied, a large fraction (˜20 -60 % ) of all crystal directions show channeling. A practical implication of this is that modern experiments on randomly oriented nanostructures will have a large probability of channeling. It also means that when ion irradiations are carried out on polycrystalline samples, channeling effects on the results cannot a priori be assumed to be negligible. The maps allow for easy selection of good `nonchanneling' directions in experiments or alternatively finding wide channels for beneficial uses of channeling. We implement channeling theory to also give the fraction of channeling directions in a manner directly comparable to the simulations. The comparison shows good qualitative agreement. In particular, channeling theory is very good at predicting which channels are active at a given energy. This is true down to sub-keV energies, provided the penetration depth is not too small.

  17. Multiple alternative substrate kinetics.

    PubMed

    Anderson, Vernon E

    2015-11-01

    The specificity of enzymes for their respective substrates has been a focal point of enzyme kinetics since the initial characterization of metabolic chemistry. Various processes to quantify an enzyme's specificity using kinetics have been utilized over the decades. Fersht's definition of the ratio kcat/Km for two different substrates as the "specificity constant" (ref [7]), based on the premise that the important specificity existed when the substrates were competing in the same reaction, has become a consensus standard for enzymes obeying Michaelis-Menten kinetics. The expansion of the theory for the determination of the relative specificity constants for a very large number of competing substrates, e.g. those present in a combinatorial library, in a single reaction mixture has been developed in this contribution. The ratio of kcat/Km for isotopologs has also become a standard in mechanistic enzymology where kinetic isotope effects have been measured by the development of internal competition experiments with extreme precision. This contribution extends the theory of kinetic isotope effects to internal competition between three isotopologs present at non-tracer concentrations in the same reaction mix. This article is part of a special issue titled: Enzyme Transition States from Theory and Experiment. Published by Elsevier B.V.

  18. Fading channel simulator

    DOEpatents

    Argo, Paul E.; Fitzgerald, T. Joseph

    1993-01-01

    Fading channel effects on a transmitted communication signal are simulated with both frequency and time variations using a channel scattering function to affect the transmitted signal. A conventional channel scattering function is converted to a series of channel realizations by multiplying the square root of the channel scattering function by a complex number of which the real and imaginary parts are each independent variables. The two-dimensional inverse-FFT of this complex-valued channel realization yields a matrix of channel coefficients that provide a complete frequency-time description of the channel. The transmitted radio signal is segmented to provide a series of transmitted signal and each segment is subject to FFT to generate a series of signal coefficient matrices. The channel coefficient matrices and signal coefficient matrices are then multiplied and subjected to inverse-FFT to output a signal representing the received affected radio signal. A variety of channel scattering functions can be used to characterize the response of a transmitter-receiver system to such atmospheric effects.

  19. Cholesterol and Kir channels

    PubMed Central

    Levitan, Irena

    2009-01-01

    To date, most of the major types of Kir channels, Kir2s, Kir3s, Kir4s and Kir6s, have been found to partition into cholesterol-rich membrane domains and/or to be regulated by changes in the level of membrane cholesterol. Surprisingly, however, in spite of the structural similarities between different Kirs, effects of cholesterol on different types of Kir channels vary from cholesterol-induced decrease in the current density (Kir2 channels) to the loss of channel activity by cholesterol depletion (Kir4 channels) and loss of channel coupling by different mediators (Kir3 and Kir6 channels). Recently, we have gained initial insights into the mechanisms responsible for cholesterol-induced suppression Kir2 channels, but mechanisms underlying cholesterol sensitivity of other Kir channels are mostly unknown. The goal of this review is to present a summary of the current knowledge of the distinct effects of cholesterol on different types of Kir channels in vitro and in vivo. PMID:19548316

  20. Calcium Channels in Planar Lipid Bilayers: Insights into Mechanisms of Ion Permeation and Gating

    NASA Astrophysics Data System (ADS)

    Rosenberg, Robert L.; Hess, Peter; Reeves, John P.; Smilowitz, Henry; Tsien, Richard W.

    1986-03-01

    Electrophysiological recordings were used to analyze single calcium channels in planar lipid bilayers after membranes from bovine cardiac sarcolemmal vesicles had been incorporated into the bilayer. In these cell-free conditions, channels in the bilayer showed unitary barium or calcium conductances, gating kinetics, and pharmacological responses that were similar to dihydropyridine-sensitive calcium channels in intact cells. The open channel current varied in a nonlinear manner with voltage under asymmetric (that is, physiological) ionic conditions. However, with identical solutions on both sides of the bilayer, the current-voltage relation was linear. In matched experiments, calcium channels from skeletal muscle T-tubules differed significantly from cardiac calcium channels in their conductance properties and gating kinetics.

  1. Safety and Efficacy of a Topical Sodium Channel Inhibitor (TV-45070) in Patients With Postherpetic Neuralgia (PHN): A Randomized, Controlled, Proof-of-Concept, Crossover Study, With a Subgroup Analysis of the Nav1.7 R1150W Genotype.

    PubMed

    Price, Nicola; Namdari, Rostam; Neville, Judith; Proctor, Katie J W; Kaber, Samer; Vest, Jeffery; Fetell, Michael; Malamut, Richard; Sherrington, Robin P; Pimstone, Simon N; Goldberg, Yigal P

    2017-04-01

    The objective was to evaluate the safety and efficacy of TV-45070 ointment, as a treatment for postherpetic neuralgia, and to explore the response in patients with the Nav1.7 R1150W gain-of-function polymorphism. This was a randomized, placebo-controlled, 2-period, 2-treatment crossover trial. Patients with postherpetic neuralgia with moderate or greater pain received TV-45070 and placebo ointments, each applied twice daily for 3 weeks. The primary efficacy measure was the difference in change in mean daily pain score from baseline compared with the last week of placebo and active treatment. Secondary endpoints included responder rate analyses and a further exploratory analysis of response in carriers of the Nav1.7 R1150W polymorphism was conducted. Seventy patients were enrolled and 54 completed the study. TV-45070 was safe and well tolerated. No statistical difference was observed between treatments for the primary endpoint. However, the proportion of patients with ≥50% reduction in mean pain scores at week 3 was greater on TV-45070 than on placebo (26.8% vs. 10.7%, P=0.0039). Similarly, a greater proportion of patients on TV-45070 had a ≥30% reduction in mean pain scores at week 3 (39.3% on TV-45070 vs. 23.2% on placebo, P=0.0784). Of note, 63% of patients with the R1150W polymorphism versus 35% of wild-type carriers had a ≥30% reduction in mean pain score on TV-45070 at week 3 (no inferential analysis performed). The 50% responder analysis suggests a subpopulation may exist with a more marked analgesic response to TV-45070.The trend toward a larger proportion of responders within Nav1.7 R1150W carriers warrants further investigation.

  2. Quantum circuit design for accurate simulation of qudit channels

    NASA Astrophysics Data System (ADS)

    Wang, Dong-Sheng; Sanders, Barry C.

    2015-04-01

    We construct a classical algorithm that designs quantum circuits for algorithmic quantum simulation of arbitrary qudit channels on fault-tolerant quantum computers within a pre-specified error tolerance with respect to diamond-norm distance. The classical algorithm is constructed by decomposing a quantum channel into a convex combination of generalized extreme channels by convex optimization of a set of nonlinear coupled algebraïc equations. The resultant circuit is a randomly chosen generalized extreme channel circuit whose run-time is logarithmic with respect to the error tolerance and quadratic with respect to Hilbert space dimension, which requires only a single ancillary qudit plus classical dits.

  3. Generalized random sequential adsorption

    NASA Astrophysics Data System (ADS)

    Tarjus, G.; Schaaf, P.; Talbot, J.

    1990-12-01

    Adsorption of hard spherical particles onto a flat uniform surface is analyzed by using generalized random sequential adsorption (RSA) models. These models are defined by releasing the condition of immobility present in the usual RSA rules to allow for desorption or surface diffusion. Contrary to the simple RSA case, generalized RSA processes are no longer irreversible and the system formed by the adsorbed particles on the surface may reach an equilibrium state. We show by using a distribution function approach that the kinetics of such processes can be described by means of an exact infinite hierarchy of equations reminiscent of the Kirkwood-Salsburg hierarchy for systems at equilibrium. We illustrate the way in which the systems produced by adsorption/desorption and by adsorption/diffusion evolve between the two limits represented by ``simple RSA'' and ``equilibrium'' by considering approximate solutions in terms of truncated density expansions.

  4. Robust vector quantization for noisy channels

    NASA Technical Reports Server (NTRS)

    Demarca, J. R. B.; Farvardin, N.; Jayant, N. S.; Shoham, Y.

    1988-01-01

    The paper briefly discusses techniques for making vector quantizers more tolerant to tranmsission errors. Two algorithms are presented for obtaining an efficient binary word assignment to the vector quantizer codewords without increasing the transmission rate. It is shown that about 4.5 dB gain over random assignment can be achieved with these algorithms. It is also proposed to reduce the effects of error propagation in vector-predictive quantizers by appropriately constraining the response of the predictive loop. The constrained system is shown to have about 4 dB of SNR gain over an unconstrained system in a noisy channel, with a small loss of clean-channel performance.

  5. Erbium hydride decomposition kinetics.

    SciTech Connect

    Ferrizz, Robert Matthew

    2006-11-01

    Thermal desorption spectroscopy (TDS) is used to study the decomposition kinetics of erbium hydride thin films. The TDS results presented in this report are analyzed quantitatively using Redhead's method to yield kinetic parameters (E{sub A} {approx} 54.2 kcal/mol), which are then utilized to predict hydrogen outgassing in vacuum for a variety of thermal treatments. Interestingly, it was found that the activation energy for desorption can vary by more than 7 kcal/mol (0.30 eV) for seemingly similar samples. In addition, small amounts of less-stable hydrogen were observed for all erbium dihydride films. A detailed explanation of several approaches for analyzing thermal desorption spectra to obtain kinetic information is included as an appendix.

  6. Relativistic Chiral Kinetic Theory

    NASA Astrophysics Data System (ADS)

    Stephanov, Mikhail

    2016-12-01

    This very brief review of the recent progress in chiral kinetic theory is based on the results of Refs. [J.-Y. Chen, D. T. Son, M. A. Stephanov, H.-U. Yee, Y. Yin, Lorentz Invariance in Chiral Kinetic Theory, Phys. Rev. Lett. 113 (18) (2014) 182302. doi:10.1103/PhysRevLett.113.182302; J.-Y. Chen, D. T. Son, M. A. Stephanov, Collisions in Chiral Kinetic Theory, Phys. Rev. Lett. 115 (2) (2015) 021601. doi: 10.1103/PhysRevLett.115.021601; M. A. Stephanov, H.-U. Yee, The no-drag frame for anomalous chiral fluid, Phys. Rev. Lett. 116 (12) (2016) 122302. doi: 10.1103/PhysRevLett.116.122302].

  7. R type anion channel

    PubMed Central

    Diatloff, Eugene; Peyronnet, Rémi; Colcombet, Jean; Thomine, Sébastien; Barbier-Brygoo, Hélène

    2010-01-01

    Plant genomes code for channels involved in the transport of cations, anions and uncharged molecules through membranes. Although the molecular identity of channels for cations and uncharged molecules has progressed rapidly in the recent years, the molecular identity of anion channels has lagged behind. Electrophysiological studies have identified S-type (slow) and R-type (rapid) anion channels. In this brief review, we summarize the proposed functions of the R-type anion channels which, like the S-type, were first characterized by electrophysiology over 20 years ago, but unlike the S-type, have still yet to be cloned. We show that the R-type channel can play multiple roles. PMID:21051946

  8. Introduction to sodium channels.

    PubMed

    Peters, Colin H; Ruben, Peter C

    2014-01-01

    Voltage-gated sodium channels (VGSCs) are present in many tissue types within the human body including both cardiac and neuronal tissues. Like other channels, VGSCs activate, deactivate, and inactivate in response to changes in membrane potential. VGSCs also have a similar structure to other channels: 24 transmembrane segments arranged into four domains that surround a central pore. The structure and electrical activity of these channels allows them to create and respond to electrical signals in the body. Because of their distribution throughout the body, VGSCs are implicated in a variety of diseases including epilepsy, cardiac arrhythmias, and neuropathic pain. As such the study of these channels is essential. This brief review will introduce sodium channel structure, physiology, and pathophysiology.

  9. Bio-inspired voltage-dependent calcium channel blockers.

    PubMed

    Yang, Tingting; He, Lin-Ling; Chen, Ming; Fang, Kun; Colecraft, Henry M

    2013-01-01

    Ca(2+) influx via voltage-dependent CaV1/CaV2 channels couples electrical signals to biological responses in excitable cells. CaV1/CaV2 channel blockers have broad biotechnological and therapeutic applications. Here we report a general method for developing novel genetically encoded calcium channel blockers inspired by Rem, a small G-protein that constitutively inhibits CaV1/CaV2 channels. We show that diverse cytosolic proteins (CaVβ, 14-3-3, calmodulin and CaMKII) that bind pore-forming α1-subunits can be converted into calcium channel blockers with tunable selectivity, kinetics and potency, simply by anchoring them to the plasma membrane. We term this method 'channel inactivation induced by membrane-tethering of an associated protein' (ChIMP). ChIMP is potentially extendable to small-molecule drug discovery, as engineering FK506-binding protein into intracellular sites within CaV1.2-α1C permits heterodimerization-initiated channel inhibition with rapamycin. The results reveal a universal method for developing novel calcium channel blockers that may be extended to develop probes for a broad cohort of unrelated ion channels.

  10. Relativistic Kinetic Theory

    NASA Astrophysics Data System (ADS)

    Vereshchagin, Gregory V.; Aksenov, Alexey G.

    2017-02-01

    Preface; Acknowledgements; Acronyms and definitions; Introduction; Part I. Theoretical Foundations: 1. Basic concepts; 2. Kinetic equation; 3. Averaging; 4. Conservation laws and equilibrium; 5. Relativistic BBGKY hierarchy; 6. Basic parameters in gases and plasmas; Part II. Numerical Methods: 7. The basics of computational physics; 8. Direct integration of Boltzmann equations; 9. Multidimensional hydrodynamics; Part III. Applications: 10. Wave dispersion in relativistic plasma; 11. Thermalization in relativistic plasma; 12. Kinetics of particles in strong fields; 13. Compton scattering in astrophysics and cosmology; 14. Self-gravitating systems; 15. Neutrinos, gravitational collapse and supernovae; Appendices; Bibliography; Index.

  11. Modular kinetic analysis.

    PubMed

    Krab, Klaas

    2011-01-01

    Modularization is an important strategy to tackle the study of complex biological systems. Modular kinetic analysis (MKA) is a quantitative method to extract kinetic information from such a modularized system that can be used to determine the control and regulatory structure of the system, and to pinpoint and quantify the interaction of effectors with the system. The principles of the method are described, and the relation with metabolic control analysis is discussed. Examples of application of MKA are given. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. qPIPSA: Relating enzymatic kinetic parameters and interaction fields

    PubMed Central

    Gabdoulline, Razif R; Stein, Matthias; Wade, Rebecca C

    2007-01-01

    Background The simulation of metabolic networks in quantitative systems biology requires the assignment of enzymatic kinetic parameters. Experimentally determined values are often not available and therefore computational methods to estimate these parameters are needed. It is possible to use the three-dimensional structure of an enzyme to perform simulations of a reaction and derive kinetic parameters. However, this is computationally demanding and requires detailed knowledge of the enzyme mechanism. We have therefore sought to develop a general, simple and computationally efficient procedure to relate protein structural information to enzymatic kinetic parameters that allows consistency between the kinetic and structural information to be checked and estimation of kinetic constants for structurally and mechanistically similar enzymes. Results We describe qPIPSA: quantitative Protein Interaction Property Similarity Analysis. In this analysis, molecular interaction fields, for example, electrostatic potentials, are computed from the enzyme structures. Differences in molecular interaction fields between enzymes are then related to the ratios of their kinetic parameters. This procedure can be used to estimate unknown kinetic parameters when enzyme structural information is available and kinetic parameters have been measured for related enzymes or were obtained under different conditions. The detailed interaction of the enzyme with substrate or cofactors is not modeled and is assumed to be similar for all the proteins compared. The protein structure modeling protocol employed ensures that differences between models reflect genuine differences between the protein sequences, rather than random fluctuations in protein structure. Conclusion Provided that the experimental conditions and the protein structural models refer to the same protein state or conformation, correlations between interaction fields and kinetic parameters can be established for sets of related enzymes

  13. HIPPI and Fibre Channel

    SciTech Connect

    Tolmie, D.E.

    1992-01-01

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

  14. Two spatial light modulator system for laboratory simulation of random beam propagation in random media.

    PubMed

    Wang, Fei; Toselli, Italo; Korotkova, Olga

    2016-02-10

    An optical system consisting of a laser source and two independent consecutive phase-only spatial light modulators (SLMs) is shown to accurately simulate a generated random beam (first SLM) after interaction with a stationary random medium (second SLM). To illustrate the range of possibilities, a recently introduced class of random optical frames is examined on propagation in free space and several weak turbulent channels with Kolmogorov and non-Kolmogorov statistics.

  15. Random Vibrations

    NASA Technical Reports Server (NTRS)

    Messaro. Semma; Harrison, Phillip

    2010-01-01

    Ares I Zonal Random vibration environments due to acoustic impingement and combustion processes are develop for liftoff, ascent and reentry. Random Vibration test criteria for Ares I Upper Stage pyrotechnic components are developed by enveloping the applicable zonal environments where each component is located. Random vibration tests will be conducted to assure that these components will survive and function appropriately after exposure to the expected vibration environments. Methodology: Random Vibration test criteria for Ares I Upper Stage pyrotechnic components were desired that would envelope all the applicable environments where each component was located. Applicable Ares I Vehicle drawings and design information needed to be assessed to determine the location(s) for each component on the Ares I Upper Stage. Design and test criteria needed to be developed by plotting and enveloping the applicable environments using Microsoft Excel Spreadsheet Software and documenting them in a report Using Microsoft Word Processing Software. Conclusion: Random vibration liftoff, ascent, and green run design & test criteria for the Upper Stage Pyrotechnic Components were developed by using Microsoft Excel to envelope zonal environments applicable to each component. Results were transferred from Excel into a report using Microsoft Word. After the report is reviewed and edited by my mentor it will be submitted for publication as an attachment to a memorandum. Pyrotechnic component designers will extract criteria from my report for incorporation into the design and test specifications for components. Eventually the hardware will be tested to the environments I developed to assure that the components will survive and function appropriately after exposure to the expected vibration environments.

  16. Calcium Channel Blockers

    MedlinePlus

    ... calcium channel blockers interact with grapefruit products. References Kaplan NM, et al. Treatment of hypertension: Drug therapy. In: Kaplan's Clinical Hypertension. 11th ed. Philadelphia, Pa.: Wolters Kluwer ...

  17. Switchable topological phonon channels

    NASA Astrophysics Data System (ADS)

    Süsstrunk, Roman; Zimmermann, Philipp; Huber, Sebastian D.

    2017-01-01

    Guiding energy deliberately is one of the central elements in engineering and information processing. It is often achieved by designing specific transport channels in a suitable material. Topological metamaterials offer a way to construct stable and efficient channels of unprecedented versatility. However, due to their stability it can be tricky to terminate them or to temporarily shut them off without changing the material properties massively. While a lot of effort was put into realizing mechanical topological metamaterials, almost no works deal with manipulating their edge channels in sight of applications. Here, we take a step in this direction, by taking advantage of local symmetry breaking potentials to build a switchable topological phonon channel.

  18. Selfcomplementary Quantum Channels

    NASA Astrophysics Data System (ADS)

    Smaczyński, Marek; Roga, Wojciech; Życzkowski, Karol

    2016-10-01

    Selfcomplementary quantum channels are characterized by such an interaction between the principal quantum system and the environment that leads to the same output states of both interacting systems. These maps can describe approximate quantum copy machines, as perfect copying of an unknown quantum state is not possible due to the celebrated no-cloning theorem. We provide here a parametrization of a large class of selfcomplementary channels and analyze their properties. Selfcomplementary channels preserve some residual coherences and residual entanglement. Investigating some measures of non-Markovianity, we show that time evolution under selfcomplementary channels is highly non-Markovian.

  19. Faster voltage-dependent activation of Na+ channels in growth cones versus somata of neuroblastoma N1E-115 cells.

    PubMed Central

    Zhang, J; Loew, L M; Davidson, R M

    1996-01-01

    Kinetics of voltage-gated ionic channels fundamentally reflect the response of the channels to local electric fields. In this report cell-attached patch-clamp studies reveal that the voltage-dependent activation rate of sodium channels residing in the growth cone membrane differs from that of soma sodium channels in differentiating N1E-115 neuroblastoma cells. Because other electrophysiological properties of these channels do not differ, this finding may be a reflection of the difference in intramembrane electric field in these two regions of the cell. This represents a new mechanism for channels to attain a range of activities both within and between cells. PMID:8913589

  20. Caged Naloxone Reveals Opioid Signaling Deactivation Kinetics

    PubMed Central

    Banghart, Matthew R.; Shah, Ruchir C.; Lavis, Luke D.

    2013-01-01

    The spatiotemporal dynamics of opioid signaling in the brain remain poorly defined. Photoactivatable opioid ligands provide a means to quantitatively measure these dynamics and their underlying mechanisms in brain tissue. Although activation kinetics can be assessed using caged agonists, deactivation kinetics are obscured by slow clearance of agonist in tissue. To reveal deactivation kinetics of opioid signaling we developed a caged competitive antagonist that can be quickly photoreleased in sufficient concentrations to render agonist dissociation effectively irreversible. Carboxynitroveratryl-naloxone (CNV-NLX), a caged analog of the competitive opioid antagonist NLX, was readily synthesized from commercially available NLX in good yield and found to be devoid of antagonist activity at heterologously expressed opioid receptors. Photolysis in slices of rat locus coeruleus produced a rapid inhibition of the ionic currents evoked by multiple agonists of the μ-opioid receptor (MOR), but not of α-adrenergic receptors, which activate the same pool of ion channels. Using the high-affinity peptide agonist dermorphin, we established conditions under which light-driven deactivation rates are independent of agonist concentration and thus intrinsic to the agonist-receptor complex. Under these conditions, some MOR agonists yielded deactivation rates that are limited by G protein signaling, whereas others appeared limited by agonist dissociation. Therefore, the choice of agonist determines which feature of receptor signaling is unmasked by CNV-NLX photolysis. PMID:23960100

  1. A linearization of quantum channels

    NASA Astrophysics Data System (ADS)

    Crowder, Tanner

    2015-06-01

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

  2. Visual alchemy: stereoscopic adaptation produces kinetic depth from random noise.

    PubMed

    Nawrot, M; Blake, R

    1993-01-01

    Observers perceive incoherent motion and no hint of depth when viewing stochastic motion, in which stimulus elements move in all possible directions. As earlier work has shown, depth can be specified by introducing a brief interocular delay between the presentation of corresponding animation frames of this 'noise' to the left and right eyes. A study is reported in which observers were adapted to a stereoscopic display consisting of coherent planes of motion at different depths. This stereoscopic adaptation caused incoherent depthless motion to take on the qualities of structure and depth, and it could nullify the depth induced by interocular delay. The findings are interpreted within the context of a neural model consisting of units selectively responsive to different directions of motion at different planes of depth.

  3. Kinetic studies on muscle glycogen synthase.

    PubMed

    Salsas, E; Larner, J

    1975-05-10

    Using the I form of rabbit muscle glycogen synthase essentially free of glycogen, the kinetics and mechanism of action was investigated. No evidence for an exchange between [14C]UDP and UDP-glucose was found. The bisubstrate kinetics of the enzyme for UDP-glucose and glycogen, as well as for UDP-glucose and maltose, was determined. An intersecting pattern in the double reciprocal plot (velocity versus substrate concentration) suggestive of a sequential mechanism (ordered or random) was found in all cases. The K-m for UDP-glucose (45 to 48 mM) was the same with either maltose or glycogen as acceptor. The K-m for maltose (230 mM) and for glycogen (1.5 mug/ml) differed.

  4. Kinetics and Catalysis Demonstrations.

    ERIC Educational Resources Information Center

    Falconer, John L.; Britten, Jerald A.

    1984-01-01

    Eleven videotaped kinetics and catalysis demonstrations are described. Demonstrations include the clock reaction, oscillating reaction, hydrogen oxidation in air, hydrogen-oxygen explosion, acid-base properties of solids, high- and low-temperature zeolite reactivity, copper catalysis of ammonia oxidation and sodium peroxide decomposition, ammonia…

  5. Kinetic tetrazolium microtiter assay

    NASA Technical Reports Server (NTRS)

    Pierson, Duane L. (Inventor); Stowe, Raymond P. (Inventor); Koeing, David W. (Inventor)

    1992-01-01

    A method for conducting an in vitro cell assay using a tetrazolium indicator is disclosed. The indicator includes a nonionic detergent which solubilizes a tetrazolium reduction product in vitro and has low toxicity for the cells. The incubation of test cells in the presence of zolium bromide and octoxynol (TRITON X-100) permits kinetics of the cell metabolism to be determined.

  6. Radiation damage annealing kinetics

    NASA Technical Reports Server (NTRS)

    Dresselhaus, M. S.

    1971-01-01

    Various spectral response studies are reported that assess lithium doping effects on the recovery process of electron damaged silicon solar cells. Measurements of both the minority carrier lifetimes and the energy level spectrum of the defects are used to predict lifetime damage constants and carrier removal rates relevant to the operation of the solar lithium-doped cell and its annealing kinetics.

  7. Kinetics and Catalysis Demonstrations.

    ERIC Educational Resources Information Center

    Falconer, John L.; Britten, Jerald A.

    1984-01-01

    Eleven videotaped kinetics and catalysis demonstrations are described. Demonstrations include the clock reaction, oscillating reaction, hydrogen oxidation in air, hydrogen-oxygen explosion, acid-base properties of solids, high- and low-temperature zeolite reactivity, copper catalysis of ammonia oxidation and sodium peroxide decomposition, ammonia…

  8. Applications of kinetic theory

    SciTech Connect

    Gidaspow, D.

    1992-01-01

    The overall objective of this investigation is to develop experimentally verified models for circulating fluidized bed (CFB) combustors. This report presents the author's derivation of analytical solutions useful in understanding the operation of a CFB. The report is in a form of a chapter that reviews the kinetic theory applications.

  9. Oxidative desulfurization: kinetic modelling.

    PubMed

    Dhir, S; Uppaluri, R; Purkait, M K

    2009-01-30

    Increasing environmental legislations coupled with enhanced production of petroleum products demand, the deployment of novel technologies to remove organic sulfur efficiently. This work represents the kinetic modeling of ODS using H(2)O(2) over tungsten-containing layered double hydroxide (LDH) using the experimental data provided by Hulea et al. [V. Hulea, A.L. Maciuca, F. Fajula, E. Dumitriu, Catalytic oxidation of thiophenes and thioethers with hydrogen peroxide in the presence of W-containing layered double hydroxides, Appl. Catal. A: Gen. 313 (2) (2006) 200-207]. The kinetic modeling approach in this work initially targets the scope of the generation of a superstructure of micro-kinetic reaction schemes and models assuming Langmuir-Hinshelwood (LH) and Eley-Rideal (ER) mechanisms. Subsequently, the screening and selection of above models is initially based on profile-based elimination of incompetent schemes followed by non-linear regression search performed using the Levenberg-Marquardt algorithm (LMA) for the chosen models. The above analysis inferred that Eley-Rideal mechanism describes the kinetic behavior of ODS process using tungsten-containing LDH, with adsorption of reactant and intermediate product only taking place on the catalyst surface. Finally, an economic index is presented that scopes the economic aspects of the novel catalytic technology with the parameters obtained during regression analysis to conclude that the cost factor for the catalyst is 0.0062-0.04759 US $ per barrel.

  10. Mechanism of gating of T-type calcium channels

    PubMed Central

    1990-01-01

    We have analyzed the gating kinetics of T-type Ca channels in 3T3 fibroblasts. Our results show that channel closing, inactivation, and recovery from inactivation each include a voltage-independent step which becomes rate limiting at extreme potentials. The data require a cyclic model with a minimum of two closed, one open, and two inactivated states. Such a model can produce good fits to our data even if the transitions between closed states are the only voltage-dependent steps in the activating pathway leading from closed to inactivated states. Our analysis suggests that the channel inactivation step, as well as the direct opening and closing transitions, are not intrinsically voltage sensitive. Single-channel recordings are consistent with this scheme. As expected, each channel produces a single burst per opening and then inactivates. Comparison of the kinetics of T-type Ca current in fibroblasts and neuronal cells reveals significant differences which suggest that different subtypes of T-type Ca channels are expressed differentially in a tissue specific manner. PMID:2172443

  11. Claudin-2-dependent paracellular channels are dynamically gated

    PubMed Central

    Weber, Christopher R; Liang, Guo Hua; Wang, Yitang; Das, Sudipto; Shen, Le; Yu, Alan S L; Nelson, Deborah J; Turner, Jerrold R

    2015-01-01

    Intercellular tight junctions form selectively permeable barriers that seal the paracellular space. Trans-tight junction flux has been measured across large epithelial surfaces, but conductance across individual channels has never been measured. We report a novel trans-tight junction patch clamp technique that detects flux across individual claudin-2 channels within the tight junction of cultured canine renal tubule or human intestinal epithelial monolayers. In both cells, claudin-2 channels display conductances of ~90 pS. The channels are gated, strictly dependent on claudin-2 expression, and display size- and charge-selectivity typical of claudin-2. Kinetic analyses indicate one open and two distinct closed states. Conductance is symmetrical and reversible, characteristic of a passive, paracellular process, and blocked by reduced temperature or site-directed mutagenesis and chemical derivatization of the claudin-2 pore. We conclude that claudin-2 forms gated paracellular channels and speculate that modulation of tight junction channel gating kinetics may be an unappreciated mechanism of barrier regulation. DOI: http://dx.doi.org/10.7554/eLife.09906.001 PMID:26568313

  12. Surfaces and boundaries in the mechanosensitive channel gating

    NASA Astrophysics Data System (ADS)

    Sukharev, Sergei

    2009-03-01

    Mechanosensitive (MS) channels are gated by tension transmitted through the surrounding lipid bilayer. Inorganic ions or amphipathic modifiers that interact with the bilayer surface alter the packing of lipids and perturb the lateral pressure. We describe the effects of lanthanide ions, fluorinated alcohols and esters of parabenzoic acid as potent modifiers of MS channel gating. The other boundary that plays a critical role in channel gating is the water-vapor interface resulting from capillary dewetting of the hydrophobic gate. Molecular simulations predict two alternate positions for this boundary in the pore of the mechanosensitive channel MscS. We approached this problem experimentally by hydrophilizing the outer segment of the pore to resolve if it is `dry' in the closed state. We observed a reduction in activating tension, substantial changes in MscS kinetics and complete removal of gating hysteresis. The kinetic treatment of channel traces recorded in response to steps of tension suggested the sequence of events that leads to the channel opening implying that pore hydration and dewetting are the rate-limiting steps in MscS transitions.

  13. Basaltic Lava Channels

    NASA Astrophysics Data System (ADS)

    Cashman, K. V.; Griffiths, R. W.; Kerr, R. C.

    2004-12-01

    In Hawaii, the mode of lava transport - through open channels or through insulating lava tubes - determines the thermal, rheological, and emplacement history of a lava flow. Most Hawaiian lavas are erupted at near-liquidus temperatures and are therefore crystal-poor; lava transport through open channels allows rapid cooling and consequent rapid increases in lava crystallinity. Solidified aa flows resulting from channelized flow are typically fine-grained throughout their thickness, indicating cooling of the entire flow thickness during transport. In contrast, transport of lava through insulating tubes permits flow over long distances with little cooling. Flows emerging from such tubes typically have pahoehoe flow surfaces with glassy crusts. Groundmass textures that coarsen from the flow rind to the interior reflect rates of post-emplacement, rather than syn-emplacement, cooling. To distinguish eruption conditions that result in lava channels from those that allow formation of lava tubes, we have performed a series of laboratory experiments involving injection of PEG 600 (a wax with a Newtonian rheology and freezing temperature of 19ºC) into cold water through both uniform and non-uniform sloping channels. In uniform channels, tube formation can be distinguished from open channel flow using a dimensionless parameter based on a solidification time scale, an advection time scale, and a Rayleigh number that describes convection by heat loss from crust-free shear zones. Theoretical analysis predicts that in the open channel regime, the width of the crust (dc) will vary with the channel width (W) as dc = W5/3. Crustal coverage of non-uniform channels in both laboratory experiments and field examples from Kilauea Volcano, Hawaii, is consistent with this prediction. However, experiments in non-uniform channels illustrate additional controls on the surface coverage of lava channels. Most important is crustal extension resulting from flow acceleration through constrictions

  14. Adaptive evolution of voltage-gated sodium channels: the first 800 million years.

    PubMed

    Zakon, Harold H

    2012-06-26

    Voltage-gated Na(+)-permeable (Nav) channels form the basis for electrical excitability in animals. Nav channels evolved from Ca(2+) channels and were present in the common ancestor of choanoflagellates and animals, although this channel was likely permeable to both Na(+) and Ca(2+). Thus, like many other neuronal channels and receptors, Nav channels predated neurons. Invertebrates possess two Nav channels (Nav1 and Nav2), whereas vertebrate Nav channels are of the Nav1 family. Approximately 500 Mya in early chordates Nav channels evolved a motif that allowed them to cluster at axon initial segments, 50 million years later with the evolution of myelin, Nav channels "capitalized" on this property and clustered at nodes of Ranvier. The enhancement of conduction velocity along with the evolution of jaws likely made early gnathostomes fierce predators and the dominant vertebrates in the ocean. Later in vertebrate evolution, the Nav channel gene family expanded in parallel in tetrapods and teleosts (∼9 to 10 genes in amniotes, 8 in teleosts). This expansion occurred during or after the late Devonian extinction, when teleosts and tetrapods each diversified in their respective habitats, and coincided with an increase in the number of telencephalic nuclei in both groups. The expansion of Nav channels may have allowed for more sophisticated neural computation and tailoring of Nav channel kinetics with potassium channel kinetics to enhance energy savings. Nav channels show adaptive sequence evolution for increasing diversity in communication signals (electric fish), in protection against lethal Nav channel toxins (snakes, newts, pufferfish, insects), and in specialized habitats (naked mole rats).

  15. Adaptive evolution of voltage-gated sodium channels: The first 800 million years

    PubMed Central

    Zakon, Harold H.

    2012-01-01

    Voltage-gated Na+-permeable (Nav) channels form the basis for electrical excitability in animals. Nav channels evolved from Ca2+ channels and were present in the common ancestor of choanoflagellates and animals, although this channel was likely permeable to both Na+ and Ca2+. Thus, like many other neuronal channels and receptors, Nav channels predated neurons. Invertebrates possess two Nav channels (Nav1 and Nav2), whereas vertebrate Nav channels are of the Nav1 family. Approximately 500 Mya in early chordates Nav channels evolved a motif that allowed them to cluster at axon initial segments, 50 million years later with the evolution of myelin, Nav channels “capitalized” on this property and clustered at nodes of Ranvier. The enhancement of conduction velocity along with the evolution of jaws likely made early gnathostomes fierce predators and the dominant vertebrates in the ocean. Later in vertebrate evolution, the Nav channel gene family expanded in parallel in tetrapods and teleosts (∼9 to 10 genes in amniotes, 8 in teleosts). This expansion occurred during or after the late Devonian extinction, when teleosts and tetrapods each diversified in their respective habitats, and coincided with an increase in the number of telencephalic nuclei in both groups. The expansion of Nav channels may have allowed for more sophisticated neural computation and tailoring of Nav channel kinetics with potassium channel kinetics to enhance energy savings. Nav channels show adaptive sequence evolution for increasing diversity in communication signals (electric fish), in protection against lethal Nav channel toxins (snakes, newts, pufferfish, insects), and in specialized habitats (naked mole rats). PMID:22723361

  16. Fractional randomness

    NASA Astrophysics Data System (ADS)

    Tapiero, Charles S.; Vallois, Pierre

    2016-11-01

    The premise of this paper is that a fractional probability distribution is based on fractional operators and the fractional (Hurst) index used that alters the classical setting of random variables. For example, a random variable defined by its density function might not have a fractional density function defined in its conventional sense. Practically, it implies that a distribution's granularity defined by a fractional kernel may have properties that differ due to the fractional index used and the fractional calculus applied to define it. The purpose of this paper is to consider an application of fractional calculus to define the fractional density function of a random variable. In addition, we provide and prove a number of results, defining the functional forms of these distributions as well as their existence. In particular, we define fractional probability distributions for increasing and decreasing functions that are right continuous. Examples are used to motivate the usefulness of a statistical approach to fractional calculus and its application to economic and financial problems. In conclusion, this paper is a preliminary attempt to construct statistical fractional models. Due to the breadth and the extent of such problems, this paper may be considered as an initial attempt to do so.

  17. Ion channels in microbes

    PubMed Central

    Martinac, Boris; Saimi, Yoshiro; Kung, Ching

    2008-01-01

    Summary Studies of ion channels have for long been dominated by the animalcentric, if not anthropocentric view of physiology. The structures and activities of ion channels had, however, evolved long before the appearance of complex multicellular organisms on Earth. The diversity of ion channels existing in cellular membranes of prokaryotes is a good example. Though at first it may appear as a paradox that most of what we know about the structure of eukaryotic ion channels is based on the structure of bacterial channels, this should not be surprising given the evolutionary relatedness of all living organisms and suitability of microbial cells for structural studies of biological macromolecules in a laboratory environment. Genome sequences of the human as well as various microbial, plant and animal organisms unambiguously established the evolutionary links, whereas crystallographic studies of the structures of major types of ion channels published over the last decade clearly demonstrated the advantage of using microbes as experimental organisms. The purpose of this review is not only to provide an account of acquired knowledge on microbial ion channels but also to show that the study of microbes and their ion channels may also hold a key to solving unresolved molecular mysteries in the future. PMID:18923187

  18. Ion channels in microbes.

    PubMed

    Martinac, Boris; Saimi, Yoshiro; Kung, Ching

    2008-10-01

    Studies of ion channels have for long been dominated by the animalcentric, if not anthropocentric, view of physiology. The structures and activities of ion channels had, however, evolved long before the appearance of complex multicellular organisms on earth. The diversity of ion channels existing in cellular membranes of prokaryotes is a good example. Although at first it may appear as a paradox that most of what we know about the structure of eukaryotic ion channels is based on the structure of bacterial channels, this should not be surprising given the evolutionary relatedness of all living organisms and suitability of microbial cells for structural studies of biological macromolecules in a laboratory environment. Genome sequences of the human as well as various microbial, plant, and animal organisms unambiguously established the evolutionary links, whereas crystallographic studies of the structures of major types of ion channels published over the last decade clearly demonstrated the advantage of using microbes as experimental organisms. The purpose of this review is not only to provide an account of acquired knowledge on microbial ion channels but also to show that the study of microbes and their ion channels may also hold a key to solving unresolved molecular mysteries in the future.

  19. TEA- and apamin-resistant KCa channels in guinea-pig myenteric neurons: slow AHP channels

    PubMed Central

    Vogalis, Fivos; Harvey, John R; Furness, John B

    2002-01-01

    The patch-clamp technique was used to record from intact ganglia of the guinea-pig duodenum in order to characterize the K+ channels that underlie the slow afterhyperpolarization (slow AHP) of myenteric neurons. Cell-attached patch recordings from slow AHP-generating (AH) neurons revealed an increased open probability (Po) of TEA-resistant K+ channels following action potentials. The Po increased from < 0.06 before action potentials to 0.33 in the 2 s following action potential firing. The ensemble averaged current had a similar time course to the current underlying the slow AHP. TEA- and apamin-resistant Ca2+-activated K+ (KCa) channels were present in inside-out patches excised from AH neurons. The Po of these channels increased from < 0.03 to approximately 0.5 upon increasing cytoplasmic [Ca2+] from < 10 nm to either 500 nm or 10 μm. Po was insensitive to changes in transpatch potential. The unitary conductance of these TEA- and apamin-resistant KCa channels measured approximately 60 pS under symmetric K+ concentrations between −60 mV and +60 mV, but decreased outside this range. Under asymmetrical [K+], the open channel current showed outward rectification and had a limiting slope conductance of about 40 pS. Activation of the TEA- and apamin-resistant KCa channels by internal Ca2+ in excised patches was not reversed by washing out the Ca2+-containing solution and replacing it with nominally Ca2+-free physiological solution. Kinetic analysis of the single channel recordings of the TEA- and apamin-resistant KCa channels was consistent with their having a single open state of about 2 ms (open dwell time distribution was fitted with a single exponential) and at least two closed states (two exponential functions were required to adequately fit the closed dwell time distribution). The Ca2+ dependence of the activation of TEA- and apamin-resistant KCa channels resides in the long-lived closed state which decreased from > 100 ms in the absence of Ca2+ to about 7 ms

  20. Athermalized channeled spectropolarimeter enhancement.

    SciTech Connect

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

    2013-09-01

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

  1. The channels of Mars

    NASA Technical Reports Server (NTRS)

    Baker, V. R.

    1982-01-01

    Early observations of Mars conducted by means of telescopes are considered. Secchi introduced the Italian word 'canale' ('channel') in 1869 to describe apparent lines on the planet's surface. Between 1877 and 1888 Schiaparelli mapped a profusion of 'canali'. Schiaparelli's work led to famous controversies about Mars. This book attempts to investigate the puzzle posed by the Martian channels, taking into account also the results of the studies conducted with the aid of the two orbiting Viking spacecraft which have produced a total number of nearly 60,000 pictures. The channel types are discussed along with questions regarding the distribution, the ages, and the proposed origins of the channels. Attention is given to the geomorphology of Mars, the patterns and networks of Martian valleys, ice and the Martian surface, the outflow channels, catastrophic flood processes, questions of analogy between terrestrial and Martian geographic features, and Martian phenomena associated with water liquid or water ice.

  2. The channels of Mars

    NASA Technical Reports Server (NTRS)

    Baker, V. R.

    1982-01-01

    Early observations of Mars conducted by means of telescopes are considered. Secchi introduced the Italian word 'canale' ('channel') in 1869 to describe apparent lines on the planet's surface. Between 1877 and 1888 Schiaparelli mapped a profusion of 'canali'. Schiaparelli's work led to famous controversies about Mars. This book attempts to investigate the puzzle posed by the Martian channels, taking into account also the results of the studies conducted with the aid of the two orbiting Viking spacecraft which have produced a total number of nearly 60,000 pictures. The channel types are discussed along with questions regarding the distribution, the ages, and the proposed origins of the channels. Attention is given to the geomorphology of Mars, the patterns and networks of Martian valleys, ice and the Martian surface, the outflow channels, catastrophic flood processes, questions of analogy between terrestrial and Martian geographic features, and Martian phenomena associated with water liquid or water ice.

  3. Random distributed feedback fibre lasers

    NASA Astrophysics Data System (ADS)

    Turitsyn, Sergei K.; Babin, Sergey A.; Churkin, Dmitry V.; Vatnik, Ilya D.; Nikulin, Maxim; Podivilov, Evgenii V.

    2014-09-01

    of a stationary near-Gaussian beam with a narrow spectrum. A random distributed feedback fibre laser has efficiency and performance that are comparable to and even exceed those of similar conventional fibre lasers. The key features of the generated radiation of random distributed feedback fibre lasers include: a stationary narrow-band continuous modeless spectrum that is free of mode competition, nonlinear power broadening, and an output beam with a Gaussian profile in the fundamental transverse mode (generated both in single mode and multi-mode fibres). This review presents the current status of research in the field of random fibre lasers and shows their potential and perspectives. We start with an introductory overview of conventional distributed feedback lasers and traditional random lasers to set the stage for discussion of random fibre lasers. We then present a theoretical analysis and experimental studies of various random fibre laser configurations, including widely tunable, multi-wavelength, narrow-band generation, and random fibre lasers operating in different spectral bands in the 1-1.6 μm range. Then we discuss existing and future applications of random fibre lasers, including telecommunication and distributed long reach sensor systems. A theoretical description of random lasers is very challenging and is strongly linked with the theory of disordered systems and kinetic theory. We outline two key models governing the generation of random fibre lasers: the average power balance model and the nonlinear Schrödinger equation based model. Recently invented random distributed feedback fibre lasers represent a new and exciting field of research that brings together such diverse areas of science as laser physics, the theory of disordered systems, fibre optics and nonlinear science. Stable random generation in optical fibre opens up new possibilities for research on wave transport and localization in disordered media. We hope that this review will provide

  4. Mean first-passage times of non-Markovian random walkers in confinement

    NASA Astrophysics Data System (ADS)

    Guérin, T.; Levernier, N.; Bénichou, O.; Voituriez, R.

    2016-06-01

    The first-passage time, defined as the time a random walker takes to reach a target point in a confining domain, is a key quantity in the theory of stochastic processes. Its importance comes from its crucial role in quantifying the efficiency of processes as varied as diffusion-limited reactions, target search processes or the spread of diseases. Most methods of determining the properties of first-passage time in confined domains have been limited to Markovian (memoryless) processes. However, as soon as the random walker interacts with its environment, memory effects cannot be neglected: that is, the future motion of the random walker does not depend only on its current position, but also on its past trajectory. Examples of non-Markovian dynamics include single-file diffusion in narrow channels, or the motion of a tracer particle either attached to a polymeric chain or diffusing in simple or complex fluids such as nematics, dense soft colloids or viscoelastic solutions. Here we introduce an analytical approach to calculate, in the limit of a large confining volume, the mean first-passage time of a Gaussian non-Markovian random walker to a target. The non-Markovian features of the dynamics are encompassed by determining the statistical properties of the fictitious trajectory that the random walker would follow after the first-passage event takes place, which are shown to govern the first-passage time kinetics. This analysis is applicable to a broad range of stochastic processes, which may be correlated at long times. Our theoretical predictions are confirmed by numerical simulations for several examples of non-Markovian processes, including the case of fractional Brownian motion in one and higher dimensions. These results reveal, on the basis of Gaussian processes, the importance of memory effects in first-passage statistics of non-Markovian random walkers in confinement.

  5. A Gas Kinetic Explanation of Simple Thermodynamic Processes.

    ERIC Educational Resources Information Center

    Waite, Boyd A.

    1985-01-01

    Heat is defined as a random or nondirected internal energy transfer between different bodies at different temperatures. Work is defined as oriented or nonrandom internal energy transfer. Both heat and work are demonstrated to lead to increases in temperature via interpretations from gas kinetic theory. (JN)

  6. A Gas Kinetic Explanation of Simple Thermodynamic Processes.

    ERIC Educational Resources Information Center

    Waite, Boyd A.

    1985-01-01

    Heat is defined as a random or nondirected internal energy transfer between different bodies at different temperatures. Work is defined as oriented or nonrandom internal energy transfer. Both heat and work are demonstrated to lead to increases in temperature via interpretations from gas kinetic theory. (JN)

  7. Linear kinetic theory and particle transport in stochastic mixtures

    SciTech Connect

    Pomraning, G.C.

    1995-12-31

    We consider the formulation of linear transport and kinetic theory describing energy and particle flow in a random mixture of two or more immiscible materials. Following an introduction, we summarize early and fundamental work in this area, and we conclude with a brief discussion of recent results.

  8. LLNL Chemical Kinetics Modeling Group

    SciTech Connect

    Pitz, W J; Westbrook, C K; Mehl, M; Herbinet, O; Curran, H J; Silke, E J

    2008-09-24

    The LLNL chemical kinetics modeling group has been responsible for much progress in the development of chemical kinetic models for practical fuels. The group began its work in the early 1970s, developing chemical kinetic models for methane, ethane, ethanol and halogenated inhibitors. Most recently, it has been developing chemical kinetic models for large n-alkanes, cycloalkanes, hexenes, and large methyl esters. These component models are needed to represent gasoline, diesel, jet, and oil-sand-derived fuels.

  9. Open-channel block by internally applied amines inhibits activation gate closure in batrachotoxin-activated sodium channels.

    PubMed Central

    Zamponi, G W; French, R J

    1994-01-01

    We have studied the action of several pore-blocking amines on voltage-dependent activation gating of batrachotoxin(BTX)-activated sodium channels, from bovine heart and rat skeletal muscle, incorporated into planar lipid bilayers. Although structurally simpler, the compounds studied show general structural features and channel-inhibiting actions that resemble those of lidocaine. When applied to the cytoplasmic end of the channel, these compounds cause a rapid, voltage-dependent, open-channel block seen as a reduction in apparent single-channel amplitude (companion paper). Internal application of phenylpropanolamine, phenylethylamine, phenylmethylamine, and diethylamine, as well as causing open-channel block, reduces the probability of channel closure, producing a shift of the steady-state activation curve toward more hyperpolarizing potentials. These gating effects were observed for both cardiac and skeletal muscle channels and were not evoked by addition of equimolar N-Methyl-D-Glucamine, suggesting a specific interaction of the blockers with the channel rather than a surface charge effect. Kinetic analysis of phenylpropanolamine action on skeletal muscle channels indicated that phenylpropanolamine reduced the closed probability via two separate mechanisms. First, mean closed durations were slightly abbreviated in its presence. Second, and more important, the frequency of the gating closures was reduced. This action was correlated with the degree, and the voltage dependence, of open-channel block, suggesting that the activation gate cannot close while the pore is occluded by the blocker. Such a mechanism might underlie the previously reported immobilization of gating charge associated with local anesthetic block of unmodified sodium channels. PMID:7811914

  10. Impact of the kinetic boundary condition on porous media flow in the lattice Boltzmann formulation

    NASA Astrophysics Data System (ADS)

    Singh, Shiwani; Jiang, Fei; Tsuji, Takeshi

    2017-07-01

    To emphasize the importance of the kinetic boundary condition for micro- to nanoscale flow, we present an ad hoc kinetic boundary condition suitable for torturous geological porous media. We found that the kinetic boundary condition is one of the essential features which should be supplemented to the standard lattice Boltzmann scheme in order to obtain accurate continuum observables. The claim is validated using a channel flow setup by showing the agreement of mass flux with analytical value. Further, using a homogeneous porous structure, the importance of the kinetic boundary condition is shown by comparing the permeability correction factor with the analytical value. Finally, the proposed alternate to the kinetic boundary condition is validated by showing its capability to capture the basic feature of the kinetic boundary condition.

  11. Data Processing for NASA's TDRSS DAMA Channel

    NASA Technical Reports Server (NTRS)

    Long, Christopher C.; Horan, Stephen

    1996-01-01

    A concept for the addition of a Demand Assignment Multiple Access (DAMA) service to NASA's current Space Network (SN) is developed. Specifically, the design of a receiver for the DAMA channel is outlined. Also, an outline of the procedures taken to process the received service request is presented. The modifications to the (SN) system are minimal. The post reception processing is accomplished using standard commercial off the shelf (COTS) packages. The result is a random access system capable of receiving requests for service.

  12. Atom location by electron channeling analysis

    SciTech Connect

    Pennycook, S.J.

    1984-07-01

    For many years the orientation dependence of the characteristic x-ray emission close to a Bragg reflection has been regarded as a hindrance to accurate microanalysis, and a random incident beam direction has always been recommended for accurate composition analysis. However, this orientation dependence can be put to use to extract information on the lattice location of foreign atoms within the crystalline matrix. Here a generalization of the technique is described which is applicable to any crystal structure including monatomic crystals, and can quantitatively determine substitutional fractions of impurities. The technique was referred to as electron channeling analysis, by analogy with the closely related and widely used bulk technique of ion channeling analysis, and was developed for lattice location studies of dopants in semiconductors at high spatial resolution. Only two spectra are required for each channeling analysis, one in each of the channeling conditions described above. If the matrix and dopant x-ray yields vary identically between the two orientations then the dopant necessarily lies within the reflecting matrix planes. If the dopant x-ray yield does not vary the dopant atoms are randomly located with respect to the matrix planes. 10 references, 2 figures.

  13. Conductance of Ion Channels - Theory vs. Experiment

    NASA Technical Reports Server (NTRS)

    Pohorille, Andrew; Wilson, Michael; Mijajlovic, Milan

    2013-01-01

    Transmembrane ion channels mediate a number of essential physiological processes in a cell ranging from regulating osmotic pressure to transmission of neural signals. Kinetics and selectivity of ion transport is of critical importance to a cell and, not surprisingly, it is a subject of numerous experimental and theoretical studies. In this presentation we will analyze in detail computer simulations of two simple channels from fungi - antiamoebin and trichotoxin. Each of these channels is made of an alpha-helical bundle of small, nongenomically synthesized peptides containing a number of rare amino acids and exhibits strong antimicrobial activity. We will focus on calculating ionic conductance defined as the ratio of ionic current through the channel to applied voltage. From molecular dynamics simulations, conductance can be calculated in at least two ways, each involving different approximations. Specifically, the current, given as the number of charges transferred through the channel per unit of time, can be obtained from the number of events in which ions cross the channel during the simulation. This method works well for large currents (high conductance values and/or applied voltages). If the number of crossing events is small, reliable estimates of current are difficult to achieve. Alternatively, conductance can be estimated assuming that ion transport can be well approximated as diffusion in the external potential given by the free energy profile. Then, the current can be calculated by solving the one-dimensional diffusion equation in this external potential and applied voltage (the generalized Nernst-Planck equation). To do so three ingredients are needed: the free energy profile, the position-dependent diffusion coefficient and the diffusive flux of ions into the channel. All these quantities can be obtained from molecular dynamics simulations. An important advantage of this method is that it can be used equally well to estimating large and small currents

  14. An Introductory Level Kinetics Investigation.

    ERIC Educational Resources Information Center

    McGarvey, J. E. B.; Knipe, A. C.

    1980-01-01

    Provides a list of the reactions commonly used for introductory kinetics studies. These reactions illustrate the kinetics concepts of rate law, rate constant, and reaction order. Describes a kinetic study of the hydrolysis of 3-bromo-3-phenylpropanoic acid which offers many educational advantages. (CS)

  15. An Introductory Level Kinetics Investigation.

    ERIC Educational Resources Information Center

    McGarvey, J. E. B.; Knipe, A. C.

    1980-01-01

    Provides a list of the reactions commonly used for introductory kinetics studies. These reactions illustrate the kinetics concepts of rate law, rate constant, and reaction order. Describes a kinetic study of the hydrolysis of 3-bromo-3-phenylpropanoic acid which offers many educational advantages. (CS)

  16. Wealth redistribution in conservative linear kinetic models

    NASA Astrophysics Data System (ADS)

    Toscani, G.

    2009-10-01

    We introduce and discuss kinetic models for wealth distribution which include both taxation and uniform redistribution. The evolution of the continuous density of wealth obeys a linear Boltzmann equation where the background density represents the action of an external subject on the taxation mechanism. The case in which the mean wealth is conserved is analyzed in full details, by recovering the analytical form of the steady states. These states are probability distributions of convergent random series of a special structure, called perpetuities. Among others, Gibbs distribution appears as steady state in case of total taxation and uniform redistribution.

  17. Sodium channel inactivation in the crayfish giant axon. Must channels open before inactivating

    SciTech Connect

    Bean, B.P.

    1981-09-01

    Experiments on sodium channel inactivation kinetics were performed on voltage-clamped crayfish giant axons. The primary goals was to investigate whether channels must open before activating. Voltage-clamp artifacts were minimized by the use of low-sodium solutions and full series resistance compensation, and the spatial uniformity of the currents was checked with a closely spaced pair of electrodes used to measure local current densities. For membrane potentials between -40 and +40 mV, sodium currents decay to zero with a single exponential time-course. The time constant for decay is a steep function of membrane potential. The time-course of inactivation measured with the double-pulse method is very similar to the decay of current at the same potential. Steady-state inactivation curves measured with different test pulses are identical. The time-course of doubling pulse inactivation shows a lag that roughly correlates with the opening of sodium channels, but it is not strictly necessary for channels to open before inactivating. Measurements of the potential dependence of the integral of sodium conductance are also inconsistent with the simplest cases of models in which channels must open before activating.

  18. Random grammars

    NASA Astrophysics Data System (ADS)

    Malyshev, V. A.

    1998-04-01

    Contents § 1. Definitions1.1. Grammars1.2. Random grammars and L-systems1.3. Semigroup representations § 2. Infinite string dynamics2.1. Cluster expansion2.2. Cluster dynamics2.3. Local observer § 3. Large time behaviour: small perturbations3.1. Invariant measures3.2. Classification § 4. Large time behaviour: context free case4.1. Invariant measures for grammars4.2. L-systems4.3. Fractal correlation functions4.4. Measures on languages Bibliography

  19. Fine Channel Networks

    NASA Technical Reports Server (NTRS)

    1997-01-01

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

  20. Fine Channel Networks

    NASA Technical Reports Server (NTRS)

    1997-01-01

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

  1. Assay for calcium channels

    SciTech Connect

    Glossmann, H.; Ferry, D.R.

    1985-01-01

    This chapter focuses on biochemical assays for Ca/sup 2 +/-selective channels in electrically excitable membranes which are blocked in electrophysiological and pharmacological experiments by verapamil, 1,4-dihydropyridines, diltiazen (and various other drugs), as well as inorganic di- or trivalent cations. The strategy employed is to use radiolabeled 1,4-dihydropyridine derivatives which block calcium channels with ED/sub 50/ values in the nanomolar range. Although tritiated d-cis-diltiazem and verapamil can be used to label calcium channels, the 1,4-dihydropyridines offer numerous advantages. The various sections cover tissue specificity of channel labeling, the complex interactions of divalent cations with the (/sup 3/H)nimodipine-labeled calcium channels, and the allosteric regulation of (/sup 3/H)nimodipine binding by the optically pure enantiomers of phenylalkylamine and benzothiazepine calcium channel blockers. A comparison of the properties of different tritiated 1,4-dihydropyridine radioligands and the iodinated channel probe (/sup 125/I)iodipine is given.

  2. Kinetic Tetrazolium Microtiter Assay

    NASA Technical Reports Server (NTRS)

    Pierson, Duane L.; Stowe, Raymond; Koenig, David

    1993-01-01

    Kinetic tetrazolium microtiter assay (KTMA) involves use of tetrazolium salts and Triton X-100 (or equivalent), nontoxic, in vitro color developer solubilizing colored metabolite formazan without injuring or killing metabolizing cells. Provides for continuous measurement of metabolism and makes possible to determine rate of action of antimicrobial agent in real time as well as determines effective inhibitory concentrations. Used to monitor growth after addition of stimulatory compounds. Provides for kinetic determination of efficacy of biocide, greatly increasing reliability and precision of results. Also used to determine relative effectiveness of antimicrobial agent as function of time. Capability of generating results on day of test extremely important in treatment of water and waste, disinfection of hospital rooms, and in pharmaceutical, agricultural, and food-processing industries. Assay also used in many aspects of cell biology.

  3. Kinetic Tetrazolium Microtiter Assay

    NASA Technical Reports Server (NTRS)

    Pierson, Duane L.; Stowe, Raymond; Koenig, David

    1993-01-01

    Kinetic tetrazolium microtiter assay (KTMA) involves use of tetrazolium salts and Triton X-100 (or equivalent), nontoxic, in vitro color developer solubilizing colored metabolite formazan without injuring or killing metabolizing cells. Provides for continuous measurement of metabolism and makes possible to determine rate of action of antimicrobial agent in real time as well as determines effective inhibitory concentrations. Used to monitor growth after addition of stimulatory compounds. Provides for kinetic determination of efficacy of biocide, greatly increasing reliability and precision of results. Also used to determine relative effectiveness of antimicrobial agent as function of time. Capability of generating results on day of test extremely important in treatment of water and waste, disinfection of hospital rooms, and in pharmaceutical, agricultural, and food-processing industries. Assay also used in many aspects of cell biology.

  4. Kinetic Damage from Meteorites

    NASA Technical Reports Server (NTRS)

    Cooke, W.; Matney, M.; Brown, P.

    2017-01-01

    Comparing the natural meteorite flux at the Earth's surface to that of space debris, reentering debris is approx. 2 orders of magnitude less of a kinetic hazard at all but the very largest (and therefore rarest) sizes compared to natural impactors. Debris re-entries over several metric tonnes are roughly as frequent as natural impactors, but the survival fraction is expected to be much higher. Kinetic hazards from meteorites are very small, with only one recorded (indirect) injury reported. We expect fatalities to be even more rare, on the order of one person killed per several millennia. That several reports exist of small fragments/sand hitting people during meteorite falls is consistent with our prediction that this should occur every decade or so.

  5. Kinetic Damage from Meteorites

    NASA Technical Reports Server (NTRS)

    Cooke, W.; Brown, P.; Matney, M.

    2017-01-01

    Comparing the natural meteorite flux at the Earth's surface to that of space debris, re-entering debris is 2 orders of magnitude less of a kinetic hazard at all but the very largest (and therefore rarest) sizes compared to natural impactors. Debris re-entries over several metric tonnes are roughly as frequent as natural impactors, but the survival fraction is expected to be much higher. Kinetic hazards from meteorites are very small, with only one recorded (indirect) injury reported. We expect fatalities to be even more rare, on the order of one person killed per several millennia. That several reports exist of small fragments/sand hitting people during meteorite falls is consistent with our prediction that this should occur every decade or so.

  6. Kinetic Modelling of Transcription Elongation

    NASA Astrophysics Data System (ADS)

    O'Maoileidigh, Daibhid; Tadigotla, Vasisht; Sengupta, Anirvan; Epshtein, Vitaly; Ebright, Richard; Nudler, Evgeny; Ruckenstein, Andrei

    2006-03-01

    Transcription is the first step in gene expression and it is at this stage that most of genetic regulation occurs. The enzyme RNA polymerase (RNAP) walks along DNA creating an RNA transcript at a highly non-uniform rate. We discuss how many non-intuitive features of the system may be experimentally and physically motivated and present first a model, which agrees qualitatively with a host of experimental evidence. We also examine intrinsic pauses where it is thought that the RNAP will move backwards along the DNA template without changing the length of the RNA transcript. We describe a simplified kinetic scheme for the recovery of intrinsic pauses with the same degree of predictive power as our thermodynamic model (presented separately). The separation of timescales between the movement of the RNAP and global changes in the RNA secondary structure is seen to be crucial for the function of RNAP. This is essentially a model of a Brownian ratchet where RNAP executes a 1D random walk in a sequence dependent potential over a range determined by the co-transcriptional RNA fold for each transcript length

  7. Reconfigurable virtual electrowetting channels.

    PubMed

    Banerjee, Ananda; Kreit, Eric; Liu, Yuguang; Heikenfeld, Jason; Papautsky, Ian

    2012-02-21

    Lab-on-a-chip systems rely on several microfluidic paradigms. The first uses a fixed layout of continuous microfluidic channels. Such lab-on-a-chip systems are almost always application specific and far from a true "laboratory." The second involves electrowetting droplet movement (digital microfluidics), and allows two-dimensional computer control of fluidic transport and mixing. The merging of the two paradigms in the form of programmable electrowetting channels takes advantage of both the "continuous" functionality of rigid channels based on which a large number of applications have been developed to date and the "programmable" functionality of digital microfluidics that permits electrical control of on-chip functions. In this work, we demonstrate for the first time programmable formation of virtual microfluidic channels and their continuous operation with pressure driven flows using an electrowetting platform. Experimental, theoretical, and numerical analyses of virtual channel formation with biologically relevant electrolyte solutions and electrically-programmable reconfiguration are presented. We demonstrate that the "wall-less" virtual channels can be formed reliably and rapidly, with propagation rates of 3.5-3.8 mm s(-1). Pressure driven transport in these virtual channels at flow rates up to 100 μL min(-1) is achievable without distortion of the channel shape. We further demonstrate that these virtual channels can be switched on-demand between multiple inputs and outputs. Ultimately, we envision a platform that would provide rapid prototyping of microfluidic concepts and would be capable of a vast library of functions and benefitting applications from clinical diagnostics in resource-limited environments to rapid system prototyping to high throughput pharmaceutical applications.

  8. Kinetic Theory of Gases

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    The theory, developed in the nineteenth century, notably by Rudolf Clausius (1822-88) and James Clerk Maxwell (1831-79), that the properties of a gas (temperature, pressure, etc) could be described in terms of the motions (and kinetic energy) of the molecules comprising the gases. The theory has wide implications in astrophysics. In particular, the perfect gas law, which relates the pressure, vol...

  9. Interactions of organic calcium channel antagonists with calcium channels in single frog atrial cells

    PubMed Central

    1985-01-01

    Inhibition of whole-cell calcium currents in enzymatically dispersed frog atrial myocytes by D-600, diltiazem, and nifedipine was studied using a single-micropipette voltage-clamp technique. The objective of these experiments was to test the applicability of a modulated-receptor hypothesis similar to that proposed for local anesthetic interactions with sodium channels to account for the tonic and frequency-dependent interactions of these organic compounds with myocardial calcium channels. Data consistent with such a hypothesis include: (a) prominent use-dependent block of iCa by D-600 and diltiazem, which are predominantly charged at physiological pH; (b) iCa block by an externally applied, permanently charged dihydropyridine derivative is greatly attenuated; (c) all three antagonists produce large negative shifts in the voltage dependence of iCa availability; (d) block of iCa by these compounds is state-dependent; (e) reactivation of iCa in the presence of all three antagonists is biexponential, which suggests that drug-free channels recover with a normal time course and drug-bound channels recover more slowly; and (f) the kinetics of the drug-induced slow iCa recovery process may be determined largely by factors such as size and molecular weight, in addition to lipid solubility of the compounds. Experiments in which the pH was modified, however, reveal some important differences for the interaction of organic calcium antagonists with myocardial calcium channels. Acidification, in addition to changing the proportion of charged and neutral antagonist in solution, was found to selectively antagonize tonic inhibition of iCa by diltiazem and nifedipine, without changing the kinetics of the drug-induced slow iCa reactivation process. It is concluded that two distinct receptor sites may be involved in block of iCa by some of these compounds: a proton-accessible site and a proton-inaccessible site. PMID:2582076

  10. Kinetic and Structural Characterization of Tunnel-Perturbing Mutants in Bradyrhizobium japonicum Proline Utilization A

    PubMed Central

    2015-01-01

    Proline utilization A from Bradyrhizobium japonicum (BjPutA) is a bifunctional flavoenzyme that catalyzes the oxidation of proline to glutamate using fused proline dehydrogenase (PRODH) and Δ1-pyrroline-5-carboxylate dehydrogenase (P5CDH) domains. Recent crystal structures and kinetic data suggest an intramolecular channel connects the two active sites, promoting substrate channeling of the intermediate Δ1-pyrroline-5-carboxylate/glutamate-γ-semialdehyde (P5C/GSA). In this work, the structure of the channel was explored by inserting large side chain residues at four positions along the channel in BjPutA. Kinetic analysis of the different mutants revealed replacement of D779 with Tyr (D779Y) or Trp (D779W) significantly decreased the overall rate of the PRODH–P5CDH channeling reaction. X-ray crystal structures of D779Y and D779W revealed that the large side chains caused a constriction in the central section of the tunnel, thus likely impeding the travel of P5C/GSA in the channel. The D779Y and D779W mutants have PRODH activity similar to that of wild-type BjPutA but exhibit significantly lower P5CDH activity, suggesting that exogenous P5C/GSA enters the channel upstream of Asp779. Replacement of nearby Asp778 with Tyr (D778Y) did not impact BjPutA channeling activity. Consistent with the kinetic results, the X-ray crystal structure of D778Y shows that the main channel pathway is not impacted; however, an off-cavity pathway is closed off from the channel. These findings provide evidence that the off-cavity pathway is not essential for substrate channeling in BjPutA. PMID:25046425

  11. Kinetic and structural characterization of tunnel-perturbing mutants in Bradyrhizobium japonicum proline utilization A.

    PubMed

    Arentson, Benjamin W; Luo, Min; Pemberton, Travis A; Tanner, John J; Becker, Donald F

    2014-08-12

    Proline utilization A from Bradyrhizobium japonicum (BjPutA) is a bifunctional flavoenzyme that catalyzes the oxidation of proline to glutamate using fused proline dehydrogenase (PRODH) and Δ(1)-pyrroline-5-carboxylate dehydrogenase (P5CDH) domains. Recent crystal structures and kinetic data suggest an intramolecular channel connects the two active sites, promoting substrate channeling of the intermediate Δ(1)-pyrroline-5-carboxylate/glutamate-γ-semialdehyde (P5C/GSA). In this work, the structure of the channel was explored by inserting large side chain residues at four positions along the channel in BjPutA. Kinetic analysis of the different mutants revealed replacement of D779 with Tyr (D779Y) or Trp (D779W) significantly decreased the overall rate of the PRODH-P5CDH channeling reaction. X-ray crystal structures of D779Y and D779W revealed that the large side chains caused a constriction in the central section of the tunnel, thus likely impeding the travel of P5C/GSA in the channel. The D779Y and D779W mutants have PRODH activity similar to that of wild-type BjPutA but exhibit significantly lower P5CDH activity, suggesting that exogenous P5C/GSA enters the channel upstream of Asp779. Replacement of nearby Asp778 with Tyr (D778Y) did not impact BjPutA channeling activity. Consistent with the kinetic results, the X-ray crystal structure of D778Y shows that the main channel pathway is not impacted; however, an off-cavity pathway is closed off from the channel. These findings provide evidence that the off-cavity pathway is not essential for substrate channeling in BjPutA.

  12. Entanglement of random subspaces via the Hastings bound

    SciTech Connect

    Fukuda, Motohisa; King, Christopher

    2010-04-15

    Recently, Hastings ['A counterexample to additivity of minimum output entropy', Nat. Phys. 5, 255 (2009); e-print arXiv:0809.3972v3] proved the existence of random unitary channels, which violate the additivity conjecture. In this paper, we use Hastings' method to derive new bounds for the entanglement of random subspaces of bipartite systems. As an application we use these bounds to prove the existence of nonunital channels, which violate additivity of minimal output entropy.

  13. Potassium channels of pig articular chondrocytes are blocked by propofol.

    PubMed

    Mozrzymas, J W; Visintin, M; Vittur, F; Ruzzier, F

    1994-07-15

    The effect of propofol on the voltage-activated potassium channels in pig articular chondrocytes was investigated. Propofol was found to reversibly block the potassium channels in a dose-dependent manner. The blocking effect was voltage-independent and the Hill coefficient was 1.85 +/- 0.18. No changes either in the slope conductance or in the single channel kinetics were observed. The half-blocking concentration (Ec50) was 6.0 +/- 0.49 microM which is much lower than the concentrations used to observe the scavenging effect of the drug in an artificial synovial fluid. Interestingly, Ec50 found in our experiments is also smaller than the blood concentration of propofol used in anaesthesia. These results show that propofol may strongly affect the potassium channels in some non-excitable cells.

  14. Homogeneous nucleation kinetics

    NASA Technical Reports Server (NTRS)

    Rasmussen, D. H.; Appleby, M. R.; Leedom, G. L.; Babu, S. V.; Naumann, R. J.

    1983-01-01

    Homogeneous nucleation kinetics are rederived in a manner fundamentally similar to the approach of classical nucleation theory with the following modifications and improvements. First, the cluster is a parent phase cluster and does not require energization to the parent state. Second, the thermodynamic potential used to describe phase stability is a continuous function along the pathway of phase decomposition. Third, the kinetics of clustering corresponds directly to the diffusional flux of monomers through the cluster distribution and are formally similar to classical theory with the resulting kinetic equation modified by two terms in the preexponential factor. These terms correct for the influence of a supersaturation dependent clustering within the parent phase and for the influence of an asymmetrical cluster concentration as a function of cluster size at the critical cluster size. Fourth, the supersaturation dependence of the nucleation rate is of the same form as that given by classical nucleation theory. This supersaturation dependence must however be interpreted in terms of a size dependent surface tension. Finally, there are two scaling laws which describe supersaturation to either constant nucleation rate or to the thermodynamically determined physical spinodal.

  15. Effective gating charges per channel in voltage-dependent K+ and Ca2+ channels

    PubMed Central

    1996-01-01

    In voltage-dependent ion channels, the gating of the channels is determined by the movement of the voltage sensor. This movement reflects the rearrangement of the protein in response to a voltage stimulus, and it can be thought of as a net displacement of elementary charges (e0) through the membrane (z: effective number of elementary charges). In this paper, we measured z in Shaker IR (inactivation removed) K+ channels, neuronal alpha 1E and alpha 1A, and cardiac alpha 1C Ca2+ channels using two methods: (a) limiting slope analysis of the conductance-voltage relationship and (b) variance analysis, to evaluate the number of active channels in a patch, combined with the measurement of charge movement in the same patch. We found that in Shaker IR K+ channels the two methods agreed with a z congruent to 13. This suggests that all the channels that gate can open and that all the measured charge is coupled to pore opening in a strictly sequential kinetic model. For all Ca2+ channels the limiting slope method gave consistent results regardless of the presence or type of beta subunit tested (z = 8.6). However, as seen with alpha 1E, the variance analysis gave different results depending on the beta subunit used. alpha 1E and alpha 1E beta 1a gave higher z values (z = 14.77 and z = 15.13 respectively) than alpha 1E beta 2a (z = 9.50, which is similar to the limiting slope results). Both the beta 1a and beta 2a subunits, coexpressed with alpha 1E Ca2+ channels facilitated channel opening by shifting the activation curve to more negative potentials, but only the beta 2a subunit increased the maximum open probability. The higher z using variance analysis in alpha 1E and alpha 1E beta 1a can be explained by a set of charges not coupled to pore opening. This set of charges moves in transitions leading to nulls thus not contributing to the ionic current fluctuations but eliciting gating currents. Coexpression of the beta 2a subunit would minimize the fraction of nulls leading to

  16. Energy cascade down to kinetic scales and the role of pressure tensor in heating of kinetic plasma

    NASA Astrophysics Data System (ADS)

    Yang, Y.; Matthaeus, W. H.; Parashar, T.; Wan, M.

    2016-12-01

    The classical energy cascade theory suggests that energy is transferred from large to small scales at a constant rate and nonlinear interactions occur predominately between comparable scales. This scenario is of great importance in explaining the heating of corona and solar wind. One can envision that energy residing in large-scale fluctuations is transported to smaller scales where dissipation occurs and finally drives kinetic processes that absorb the energy flux and energize charged particles. The energy cascade well above kinetic scales has been studied, while little is known about that when getting close to ion kinetic scales. When filtering the Vlasov equation, we can introduce several energy transfer functions across scales and filtered energy equations resembling to those in MHD. We propose to use kinetic plasma simulations and investigate how the characteristics of energy transfer vary going from MHD to kinetic scales. It has been shown that in compressible MHD turbulence [1] , apart from dissipation, the pressure dilation, p ∇ \\cdot {u}, can trigger an alternative channel of the conversion between kinetic and internal energy. We will address the analogous roles of the (tensor) pressure dilation, which now reads ( {P} \\cdot ∇ ) \\cdot {u} in collisionless plasma. We study, for example, effects of anisotropic and isotropic pressure, and of the diagonal and off-diagonal pressure tensor, and related influences on dissipation and heating. [1] Y. Yang et al, Phys. Rev. E, 93, 061102(R) (2016)

  17. Channel Access in Erlang

    SciTech Connect

    Nicklaus, Dennis J.

    2013-10-13

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

  18. ARQ on fading channels

    NASA Astrophysics Data System (ADS)

    Beirouti, Patrick; Leib, Harry; Morgera, Salvatore D.

    A recursive procedure for obtaining a (2 to the power n)-state extended Gilbert-Elliott fading channel model suitable for n-bit block codes is described. The extended model may be used for numerical assessment of the throughput of a variety of popular automatic repeat-request schemes used over fading channels such as those encountered in mobile communications systems. Computationally efficient lower and upper performance bounds are also developed for low memory fading channels. It is found that the throughput of the stop-and-wait protocol exhibits a maximum; therefore, there exists an optimum codeword length for this automatic repeat-request scheme.

  19. Fractional channel multichannel analyzer

    DOEpatents

    Brackenbush, Larry W.; Anderson, Gordon A.

    1994-01-01

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

  20. Fractional channel multichannel analyzer

    DOEpatents

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

    1994-08-23

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

  1. Kinetic model of excitatory synaptic transmission to cerebellar Purkinje cells.

    PubMed

    Marienhagen, J; Keller, B U; Zippelius, A

    1997-09-21

    We present a minimal kinetic model for excitatory synaptic transmission to cerebellar Purkinje cells. The main components are a kinetic model for a single glutamate receptor, which is calibrated with the help of patch clamp data, and a mean field approximation for the dynamics of a population of channels, which generate an EPSC. The resulting minimal model of the parallel fiber-Purkinje cell synapse is used to estimate the dynamics of glutamate in the synaptic cleft and to clarify the role of receptor desensitization in synaptic transmission. We also apply the model to different aspects of synaptic modulation, like long-term depression and potentiation by pharmacological application of ampakines. In the framework of the minimal model these effects can be understood as the result of modified receptor kinetics.

  2. Synthesis, characterization, and evaluation of a superficially porous particle with unique, elongated pore channels normal to the surface.

    PubMed

    Wei, Ta-Chen; Mack, Anne; Chen, Wu; Liu, Jia; Dittmann, Monika; Wang, Xiaoli; Barber, William E

    2016-04-01

    In recent years, superficially porous particles (SPPs) have drawn great interest because of their special particle characteristics and improvement in separation efficiency. Superficially porous particles are currently manufactured by adding silica nanoparticles onto solid cores using either a multistep multilayer process or one-step coacervation process. The pore size is mainly controlled by the size of the silica nanoparticles and the tortuous pore channel geometry is determined by how those nanoparticles randomly aggregate. Such tortuous pore structure is also similar to that of all totally porous particles used in HPLC today. In this article, we report on the development of a next generation superficially porous particle with a unique pore structure that includes a thinner shell thickness and ordered pore channels oriented normal to the particle surface. The method of making the new superficially porous particles is a process called pseudomorphic transformation (PMT), which is a form of micelle templating. Porosity is no longer controlled by randomly aggregated nanoparticles but rather by micelles that have an ordered liquid crystal structure. The new particle possesses many advantages such as a narrower particle size distribution, thinner porous layer with high surface area and, most importantly, highly ordered, non-tortuous pore channels oriented normal to the particle surface. This PMT process has been applied to make 1.8-5.1μm SPPs with pore size controlled around 75Å and surface area around 100m(2)/g. All particles with different sizes show the same unique pore structure with tunable pore size and shell thickness. The impact of the novel pore structure on the performance of these particles is characterized by measuring van Deemter curves and constructing kinetic plots. Reduced plate heights as low as 1.0 have been achieved on conventional LC instruments. This indicates higher efficiency of such particles compared to conventional totally porous and

  3. Calcite Dissolution Kinetics

    NASA Astrophysics Data System (ADS)

    Berelson, W.; Subhas, A.; Dong, S.; Naviaux, J.; Adkins, J. F.

    2016-12-01

    A geological buffer for high atmospheric CO2 concentrations is neutralization via reaction with CaCO3. We have been studying the dissolution kinetics of carbonate minerals using labeled 13C calcite and Picarro-based measurements of 13C enrichments in solution DIC. This methodology has greatly facilitated our investigation of dissolution kinetics as a function of water carbonate chemistry, temperature and pressure. One can adjust the saturation state Omega by changing the ion activity product (e.g. adjusting carbonate ion concentration), or by changing the solubility product (e.g. adjusting temperature or pressure). The canonical formulation of dissolution rate vs. omega has been refined (Subhas et al. 2015) and shows distinct non-linear behavior near equilibrium and rates in sea water of 1-3 e-6 g/cm2day at omega = 0.8. Carbonic anhydrase (CA), an enzyme that catalyzes the hydration of dissolved CO2 to carbonic acid, was shown (in concentrations <=0.04 g/L) to enhance the dissolution rate at low degrees of undersaturation by >500x. This result points to the importance of carbonic acid in enhancing dissolution at low degrees of undersaturation. CA activity and abundance in nature must be considered regarding the role it plays in catalyzing dissolution. We also have been investigating the role of temperature on dissolution kinetics. An increase of 16C yields an order of magnitude increase in dissolution rate. Temperature (and P) also change Omega critical, the saturation state where dissolution rates change substantially. Increasing pressure (achieved in a pressure reaction chamber we built) also shifts Omega critical closer to equilibrium and small pressure increases have large impact on dissolution kinetics. Dissolution rates are enhanced by an order of magnitude for a change in pressure of 1500 psi relative to the dissolution rate achieved by water chemistry effects alone for an omega of 0.8. We've shown that the thermodynamic determination of saturation state

  4. The trapping block of NMDA receptor channels in acutely isolated rat hippocampal neurones

    PubMed Central

    Sobolevsky, Alexander I; Yelshansky, Maria V

    2000-01-01

    N-methyl-d-aspartate (NMDA) receptor responses were recorded from acutely isolated rat hippocampal neurones using the whole-cell patch-clamp technique. A rapid perfusion system was used to study the voltage-dependent block of NMDA channels by Mg2+, amantadine (AM) and N-2-(adamantyl)-hexamethylenimine (A-7). Mg2+, AM and A-7-induced stationary blockade of NMDA channels increased with the blocker concentration but did not depend on the agonist (aspartate; Asp) concentration. Blockade by AM and A-7, but not Mg2+, was weakly use dependent. ‘Hooked’ tail currents were observed after coapplication of Asp and Mg2+, AM or A-7. The hooked tail current kinetics, amplitude and carried charge indicated that Mg2+, AM and A-7 did not prevent closure and desensitization of NMDA channels nor agonist dissociation. Tail currents following Asp application in the absence and continuous presence of Mg2+, AM or A-7 had similar kinetics. Application of multiple stationary and kinetic criteria to the Mg2+, AM and A-7 blockade led us to conclude that their effects on NMDA channels can be described in terms of a ‘trapping’ model, which is fully symmetrical with respect to the blocking transition. In general, the apparent blocking/recovery kinetics predicted by the fully symmetrical trapping model differ significantly from the microscopic kinetics and depend on the rate of binding and unbinding of the blocker, the NMDA channel open probability and the rate of solution exchange. PMID:10922002

  5. Ion permeation of AQP6 water channel protein. Single channel recordings after Hg2+ activation.

    PubMed

    Hazama, Akihiro; Kozono, David; Guggino, William B; Agre, Peter; Yasui, Masato

    2002-08-09

    Aquaporin-6 (AQP6) has recently been identified as an intracellular vesicle water channel with anion permeability that is activated by low pH or HgCl2. Here we present direct evidence of AQP6 channel gating using patch clamp techniques. Cell-attached patch recordings of AQP6 expressed in Xenopus laevis oocytes indicated that AQP6 is a gated channel with intermediate conductance (49 picosiemens in 100 mm NaCl) induced by 10 microm HgCl2. Current-voltage relationships were linear, and open probability was fairly constant at any given voltage, indicating that Hg2+-induced AQP6 conductance is voltage-independent. The excised outside-out patch recording revealed rapid activation of AQP6 channels immediately after application of 10 microm HgCl2. Reduction of both Na+ and Cl- concentrations from 100 to 30 mm did not shift the reversal potential of the Hg2+-induced AQP6 current, suggesting that Na+ is as permeable as Cl-. The Na+ permeability of Hg2+-induced AQP6 current was further demonstrated by 22Na+ influx measurements. Site-directed mutagenesis identified Cys-155 and Cys-190 residues as the sites of Hg2+ activation both for water permeability and ion conductance. The Hill coefficient from the concentration-response curve for Hg2+-induced conductance was 1.1 +/- 0.3. These data provide the first evidence of AQP6 channel gating at a single-channel level and suggest that each monomer contains the pore region for ions based on the number of Hg2+-binding sites and the kinetics of Hg2+-activation of the channel.

  6. Src tyrosine kinase alters gating of hyperpolarization-activated HCN4 pacemaker channel through Tyr531.

    PubMed

    Li, Chen-Hong; Zhang, Qi; Teng, Bunyen; Mustafa, S Jamal; Huang, Jia